Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patient- a Case Report

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patient- a Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patient- a Case Report Elena Jordanova, Marija Karapandzic, Rodoljub Markovic, Maja Zivotic, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8484421/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Mar, 2026 Read the published version in BMC Nephrology → Version 1 posted 12 You are reading this latest preprint version Abstract Background We report a type 2 diabetes mellitus (T2DM) patient with clinical and laboratory features of nephrotic syndrome. Pathohystological findings (PH) of the biopsy performed idiopathic membranous nephropathy (MN). Case presentation: The 54 years old male patient was admitted to the hospital with clinical and laboratory features of nephrotic syndrome (initial value of serume creatinine was 1.87 mg/dl, creatinine clearance was 57 ml/ min, daily proteinuria was 16 g). Immunological analyses (ANA-Hep2(IgG), ANCA, anti GBM At(IgG), antiPLA2R(IgG) antibodies) and tumour markers were negative. Abdominal ultrasound examination showed both kidneys to be normal diameter with parenchyma thickness of 17–18 mm, emphasized pyramids on both sides, without stasis or calculosis. Then macrohematuria appeared (value sCr 4.38 mg/dl) and CT urography was done- thrombosis of the left renal vein along it’s entire length, venous stasis and edema of the left kidney, ureterohydronephrosis stage I/ II left; signs of ureteritis on the left side and subsequent tumour of the proximal part of the ureter - focally thickened wall of the ureter in that part. The urethritis was treated with quinolones. After 7 days CT scan was repeated and confirmed the high suspicion of a tumour of the ureteropelvic junction and the proximal part of the ureter; stage II ureterohydronephrosis remained on the left side. An exploratory retrograde ureterorenoscopy was performed. The procedure revealed no evidence of tumour, and JJ stent has been placed in the left ureter. Daily proteinuria was still nephrotic range (13.45 g). After one month, the JJ stent was removed. Two months later, a control CT scan of the abdomen and pelvis was conducted, and a kidney biopsy was performed. The PH findings showed MN. The patient received the first dose of Rituximab at 375 mg/m 2 (750 mg intravenously). This same dose was administered again after two weeks. Conclusions Patients with T2DM, nephrotic syndrome and rapidly declining renal function present diagnostic challenges due to the potential presence of associated non diabetic renal disease. Kidney biopsy is essential for PH diagnosis. Understanding of different types non diabetic renal disease in T2DM patients is necessary to improve future patient's outcomes. type 2 diabetes mellitus diabetic nephopathy non diabetic renal disease kidney biopsy membranous nephropathy Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Diabetic nephropathy (DN) is microvascular complication of both type 1 and type 2 diabetes mellitus (T2DM). It is chronic kidney disease characterized by the presence of persistent albuminuria, decline in estimated glomerular filtration rate (eGFR) or both for more than 3 months, and it is often associated with hypertension [ 1 ]. The rising number of diabetes nephropathy patients with end- stage renal disease (ESRD) has made this disease the main cause of ESRD in Western Europe and USA [ 1 ]. DN is not the only type of renal disease in T2DM patients, but non diabetic renal disease (NDRD) can also appear: glomerular, tubulointerstitial or vascular diseases. One-third T2DM patients in biopsy findings have, in adition to DN, glomerular diseases such as IgA nephropathy (IgAN), minimal change disease, membranous, membranoproliferative or cryoglobulinemic glomerulonephritis (GN) [ 2 , 3 ]. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults [ 4 , 5 ]. It could be: primary and secondary MN which occurs as a consequence of a wide range of well-known diseases. A major advance in distinguishing these entities in recent years was the discovery of M- type phospholipase A2 receptor antibodies (anti- PLA2R) on the surface of podocytes in primary MN patients. It has been shown that primary MN is an autoimmune kidney specific disease in which glomerular lesion occurs due to the subepithelial formation of immune complex in situ. The course of primary MN is unpredictable and varies significantly, so it is important to determine which patients should be treated with immunosuppressive therapy and which should be treated with symptomatic therapy [ 6 ]. We report T2DM patient with clinical and laboratory features of nephrotic syndrome. Pathohystological (PH) findings of kidney biopsy performed idiopathic MN. Case presentation The 54 years old male patient was referred to a nephrologist examination due to swelling of the legs, pain in the abdomen, nausea, and urge to vomit. The leg swelling appeared 4–6 weeks before other symptoms which occurred two days prior the first nephrologist examination. Hypoproteinemia, hypoalbuminemia, hypercholesterolemia, and hypertriglyceridemia were verified in the laboratory analyzes performed at the Health Center. eGFR calculated by CKD-EPI formula was 106 ml/min/1.73m 2 . The patient was hospitalized at the Department of Nephrology Clinical Hospital Center Zemun for examination and diagnosis of nephrotic syndrome. In medical history a patient had T2DM diagnosed for one year treated with oral antidiabetics (metformin, SGLT2 inhibitors). Patient has on previous surgeries or drug allergies. Table 1 shows the patient`s clinical and laboratory data on the admission to the hospital. Initial value of serum creatinine (sCr) was 1.87 mg/dl, eGFR calculated by CKD- EPI formula was 42.3 ml/min/1.73m 2 , creatinine clearance was 57 ml/ min, daily proteinuria was nephrotic range (16g/day, diuresis 15.00ml). Body weight on admission was 74.8kg (BMI 23.3kg/m 2 ). In the urine sediment were a mass of fresh red blood cells, a lot of pale red blood cells, a mass of dysmorphic red blood cells, 3–4 leukocytes, and rare bacteria. Immunological analysis: ANA-Hep2(IgG), ANCA, anti GBM At(IgG), antiPLA2R(IgG) antibodies were negative. The complement system components (C3, C4, CIC), serum immunoglobulins (IgG, IgA, IgM), and beta 2-microglobuline levels were all within reference ranges. Electrophoresis and immunoelectrophoresis