Nutcracker syndrome and glomerulonephritis in pediatric patients: A causal or coincidental association?

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So Hyun Ki, Min Hwa Son, Hyung Eun Yim This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4418523/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Nutcracker syndrome (NCS) has been reported to coexist with various glomerulonephritis (GN). This study investigated clinical features of NCS combined with GN in a pediatric case series and the possible relationship between these two conditions. Methods Clinical and pathologic findings of 15 children with NCS and biopsy-proven GN were analyzed. NCS was diagnosed with renal Doppler ultrasonography, abdominal computed tomography, and/or magnetic resonance imaging. Glomerular lesions were divided into two pathological categories: minor glomerular abnormalities (MGAs) and definite GN. Results Mean age of all patients was 11 ± 3.36 years and mean follow-up duration was 53.2 ± 28.7 months. Chief complaint was proteinuria with or without hematuria. During follow-up, five patients developed left kidney enlargement. Abnormal levels in immunological tests were revealed in 10 patients. Extrarenal symptoms including gonadal varicocle, splenic cyst, syncope, and anemia were found in 7 patients. On kidney biopsy, 7 patients had MGAs and 8 children showed definite GN (one case of focal GN, one case of mesangial proliferative GN, one case of focal segmental glomerulosclerosis, two cases of IgA vasculitis nephritis, and three cases of IgA nephropathy). While there were no differences in age, baseline estimated glomerular filtration rate (eGFR), immunological tests, clinical features of NCS, or extrarenal symptoms between the two groups, patients with NCS combined with MGAs showed higher proportion of isolated proteinuria and eGFR decline (both P < 0.05). Conclusions NCS may be associated with the presence of various GN. The causal relationship between NCS and GN should be further investigated. Glomerulonephritis Immunity Proteinuria Renal nutcracker syndrome Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Nutcracker phenomenon (NCP), also known as left renal vein (LRV) entrapment, is caused by a compression of LRV between abdominal aorta and superior mesenteric artery (SMA). NCP is characterized by this specific anatomical condition which can be a normal variant or an incidental finding while nutcracker syndrome (NCS) describes LRV entrapment with clinical manifestations [ 1 , 2 ]. Recently, the prevalence and knowledge of NCS are increasing owing to an increased attention to NCS and the development of several diagnostic techniques [ 3 , 4 ]. Although it is increasingly perceived, NCS is a challenging condition due to the lack of gold standards for its diagnosis and management [ 4 ]. NCS can occur at any age from children to older people. Patients with NCS may have a variety of signs or symptoms such as macro- or micro-hematuria, proteinuria, left flank or pelvic pain, varicocele, and anemia [ 5 , 6 ]. Autonomic dysfunction symptoms such as orthostatic hypotension, dizziness, and syncope have also been reported occasionally [ 6 – 8 ]. While NCS is known to be associated with a non-glomerular cause of hematuria, increased LRV pressure in NCP could lead to glomerular hematuria as well [ 9 ]. In addition, orthostatic proteinuria is a common feature of NCS [ 10 ], however, all patients with NCS do not present postural proteinuria. Proteinuria may result from increased glomerular transcapillary hydraulic pressure differences and enhanced action of angiotensin II caused by the NCP. Hematuria can take place by rupture of thin-walled septum between small renal veins and the collecting system [ 11 ]. On the other hand, symptoms like micro- or macro-hematuria and/or proteinuria are also common findings in various glomerulonephritis (GN). Glomerulopathy such as minor glomerular abnormalities (MGAs) is frequently detected in patients with persistent isolated proteinuria or microscopic hematuria [ 12 ]. Notably, reports for combined cases of coexistence of NCS and GN have been steadily increasing, especially in immunoglobulin A nephropathy (IgAN) [ 3 , 13 – 18 ]. While these two conditions could be simply coincidental findings, several studies have shown the impact of renal venous pressure elevation and consequent renal congestion on renal hemodynamics, inflammation, and endothelial activation [ 19 – 22 ]. In a rat renal congestion model [ 19 ], left kidney congestion induced by inferior vena cava ligation between renal veins resulted in diminished renal blood flow and glomerular filtration rate (GFR) and elevated renal interstitial hydrostatic pressure. Tubulointerstitial and glomerular damage and hypoxic injury to medullary thick ascending limbs were detected in congestive kidneys [ 19 ]. Furthermore, congestive nephropathy has emerged as an important cause of renal dysfunction that is associated with decreased renal perfusion, hormonal activation, inflammation, and endothelial dysfunction [ 21 , 22 ]. Therefore, renal venous congestion caused by NCP and/or NCS appears to be related to functional and histopathological changes in kidneys. Whether long-term congestion will sustain renal disease progression to interstitial fibrosis and tubular atrophy remains unknown. Evidence on the diagnosis and management in combined cases of NCS and GN is also limited. Previous studies have rarely clarified the relationship between these two entities. In the present study, we hypothesized that NCS could be a trigger factor for the development or aggravation of GN and examined clinical and pathologic findings of NCS combined with biopsy-proven GN. Glomerular lesions were divided into two pathological categories: minor glomerular abnormalities (MGAs) and definite GN. The causal or coincidental association between NCS and GN was investigated in pediatric patients presenting with proteinuria with or without hematuria. Methods Study population and evaluation Clinical, radiologic, and pathologic findings of 15 patients under 20 years old who were diagnosed with NCS and GN between May 2018 and January 2024 were retrospectively reviewed. Proteinuria and hematuria were all initially detected on a school or daycare center health check-up except for two patients with IgA vasculitis nephritis (IgAVN, formerly Henoch-Schonlein purpura nephritis). Proteinuria was evaluated from urinalysis, urine protein to creatinine ratio (uPCR), and/or the amount of protein per day (24-h proteinuria). Orthostatic proteinuria was confirmed from the amount of protein measured at recumbent or standing position for 12 hours. Kidney Doppler ultrasonography (US) was initially performed and followed up at the time of aggravation or improvement of proteinuria and/or hematuria. Doppler US was done by two well experienced pediatric radiologists in our medical center. Magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT) was additionally performed in 13 patients for further confirmation of NCS. Kidney biopsy was done in all patients to evaluate GN. Clinical, laboratory, and radiologic features as well as biopsy findings of all patients were summarized. Baseline characteristics and renal outcomes were also compared between patients with MGAs and those with definite GN. Definition Proteinuria was defined as uPCR of greater than 0.2 mg/mg and/or 24-h proteinuria of ≥ 4 mg/m 2 /hr. Microscopic hematuria was confirmed through red blood cell (RBC) counts per high-power field (HPF) greater than 5 in urinalysis. On renal Doppler US, the NCS was diagnosed when the peak velocity ratio (PVR) between the aortomesenteric and hilar portion of the LRV was greater than 4.0 [ 10 ]. In abdomen CT or MRI, a reduced aorta-to-SMA angle less than 35 degrees and the anteroposterior diameter ratio of pre/post compressed LRV above 2.25 were criteria used for the diagnosis of NCS [ 23 ]. MGA on kidney biopsy was defined as unclassified glomerular lesions with minor structural abnormalities insufficient for specific pathological diagnosis [ 12 ]. Left kidney enlargement was characterized by the presence of a renal length discrepancy > 10 mm between right and left kidneys (left kidney longer) by renal US, CT, and/or MRI [ 24 ]. Statistical analysis Baseline characteristics are described using means ± standard deviations for continuous variables and numbers (%) for categorical variables. For comparison between the two groups, the Wilcoxon Rank-Sum test was used for continuous variables and the Fisher’s exact test or Pearson chi-square test was used for categorical variables. Results with P- values < 0.05 were considered statistically significant. All statistical analyses were performed using R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria) or GraphPad Prism v.7.0 (San Diego, CA, USA). Results Case 1 A 14-year-old boy presented with proteinuria on a school health check-up and foamy urine for the past two weeks. He had a family history of nephrectomy (grandmother and aunt). His body mass index (BMI) was 16.4 kg/m 2 (2 th percentile) and his blood pressure (BP) was 107/65 mmHg. Laboratory test results showed an elevated serum creatinine (Cr) level of 0.93 mg/dL (estimated GFR [eGFR] using B edside Schwartz Formula , 76.9 ml/min/1.73m 2 ). Complement (C)3 was reduced with a value of 81 mg/dL (reference range: 90-180 mg/dL), and C4 was normal (11.3 mg/dL, reference range: 10-40 mg/dL). IgA level was elevated with 300 mg/dL (reference range: 47-249 mg/dL). However, his results for anti-double-stranded DNA antibody (Ab), antinuclear Ab, antineutrophil cytoplasmic Ab, and anti-glomerular basement membrane (GBM) Ab were all negative. The uPCR was 0.97. Orthostatic proteinuria was not definite. Kidney Doppler US showed increased renal cortical echogenicity of both kidneys and compressed LRV at aortomesenteric angle with a PVR of 8.08, suggesting NCS (Fig. 1a, b). On kidney biopsy, MGA was revealed with focal foot process effacement (Fig. 1c, d). He started taking enalapril. However, proteinuria was aggravated with a uPCR of 5.37. Since C3 and C4 were also much more reduced with the lowest level at 64 mg/dL and 7.1 mg/dL, respectively, oral steroid was added. Levels of serum Cr was elevated up to 1.34 mg/dL (eGFR: 67.4 ml/min/1.73m 2 ). Kidney Doppler US showed the NCS for 4 years consecutively. Low levels of C3, C4 and high IgA concentration also persisted. Proteinuria was worsened or lessened depending on the steroid dose. Recent abdomen CT revealed enlarged left kidney size together with NCP (Fig. 1e). At present, he is taking low dose steroid and angiotensin converting enzyme inhibitor (ACEi). An open surgery for NCP is being planned by the urologist. The last follow-up eGFR was 80.8 ml/min/1.73m 2 . The patient’s clinical course is shown in Fig. 1f. Case 2 A 6-year-old boy presented with microscopic hematuria on a school health check-up. His BMI and BP were within normal ranges. Urinalysis showed a high amount of hematuria (RBC > 60/HPF, dysmorphic RBCs 80%) and proteinuria (uPCR 0.94). During one year follow-up, uPCR was fluctuating from 0.2 to 2.1 and dysmorphic RBCs in urine were frequently found (dymorphic RBCs: 50 to 90%) with micro-hematuria. Kidney biopsy showed MGAs with mild foot process effacement. However, he showed severely fluctuating proteinuria with uPCR of 0.2 to 7.3 and normal serum protein level. Renal Doppler US was not specific. Four years after the initial presentation, abdomen CT revealed NCS with an engorged left renal venous system. Enlarged sizes of left kidney and left gonadal varicocele were detected (Fig. 2a, b). Follow-up Doppler US confirmed the presence of NCS with PVR of 5.07 and abdomen CT one year later persistently showed the presence of NCP (Fig. 2c, d). During 6-year follow-up, the level of uPCR was inconsistent with that of 24 h-proteinuria. His proteinuria still waxes and wanes. ACEi and oral steroid seemed not to be effective in this patient. Surgical treatment is being considered by the urologist. His clinical course is shown in Fig. 2e. Case 3 A 10-year-old girl presented with proteinuria confirmed on a school health check-up. Seven years ago, she had visited our hospital for proteinuria (uPCR 0.56) and micro-hematuria (RBC > 60/HPF). However, she was lost to follow-up after 3 months. Her BMI and BP were within normal ranges. Initial laboratory findings showed mildly decreased serum protein (5.6 mg/dL) and increased cholesterol level (223 mg/dL). She had a nephrotic range of proteinuria (uPCR 3.95, 24-h proteinuria 55 mg/m 2 /hr) but no hematuria. Orthostatic proteinuria was excluded and NCS was revealed on kidney Doppler US (Fig. 3a). However, kidney biopsy also confirmed the presence of focal segmental glomerulosclerosis (FSGS) (Fig. 3b, c). She was treated with ACEi, deflazacort, and cyclosporine. Eighteen months later, her proteinuria was reduced (54 mg/day) and ACEi only was used. At that time, the NCS was not observed. However, here proteinuria waxed and waned thereafter for one year (uPCR 0.29-1.21). Kidney Doppler US showed the NCS again with a PVR of 7.43. Abdomen CT also confirmed the presence of NCS (aorta-to-SMA angle: 31 degrees, CR: 2.64). The patient’s clinical course is shown in Fig. 3d. Case 4 A 15-year-old girl presented with purpura on lower extremities and left knee arthralgia for two weeks. She had a history of syncope and normochromic normocytic anemia (10.0-11.1g/dL) two years ago. Her BMI was 18.1 kg/m 2 (8 th percentile) and her BP was 107/63 mmHg. Laboratory findings were as follows: Hb level of 12.2 g/dL, RBC count of 3.89×10 6 /uL (reference: 4.5-5.3×10 6 /uL), protein level of 7.0 mg/dL, albumin level of 4.8 mg/dL, and cholesterol level of 166 mg/dL. Hematuria (10-29 RBCs/HPF) and nephrotic range of proteinuria (76 mg/m 2 /hr) were found, but uPCR was not so high (1.01). Kidney biopsy revealed mild IgAVN (International Study of Kidney Disease in Children classification grade I). ACEi, oral steroid, and short-term cyclosporine were given. Her proteinuria was reduced two years after renal biopsy. During follow-up, she intermittently complained of left arm numbness, left knee arthralgia, dizziness, nausea, and chest tightness. After quitting steroid, intermittent