of serum proteins indicated decreased levels of gamma globulins. Additionally, electrophoresis and immunoelectrophoresis of urine proteins demonstrated selective glomerular proteinuria. Tumour markers were negative. Regarding the coagulation status, D-dimer was elevated at 1803ng/ml. The aPTT was 31.9sec, PT was 9.9sec, INR was 0.9, and TT was 15.1sec. Antithrombin 3 was 114%. Tests for HIV, hepatitis B surface antigen, and hepatitis C antibodies returned negative results. Table 1 Patient's clinical and laboratory data on first admission to the hospital Variable The values Glycemia (mmol/l) 6.3 HbA1c (%) 6.1 Hemoglobin (g/l) 131 Serum protein (g/l) 52 Serum albumin (g/l) 25 Cholesterol (mmol/l) 8.42 Triglyceride (mmol/l) 2.49 Serum creatinine (mg/dl) 1.87 eGFR CKD- EPI (ml/min/1.73m 2 ) 42.3 Serum urea (mmol/l) 9.8 CRP (mg/l) 96.4 Acidum uricum 357 Potassium (mmol/l) 3.8 Calcium (mmol/l) 2.04 Phosphorus (mmol/l) 1.44 PTH (pg/ml) 59.6 Iron (µmol/l) 5.5 Ferritin (µg/l) 1136 Proteinuria (g/ day) 16 Bilirubin total (µmol/l) 10.35 Bilirubin direct (µmol/l) 1.45 AST (U/L) 12 ALT (U/L) 11 GGT(U/L) 33 Legend: HbA1c - glycated hemoglobin; eGFR - estimated glomerular filtration rate; CRP - C reactive protein; PTH - parathyroid hormone; AST - aspartate aminotransferase; ALT - alanine aminotransferase; GGT - gamma glutamyl transferase; Abdominal ultrasound examination showed both kidneys to be usually positioned and of normal diameter with parenchyma thickness of 17–18 mm and emphasized pyramids on both sides, without stasis, or calculosis. Funduscopy was normal. Initially, therapy included loop diuretics, angiotensin II receptor antagonists, low-molecular-weight heparin, proton pump inhibitors, and oral antidiabetics (metformin, sulfonylurea derivates). On the third day of hospitalization, macrohematuria appeared with an increase in serum creatinine value (sCr 4.38 mg/dl). CT urography was done- thrombosis of the left renal vein along it’s entire length, venous stasis and edema of the left kidney, ureterohydronephrosis stage I/ II left. CT signs of ureteritis on the left side, and subsequent tumour of the proximal part of the ureter - focally thickened wall of the ureter in that part were confirmed (Fig. 1 ). Consultations were conducted with a urologist, radiologist, and vascular surgeon. The decision was made to treat the urethritis with antibiotic therapy (quinolones with probiotic), and to repeat CT urography in 7 days. A follow-up CT scan, after treatment of the ureteritis, confirmed still present thrombosis of the left renal vein, high suspicion of a tumour of the ureteropelvic junction, and the proximal part of the ureter, stage II ureterohydronephrosis remained on the left side (Fig. 2 ). During hospitalization, the patient was conscious and oriented, afebrile, hemodynamically stable, and had a blod pressure (BP) of 130/70 mmHg. The initial hematuria resolved with treatment, and the urine cleared with diuresis of up to 3.500 ml. An exploratory retrograde ureterorenoscopy (URS) was scheduled. Meanwhile, three urine samples were sent for cytology examination to detect malignant cells; all results were negative. The patient was transferred to the Urology Department. An exploratory retrograde URS was done under general anaestethesia. No pathological changes were observed in the left ureter. The existence of a tumour lesion has not been proven, the ureteral JJ stent has been placed in the left ureter. The value of sCr on discharge from the Urology Department was 1.05mg/dl, eGFR CKD- EPI was 84.2 ml/min/1.73m 2 , daily proteinuria was 13.45 g, diuresis 1700 ml. After a month the JJ stent was taken out. Two months later, the patient was hospitalized again in the Department of Nephrology. In order to continue diagnostic and etiology of nephrotic syndrome, a kidney biopsy was planned. At the time of kidney biopsy patient's clinical and laboratory data were presented in Table 2 . Table 2 Clinical and laboratory data at time of kidney biopsy and at time of received therapy Variable At the time of kidney biopsy First dose Rx Second dose Rx Glycemia (mmol/l) 6.9 5.7 6.3 HbA1c (%) 6.4 6.1 6.1 Hemoglobin (g/l) 133 131 135 Serum protein (g/l) 49 47 46 Serum albumin (g/l) 26 23 23 Cholesterol (mmol/l) 5.69 5.98 5.42 Triglyceride (mmol/l) 2.83 2.0 2.63 Setum creatinine (mg/dl) 1.14 1.04 1.05 eGFR CKD-EPI(ml/min/1.73m 2 ) 76.2 84.7 83.6 Serum urea (mmol/l) 8.6 7.0 7.1 CRP (mg/l) 0.7 0.4 0.6 Acidum uricum 425 459 129 Potassium (mmol/l) 4.4 4.5 3.9 Calcium (mmol/l) 2.1 2.07 2.02 Phosphorus (mmol/l) 1.22 1.2 1.06 PTH (pg/ml) 53.7 63.2 44.3 Iron (µmol/l) 8.0 12.8 9.1 Ferritin (µg/l) 538 516 402 Proteinuria (g/ day) 13.43 10.48 7.51 Bilirubin total (µmol/l) 5.73 6.31 6.78 Bilirubin direct (µmol/l) 0.13 1.03 1.28 AST (U/L) 19 19 21 ALT (U/L) 15 19 20 GGT (U/L) 22 23 25 Antithrombin (%) 114 110 85 Legend: HbA1c - glycated hemoglobin; eGFR - estimated glomerular filtration rate; CRP - C reactive protein; PTH - parathyroid hormone; AST - aspartate aminotransferase; ALT - alanine aminotransferase; GGT - gamma glutamyl transferase; Rx - Rituximab Repeated immunological tests (ANA, ANCA, anti ds-DNA, anti MPO, antiPR3, anti GBM antibodies, anti PLA2R antibodies), and tests for the presence of thrombophilia (protein C, protein S, anticardiolipin IgG and IgM antibodies, beta- 2 glycoprotein IgG and IgM antibodies, activated protein C resistance-Factor V Leiden, lupus anticoagulant, homocysteine) were negative. Control CT of abdomen and pelvis confirmed the left vein was recanalized, with minor sequelae of previous thrombosis, both kidneys enlarged and that irregular opacified wall thickening of the proximal part of the ureter and part of the pyelon, as well as the distal part of the ureter on the left side was now described without ureterohydronephrosis (Fig. 3 ). The kidney biopsy was performed under ultrasound guidance. PH examination indicated the presence of MN. Immunofluorescence analysis was performed on a fresh frozen tissue section containing eight glomeruli and revealed intense fine granular deposits along the glomerular basement membranes (GBM). IgG showed strong granular capillary wall staining, accompanied by granular C3 positivity, while IgA, IgM, C1q, kappa and lambda light chains, and fibrinogen were negative. On light microscopy, the biopsy consisted of a renal cortical core measuring approximately 10 mm in length and containing up to 20 glomeruli on serial sections, two of which were globally sclerotic (Fig. 4A and 4B). The remaining glomeruli demonstrated mild to moderate, diffuse and uniform thickening of the GBM, consistent with a membranous pattern of injury. Segmental mesangial expansion with mild mesangial hypercellularity and increased mesangial matrix was observed in a minority of glomeruli. The tubulointerstitial compartment showed diffuse chronic changes, including interstitial fibrosis involving approximately 50% of the cortical parenchyma and associated tubular atrophy affecting around 40% of tubules. A mild focal mononuclear inflammatory infiltrate was present (Fig. 4C and 4D). Immunohistochemistry demonstrated diffuse granular C4d (Fig. 4E) and PLA2R (Fig. 4F) positivity along the GBM. IgG4 showed segmental granular staining (Fig. 4G). NELL1 (Fig. 4H ) and Netrin G1 (Fig. 4I) were focally positive along the GBM, while EXT1, EXT2, NCAM, SEMA3B, and PACE4 were negative. Figure 4 Renal biopsy findings - membranous nephropathy A and B , periodic acid-Schiff, 200x, C Jines methenamine silver staining, 200x and D massin trichrome staining, 100x, E , F , G , H and I immunohistochemical staining Immunofluorescence analysis was performed on a fresh frozen tissue section containing eight glomeruli and revealed intense fine granular deposits along the glomerular basement membranes (GBM). IgG showed strong granular capillary wall staining, accompanied by granular C3 positivity, while IgA, IgM, C1q, kappa and lambda light chains, and fibrinogen were negative. On light microscopy, the biopsy consisted of a renal cortical core measuring approximately 10 mm in length and containing up to 20 glomeruli on serial sections, two of which were globally sclerotic. The remaining glomeruli demonstrated mild to moderate, diffuse and uniform thickening of the GBM, consistent with a membranous pattern of injury. Segmental mesangial expansion with mild mesangial hypercellularity and increased mesangial matrix was observed in a minority of glomeruli. The tubulointerstitial compartment showed diffuse chronic changes, including interstitial fibrosis involving approximately 50% of the cortical parenchyma and associated tubular atrophy affecting around 40% of tubules. A mild focal mononuclear inflammatory infiltrate was present. Immunohistochemistry demonstrated diffuse granular C4d ( E , 200x) and PLA2R ( F , 200x) positivity along the GBM. IgG4 showed segmental granular staining ( G , 200x). NELL1 ( H , 200x) and Netrin G1 ( I , 200x) were focally positive along the GBM, while EXT1, EXT2, NCAM, SEMA3B, and PACE4 were negative. Off-label* use of Rituximab (Rtx), as the first line therapy for treatment of idiopathic membranous glomerulonephritis, is indicated according to the KDIGO guidelines [ 6 ]. Patient has received the first dose of Rtx (375 mg/m 2 or 750 mg intravenously). After two weeks the same dose was repeated. Table 2 shows the laboratory data at the time patient received the therapy. At the time of discharge from our department, the patient's body weight was reduced by 6 kg compared to his weight upon admission to the hospital. *In Serbia, Rituximab is not registered for the indication of treatment of primary glomerulonephritis and systemic diseases, but only for the treatment of B lymphomas. Discussion At the time of diagnosis, a third of newly diagnosed T2DM patients already have one or more late complications: ischemic heart disease, diabetic foot, retinopathy, neuropathy or nephropathy [ 1 ]. GN is the most common renal complication in T2DM patients with co-existing DN and NDRD. Chines researcher Li Zho summarized studies that have been published between 1983 and 2012 year and found that in T2DM patients could also be find GN: IgAN (14.1%), mesangial proliferative GN (10%), and post-infectious GN (10%) [ 7 ]. In 1973 year the first case report of kidney biopsy findings of MN and DN was reported by Warms et al. [ 8 ]. In the period of next 20 years, other authors also showed the connection between the appearance of DN and MN [ 9 , 10 ]. Different studies have described different percentage of NDRD in T2DM patients: Prakash et al. [ 11 ] showed 12.3%, Zhuo et al. [ 12 ] 7.8%, and even more than 60% in study of Grujicic et al. [ 3 ]. Authors showed that in T2DM patients for whom kidney biopsy was performed, significantly lower duration of T2DM was found in NDRD patients compared to DN patients [ 13 , 14 ]. The suspicion that our patient did not have DN arose from several factors. These included significant nephrotic proteinuria that appered after a shorter duration of T2DM than is typical for DN, as well as the absence of retinopathy and hypertension. Additionally, the presence of erythrocyte casts and dysmorphic erythrocytes in the urine sediment, suggested GN rather than DN. Kidney biopsy is not typically conducted in T2DM patients who show abnormal urine sediment findings or renal failure. However, our case report, along with other studies [ 2 , 3 , 7 ], confirm that kidney biopsy can be beneficial for T2DM patients who exhibit clinical and laboratory abnormalities that are not characteristic of DN. Thromboembolic complications are not rare in patients with MN. Reported literature indicate incidence of about 15% of deep vein thrombosis (DVT), up to 30% of pulmonary thromboembolism (PTE), and 25–37% of renal vein thrombosis (RVT) [ 15 ]. Anti PLA2R antibody is found to correlate with development of venous thromboembolism (VTE) (most often PTE, RVT and DVT) in MN. But, there are also PLA2R antibody seronegative patients who are in high risk of developing VTE despite seronegativity [ 16 , 17 ]. Jeyalan et al. in their study found that PLA2R seronegative patients had higher mean values of proteinuria and serum albumin in MN patients. In this study anti PLA2R positive patients had higher thrombosis risk despite lower mean proteinuria and higher values of serum albumin compared to seronegative group, but both groups showed significant thrombosis risk [ 17 ]. In study by Henry HLW et al. is shown that patients with anti PLA2R seronegative MN who had VTE event, have lower serum albumin values, higher cholesterol level, increased daily proteinuria and proteinuria-albumin ratio. Serum cholesterol was also associated with higher risk for VTE, in both anti PLA2R seropositive and seronegative group. They also showed that in anti PLA2R seronegative group of patients low serum albumin and higher proteinuria were