proteinuria (uPCR: 0.22-0.75) and low C3 level (78-79 mg/dL) were revealed. Her RBC count for 3 years was persistently low (3.71×10 6 /uL to 4.12×10 6 /uL) with a normal hemoglobin level. Kidney Doppler US showed abrupt narrowing of LRV between SMA and aorta with a PVR of 7.9 with consistent findings of NCS (Fig. 4a, b). Recent abdomen CT also confirmed the presence of NCP. Fig. 4c shows her clinical course. Summary of patients with NCS and glomerulopathy Demographic, clinical, and laboratory features of a total of 15 patients with NCS and glomerulopathy are summarized in Table 1. Their mean age was 11 ± 3.36 years, and the proportion of males was 53.3%. Mean follow-up duration was 53.2 ± 28.7 months. Two out of 15 patients had BMI under 5 percentiles, and mean BMI was 18.9 ± 3.35 kg/m 2 (32 ± 32.1 percentile). Chief complaints at initial visit were isolated proteinuria in 6 patients and proteinuria with microscopic hematuria in 9 patients. Orthostatic proteinuria and isolated hematuria were absent in our case series. Two patients (case 7 and case 13) showed intermittent episodes of gross hematuria. Only 4 patients with proteinuria and hematuria were examined for urine RBC morphology. One of them showed non-glomerular hematuria (case 7). BP levels of all patients were within normal ranges. Four patients had a family history of kidney diseases (cases 1, 7, 10, 14). Notably, father of case 14 had a history of NCS combined with thin basement membrane disease (TBMD) in his late 10’s and the patient showed renal biopsy findings of IgAN with diffuse thin GBM. Intermittent normochromic normocytic anemia was observed in 4 children (cases 1, 4, 7, 15; range: 10.0 to 11.1 g/dL) and leukopenia in 3 patients (cases 5, 7, 10; range: 3,150 to 4,380/mm 3 ). C3 and/or C4 levels were reduced in 4 patients (cases 1, 4, 5, 6; range: C3, 64 to 80 mg/dL; C4, 7.1 to 9.6 mg/dL) and serum IgA levels were elevated in four patients (cases 1, 12, 14, 15; range: 250 to 354 mg/dL). Six patients (case 6-8, 10, 12, 14) showed intermittent low IgD level (< 0.63 mg/dL, reference: 0.77-13.2). While all patients showed no difference in kidney length at first, five patients developed left kidney enlargement (cases 1, 2, 6, 7, 8; mean length difference of both kidneys: 13.3 mm). Extrarenal symptoms included left gonadal varicocele (Fig. 2b), a splenic cyst (Fig. 5a), syncope, palpitation, anemia, and left chest wall deformity (Fig. 5b). Eight patients were diagnosed with NCS at initial US and 7 children were detected during a follow-up with aggravation of proteinuria. Kidney Doppler US was performed at least two times in all patients except for two (cases 4 and 15). Three patients showed resolution and reappearance of NCS (cases 3, 5, 9). Ten of 15 patients were taken kidney biopsy within one year from the initial presentation. MGAs (Fig. 1c, d) in 7 children, focal GN in one (Fig. 5c, d), mesangial proliferative GN in one, and FSGS in one (Fig. 3b, c), IgAVN in two, and IgAN in three patients (Fig. 5e, f) were diagnosed. To clarify pathologic findings, we performed biopsy of the right kidney in one patient (case 7). All patients showed persistent proteinuria with or without hematuria except for one patient with a relatively short follow-up period (case 8). Proteinuria has been fluctuating, and correlation between uPCR and 24-h proteinuria was not evident in some patients (Table 1). Comparisons of clinical features and outcomes between patients with and without definite GN To evaluate the causal or coincidental association between NCS and glomerulopathy, we compared clinical features and outcomes of patients with MGAs and those with definite GN. Age, follow-up duration, BMI, baseline and lowest eGFR, immunological abnormalities, clinical features of NCS, extrarenal symptoms, and persistent proteinuria were all similar between the two groups. However, the proportion of isolated proteinuria was more common in children with MGAs than in those with definite GN (71.4% vs. 12.5%, P < 0.05) (Fig. 6a) and peak level of uPCR tended to be higher in the MGA group (3.57 ± 2.49 vs. 1.77 ± 1.38, P = 0.10) (Fig. 6b). Specifically, the last follow-up eGFR was significantly reduced in patients with MGAs compared to that in those with definite GN (90.3 ± 14.3 ml/min/1.73m 2 vs. 108 ± 15.6 ml/min/1.73m 2 , P < 0.05) (Fig. 6c). Most patients with definite GN were treated with immunosuppressive agents (ISAs) and ACEi. However, the management was more diverse in patients with MGAs (Table 2). Discussion In the present study, we report 15 cases of NCS combined with biopsy-proven GN presenting with proteinuria with or without hematuria. MGAs were most frequently found, followed by IgAN, IgAVN, and the same number of focal GN, mesangial proliferative GN, and FSGS. Almost all patients showed unusual clinical courses in comparison with biopsy findings. Isolated proteinuria was more common in the MGA group. The correlation between spot uPCR and 24-h proteinuria was inconsistent in some patients. A more considerable reduction in eGFR on the last follow-up was revealed in children with MGAs compared to those with definite GN. Associations of NCS with various GN should be considered in patients with persistent proteinuria with or without hematuria. A close long-term follow-up is needed for patients with these two combined conditions. Patients with NCS have been shown to correlate with a low BMI. Some NCS patients’ symptoms resolved with increasing BMI in previous studies [ 5 , 25 ]. A lack of supporting mesenteric fat, which reduces aortomesenteric angle, is one possible contributor to the development of NCP [ 23 ]. Renal ptosis, in which the kidney descends into the pelvis with the position change from supine to upright, has been proposed as another etiology of NCP [ 23 ]. LRV stretching over the abdominal aorta and venous congestion may be worsened by a lack of supporting retroperitoneal fat [ 23 , 26 ]. Common manifestations of NCS-hematuria, proteinuria, and flank/pelvic pain are probably related to renal venous congestion and increased LRV pressure [ 23 ]. Venous hypertension and collateralization in NCS can also cause left sided varicocele in males and pelvic congestion in females [ 23 , 26 ]. Although rare, symptoms and signs related to autonomic dysfunction may occur, including orthostatic hypotension, dizziness, syncope, and nausea [ 7 , 27 ]. Cases of a splenic cyst and splenic vein enlargement have also been described [ 6 , 28 ]. Compared to this epidemiology, the BMI percentile under 5 percentile was found in only two out of 15 patients in the present study. While hematuria and orthostatic proteinuria are relatively common in the NCS [ 5 ], isolated hematuria and orthostatic proteinuria were absent in our study group. Atypical presentations such as a splenic cyst, left gonadal varicocele, syncope, anemia, and so on were observed in our patients. While persistent severe hematuria is considered as a cause of anemia in the NCS [ 29 ], sustained hematuria was present only in one (case 7) out of 4 patients with anemia. Given that anemia is often associated with clinical signs of congestion [ 30 ], renal congestion induced by NCP can compromise microvascular blood flow, which may contribute to renal hypoxia, ineffective erythropoiesis, and resultant anemia [ 31 ]. Diagnosis of NCS can be confirmed by a variety of tools such as kidney Doppler US, contrast-enhanced CT, MRI, and venography. The first imaging tool with suspected NCS is Doppler US [ 29 ]. Although venography is considered the gold standard for the diagnosis of NCS, it remains unclear whether the invasive procedure for measuring the pressure gradient is truly needed [ 23 , 32 ]. In our cases, all patients were initially diagnosed with kidney Doppler US. Instead of venography, CT or MRI was additionally performed except for two patients. Some patients who had presented with NCS from the beginning showed resolution and reappearance of NCS depending on the level of proteinuria. Others who had been diagnosed with GN revealed the NCS later along with persistent proteinuria with or without hematuria. In case 2, Doppler US was ineffective for the initial diagnosis of NCS. We were able to confirm the NCS with abdomen CT. Since proliferation of fibrous tissue at the origin of the SMA and increase of retroperitoneal adipose tissue can occur during normal growth, the LRV entrapment between SMA and abdominal aorta may appear or disappear, affecting proteinuria and/or hematuria [ 33 ]. Therefore, the relevance between the NCS and clinical course in our series is plausible. The presence of NCP and/or NCS should be suspected in children with persistent proteinuria. Although NCS with co-existing GN is not common, combined cases have been increasingly reported. Among them, IgAN and IgAVN were common conditions in patients with NCS and various GN [ 3 , 13 , 14 , 17 ]. Other than IgAN, a case of NCS combined with TBMD in a 21-year-old woman presenting with persistent flank pain and larger left kidney has been reported [ 15 ]. She showed a higher proteinuria than typical cases of TBMD. Interestingly, the father of one patient (case 14) with NCS and IgAN in our case series had a history of NCS combined with TBMD in his late 10’s. NCS complicated by membranoproliferative GN or moderate mesangial hypercellularity was also reported in patients with sustained proteinuria [ 18 , 34 ]. Notably, several animal studies have shown that acute increase in renal venous pressure from renal vein constriction can cause an elevation of renal interstitial hydrostatic pressure, a reduction of renal blood flow, and a subsequent decrease of GFR via the renin-angiotensin system (RAS) [ 35 , 36 ]. Compression of peritubular capillaries and tubules, renal hypoxia, and physical stress caused by the left kidney congestion could induce pericyte detachment, which could lead to extracellular matrix expansion and tubular injury [ 19 ]. Emerging evidence also persistently indicates that a low renal perfusion pressure can negatively impact renal function and histopathology with time [ 22 ]. Meanwhile, within the nephron, venous hypertension is associated with activation of a subclinical immune cascade in the vessel wall [ 37 ]. Venous congestion can induce vascular stretch which can activate vascular endothelial cells [ 20 ]. Endothelial cells actively participate in innate and adaptive immune responses, including complement production and control and pro-inflammatory, pro-oxidant, and vasoconstricting responses [ 38 ]. Recent studies have also revealed that immunomodulatory endothelial cells in the kidney can closely interact with resident immune cells, which are involved in rapid responses to circulating immune complexes [ 39 ]. It is well known that immune complexes containing galactose deficient IgA1 play a crucial role in the pathogenesis of IgAN. While the pathogenesis of IgAV remains largely unknown, it has been proposed that in IgAV, IgA1 antibodies against endothelial cells are produced. Such IgA complexes can activate neutrophils via the IgA Fc receptor, thereby causing tissue damage [ 40 ]. Intriguingly, glomerular IgA and galactose deficient IgA1 deposition were more commonly reported in patients with NCP than in those without NCP [ 17 ]. In the present study, our patients with NCS showed various kidney biopsy findings of MGAs, IgAN, IgAVN, focal GN, mesangial proliferative GN, and FSGS. While MGA was most often diagnosed, IgAN and IgAVN were common in the next order. Immunologic alterations such as leukopenia, high IgA level, and low C3/C4 and IgD concentration were also found in 64% of our patients. Specifically, case 1 with MGAs showed a high IgA level but low C3 and C4 concentrations. Decreased IgD level was the most frequently found immunologic alteration among tested. While IgD concentration is low in human serum, IgD is known as a key regulator for balanced antibody responses [ 41 ]. Defective IgD function can result in deregulated activation of B cells and defective immune responses [ 42 ]. In an animal experiment, lupus mice with IgD deficiency showed elevated autoantibody production, increased immune complex deposition, and more severe nephritis [ 43 ]. Therefore, decreased IgD level might be involved in abnormal immune responses in our clinical context. Collectively, elevated LRV pressure by NCP may increase glomerular and interstitial hydrostatic pressure, decrease renal blood flow, and activate vascular endothelial cells. All of these can synergistically contribute to glomerular or tubular damage and extracellular matrix expansion. They may also induce RAS activation, renal hypoxia, pericyte loss, and alteration of mucosal immunity. Dysregulated activation of the immune system in our case series can contribute to the genesis or worsening of various glomerular lesions. Treatment options of NCS should be based on the severity of symptoms and expected reversibility according to the patient’s age [ 5 , 23 ]. For children with NCS only, the first line management is a conservative approach. ACEi can be used for cases with severe and prolonged proteinuria [ 23 , 34 ]. Surgery may be considered for a frustrated conservative approach with continuing or severe symptoms [ 6 ]. In adults, the gold standard of care is LRV transposition with or without renal autotransplantation. However, it has disadvantages such as severe bleeding, vessel thrombosis, LRV restenosis, and paralytic ileus [ 6 ]. Due to a minimally invasive nature, endovascular or laparoscopic exovascular stent can be alternative treatment of choice in managing NCS [ 6 , 23 ]. In our patients showing NCS combined with GN, surgical procedures were not performed. Instead, all patients except three were treated with ACEi with/without ISAs. While some patients did not improve with ISAs including steroids, others showed worsened proteinuria after quitting ISAs. Particularly, patients with C activation or immune dysregulation showed good responses with ISAs. Fluctuation of uPCR was severe in some children with MGAs. Proteinuria with or without hematuria persisted for a long time relative to renal biopsy findings in almost all patients. Given that the relevance of MGAs and renal function decline has been suggested in previous studies [ 12 , 44 ], clinicians should pay attention to not only patients with definite GN, but also those with MGAs. In the present study, the last follow-up eGFR was more reduced in patients with MGAs than in those with definite GN. Baseline and lowest eGFR tended to be lower while uPCR tended to be higher in the MGA group than in the definite GN group. To put it simply, MGA could be a secondary change of NCS and definite GN would be a coincidental finding with NCS. If not, older age and less aggressive therapy with ACEi and/or ISAs in the MGA group –although the differences were not statistically significant– could affect these results. It is difficult to conclude the causal or coincidental link between NCS and different GN. Nevertheless, we identified some cause-and-effect relationships between NCS and GN in our case series, such as renal histologic alterations, immune dysregulation, and renal dysfunction. Our study has some limitations. First, a small sample size might be not enough to prove the causal relationship between NCS and GN. Studies including multi-centers and large sized participants are needed to clarify the influence of NCS on the triggering and progression of GN. In our clinical context, NCS might induce MGAs, focal GN, mesangial proliferative GN, and FSGS consecutively. It can also play a role in the triggering or worsening immune-mediated GN such as IgAN and IgAVN. Second, renal venography with direct pressure measurements was not done in our patients due to its invasive nature. However, NCS was confirmed repeatedly with Doppler US, CT, or MRI in our cases. Third, renal biopsies of patients were done on their left side except for one patient. While NCP could lead to decreased renal blood flow and histologic changes in the congested left kidney only at first, histopathologic changes would take place in the right kidney as well with time. As a way to support this, we confirmed renal histologic changes of MGAs of the right kidney in one patient (case 7). In conclusion, NCS may be associated with the presence of various GN. The causal relationship of NCS and GN should be further investigated. We may assume that NCS combined with GN is not rare. Its prevalence could be higher than previously thought. Renal biopsy should be performed without hesitation to confirm the co-existence of GN with NCS. Inversely, NCS evaluation could be considered in patients with atypical and uncommon courses of various GN. Declarations Authors have no financial interests that are directly or indirectly related to the work submitted here for publication Acknowledgments This work was supported by a grant funded by Korea University (No. K2310611 ) . We also would like to express our gratitude to Professor Bo-Kyung Je (Department of Radiology, Korea University Ansan Hospital) who provided assistance for radiologic evaluation. Author contribution Dr. Hyung Eun Yim contributed to the study conception, study design, and project administration. Material preparation and data collection were performed by So Hyun Ki, Min Hwa Son, and Hyung Eun Yim. Statistical analyses were performed by So Hyun Ki. Visualization was performed by So Hyun Ki and Min Hwa Son. The first draft of the manuscript was written by So Hyun Ki. It was reviewed and revised by So Hyun Ki, Min Hwa Son, and Hyung Eun Yim. All authors read and approved the final manuscript. Data availability All data generated or analyzed during this study are included in this published article. Ethics statement This study was approved by the Institutional Review Board (IRB) of the Korea University Ansan Hospital (IRB No. 2023AS0067) before initiation. It was performed according to the ethical standards of the Declaration of Helsinki. The IRB waived the requirement to obtain informed consent since this study involved a retrospective chart review of anonymous patient data. Patients' data from our previous paper [45] were partially included. 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Dev Comp Immunol 124:104198. https://doi.org/10.1016/j.dci.2021.104198 Amendt T, Ayoubi OE, Linder AT et al (2021) Primary immune responses and affinity maturation are controlled by IgD. Front Immunol 12:709240. https://doi.org/10.3389/fimmu.2021.709240 Guo L, Tian J, Guo Z, Zheng B, Han S (2011) The absence of immunoglobulin D B cell receptor-mediated signals promotes the production of autoantibodies and exacerbates glomerulonephritis in murine lupus. Clin Exp Immunol 164:227–235. https://doi.org/10.1111/j.1365-2249.2011.04332.x Takashima T, Onozawa K, Rikitake S et al (2014) Two cases of minor glomerular abnormalities with proteinuria disproportionate to the degree of hypoproteinemia. CEN Case Rep 3:172–177. https://doi.org/10.1007/s13730-014-0112-7 Ki SH, Son MH, Park E, Yim HE (2023) Nutcracker syndrome combined with immunoglobulin A nephropathy: two case reports. Child Kidney Dis 27:133–138. https://doi.org/10.3339/ckd.23.013 Tables Table 1. Summary of 15 pediatric cases with NCS combined with glomerulopathy N Sex /age BMI (kg/m 2 ) Initial Sx RBC morphology Event Baseline eGFR (ml/min/1.73m 2 ) Lowest eGFR (ml/min/1.73m 2 ) Last eGFR (ml/min/1.73m 2 ) uPCR (mg/mg) Diagnostic tool for NCS PV at RH (cm/s)/PV at AM (cm/s) (PVR) Time to NCS Renal pathology (Time to renal biopsy) F/u duration (mo) 1 M/14 16.4 (2p) Isolated proteinuria - LK enlargement, anemia, low C3/C4, high IgA, family Hx of nephrectomy 76.9 53.9 64.3 5.37 Doppler US, CT 30/200 (6.67) Initial MGAs (4 mo) 59 2 M/6 17.2 (17p) Hematuria, proteinuria Dysmorphic RBC 80% LK enlargement, Left gonadal varicocele 137.3 109.0 109.0 7.27 Doppler US, CT 29/147 (5.07) 5 y MGAs (10 mo) 71 3 F/10 18.6 (51p) Hematuria, proteinuria Unexamined F/u loss for 7 years 147.7 116.7 116.7 3.95 Doppler US, CT 28/134 (4.79) 7 y FSGS (7 y) 131 4 F/15 18 (8p) Purpura, Hematuria, proteinuria Unexamined Syncope, anemia, low C3 108.0 81.5 108.0 1.65 Doppler US, CT 19/149 (7.84) 33 mo IgAVN (ISKDC class I, Initial) 39 5 F/13 15.2 (2p) Isolated proteinuria - Splenic cyst, Leukopenia, low C3/C4, 122.6 89.6 113.2 3.94 Doppler US, CT 18/>100 (5.56) Initial Mesangial proliferative GN (Initial) 31 6 F/9 14.8 (12p) Hematuria, proteinuria Unexamined LK enlargement, low C3, low IgD 116.2 108.3 118.4 0.9 Doppler US, CT 17/190 (11.2) Initial Focal GN (3 mo) 33 7 M/13 19 (8p) Hematuria, proteinuria No dysmorphic RBC LK enlargement, gross hematuria, palpitation, anemia, leukopenia, low IgD, family Hx of hematuria 113.9 83.5 92.1 0.21 Doppler US, CT 20/120 (6.0) Initial MGAs (4 y) 60 8 F/16 22.0 (65p) Isolated proteinuria - LK enlargement, pectus arcuatum, low IgD 98.6 98.6 99.2 0.67 Doppler US, CT 19/129 (6.79) Initial MGA (18 mo) 28 9 F/11 17.2 (12p) Isolated proteinuria - - 86 72 87 3.44 Doppler US 18/74 (4.11) 30 mo MGAs (3 mo) 63 10 M/12 20.7 (58p) Isolated proteinuria - Leukopenia, low IgD, family Hx of GN 103.6 86.1 97.4 4.24 Doppler US, MRI 31/212 (6.84) Initial MGAs (4 mo) 23 11 M/13 24.2 (89p) Isolated proteinuria - Early puberty 100 83 83 3.77 Doppler US, CT 10/75 (7.5) Initial MGAs (7 mo) 23 12 M/11 17.8 (25p) Hematuria, proteinuria Unexamined High IgA, low IgD 111.5 75.2 78.4 0.82 Doppler US, CT 29/161 (5.55) Initial IgAN (M1 E0 S1 T0 C0, 3 mo) 60 13 M/10 17.5 (19p) Hematuria, proteinuria Dysmorphic RBC 30 % Gross hematuria 120.7 92.5 94.7 0.81 Doppler US, CT 24/154 (6.42) 17 mo IgAN (M1 E1 S1 T0 C0, 17 mo) 31 14 M/7 27.2 (99p) Hematuria, proteinuria Dysmorphic RBC 13% High IgA, low IgD, family Hx of NCS with TBMD 108.9 83.7 101.6 1.3 Doppler US, CT 24/142 (5.92) 4 y IgAN (M1 E0 S0 T0 C0, 4 y) with diffuse thin GBM 59 15 F/11 17.9 (13p) Purpura, Hematuria, proteinuria Unexamined Anemia, high IgA 113 105 128 0.75 Doppler US 17/129 (7.6) 7 y IgAVN (ISKDC class IIIb, Initial) 87 NCS, nutcracker syndrome; N, number; BMI, body mass index; Sx, symptom; RBC, red blood cell; eGFR, estimated glomerular filtration rate; uPCR, urine protein to creatinine ratio; PV at RH /PV at AM, peak velocity at the renal hilum/peak velocity at the aortomesenteric portion; PVR, peak velocity ratio; F/u, follow-up; mo, months; M, male; p, percentile; LK, left kidney; C, complement; Ig, immunoglobulin; Hx, history; US, ultrasonography; CT, computed tomography; MGAs, minor glomerular abnormalities; y, year; F, female; FSGS, focal segmental glomerulosclerosis; IgAVN, IgA vasculitis nephritis; ISKDC, International Study of Kidney Disease in Children; GN, glomerulonephritis; MRI, magnetic resonance imaging; IgAN, IgA nephropathy; M 1, mesangial hypercellularity 1; E, endothelial hypercellularity; S, segmental glomerulosclerosis; T, tubular atrophy/interstitial fibrosis; C, cellular/fibrocellular crescents; TBMD, thin basement membrane disease; GBM, glomerular basement membrane. Table 2. Comparisons between the MGA and GN groups MGAs (n=7) GN (n=8) P value Age at initial presentation (y) 12.1 ± 3.13 10 ± 3.42 0.231 a Age at NCS (y) 13.3 ± 1.60 12.9 ± 3.36 0.773 a Mean f/u duration (mo) 46.7 ± 21.1 58.9 ± 35.1 0.439 a Body mass index (kg/m 2 ) 19.5 ± 2.89 18.4 ± 3.82 0.527 a Isolated proteinuria, n (%) 5 (71.4%) 1 (12.5%) 0.041 b uPCR (mg/mg) lowest 0.27 ± 0.51 0.11 ± 0.05 0.479 a highest 3.57 ± 2.49 1.77 ± 1.38 0.101 a eGFR Baseline 102 ± 19.5 119 ± 12.9 0.076 a Lowest 83.7 ± 17.8 94.1 ± 14.5 0.237 a Last follow-up 90.3 ± 14.3 108 ± 15.6 0.045 a Complement dysregulation (n) 1 (14.3%) 3 (37.5%) 0.569 b Immunoglobulin abnormality (n) 4 (57.1%) 4 (50%) 1.000 b Leukopenia, n (%) 2 (28.6%) 1 (12.5%) 0.569 b Anemia, n (%) 2 (28.6%) 2 (25%) 1.000 b NCS PVR 6.14 ± 1.18 6.86 ± 2.04 0.427 a CR 3.20 ± 1.61 2.90 ± 0.08 0.868 a Initial presentation, n (%) 5 (71.4%) 3 (37.5%) 0.315 b Reappearance, n (%) 1 (14.3%) 2 (25%) 1.000 b LK enlargement, n (%) 4 (57.1%) 1 (12.5%) 0.119 b Extrarenal symptoms, n (%) 4 (57.1%) 3 (37.5%) 0.619 b Management 0.103 c Observation 3 (42.9%) 0 (0.0%) ACEi only 1 (14.3%) 1 (12.5%) ISAs + ACEi 3 (42.9%) 7 (87.5%) Persistent proteinuria (n) 6 (85.7%) 8 (100%) 0.467 b Values are presented as means ± standard deviations or numbers (%). a Wilcoxon rank sum test, b Fisher’s exact test, c Chi-sqaure test. MGAs, minor glomerular abnormalities; GN, glomerulonephritis; y, years; NCS, nutcracker syndrome; mo, months; n, number; uPCR, urine protein to creatinine ratio; eGFR, estimated glomerular filtration rate; PVR, peak velocity ratio; CR, compression ratio; LK, left kidney; ACEi, angiotensin converting enzyme inhibitor; ISAs, immunosuppressive agents. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4418523","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":303353577,"identity":"22a95a4d-85cc-48b1-b9d2-e998f03f85ac","order_by":0,"name":"So Hyun Ki","email":"","orcid":"","institution":"Korea University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"So","middleName":"Hyun","lastName":"Ki","suffix":""},{"id":303353578,"identity":"1f3abbf1-49f2-47b3-8d37-5db11b417499","order_by":1,"name":"Min Hwa Son","email":"","orcid":"","institution":"Korea University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Min","middleName":"Hwa","lastName":"Son","suffix":""},{"id":303353579,"identity":"43da20ba-7531-44f5-aa94-37adf6a3d8d7","order_by":2,"name":"Hyung Eun Yim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYBACAxCRwGCTAOYlFBCvJQ2qBcRlI0YLA8PhBASXkBZz9gY2iYc55/P4Z3cnfnhgwJDHL9+AX4tlzwE2icRtt4sl7pzdLAF0WLFkGyGH3cj/BtKS2HAjdwNIS+KGY4S03H8AsuVc4vwbuZt/gLTsJ6jlBgNIy4HEDTdyt0FsIRhiZxKYLRK3JSduBGqxSDCQSJxxLIGAluMHGG/+3GaXOA/osJs/KmwS+5sPELCGgYFFAokjgVMZMmD+QJSyUTAKRsEoGLkAADvJSB2W0ONsAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-9805-9278","institution":"Korea University College of Medicine and School of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hyung","middleName":"Eun","lastName":"Yim","suffix":""}],"badges":[],"createdAt":"2024-05-14 10:36:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4418523/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4418523/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57518714,"identity":"4a4a4686-967e-4a27-aa22-633b51240a53","added_by":"auto","created_at":"2024-05-31 20:37:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":690857,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eKidney Doppler ultrasonography showing left\u003cstrong\u003e \u003c/strong\u003erenal venous velocity at hilum of 25.0 cm/sec (yellow arrow), \u003cstrong\u003eb\u003c/strong\u003e Left renal venous velocity at aorta-SMA junction of 202.0 cm/sec (yellow arrow), \u003cstrong\u003ec \u003c/strong\u003eLight microscopic finding showing\u003cstrong\u003e \u003c/strong\u003emild mesangial expansion (black arrow)(Periodic acid-Schiff stain, ×400, bar = 50 µm),\u003cstrong\u003e d \u003c/strong\u003eElectron microscopic finding showing focal foot process effacement (blue arrows) (×5,000, bar = 2.0 µm), \u003cstrong\u003ee \u003c/strong\u003eAbrupt narrowing of left renal vein at the aortomesenteric portion (red arrow) with enlargement of left kidney (yellow arrow), \u003cstrong\u003ef\u003c/strong\u003eClinical course during 4.5 years. Blue bars, urine protein to creatinine ratio (mg/mg); gray line, 24-h proteinuria (mg/day); dotted black line, serum IgA level (mg/dL); black line, serum C3 concentration (mg/dL); triangular mark symbols, peak velocity ratio of LRV. SMA, superior mesenteric artery; Ao, aorta; LRV, left renal vein; ACEi, angiotensin converting enzyme inhibitor; CT, computed tomography\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4418523/v1/75c0b6e1ef393f2b7834f23e.png"},{"id":57518716,"identity":"0ffdb408-b1fa-4b8e-b325-49a2bc9dd380","added_by":"auto","created_at":"2024-05-31 20:37:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":479867,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eAbdomen CT findings with engorged left renal venous system (red arrow), enlarged size of left kidney and prominent hypodense left renal medulla (yellow arrow), \u003cstrong\u003eb\u003c/strong\u003e Left gonadal varicocele (red circle), \u003cstrong\u003ec\u003c/strong\u003eFollow-up CT showing the persistent LRV entrapment with a compression ratio (A/B) of 4.55, \u003cstrong\u003ed \u003c/strong\u003eFollow-up CT showing a reduced aorta-to-SMA angle of 26.6 degrees (blue arrow),\u003cstrong\u003e e\u003c/strong\u003eClinical course during 5.5 