significant risk factors for VTE [ 18 , 19 ]. Treatment of primary MN involves the application of symptomatic therapy and immunosuppressive therapy only in certain patients. Considering that literature data suggest 1/3 of patients achieve spontaneous remission within 6 months, initially therapy should be based on the "watch-and-wait" principle [ 20 , 21 ]. The main goal of therapy is to reduce proteinuria, as one of the most important factors in the progression of kidney disease due to the direct toxic effect on the tubules and the resulting interstitial fibrosis and tubular atrophy [ 4 , 5 , 22 ]. Conservative treatment measures such as restricting dietary sodium to less than 2g/day, protein intake (0.8-1g/kg/day) and BP control (systolic BP < 120mmHg), hyperlipidemia are of crucial importance. Medicaments that reduced proteinuria are renin angiotensin system (RAS) blockers, which effect was confirmed in the Athavale A. s tudy [ 23 ]. Additionally, it is recommended to use diuretics of the loop of Henle and recently SGLT2 inhibitors might also be of significant benefit [ 24 ]. High risk of thromboembolic events in patients with nephrotic syndrome can be prevented by oral anticoagulant therapy [ 25 , 26 ]. Current recommendations for treating MN highlight the importance of recognizing disease progression risks [ 6 ]. Immunosuppressive therapy should begin for patients with persistent nephrotic syndrome or significant proteinuria despite RAS blockers, especially those with reduced kidney function or high anti-PLA2R autoantibodies. Rtx, a chimeric monoclonal antibody that targets the extracellular domain of the CD20 molecule, on the surface of B lymphocytes, has been increasingly used in the last fifteen years. It's positive effect on remission has been proven in several studies [ 6 , 27 , 28 , 29 , 30 ]. According to the clinical course, our patient was at high risk for progressive loss of renal function (complete nephrotic syndrome, daily proteinuria 13g, eGFR CKD-EPI 84.7ml/min/1.73m 2 ). The use of Rtx, as the treatment of idiopathic MN, was indicated according to the KDIGO guidelines [ 6 ]. Patient has received two doses of Rtx two weeks apart. Pneumococcal vaccination was performed six weeks before the first dose of Rtx. In the coming weeks, we anticipate seeing the effects of the treatment that has been applied. Conclusion Patients with type 2 diabetes mellitus, nephrotic syndrome, and rapidly declining renal function are diagnostic challenges due to the potential presence of associated NDRD. The presence of complications further complicates the differentiation between primary and secondary NDRD. Anti-PLA2R serology is highly specific for MN; however, a negative result does not rule out the disease. A kidney biopsy is essential for the definitive diagnosis and, along with clinical presentation, helps determine the appropriate treatment. Understanding the different types of NDRD in T2DM patients is necessary to improve future patient's outcomes. Abbreviations anti- PLA2R phospholipase A2 receptor antibodies BP blod pressure DN diabetic nephropathy DVT deep vein thrombosis eGFR estimated glomerular filtration rate ESRD end stage renal disease GN glomerulonephritis IgAN Ig A nephropathy MN membranous nephropathy NDRD non diabetic renal disease PH pathohystological PTE pulmonary thromboembolism RAS renin angiotensin system RVT renal vein thrombosis Rx Rituximab T2DM type 2 diabetes mellitus URS ureterorenoscopy VTE venous thromboembolism Declarations Ethical approval and consent to participate The case report was written and conceived in accordance with the Declaration of Helsinki. Since in Serbia, Rituximab is not registered for the indication of treatment of primary glomerulonephritis and systemic diseases, the Ethical Committee of Clinical Hospital Centre Zemun approved off-label use of drug (number of ethical approval 86/1). Patient provided written informed consent before administration of the drug (number of informed consent 61/1). Consent for publication Patient provided written informed consent for publication of his anonymous and confidential information to be used in our case report (number of informed consent 120/1). Funding No funds, grants or other support were received. Author contributions: Conceptualization E.J.; design of the work: E.J.,T.J.,R.M.; data curation E.J., M.K; writing original draft preparation E.J.; writing- review and editing T.J.; visualisation M.K.,R.M.,M.Z.,P.P.; supervision: T.J. All authors have read and agreed to the published version of the manuscript. Acknowledgements "Not applicable" Data availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request Competing interests The authors declare no competing interests. References Kidney Disease. Improving Global Outcomes (KDIGO). Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int Suppl. 2022;102(55):S1–127. . Tarrass F, Anabi A, Zamb A, Ramdani B, Benghanem MG, Zaid D, et al. Idiopathic membranous glomerulonephritis in patients with type 2 diabetes mellitus. Hong Kong J Nephrol. 2005;7(1):34–7. 10.1016/s1561-5413(09)60178-2 . Grujicic M, Salapura A, Basta-Jovanovic G, Figurek A, Micic-Zrnic D, Grbic A. Non-Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus-11-Year Experience from a Single Center. Med Arch. 2019;73(2):87–91. 10.5455/medarh.2019.73.87-91 . Ponticelli C. Membranous nephropathy. J Clin Med. 2025;14(3):761. doi.org/10.3390/jcm14030761 . Ponticelli C, Glassock RJ. Glomerular diseases: Membranous nephropathy- A modern view. Clin J Am Soc Nephrol. 2014;9(3):609–16. 10.2215/CJN.04160413 . Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group KDIGO Clinical Practice Guideline for Management of Glomerular Diseases. Kidney Int Suppl. 2021;100(45):S1–276. 10.1016/j.kint.2021.05.021 . Zhuo L, Zou G, Li W, Lu J, Ren W. Prevalence of diabetic nephropathy complicating non-diabetic renal disease among Chinese patients with type 2 diabetes mellitus. Eur J Med Res. 2013;18(4):1–8. doi.org/10.1186/2047-783X-18-4 . Warms PC, Rosenbaum BJ, Michelis MF, Haas JE. Idiopathic membranous glomerulonephritis occurring with diabetes mellitus. Arch Intern Med. 1973;132:735–8. Amoah E, Glickman JL, Malchoff C, Sturgill BC, Kaiser DL, Bolton WK. Clinical identification of nondiabetic renal disease in diabetic patients with type I and type II disease presenting with renal dysfunction. Am J Nephrol. 1988;8:204–11. 