years. Blue bars, urine protein to creatinine ratio (mg/mg); gray line, 24-h proteinuria (mg/day); rectangular mark symbols, grade of hematuria (1, RBCs 5-9/HPF; 2, RBCs 10-29/HPF, 3, RBCs 30-60/HPF; 4, RBCs ≥ 60/HPF); triangle mark symbols, peak velocity ratio of LRV. SMA, superior mesenteric artery; Ao, aorta; LRV, left renal vein; ACEi, angiotensin converting enzyme inhibitor; CT, computed tomography; RBC, red blood cells; HPF, high power field\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-4418523/v1/8d8f567d7900ad483b17e919.png"},{"id":57518715,"identity":"2f7f2160-2f8b-473c-b604-ecb39f891952","added_by":"auto","created_at":"2024-05-31 20:37:14","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":711549,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eKidney Doppler sonography showing LRV entrapment between abdominal aorta and SMA (red arrow), \u003cstrong\u003eb\u003c/strong\u003e A glomerulus with segmental sclerosis (black arrow) and tubulointerstitial change (blue arrow) (Periodic acid-Schiff stain, ×400, bar = 50 µm), \u003cstrong\u003ec\u003c/strong\u003e Slight glomerular basement membrane thinning (blue arrow) and focal foot process effacement(red arrow) (×2,000, bar = 5 µm), \u003cstrong\u003ed\u003c/strong\u003eClinical course during 10 years. Blue bars, urine protein to creatinine ratio (mg/mg); gray line, 24-h proteinuria (mg/day); triangular mark symbols, peak velocity ratio of LRV. SMA, superior mesenteric artery; Ao, aorta; LRV, left renal vein; ACEi, angiotensin converting enzyme inhibitor; DFZ, deflazacort; CNI, calcineurin inhibitor; CT, computed tomography\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-4418523/v1/899d8b95486ab5d95dd93959.png"},{"id":57518719,"identity":"877e4a45-2879-479b-8959-805cbad70a88","added_by":"auto","created_at":"2024-05-31 20:37:14","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":309603,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eRenal Doppler sonography showing left\u003cstrong\u003e \u003c/strong\u003erenal venous velocity at hilum of 18.9 cm/sec (yellow arrow), \u003cstrong\u003eb\u003c/strong\u003e Left renal venous velocity at aorta-superior mesenteric artery junction of 149 cm/sec (yellow arrow), \u003cstrong\u003ec\u003c/strong\u003e Clinical course during 4.5 years. Blue bars, urine protein to creatinine ratio (mg/mg); gray line, 24-h proteinuria (mg/day); yellow line, red blood cell counts in serum (× 10\u003csup\u003e6\u003c/sup\u003e/ul); hatched bar, reference red blood cell count 4.5-5.3 × 10\u003csup\u003e6\u003c/sup\u003e/ul; triangular mark symbol, peak velocity ratio of left renal vein. ACEi, angiotensin converting enzyme inhibitor; DFZ, deflazacort; CNI, calcineurin inhibitor; C3, complement 3; Lt, left; D/N, dizziness/nausea; CT, computed tomography\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-4418523/v1/bda4bd7e466c43823065ab7f.png"},{"id":57518720,"identity":"00c0394e-6efe-4cd0-a17d-ed2b99549a02","added_by":"auto","created_at":"2024-05-31 20:37:15","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1205733,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e A splenic cyst measuring 2.62 cm ⅹ 1.75 cm (blue arrow) in case 5, with compressed left renal vein at aortomesenteric angle (red arrow) and left kidney enlargement (yellow arrow), \u003cstrong\u003eb \u003c/strong\u003ePectus arcuatum showing asymmetric protrusion of left rib cage and sternum in case 8 (blue arrow), \u003cstrong\u003ec\u003c/strong\u003eLight microscopic finding of case 6 showing mesangial hypercellularity (black arrow) and mild focal tubular atrophy with interstitial fibrosis (blue arrow)(Periodic acid-Schiff stain, ×400, bar = 50 µm), \u003cstrong\u003ed\u003c/strong\u003e Focal effacement of foot processes in case 6 (red arrow) (×5,000, bar = 2.0 µm), \u003cstrong\u003ee\u003c/strong\u003e Focal to diffuse mesangial proliferation (black arrows) and mild focal tubular damage in case 14 (blue arrow) (Periodic acid-Schiff stain, ×400, bar = 50 µm), \u003cstrong\u003ef\u003c/strong\u003e Mesangial immunoglobulin A staining (3+) on immunofluorescence in case 14 (×400, bar = 50 µm)\u003c/p\u003e","description":"","filename":"Fig5.png","url":"https://assets-eu.researchsquare.com/files/rs-4418523/v1/58d0dabf7f90c8aed88e31fb.png"},{"id":57519492,"identity":"d7180eac-215b-4264-b89e-13573d430243","added_by":"auto","created_at":"2024-05-31 20:45:14","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":107931,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e Number of patients with isolated proteinuria (black bars) or proteinuria with hematuria (white bars) in the MGA and definite GN groups, \u003cstrong\u003eb\u003c/strong\u003e Peak uPCR level of both two groups, \u003cstrong\u003ec\u003c/strong\u003e Last follow-up eGFR between the MGA and definite GN groups. \u003csup\u003e*\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05, MGAs vs. GN.\u003cstrong\u003e \u003c/strong\u003eMGAs, minor glomerular abnormalities; GN, glomerulonephritis; uPCR, urine protein to creatinine ratio; eGFR, estimated glomerular filtration rate\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e","description":"","filename":"Fig6.png","url":"https://assets-eu.researchsquare.com/files/rs-4418523/v1/82242049a952215a4421e58e.png"},{"id":58687778,"identity":"ac840cd1-b18c-45ff-822a-10ffed1f2e40","added_by":"auto","created_at":"2024-06-19 21:00:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4927050,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4418523/v1/9e910f6b-fa0a-4ab7-93e5-4da2620d76be.pdf"}],"financialInterests":"","formattedTitle":"Nutcracker syndrome and glomerulonephritis in pediatric patients: A causal or coincidental association?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNutcracker phenomenon (NCP), also known as left renal vein (LRV) entrapment, is caused by a compression of LRV between abdominal aorta and superior mesenteric artery (SMA). NCP is characterized by this specific anatomical condition which can be a normal variant or an incidental finding while nutcracker syndrome (NCS) describes LRV entrapment with clinical manifestations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Recently, the prevalence and knowledge of NCS are increasing owing to an increased attention to NCS and the development of several diagnostic techniques [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although it is increasingly perceived, NCS is a challenging condition due to the lack of gold standards for its diagnosis and management [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNCS can occur at any age from children to older people. Patients with NCS may have a variety of signs or symptoms such as macro- or micro-hematuria, proteinuria, left flank or pelvic pain, varicocele, and anemia [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Autonomic dysfunction symptoms such as orthostatic hypotension, dizziness, and syncope have also been reported occasionally [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. While NCS is known to be associated with a non-glomerular cause of hematuria, increased LRV pressure in NCP could lead to glomerular hematuria as well [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In addition, orthostatic proteinuria is a common feature of NCS [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], however, all patients with NCS do not present postural proteinuria. Proteinuria may result from increased glomerular transcapillary hydraulic pressure differences and enhanced action of angiotensin II caused by the NCP. Hematuria can take place by rupture of thin-walled septum between small renal veins and the collecting system [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. On the other hand, symptoms like micro- or macro-hematuria and/or proteinuria are also common findings in various glomerulonephritis (GN). Glomerulopathy such as minor glomerular abnormalities (MGAs) is frequently detected in patients with persistent isolated proteinuria or microscopic hematuria [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Notably, reports for combined cases of coexistence of NCS and GN have been steadily increasing, especially in immunoglobulin A nephropathy (IgAN) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15 CR16 CR17\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. While these two conditions could be simply coincidental findings, several studies have shown the impact of renal venous pressure elevation and consequent renal congestion on renal hemodynamics, inflammation, and endothelial activation [\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In a rat renal congestion model [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], left kidney congestion induced by inferior vena cava ligation between renal veins resulted in diminished renal blood flow and glomerular filtration rate (GFR) and elevated renal interstitial hydrostatic pressure. Tubulointerstitial and glomerular damage and hypoxic injury to medullary thick ascending limbs were detected in congestive kidneys [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Furthermore, congestive nephropathy has emerged as an important cause of renal dysfunction that is associated with decreased renal perfusion, hormonal activation, inflammation, and endothelial dysfunction [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Therefore, renal venous congestion caused by NCP and/or NCS appears to be related to functional and histopathological changes in kidneys. Whether long-term congestion will sustain renal disease progression to interstitial fibrosis and tubular atrophy remains unknown. Evidence on the diagnosis and management in combined cases of NCS and GN is also limited. Previous studies have rarely clarified the relationship between these two entities.\u003c/p\u003e \u003cp\u003eIn the present study, we hypothesized that NCS could be a trigger factor for the development or aggravation of GN and examined clinical and pathologic findings of NCS combined with biopsy-proven GN. Glomerular lesions were divided into two pathological categories: minor glomerular abnormalities (MGAs) and definite GN. The causal or coincidental association between NCS and GN was investigated in pediatric patients presenting with proteinuria with or without hematuria.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and evaluation\u003c/h2\u003e \u003cp\u003eClinical, radiologic, and pathologic findings of 15 patients under 20 years old who were diagnosed with NCS and GN between May 2018 and January 2024 were retrospectively reviewed. Proteinuria and hematuria were all initially detected on a school or daycare center health check-up except for two patients with IgA vasculitis nephritis (IgAVN, formerly Henoch-Schonlein purpura nephritis). Proteinuria was evaluated from urinalysis, urine protein to creatinine ratio (uPCR), and/or the amount of protein per day (24-h proteinuria). Orthostatic proteinuria was confirmed from the amount of protein measured at recumbent or standing position for 12 hours. Kidney Doppler ultrasonography (US) was initially performed and followed up at the time of aggravation or improvement of proteinuria and/or hematuria. Doppler US was done by two well experienced pediatric radiologists in our medical center. Magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT) was additionally performed in 13 patients for further confirmation of NCS. Kidney biopsy was done in all patients to evaluate GN. Clinical, laboratory, and radiologic features as well as biopsy findings of all patients were summarized. Baseline characteristics and renal outcomes were also compared between patients with MGAs and those with definite GN.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDefinition\u003c/h2\u003e \u003cp\u003eProteinuria was defined as uPCR of greater than 0.2 mg/mg and/or 24-h proteinuria of \u0026ge;\u0026thinsp;4 mg/m\u003csup\u003e2\u003c/sup\u003e/hr. Microscopic hematuria was confirmed through red blood cell (RBC) counts per high-power field (HPF) greater than 5 in urinalysis. On renal Doppler US, the NCS was diagnosed when the peak velocity ratio (PVR) between the aortomesenteric and hilar portion of the LRV was greater than 4.0 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In abdomen CT or MRI, a reduced aorta-to-SMA angle less than 35 degrees and the anteroposterior diameter ratio of pre/post compressed LRV above 2.25 were criteria used for the diagnosis of NCS [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. MGA on kidney biopsy was defined as unclassified glomerular lesions with minor structural abnormalities insufficient for specific pathological diagnosis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Left kidney enlargement was characterized by the presence of a renal length discrepancy\u0026thinsp;\u0026gt;\u0026thinsp;10 mm between right and left kidneys (left kidney longer) by renal US, CT, and/or MRI [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eBaseline characteristics are described using means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations for continuous variables and numbers (%) for categorical variables. For comparison between the two groups, the \u003cem\u003eWilcoxon Rank-Sum\u003c/em\u003e test was used for continuous variables and the \u003cem\u003eFisher\u0026rsquo;s exact\u003c/em\u003e test or \u003cem\u003ePearson chi-square\u003c/em\u003e test was used for categorical variables. Results with \u003cem\u003eP-\u003c/em\u003evalues\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. All statistical analyses were performed using R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria) or GraphPad Prism v.7.0 (San Diego, CA, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCase 1\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 14-year-old boy presented with proteinuria on a school health check-up and foamy urine for the past two weeks. He had a family history of nephrectomy (grandmother and aunt).\u0026nbsp;His\u0026nbsp;body mass index (BMI) was 16.4 kg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e(2\u003csup\u003eth\u003c/sup\u003e percentile) and his blood pressure (BP) was 107/65 mmHg.