10.1159/000167584 . Yoshikawa Y, Truong LD, Mattioli CA, Ordonez NG, Balsaver AM. Membranous glomerulonephritis in diabetic patients: a study of 15 cases and review of the literature. Mod Pathol. 1990;3:36–42. Prakash J, Lodha M, Singh SK, Vohra R, Raja R. Diabetic retinopathy is a poor predictor of type of nephropathy in proteinuric type 2 diabetic patients. J Assoc Physicians India. 2007;55:412–6. Zhuo L, Zou G, Li W, Lu J, Ren W. Prevalence of diabetic nephropathy complicating non-diabetic renal disease among Chinese patients with type 2 diabetes mellitus. Eur J Med Res. 2013;18(4):2047–58. 10.1186/2047-783X-18-4 . Yaqub S, Kashi W, Hussain SA. Non-diabetic renal disease in patients with type-2 diabetes mellitus. Saudi J Kidney Dis Transpl. 2012;23(5):1000–7. 10.4103/1319-2442.100882 . Chong YB, Keng TC, Tan LP, Ng KP, Kong WY, Wong CM, et al. Clinical predictors of non diabetic renal disease and role of renal biopsy in diabetic patients with renal involvement: a single centre review. Ren Fail. 2012;34:323–8. 10.3109/0886022X.2011.647302 . Casey D, Romero K, Patel R, Ouelle T, Anasseri Sh. Bilateral Renal Vein Thrombosis in Membranous Nephropathy: Hypoalbuminemia Predictive of Venous Thromboembolism in Nephrotic Syndrome. Cureus. 2022;14(10):e30032. 10.7759/cureus.30032 . Zhu H, Xu L, Liu X, Liu B, Zhai C, Wang R, et al. Anti-PLA2R antibody measured by ELISA predicts the risk of vein, thrombosis in patients with primary membranous nephropathy. Ren Fail. 2022;44(1):594–600. 10.1080/0886022X.2022.2057861 . Jeyalan V, Straus M, Liew Kang S, Ponnusamy A. A retrospective analysis of venous thromboembolism incidence among patients with membranous nephropathy: a single centre experience. Is anti-PLA2R an accessory or an accomplice? Kidney Int Rep. 2022;7(2):S209. doi.org/10.1016/j.rpth.2023.102162 . Wu H, Alozai A, Li J, Elmowafy A, Ponnusamy A, Woywodt A, et al. Risk factors of venous thromboembolism in anti-PLA2R-positive and - negative primary membranous nephropathy. Clin Kidney J. 2022;15(8):1636–8. 10.1093/ckj/sfac052 . Jobson C, Krishnan N. Thrombotic Risks in Primary Membranous Nephropathy. Kidney 360. 2025;6(6):886–8. doi.org/10.34067/KID.0000000807 . Troyanov S, Wall AC, Scholey JW, Miller Cattran D. Idiopathic membranous nephropathy: Definition and relevance of a partial remission. Kidney Int. 2004;66(3):1199–205. 10.1111/j.1523-1755.2004.00873.x . Zucchelli P, Ponticelli C, Cagnoli L, Passerini P. Long-term outcome of idiopathic membranous nephropathy with nephrotic syndrome. Nephrol Dial Transpl. 1987;2(2):73–8. Sharma S, Smyth B. From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options. Kidney Blood Press Res. 2021;46(4):411–20. 10.1159/000516911 . Athavale A, Roberts DM. Management of proteinuria: blockade of the renin-angiotensin-aldosterone system. Aust Prescr. 2020;43(4):121–5. 10.18773/austprescr.2020.021 . Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium. The Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials Lancet. 2022; 400:1788-1801.36351458. Lu X, Kan C, Zhang R. Phospholipase A2 receptor is associated with hypercoagulable status in membranous nephropathy: A narrative review. Ann Transl Med. 2022;10(17):938. 10.21037/atm-22-3572 . Parker K, Ragy O, Hamilton P, Thachil J, Kanigicherla D. Thromboembolism in nephrotic syndrome: Controversies and uncertainties. Res Pract Thromb Haemost. 2023;7(6):102162. 10.1016/j.rpth.2023.102162 . Ponticelli C. Membranous nephropathy: an endless story. J Nephrol. 2023;36(2):563–74. 10.1007/s40620-022-01461-3 . Dahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, et al. GEMRITUX Study Group. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up. J Am Soc Nephrol. 2017;28(1):348–58. 10.1681/ASN.2016040449 . Gauckler P, Shin JI, Alberici F, Audard V, Bruchfeld A, Busch M, et al. Rituximab in Membranous Nephropathy. Kidney Int Rep. 2021;6(4):881–93. 10.1681/ASN.2016040449 . Ronco P, Plaisier E, Debiec H. Advances in Membranous Nephropathy. J Clin Med. 2021;10(4):607. doi.org/10.3390/,jcm1004060 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Mar, 2026 Read the published version in BMC Nephrology → Version 1 posted Editorial decision: Revision requested 26 Jan, 2026 Reviews received at journal 24 Jan, 2026 Reviewers agreed at journal 16 Jan, 2026 Reviews received at journal 15 Jan, 2026 Reviewers agreed at journal 14 Jan, 2026 Reviews received at journal 12 Jan, 2026 Reviews received at journal 12 Jan, 2026 Reviewers agreed at journal 12 Jan, 2026 Reviewers agreed at journal 12 Jan, 2026 Reviewers invited by journal 12 Jan, 2026 Submission checks completed at journal 11 Jan, 2026 First submitted to journal 11 Jan, 2026 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 Advisory Board 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-8484421","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":573995702,"identity":"f50ac63d-9ad8-4927-9bff-cbc2f5384f27","order_by":0,"name":"Elena Jordanova","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYBACxgYGBgkY+wCQkAOxDjwgUgsDSIsxmJFAwCYULYkNIBY+LcztvQ9v/Nxhk9jfwHzgwMcddunzww4/BNpiJ6fbgMNhPceNLXvPpCXOOMCWcHDmmeTcjbfTDIBako3NDuDQMiONTYK37bAxwwEeg8O8bcy5G2cngLQcSNyGR4vkX6AW+QP8Hw7/batPN5yd/oGgFmmgLXIGB3gYDjO2HU6Ql84hYEvPMWZr2bY0OcPDbAYHe9uOG26Qzik4kGCA2y+G7W2MN9+22fDIHW9++OBnW7W8/Oz0zR8+VNjJ4dTSAGMxQ2kDsEoD7MpBQB5TpAFT1SgYBaNgFIxsAAAs72RWJld0iQAAAABJRU5ErkJggg==","orcid":"","institution":"Clinical Hospital Center Zemun","correspondingAuthor":true,"prefix":"","firstName":"Elena","middleName":"","lastName":"Jordanova","suffix":""},{"id":573995705,"identity":"3a9e86af-2803-46f7-8024-1507c365592c","order_by":1,"name":"Marija Karapandzic","email":"","orcid":"","institution":"Clinical Hospital Center Zemun","correspondingAuthor":false,"prefix":"","firstName":"Marija","middleName":"","lastName":"Karapandzic","suffix":""},{"id":573995706,"identity":"f034dee0-7c8a-441c-ab60-8624e6c4d119","order_by":2,"name":"Rodoljub Markovic","email":"","orcid":"","institution":"Clinical Hospital Center Zemun","correspondingAuthor":false,"prefix":"","firstName":"Rodoljub","middleName":"","lastName":"Markovic","suffix":""},{"id":573995711,"identity":"a635f8fe-2e09-4993-9f0b-decf916ac89a","order_by":3,"name":"Maja Zivotic","email":"","orcid":"","institution":"Institute of Pathology, Faculty of Medicine, University of Belgrade","correspondingAuthor":false,"prefix":"","firstName":"Maja","middleName":"","lastName":"Zivotic","suffix":""},{"id":573995712,"identity":"b4a480b9-1700-4d14-90dc-65dc2d9189bb","order_by":4,"name":"Predrag