\u0026nbsp;Laboratory test results showed an elevated serum creatinine (Cr) level of 0.93 mg/dL (estimated GFR [eGFR] using B\u003cem\u003eedside Schwartz Formula\u003c/em\u003e, 76.9 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e). Complement (C)3 was reduced with a value of 81 mg/dL\u0026nbsp;(reference range: 90-180 mg/dL), and C4 was normal (11.3 mg/dL,\u0026nbsp;reference range: 10-40 mg/dL). IgA level was elevated with 300 mg/dL\u0026nbsp;(reference range: 47-249 mg/dL). However, his\u0026nbsp;results for anti-double-stranded DNA antibody (Ab), antinuclear Ab, antineutrophil cytoplasmic Ab, and anti-glomerular basement membrane (GBM) Ab were all negative. The uPCR was 0.97. Orthostatic proteinuria was not definite.\u0026nbsp;Kidney Doppler US showed increased renal cortical echogenicity of both kidneys and compressed LRV at aortomesenteric angle with a\u0026nbsp;PVR of 8.08, suggesting\u0026nbsp;NCS (Fig. 1a, b). On kidney biopsy, MGA was revealed with focal foot process effacement (Fig. 1c, d). He started taking enalapril. However, proteinuria was aggravated with a uPCR of 5.37. Since C3 and C4 were also much more reduced with the lowest level at 64 mg/dL and 7.1 mg/dL,\u0026nbsp;respectively, oral steroid was added. Levels of serum Cr was elevated up to 1.34 mg/dL (eGFR: 67.4 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e). Kidney Doppler US showed the NCS for 4 years consecutively.\u0026nbsp;Low levels of C3, C4 and high IgA concentration also persisted. Proteinuria was worsened or lessened depending on the steroid dose. Recent abdomen CT revealed enlarged left kidney size together with NCP (Fig. 1e). At present, he is taking low dose steroid and angiotensin converting enzyme inhibitor (ACEi). An open surgery for NCP is being planned by the urologist. The last follow-up eGFR\u0026nbsp;was 80.8\u0026nbsp;ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e. The patient\u0026rsquo;s clinical course is shown in Fig. 1f.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCase 2\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 6-year-old boy presented with microscopic hematuria on a\u0026nbsp;school health check-up. His BMI and BP were within normal ranges. Urinalysis showed a high amount of hematuria (RBC \u0026gt; 60/HPF, dysmorphic RBCs 80%) and proteinuria (uPCR 0.94). During one year follow-up, uPCR was fluctuating from 0.2 to 2.1 and dysmorphic RBCs in urine were frequently found (dymorphic RBCs: 50 to 90%) with micro-hematuria. Kidney biopsy showed MGAs with mild foot process effacement. However, he showed severely fluctuating proteinuria with uPCR of 0.2 to 7.3 and normal serum protein level. Renal Doppler US was not specific.\u0026nbsp;Four years after the initial presentation, abdomen CT revealed NCS with an engorged left renal venous system. Enlarged sizes of left kidney and left gonadal varicocele were detected (Fig. 2a, b). Follow-up Doppler US confirmed the presence of NCS with PVR of 5.07 and abdomen CT one year later persistently showed the presence of NCP (Fig. 2c, d). During 6-year follow-up, the level of uPCR was inconsistent with that of 24 h-proteinuria. His proteinuria still waxes and wanes. ACEi and oral steroid seemed not to be effective in this patient. Surgical treatment is being considered by the urologist.\u0026nbsp;His clinical course is shown in\u0026nbsp;Fig. 2e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCase 3\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 10-year-old girl presented with proteinuria confirmed on a school health check-up. Seven years ago, she had visited our hospital for proteinuria (uPCR 0.56) and micro-hematuria (RBC \u0026gt; 60/HPF). However, she was lost to follow-up after 3 months.\u0026nbsp;Her BMI and BP were within normal ranges.\u0026nbsp;Initial laboratory findings showed mildly decreased serum protein (5.6 mg/dL) and increased cholesterol level (223 mg/dL). She had a nephrotic range of proteinuria (uPCR 3.95, 24-h proteinuria 55 mg/m\u003csup\u003e2\u003c/sup\u003e/hr) but no hematuria. Orthostatic proteinuria was excluded and NCS was revealed on kidney Doppler US (Fig. 3a). However, kidney\u0026nbsp;biopsy also confirmed the presence of focal segmental glomerulosclerosis (FSGS) (Fig. 3b, c). She was treated with ACEi, deflazacort, and cyclosporine. Eighteen months later, her proteinuria was reduced (54 mg/day) and ACEi only was used. At that time, the NCS was not observed. However, here proteinuria waxed and waned thereafter for one year (uPCR 0.29-1.21). Kidney Doppler US showed the NCS again with a PVR of 7.43. Abdomen CT also confirmed the presence of NCS (aorta-to-SMA angle: 31 degrees, CR: 2.64).\u0026nbsp;The patient\u0026rsquo;s clinical course is shown in\u0026nbsp;Fig. 3d.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCase 4\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 15-year-old girl presented with purpura on lower extremities and left knee arthralgia for two weeks. She had a history of syncope and normochromic normocytic anemia (10.0-11.1g/dL)\u0026nbsp;two years ago.\u0026nbsp;Her BMI was 18.1 kg/m\u003csup\u003e2\u003c/sup\u003e (8\u003csup\u003eth\u003c/sup\u003e percentile)\u0026nbsp;and her BP was 107/63 mmHg.\u0026nbsp;Laboratory findings were as follows: Hb level of 12.2 g/dL, RBC count of 3.89\u0026times;10\u003csup\u003e6\u003c/sup\u003e/uL (reference: 4.5-5.3\u0026times;10\u003csup\u003e6\u003c/sup\u003e/uL), protein level of 7.0 mg/dL, albumin level of 4.8 mg/dL, and cholesterol level of 166 mg/dL. Hematuria (10-29 RBCs/HPF) and nephrotic range of proteinuria (76 mg/m\u003csup\u003e2\u003c/sup\u003e/hr) were found, but uPCR was not so high (1.01). Kidney biopsy revealed mild IgAVN (International Study of Kidney Disease in Children\u0026nbsp;classification grade I). ACEi, oral steroid, and short-term cyclosporine were given. Her proteinuria was reduced two years after renal biopsy. During follow-up, she intermittently complained of\u0026nbsp;left arm numbness, left knee arthralgia, dizziness, nausea, and chest tightness. After quitting steroid, intermittent proteinuria (uPCR: 0.22-0.75) and low C3 level (78-79 mg/dL) were revealed. Her RBC count for 3 years was persistently low (3.71\u0026times;10\u003csup\u003e6\u003c/sup\u003e/uL to 4.12\u0026times;10\u003csup\u003e6\u003c/sup\u003e/uL)\u0026nbsp;with a normal hemoglobin level.\u0026nbsp;Kidney Doppler US showed abrupt narrowing of LRV between SMA and aorta\u0026nbsp;with a\u0026nbsp;PVR of 7.9 with consistent findings of NCS (Fig. 4a, b). Recent abdomen CT also confirmed the presence of NCP. Fig. 4c shows her clinical course.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSummary of patients with NCS and glomerulopathy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDemographic, clinical, and laboratory features of a total of 15 patients with NCS and glomerulopathy are summarized\u0026nbsp;in Table 1. Their mean age was\u0026nbsp;11 \u0026plusmn; 3.36 years, and the proportion of males was 53.3%.\u0026nbsp;Mean follow-up duration was\u0026nbsp;53.2 \u0026plusmn;\u0026nbsp;28.7\u0026nbsp;months. Two out of 15 patients had BMI\u0026nbsp;under 5 percentiles, and mean BMI was\u0026nbsp;18.9 \u0026plusmn; 3.35 kg/m\u003csup\u003e2\u003c/sup\u003e (32 \u0026plusmn; 32.1 percentile).\u0026nbsp;Chief complaints at initial visit were isolated proteinuria in 6 patients and proteinuria with microscopic hematuria in 9 patients. Orthostatic proteinuria and isolated hematuria were absent in our case series. Two patients (case 7 and case 13) showed intermittent episodes of gross hematuria. Only 4 patients with proteinuria and hematuria were examined for urine RBC morphology. One of them showed non-glomerular hematuria (case 7). BP levels of all patients were within normal ranges. Four patients had a family history of kidney diseases (cases 1, 7, 10, 14). Notably, father of case 14 had a history of NCS combined with thin basement membrane disease (TBMD) in his late 10\u0026rsquo;s and the patient showed renal biopsy findings of IgAN with diffuse thin GBM. Intermittent normochromic normocytic anemia was observed in 4 children (cases 1, 4, 7, 15; range: 10.0 to 11.1 g/dL) and leukopenia in 3 patients (cases 5, 7, 10; range: 3,150 to 4,380/mm\u003csup\u003e3\u003c/sup\u003e). C3 and/or C4 levels were reduced in 4 patients (cases 1, 4, 5, 6; range:\u0026nbsp;C3, 64 to 80 mg/dL; C4, 7.1 to 9.6 mg/dL)\u0026nbsp;and serum IgA levels were elevated in four patients (cases 1, 12, 14, 15; range:\u0026nbsp;250 to 354 mg/dL). Six patients (case 6-8, 10, 12, 14) showed intermittent low IgD level (\u0026lt; 0.63 mg/dL, reference: 0.77-13.2).\u0026nbsp;While all patients showed no difference in kidney length at first, five patients developed left kidney enlargement (cases 1, 2, 6, 7, 8; mean length difference of both kidneys: 13.3 mm). Extrarenal symptoms included left gonadal varicocele (Fig. 2b), a splenic cyst (Fig. 5a), syncope, palpitation, anemia, and left chest wall deformity\u0026nbsp;(Fig. 5b). Eight patients were diagnosed with NCS at initial US and 7 children were detected during a follow-up\u0026nbsp;with aggravation of proteinuria.\u0026nbsp;Kidney Doppler US was performed at least two times in all patients except for two (cases 4 and 15). Three patients showed resolution and reappearance of NCS (cases 3, 5, 9).\u0026nbsp;Ten of 15 patients were taken kidney biopsy within one year from the initial presentation. MGAs (Fig. 1c, d) in 7 children, focal GN in one (Fig. 5c, d), mesangial proliferative GN in one, and FSGS in one (Fig. 3b, c), IgAVN in two,\u0026nbsp;and IgAN in three patients (Fig. 5e, f)\u0026nbsp;were diagnosed. To clarify pathologic findings, we performed biopsy of the right kidney in one patient (case 7). All patients\u0026nbsp;showed persistent proteinuria with or without hematuria except for one patient with a relatively short follow-up period (case 8). Proteinuria has been fluctuating, and correlation between uPCR and 24-h proteinuria was not evident in some patients (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComparisons of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eclinical\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;features and outcomes between\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003epatients with and without definite GN\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the\u0026nbsp;causal or coincidental association between NCS and glomerulopathy, we compared clinical features and outcomes\u0026nbsp;of patients with MGAs and those with definite GN.\u0026nbsp;Age, follow-up duration, BMI, baseline and lowest eGFR, immunological abnormalities, clinical features of NCS, extrarenal symptoms, and persistent proteinuria were all similar between the two groups. However, the proportion of isolated proteinuria was more common in children with MGAs than in those with definite GN (71.4% vs. 12.5%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.05) (Fig. 6a) and peak level of uPCR tended to be higher in the MGA group (3.57 \u0026plusmn; 2.49 vs. 1.77 \u0026plusmn; 1.38, \u003cem\u003eP\u003c/em\u003e = 0.10) (Fig. 6b). Specifically, the last follow-up eGFR was significantly reduced in patients with MGAs compared to that in those with definite GN (90.3 \u0026plusmn; 14.3 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e vs. 108 \u0026plusmn; 15.6 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05) (Fig. 6c). Most patients with definite GN were treated with immunosuppressive agents (ISAs) and ACEi. However, the management was more diverse in patients with MGAs (Table 2).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, we report 15 cases of NCS combined with biopsy-proven GN presenting with proteinuria with or without hematuria. MGAs were most frequently found, followed by IgAN, IgAVN, and the same number of focal GN, mesangial proliferative GN, and FSGS. Almost all patients showed unusual clinical courses in comparison with biopsy findings. Isolated proteinuria was more common in the MGA group. The correlation between spot uPCR and 24-h proteinuria was inconsistent in some patients. A more considerable reduction in eGFR on the last follow-up was revealed in children with MGAs compared to those with definite GN. Associations of NCS with various GN should be considered in patients with persistent proteinuria with or without hematuria. A close long-term follow-up is needed for patients with these two combined conditions.