Popovic","email":"","orcid":"","institution":"Clinical Hospital Center Zemun","correspondingAuthor":false,"prefix":"","firstName":"Predrag","middleName":"","lastName":"Popovic","suffix":""},{"id":573995714,"identity":"d8b1f8a7-ab16-433d-8d9d-17294539748a","order_by":5,"name":"Tamara Jemcov","email":"","orcid":"","institution":"Clinical Hospital Center Zemun","correspondingAuthor":false,"prefix":"","firstName":"Tamara","middleName":"","lastName":"Jemcov","suffix":""}],"badges":[],"createdAt":"2025-12-30 22:08:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8484421/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8484421/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12882-026-04919-9","type":"published","date":"2026-03-21T15:59:48+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":100402442,"identity":"daab1e3a-8592-4bba-97fd-a8a6132b8e3c","added_by":"auto","created_at":"2026-01-16 12:00:11","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":766147,"visible":true,"origin":"","legend":"","description":"","filename":"MANUSCRIPT.docx","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/90e811ab772d8a0468bafa05.docx"},{"id":100401938,"identity":"1fd05f28-35a8-4fa2-875c-6207976cc5b6","added_by":"auto","created_at":"2026-01-16 11:59:30","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8114,"visible":true,"origin":"","legend":"","description":"","filename":"aa8c0a03e1554135976c293527effb15.json","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/c3fcea82f86aa3f99d09ad16.json"},{"id":100401507,"identity":"2ea8dd9e-05f8-4eef-aa16-c87dfbd122ea","added_by":"auto","created_at":"2026-01-16 11:58:57","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":93829,"visible":true,"origin":"","legend":"","description":"","filename":"aa8c0a03e1554135976c293527effb151enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/446bfd6116612d30ffc16a9c.xml"},{"id":100402511,"identity":"9af6a4a6-24b7-498a-9166-212fddab5f27","added_by":"auto","created_at":"2026-01-16 12:00:17","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":143904,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/38b5a9bd3cf4e198f375860d.png"},{"id":100402151,"identity":"f09572fd-103b-4e1a-ba89-e8bdde781554","added_by":"auto","created_at":"2026-01-16 11:59:46","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":153320,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/98498334b4c6c44f70421e97.png"},{"id":100401516,"identity":"ee915f9b-b03c-4b01-b33b-3042a0097c6e","added_by":"auto","created_at":"2026-01-16 11:59:02","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":142992,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/c00f64bdaf820ea34d6d8b41.png"},{"id":100402432,"identity":"1b35c04a-50a6-476d-afbb-67534dff65c0","added_by":"auto","created_at":"2026-01-16 12:00:07","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":319148,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/31b072ad035663f71d575349.png"},{"id":100402422,"identity":"420218f6-75ad-43b7-952b-acd3fd47ef62","added_by":"auto","created_at":"2026-01-16 12:00:06","extension":"xml","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":92560,"visible":true,"origin":"","legend":"","description":"","filename":"aa8c0a03e1554135976c293527effb151structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/7d8fddecd30a7ebd86b8255e.xml"},{"id":100402523,"identity":"4c833824-2d92-4701-ab9b-ea035982be61","added_by":"auto","created_at":"2026-01-16 12:00:20","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":102740,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/b02c7429faebece989085eb0.html"},{"id":100402516,"identity":"7dc6fddd-7536-49bd-9971-ebea2fdd814e","added_by":"auto","created_at":"2026-01-16 12:00:19","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":129248,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCT urography three days after patient's admission to the hospital\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA. \u003c/strong\u003eComplete left renal vain thrombosis with thrombus entering inferior vena cava; \u003cstrong\u003eB\u003c/strong\u003e. Left kidney with parenchymal oedema and slower contrast excretion then the right kidney; \u003cstrong\u003eC\u003c/strong\u003e. Ureterohydronephrosis grade I/II of left kidney; \u003cstrong\u003eD\u003c/strong\u003e. Suspected neoplasm/ureteritis of left ureter described as focally thickened ureter wall of diameter 10x34mm.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/cee05159cc2fc3aea7912844.jpeg"},{"id":100401637,"identity":"d09207d8-d34a-47b1-9632-a64581c8c32b","added_by":"auto","created_at":"2026-01-16 11:59:08","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":138566,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eControl CT urography after 7 days antibiotic treatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA. \u003c/strong\u003eStill present complete left renal vain thrombosis with thrombus prominating into inferior vena cava; \u003cstrong\u003eB\u003c/strong\u003e. Still present suspected neoplasm infiltration/ureteritis of left ureter seen as thickening of ureter wall; \u003cstrong\u003eC\u003c/strong\u003e. Ureterohydronephrosis grade II of left kidney; \u003cstrong\u003eD\u003c/strong\u003e. Left kidney with parenchymal oedema and slower contrast excretion compared to the right kidney.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/a0eb2709f9412cfcaa802582.jpeg"},{"id":100402161,"identity":"acba891e-dd36-4e15-b79b-cf1eac1aa41f","added_by":"auto","created_at":"2026-01-16 11:59:47","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":129640,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCT urography before the kidney biopsy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA. \u003c/strong\u003eRecanalized left renal vain with sequelae of prior thrombosis but without venous stasis; B. Left kidney with recovered contrast excretion; \u003cstrong\u003eB\u003c/strong\u003e. No ureterohydronephrosis of left kidney; \u003cstrong\u003eC\u003c/strong\u003e. Still present irregular opacified wall thickening of proximal left ureter; \u003cstrong\u003eD\u003c/strong\u003e. No ureterohydronephrosis of left kidney.