\u003c/p\u003e \u003cp\u003ePatients with NCS have been shown to correlate with a low BMI. Some NCS patients\u0026rsquo; symptoms resolved with increasing BMI in previous studies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. A lack of supporting mesenteric fat, which reduces aortomesenteric angle, is one possible contributor to the development of NCP [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Renal ptosis, in which the kidney descends into the pelvis with the position change from supine to upright, has been proposed as another etiology of NCP [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. LRV stretching over the abdominal aorta and venous congestion may be worsened by a lack of supporting retroperitoneal fat [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Common manifestations of NCS-hematuria, proteinuria, and flank/pelvic pain are probably related to renal venous congestion and increased LRV pressure [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Venous hypertension and collateralization in NCS can also cause left sided varicocele in males and pelvic congestion in females [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Although rare, symptoms and signs related to autonomic dysfunction may occur, including orthostatic hypotension, dizziness, syncope, and nausea [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Cases of a splenic cyst and splenic vein enlargement have also been described [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Compared to this epidemiology, the BMI percentile under 5 percentile was found in only two out of 15 patients in the present study. While hematuria and orthostatic proteinuria are relatively common in the NCS [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], isolated hematuria and orthostatic proteinuria were absent in our study group. Atypical presentations such as a splenic cyst, left gonadal varicocele, syncope, anemia, and so on were observed in our patients. While persistent severe hematuria is considered as a cause of anemia in the NCS [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], sustained hematuria was present only in one (case 7) out of 4 patients with anemia. Given that anemia is often associated with clinical signs of congestion [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], renal congestion induced by NCP can compromise microvascular blood flow, which may contribute to renal hypoxia, ineffective erythropoiesis, and resultant anemia [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDiagnosis of NCS can be confirmed by a variety of tools such as kidney Doppler US, contrast-enhanced CT, MRI, and venography. The first imaging tool with suspected NCS is Doppler US [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Although venography is considered the gold standard for the diagnosis of NCS, it remains unclear whether the invasive procedure for measuring the pressure gradient is truly needed [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In our cases, all patients were initially diagnosed with kidney Doppler US. Instead of venography, CT or MRI was additionally performed except for two patients. Some patients who had presented with NCS from the beginning showed resolution and reappearance of NCS depending on the level of proteinuria. Others who had been diagnosed with GN revealed the NCS later along with persistent proteinuria with or without hematuria. In case 2, Doppler US was ineffective for the initial diagnosis of NCS. We were able to confirm the NCS with abdomen CT. Since proliferation of fibrous tissue at the origin of the SMA and increase of retroperitoneal adipose tissue can occur during normal growth, the LRV entrapment between SMA and abdominal aorta may appear or disappear, affecting proteinuria and/or hematuria [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Therefore, the relevance between the NCS and clinical course in our series is plausible. The presence of NCP and/or NCS should be suspected in children with persistent proteinuria.\u003c/p\u003e \u003cp\u003eAlthough NCS with co-existing GN is not common, combined cases have been increasingly reported. Among them, IgAN and IgAVN were common conditions in patients with NCS and various GN [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Other than IgAN, a case of NCS combined with TBMD in a 21-year-old woman presenting with persistent flank pain and larger left kidney has been reported [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. She showed a higher proteinuria than typical cases of TBMD. Interestingly, the father of one patient (case 14) with NCS and IgAN in our case series had a history of NCS combined with TBMD in his late 10\u0026rsquo;s. NCS complicated by membranoproliferative GN or moderate mesangial hypercellularity was also reported in patients with sustained proteinuria [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Notably, several animal studies have shown that acute increase in renal venous pressure from renal vein constriction can cause an elevation of renal interstitial hydrostatic pressure, a reduction of renal blood flow, and a subsequent decrease of GFR via the renin-angiotensin system (RAS) [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Compression of peritubular capillaries and tubules, renal hypoxia, and physical stress caused by the left kidney congestion could induce pericyte detachment, which could lead to extracellular matrix expansion and tubular injury [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Emerging evidence also persistently indicates that a low renal perfusion pressure can negatively impact renal function and histopathology with time [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Meanwhile, within the nephron, venous hypertension is associated with activation of a subclinical immune cascade in the vessel wall [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Venous congestion can induce vascular stretch which can activate vascular endothelial cells [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Endothelial cells actively participate in innate and adaptive immune responses, including complement production and control and pro-inflammatory, pro-oxidant, and vasoconstricting responses [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Recent studies have also revealed that immunomodulatory endothelial cells in the kidney can closely interact with resident immune cells, which are involved in rapid responses to circulating immune complexes [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. It is well known that immune complexes containing galactose deficient IgA1 play a crucial role in the pathogenesis of IgAN. While the pathogenesis of IgAV remains largely unknown, it has been proposed that in IgAV, IgA1 antibodies against endothelial cells are produced. Such IgA complexes can activate neutrophils via the IgA Fc receptor, thereby causing tissue damage [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Intriguingly, glomerular IgA and galactose deficient IgA1 deposition were more commonly reported in patients with NCP than in those without NCP [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In the present study, our patients with NCS showed various kidney biopsy findings of MGAs, IgAN, IgAVN, focal GN, mesangial proliferative GN, and FSGS. While MGA was most often diagnosed, IgAN and IgAVN were common in the next order. Immunologic alterations such as leukopenia, high IgA level, and low C3/C4 and IgD concentration were also found in 64% of our patients. Specifically, case 1 with MGAs showed a high IgA level but low C3 and C4 concentrations. Decreased IgD level was the most frequently found immunologic alteration among tested. While IgD concentration is low in human serum, IgD is known as a key regulator for balanced antibody responses [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Defective IgD function can result in deregulated activation of B cells and defective immune responses [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. In an animal experiment, lupus mice with IgD deficiency showed elevated autoantibody production, increased immune complex deposition, and more severe nephritis [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Therefore, decreased IgD level might be involved in abnormal immune responses in our clinical context. Collectively, elevated LRV pressure by NCP may increase glomerular and interstitial hydrostatic pressure, decrease renal blood flow, and activate vascular endothelial cells. All of these can synergistically contribute to glomerular or tubular damage and extracellular matrix expansion. They may also induce RAS activation, renal hypoxia, pericyte loss, and alteration of mucosal immunity. Dysregulated activation of the immune system in our case series can contribute to the genesis or worsening of various glomerular lesions.\u003c/p\u003e \u003cp\u003eTreatment options of NCS should be based on the severity of symptoms and expected reversibility according to the patient\u0026rsquo;s age [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. For children with NCS only, the first line management is a conservative approach. ACEi can be used for cases with severe and prolonged proteinuria [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Surgery may be considered for a frustrated conservative approach with continuing or severe symptoms [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In adults, the gold standard of care is LRV transposition with or without renal autotransplantation. However, it has disadvantages such as severe bleeding, vessel thrombosis, LRV restenosis, and paralytic ileus [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Due to a minimally invasive nature, endovascular or laparoscopic exovascular stent can be alternative treatment of choice in managing NCS [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In our patients showing NCS combined with GN, surgical procedures were not performed. Instead, all patients except three were treated with ACEi with/without ISAs. While some patients did not improve with ISAs including steroids, others showed worsened proteinuria after quitting ISAs. Particularly, patients with C activation or immune dysregulation showed good responses with ISAs. Fluctuation of uPCR was severe in some children with MGAs. Proteinuria with or without hematuria persisted for a long time relative to renal biopsy findings in almost all patients. Given that the relevance of MGAs and renal function decline has been suggested in previous studies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e], clinicians should pay attention to not only patients with definite GN, but also those with MGAs. In the present study, the last follow-up eGFR was more reduced in patients with MGAs than in those with definite GN. Baseline and lowest eGFR tended to be lower while uPCR tended to be higher in the MGA group than in the definite GN group. To put it simply, MGA could be a secondary change of NCS and definite GN would be a coincidental finding with NCS. If not, older age and less aggressive therapy with ACEi and/or ISAs in the MGA group \u0026ndash;although the differences were not statistically significant\u0026ndash; could affect these results. It is difficult to conclude the causal or coincidental link between NCS and different GN. Nevertheless, we identified some cause-and-effect relationships between NCS and GN in our case series, such as renal histologic alterations, immune dysregulation, and renal dysfunction.\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, a small sample size might be not enough to prove the causal relationship between NCS and GN. Studies including multi-centers and large sized participants are needed to clarify the influence of NCS on the triggering and progression of GN. In our clinical context, NCS might induce MGAs, focal GN, mesangial proliferative GN, and FSGS consecutively. It can also play a role in the triggering or worsening immune-mediated GN such as IgAN and IgAVN. Second, renal venography with direct pressure measurements was not done in our patients due to its invasive nature. However, NCS was confirmed repeatedly with Doppler US, CT, or MRI in our cases. Third, renal biopsies of patients were done on their left side except for one patient. While NCP could lead to decreased renal blood flow and histologic changes in the congested left kidney only at first, histopathologic changes would take place in the right kidney as well with time. As a way to support this, we confirmed renal histologic changes of MGAs of the right kidney in one patient (case 7).\u003c/p\u003e \u003cp\u003eIn conclusion, NCS may be associated with the presence of various GN. The causal relationship of NCS and GN should be further investigated. We may assume that NCS combined with GN is not rare. Its prevalence could be higher than previously thought. Renal biopsy should be performed without hesitation to confirm the co-existence of GN with NCS. Inversely, NCS evaluation could be considered in patients with atypical and uncommon courses of various GN.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAuthors have no financial interests that are directly or indirectly related to the work submitted here for publication\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by a grant funded by Korea University (No.\u0026nbsp;\u003cstrong\u003eK2310611\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e. We also would like to express our gratitude to Professor Bo-Kyung Je (Department of Radiology, Korea University Ansan Hospital) who provided assistance for radiologic evaluation.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAuthor contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Hyung Eun Yim contributed to the study conception, study design, and project administration. Material preparation and data collection were performed by So Hyun Ki,\u0026nbsp;Min Hwa Son, and Hyung Eun Yim. Statistical analyses were performed by So Hyun Ki. Visualization was performed by So Hyun Ki and Min Hwa Son. The first draft of the manuscript was written by So Hyun Ki. It was\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ereviewed and revised by So Hyun Ki,\u0026nbsp;Min Hwa Son, and Hyung Eun Yim. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board (IRB) of the Korea University Ansan Hospital (IRB No. 2023AS0067) before initiation. It was performed according to the ethical standards of the Declaration of Helsinki. The IRB waived the requirement to obtain informed consent since this study involved a retrospective chart review of anonymous patient data. Patients\u0026apos; data from our previous paper [45] were partially included.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGranata A, Distefano G, Sturiale A, Figuera M, Foti PV, Palmucci S, Basile A (2021) From nutcracker phenomenon to nutcracker syndrome: A pictorial review. Diagnostics (Basel) 11:101. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/diagnostics11010101\u003c/span\u003e\u003cspan address=\"10.3390/diagnostics11010101\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalantar DS, Park SJ, Shin JI (2023) Nutcracker syndrome in children: review of symptom, diagnosis, and treatment. 