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/a770a25206d515c2da9782e0.jpeg"},{"id":100401927,"identity":"7f2460a1-8c1e-4b6c-9d17-3fe06e1ee25f","added_by":"auto","created_at":"2026-01-16 11:59:30","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":336661,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRenal biopsy findings - membranous nephropathy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA \u003c/strong\u003eand \u003cstrong\u003eB\u003c/strong\u003e, periodic acid-Schiff, 200x, \u003cstrong\u003eC\u003c/strong\u003eJines methenamine silver staining, 200x and \u003cstrong\u003eD\u003c/strong\u003e massin trichrome staining, 100x, \u003cstrong\u003eE\u003c/strong\u003e, \u003cstrong\u003eF\u003c/strong\u003e, \u003cstrong\u003eG\u003c/strong\u003e, \u003cstrong\u003eH \u003c/strong\u003eand \u003cstrong\u003eI \u003c/strong\u003eimmunohistochemical staining\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/85fa285911f0ec2ae6150c4f.jpeg"},{"id":105224549,"identity":"78f41c05-4853-47c1-8d0d-9d1781b7c17e","added_by":"auto","created_at":"2026-03-23 16:15:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1485327,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8484421/v1/84dad55f-7f1a-4c11-b7e0-3f42c0485e97.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eNon-Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patient- a Case Report\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eDiabetic nephropathy (DN) is microvascular complication of both type 1 and type 2 diabetes mellitus (T2DM). It is chronic kidney disease characterized by the presence of persistent albuminuria, decline in estimated glomerular filtration rate (eGFR) or both for more than 3 months, and it is often associated with hypertension [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The rising number of diabetes nephropathy patients with end- stage renal disease (ESRD) has made this disease the main cause of ESRD in Western Europe and USA [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. DN is not the only type of renal disease in T2DM patients, but non diabetic renal disease (NDRD) can also appear: glomerular, tubulointerstitial or vascular diseases. One-third T2DM patients in biopsy findings have, in adition to DN, glomerular diseases such as IgA nephropathy (IgAN), minimal change disease, membranous, membranoproliferative or cryoglobulinemic glomerulonephritis (GN) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMembranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It could be: primary and secondary MN which occurs as a consequence of a wide range of well-known diseases. A major advance in distinguishing these entities in recent years was the discovery of M- type phospholipase A2 receptor antibodies (anti- PLA2R) on the surface of podocytes in primary MN patients. It has been shown that primary MN is an autoimmune kidney specific disease in which glomerular lesion occurs due to the subepithelial formation of immune complex in situ. The course of primary MN is unpredictable and varies significantly, so it is important to determine which patients should be treated with immunosuppressive therapy and which should be treated with symptomatic therapy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe report T2DM patient with clinical and laboratory features of nephrotic syndrome. Pathohystological (PH) findings of kidney biopsy performed idiopathic MN.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eThe 54 years old male patient was referred to a nephrologist examination due to swelling of the legs, pain in the abdomen, nausea, and urge to vomit. The leg swelling appeared 4\u0026ndash;6 weeks before other symptoms which occurred two days prior the first nephrologist examination. Hypoproteinemia, hypoalbuminemia, hypercholesterolemia, and hypertriglyceridemia were verified in the laboratory analyzes performed at the Health Center. eGFR calculated by CKD-EPI formula was 106 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e. The patient was hospitalized at the Department of Nephrology Clinical Hospital Center Zemun for examination and diagnosis of nephrotic syndrome. In medical history a patient had T2DM diagnosed for one year treated with oral antidiabetics (metformin, SGLT2 inhibitors). Patient has on previous surgeries or drug allergies.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the patient`s clinical and laboratory data on the admission to the hospital. Initial value of serum creatinine (sCr) was 1.87 mg/dl, eGFR calculated by CKD- EPI formula was 42.3 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e, creatinine clearance was 57 ml/ min, daily proteinuria was nephrotic range (16g/day, diuresis 15.00ml). Body weight on admission was 74.8kg (BMI 23.3kg/m\u003csup\u003e2\u003c/sup\u003e). In the urine sediment were a mass of fresh red blood cells, a lot of pale red blood cells, a mass of dysmorphic red blood cells, 3\u0026ndash;4 leukocytes, and rare bacteria. Immunological analysis: ANA-Hep2(IgG), ANCA, anti GBM At(IgG), antiPLA2R(IgG) antibodies were negative. The complement system components (C3, C4, CIC), serum immunoglobulins (IgG, IgA, IgM), and beta 2-microglobuline levels were all within reference ranges. Electrophoresis and immunoelectrophoresis of serum proteins indicated decreased levels of gamma globulins. Additionally, electrophoresis and immunoelectrophoresis of urine proteins demonstrated selective glomerular proteinuria. Tumour markers were negative. Regarding the coagulation status, D-dimer was elevated at 1803ng/ml. The aPTT was 31.9sec, PT was 9.9sec, INR was 0.9, and TT was 15.1sec. Antithrombin 3 was 114%. Tests for HIV, hepatitis B surface antigen, and hepatitis C antibodies returned negative results.