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Summary of 15 pediatric cases with NCS combined with glomerulopathy\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1040\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003cp\u003e/age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eInitial\u003c/p\u003e\n \u003cp\u003eSx\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eRBC morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003eEvent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eBaseline eGFR\u003c/p\u003e\n \u003cp\u003e(ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003eLowest eGFR\u003c/p\u003e\n \u003cp\u003e(ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003eLast eGFR\u003c/p\u003e\n \u003cp\u003e(ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003euPCR\u003c/p\u003e\n \u003cp\u003e(mg/mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDiagnostic tool\u0026nbsp;\u003c/p\u003e\n \u003cp\u003efor NCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePV at RH (cm/s)/PV at AM (cm/s)\u003c/p\u003e\n \u003cp\u003e(PVR)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eTime to NCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eRenal pathology\u003c/p\u003e\n \u003cp\u003e(Time to renal biopsy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003eF/u duration (mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eM/14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003e16.4\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(2p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eIsolated proteinuria\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003eLK enlargement,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eanemia,\u0026nbsp;low C3/C4, high IgA, family Hx of nephrectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e76.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e53.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e64.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003e5.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e30/200 (6.67)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eInitial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eMGAs\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(4 mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003e2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eM/6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003e17.2\u003c/p\u003e\n \u003cp\u003e(17p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eHematuria, proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eDysmorphic RBC 80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003eLK enlargement,\u003c/p\u003e\n \u003cp\u003eLeft gonadal varicocele\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e137.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e109.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e109.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003e7.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e29/147 (5.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e5 y\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eMGAs\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(10 mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003e3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eF/10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003e18.6\u003c/p\u003e\n \u003cp\u003e(51p)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eHematuria, proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eUnexamined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003eF/u loss for 7 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e147.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e116.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e116.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003e3.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e28/134 (4.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e7 y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eFSGS\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(7 y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003e4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eF/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003e18 (8p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003ePurpura,\u003c/p\u003e\n \u003cp\u003eHematuria, proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eUnexamined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003eSyncope, anemia,\u003c/p\u003e\n \u003cp\u003elow C3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e108.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e81.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e108.0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003e1.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e19/149 (7.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e33 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eIgAVN (ISKDC class I, Initial)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003e5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eF/13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003e15.2\u003c/p\u003e\n \u003cp\u003e(2p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eIsolated proteinuria\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003eSplenic cyst, Leukopenia,\u003c/p\u003e\n \u003cp\u003elow C3/C4,\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e122.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e89.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e113.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003e3.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e18/\u0026gt;100 (5.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eInitial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eMesangial proliferative GN (Initial)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003e6\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eF/9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003e14.8\u003c/p\u003e\n \u003cp\u003e(12p)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eHematuria, proteinuria\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eUnexamined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003eLK enlargement,\u003c/p\u003e\n \u003cp\u003elow C3, low IgD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e116.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e108.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e118.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e17/190 (11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eInitial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eFocal GN\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(3 mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003e7\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eM/13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003e19 (8p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eHematuria, proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eNo dysmorphic RBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003eLK enlargement,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003egross hematuria,\u003c/p\u003e\n \u003cp\u003epalpitation, anemia, leukopenia, low IgD, family Hx of hematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e113.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e83.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e92.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e20/120\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eInitial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eMGAs\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(4 y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003e8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eF/16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003e22.0\u003c/p\u003e\n \u003cp\u003e(65p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eIsolated proteinuria\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003eLK enlargement, pectus arcuatum,\u003c/p\u003e\n \u003cp\u003elow IgD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e98.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e98.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e99.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e19/129 \u0026nbsp;(6.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eInitial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eMGA\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(18 mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6948989412897015%\" valign=\"top\"\u003e\n \u003cp\u003e9\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003eF/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" valign=\"top\"\u003e\n \u003cp\u003e17.2\u003c/p\u003e\n \u003cp\u003e(12p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eIsolated proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.875842155919154%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.523580365736285%\" valign=\"top\"\u003e\n \u003cp\u003e3.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.314725697786333%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e18/74\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(4.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.48604427333975%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e30 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.180943214629451%\" valign=\"top\"\u003e\n \u003cp\u003eMGAs\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(3 mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.352261790182868%\" valign=\"top\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6923076923076925%\" valign=\"top\"\u003e\n \u003cp\u003e10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003eM/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e20.7\u003c/p\u003e\n \u003cp\u003e(58p)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eIsolated proteinuria\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.173076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.865384615384615%\" valign=\"top\"\u003e\n \u003cp\u003eLeukopenia,\u003c/p\u003e\n \u003cp\u003elow IgD, family Hx of GN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.173076923076923%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e103.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e86.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e97.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003e4.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, MRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003e31/212 (6.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eInitial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.134615384615385%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMGAs\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(4 mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6923076923076925%\" valign=\"top\"\u003e\n \u003cp\u003e11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003eM/13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e24.2\u003c/p\u003e\n \u003cp\u003e(89p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eIsolated proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.173076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.692307692307692%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eEarly puberty\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003e3.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003e10/75\u003c/p\u003e\n \u003cp\u003e(7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eInitial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.134615384615385%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMGAs\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(7 mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6923076923076925%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.173076923076923%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.692307692307692%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.134615384615385%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6923076923076925%\" valign=\"top\"\u003e\n \u003cp\u003e12\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003eM/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e17.8\u003c/p\u003e\n \u003cp\u003e(25p)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eHematuria, proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.173076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eUnexamined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.692307692307692%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHigh IgA, low IgD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e111.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e75.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e78.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003e29/161 (5.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eInitial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.134615384615385%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIgAN (M1 E0 S1 T0 C0,\u003c/p\u003e\n \u003cp\u003e3 mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6923076923076925%\" valign=\"top\"\u003e\n \u003cp\u003e13\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003eM/10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e17.5\u003c/p\u003e\n \u003cp\u003e(19p)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eHematuria, proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.173076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eDysmorphic RBC 30 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.692307692307692%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGross hematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e120.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e92.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e94.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003e24/154 (6.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e17 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.134615384615385%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIgAN (M1 E1 S1 T0 C0,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6923076923076925%\" valign=\"top\"\u003e\n \u003cp\u003e14\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003eM/7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e27.2\u003c/p\u003e\n \u003cp\u003e(99p)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eHematuria, proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.173076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eDysmorphic RBC 13%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.692307692307692%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eHigh IgA, low IgD, family Hx of NCS with TBMD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e108.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e83.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e101.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US, CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003e24/142 (5.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e4 y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.134615384615385%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIgAN (M1 E0 S0 T0 C0, 4 y) with diffuse thin GBM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.6923076923076925%\" valign=\"top\"\u003e\n \u003cp\u003e15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003eF/11\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" valign=\"top\"\u003e\n \u003cp\u003e17.9\u003c/p\u003e\n \u003cp\u003e(13p)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003ePurpura,\u003c/p\u003e\n \u003cp\u003eHematuria, proteinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.173076923076923%\" valign=\"top\"\u003e\n \u003cp\u003eUnexamined\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.692307692307692%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAnemia, high IgA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.519230769230769%\" valign=\"top\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003eDoppler US\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.3076923076923075%\" valign=\"top\"\u003e\n \u003cp\u003e17/129 (7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.480769230769231%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e7 y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.134615384615385%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eIgAVN (ISKDC class IIIb, Initial)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.346153846153846%\" valign=\"top\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.3408239700374533%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"4.02621722846442%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"5.149812734082397%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"6.928838951310861%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.771535580524344%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.865168539325842%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"1.404494382022472%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"8.239700374531836%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.737827715355806%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.737827715355806%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"5.711610486891386%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"6.741573033707865%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"6.367041198501872%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"0.18726591760299627%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"4.213483146067416%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"0.4681647940074906%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.584269662921348%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"5.52434456928839%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNCS, nutcracker syndrome; N, number; BMI, body mass index; Sx, symptom; RBC, red blood cell; eGFR, estimated glomerular filtration rate; uPCR, urine protein to creatinine ratio; PV at RH /PV at AM, peak velocity at the renal hilum/peak velocity at the aortomesenteric portion; PVR, peak velocity ratio; F/u, follow-up; mo, months; M, male; p, percentile; LK, left kidney; C, complement; Ig, immunoglobulin; Hx, history; US, ultrasonography; CT, computed tomography; MGAs, minor glomerular abnormalities; y, year; F, female; FSGS, focal segmental glomerulosclerosis; IgAVN, IgA vasculitis nephritis; ISKDC, International Study of Kidney Disease in Children; GN, glomerulonephritis; MRI, magnetic resonance imaging; IgAN, IgA nephropathy; M 1, mesangial hypercellularity 1; E, endothelial hypercellularity; S, segmental glomerulosclerosis; T, tubular atrophy/interstitial fibrosis; C, cellular/fibrocellular crescents; TBMD, thin basement membrane disease; GBM, glomerular basement membrane.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Comparisons between the MGA and GN groups\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003eMGAs (n=7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003eGN (n=8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eAge at initial presentation (y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e12.1 \u0026plusmn; 3.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e10 \u0026plusmn; 3.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.231\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eAge at NCS (y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e13.3 \u0026plusmn; 1.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e12.9 \u0026plusmn; 3.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.773\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eMean f/u duration (mo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e46.7 \u0026plusmn; 21.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e58.9 \u0026plusmn; 35.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.439\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e19.5 \u0026plusmn; 2.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e18.4 \u0026plusmn; 3.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.527\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIsolated proteinuria, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e5 (71.4%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 (12.5%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.041\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003euPCR (mg/mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003elowest\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e0.27 \u0026plusmn; 0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e0.11 \u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.479\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003ehighest\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e3.57 \u0026plusmn; 2.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e1.77 \u0026plusmn; 1.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.101\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eeGFR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eBaseline\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e102 \u0026plusmn; 19.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e119 \u0026plusmn; 12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.076\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eLowest\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e83.7 \u0026plusmn; 17.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e94.1 \u0026plusmn; 14.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.237\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLast follow-up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e90.3 \u0026plusmn; 14.3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e108 \u0026plusmn; 15.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.045\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eComplement dysregulation (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e1 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e3 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.569\u003cstrong\u003e\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eImmunoglobulin abnormality (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e4 (57.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e4 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003cstrong\u003e\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eLeukopenia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e2 (28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.569\u003cstrong\u003e\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eAnemia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e2 (28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e2 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003cstrong\u003e\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eNCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003ePVR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e6.14 \u0026plusmn; 1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e6.86 \u0026plusmn; 2.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.427\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e3.20 \u0026plusmn; 1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e2.90 \u0026plusmn; 0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.868\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eInitial presentation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e5 (71.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e3 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.315\u003cstrong\u003e\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Reappearance, n (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e1 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e2 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003cstrong\u003e\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eLK enlargement, n (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e4 (57.1%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.119\u003cstrong\u003e\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eExtrarenal symptoms, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e4 (57.1%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e3 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.619\u003cstrong\u003e\u003csup\u003e\u0026nbsp;b\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eManagement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.103\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eObservation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e3 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eACEi only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e1 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e1 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003eISAs + ACEi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e3 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e7 (87.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.27598566308244%\" valign=\"top\"\u003e\n \u003cp\u003ePersistent proteinuria (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.655913978494624%\" valign=\"top\"\u003e\n \u003cp\u003e6 (85.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.25089605734767%\" valign=\"top\"\u003e\n \u003cp\u003e8 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.817204301075268%\" valign=\"top\"\u003e\n \u003cp\u003e0.467\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues are presented as means \u0026plusmn; standard deviations or numbers (%). \u003csup\u003ea\u003c/sup\u003e\u003cem\u003eWilcoxon\u003c/em\u003e \u003cem\u003erank sum\u003c/em\u003e test,\u0026nbsp;\u003csup\u003eb\u003c/sup\u003e\u003cem\u003eFisher\u0026rsquo;s exact\u003c/em\u003e test, \u003csup\u003ec\u003c/sup\u003e\u003cem\u003eChi-sqaure\u0026nbsp;\u003c/em\u003etest.\u0026nbsp;MGAs, minor glomerular abnormalities; GN,\u0026nbsp;glomerulonephritis; y, years; NCS,\u0026nbsp;nutcracker syndrome; mo, months; n, number;\u0026nbsp;uPCR,\u0026nbsp;urine protein to creatinine ratio;\u0026nbsp;eGFR, estimated glomerular filtration rate;\u0026nbsp;PVR, peak velocity ratio;\u0026nbsp;CR, compression ratio; LK, left kidney; ACEi, angiotensin converting enzyme inhibitor; ISAs, immunosuppressive agents.\u0026nbsp;\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Glomerulonephritis, Immunity, Proteinuria, Renal nutcracker syndrome","lastPublishedDoi":"10.21203/rs.3.rs-4418523/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4418523/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eNutcracker syndrome (NCS) has been reported to coexist with various glomerulonephritis (GN). This study investigated clinical features of NCS combined with GN in a pediatric case series and the possible relationship between these two conditions.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eClinical and pathologic findings of 15 children with NCS and biopsy-proven GN were analyzed. NCS was diagnosed with renal Doppler ultrasonography, abdominal computed tomography, and/or magnetic resonance imaging. Glomerular lesions were divided into two pathological categories: minor glomerular abnormalities (MGAs) and definite GN.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eMean age of all patients was 11\u0026thinsp;\u0026plusmn;\u0026thinsp;3.36 years and mean follow-up duration was 53.2\u0026thinsp;\u0026plusmn;\u0026thinsp;28.7 months. Chief complaint was proteinuria with or without hematuria. During follow-up, five patients developed left kidney enlargement. Abnormal levels in immunological tests were revealed in 10 patients. Extrarenal symptoms including gonadal varicocle, splenic cyst, syncope, and anemia were found in 7 patients. On kidney biopsy, 7 patients had MGAs and 8 children showed definite GN (one case of focal GN, one case of mesangial proliferative GN, one case of focal segmental glomerulosclerosis, two cases of IgA vasculitis nephritis, and three cases of IgA nephropathy). While there were no differences in age, baseline estimated glomerular filtration rate (eGFR), immunological tests, clinical features of NCS, or extrarenal symptoms between the two groups, patients with NCS combined with MGAs showed higher proportion of isolated proteinuria and eGFR decline (both \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eNCS may be associated with the presence of various GN. The causal relationship between NCS and GN should be further investigated.\u003c/p\u003e","manuscriptTitle":"Nutcracker syndrome and glomerulonephritis in pediatric patients: A causal or coincidental association?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-31 20:37:10","doi":"10.21203/rs.3.rs-4418523/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eb4c4c44-6c1c-4098-bbcd-6acd4a9f153b","owner":[],"postedDate":"May 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-19T20:52:09+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-31 20:37:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4418523","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4418523","identity":"rs-4418523","version":["v1"]},"buildId":"wLkW0s4AflPzk-lpfg-fK","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}