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient's clinical and laboratory data on first admission to the hospital\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe values\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlycemia (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum protein (g/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum albumin (g/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholesterol (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriglyceride (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR CKD- EPI (ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum urea (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcidum uricum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e357\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePotassium (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalcium (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhosphorus (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTH (pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIron (\u0026micro;mol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (\u0026micro;g/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1136\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProteinuria (g/ day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin total (\u0026micro;mol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin direct (\u0026micro;mol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGGT(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLegend: HbA1c - glycated hemoglobin; eGFR - estimated glomerular filtration rate; CRP - C reactive protein; PTH - parathyroid hormone; AST - aspartate aminotransferase; ALT - alanine aminotransferase; GGT - gamma glutamyl transferase;\u003c/p\u003e \u003cp\u003eAbdominal ultrasound examination showed both kidneys to be usually positioned and of normal diameter with parenchyma thickness of 17\u0026ndash;18 mm and emphasized pyramids on both sides, without stasis, or calculosis. Funduscopy was normal. Initially, therapy included loop diuretics, angiotensin II receptor antagonists, low-molecular-weight heparin, proton pump inhibitors, and oral antidiabetics (metformin, sulfonylurea derivates).\u003c/p\u003e \u003cp\u003eOn the third day of hospitalization, macrohematuria appeared with an increase in serum creatinine value (sCr 4.38 mg/dl). CT urography was done- thrombosis of the left renal vein along it\u0026rsquo;s entire length, venous stasis and edema of the left kidney, ureterohydronephrosis stage I/ II left. CT signs of ureteritis on the left side, and subsequent tumour of the proximal part of the ureter - focally thickened wall of the ureter in that part were confirmed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConsultations were conducted with a urologist, radiologist, and vascular surgeon. The decision was made to treat the urethritis with antibiotic therapy (quinolones with probiotic), and to repeat CT urography in 7 days. A follow-up CT scan, after treatment of the ureteritis, confirmed still present thrombosis of the left renal vein, high suspicion of a tumour of the ureteropelvic junction, and the proximal part of the ureter, stage II ureterohydronephrosis remained on the left side (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDuring hospitalization, the patient was conscious and oriented, afebrile, hemodynamically stable, and had a blod pressure (BP) of 130/70 mmHg. The initial hematuria resolved with treatment, and the urine cleared with diuresis of up to 3.500 ml. An exploratory retrograde ureterorenoscopy (URS) was scheduled. Meanwhile, three urine samples were sent for cytology examination to detect malignant cells; all results were negative. The patient was transferred to the Urology Department. An exploratory retrograde URS was done under general anaestethesia. No pathological changes were observed in the left ureter. The existence of a tumour lesion has not been proven, the ureteral JJ stent has been placed in the left ureter. The value of sCr on discharge from the Urology Department was 1.05mg/dl, eGFR CKD- EPI was 84.2 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e, daily proteinuria was 13.45 g, diuresis 1700 ml. After a month the JJ stent was taken out.\u003c/p\u003e \u003cp\u003eTwo months later, the patient was hospitalized again in the Department of Nephrology. In order to continue diagnostic and etiology of nephrotic syndrome, a kidney biopsy was planned. At the time of kidney biopsy patient's clinical and laboratory data were presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical and laboratory data at time of kidney biopsy and at time of received therapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt the time of kidney biopsy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFirst dose Rx\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSecond dose Rx\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlycemia (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e135\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum protein (g/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum albumin (g/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholesterol (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriglyceride (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSetum creatinine (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR CKD-EPI(ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum urea (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcidum uricum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e459\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e129\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePotassium (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalcium (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhosphorus (mmol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTH (pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIron (\u0026micro;mol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (\u0026micro;g/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e538\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e516\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e402\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProteinuria (g/ day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin total (\u0026micro;mol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin direct (\u0026micro;mol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGGT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntithrombin (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLegend: HbA1c - glycated hemoglobin; eGFR - estimated glomerular filtration rate; CRP - C reactive protein; PTH - parathyroid hormone; AST - aspartate aminotransferase; ALT - alanine aminotransferase; GGT - gamma glutamyl transferase; Rx - Rituximab\u003c/p\u003e \u003cp\u003eRepeated immunological tests (ANA, ANCA, anti ds-DNA, anti MPO, antiPR3, anti GBM antibodies, anti PLA2R antibodies), and tests for the presence of thrombophilia (protein C, protein S, anticardiolipin IgG and IgM antibodies, beta- 2 glycoprotein IgG and IgM antibodies, activated protein C resistance-Factor V Leiden, lupus anticoagulant, homocysteine) were negative. Control CT of abdomen and pelvis confirmed the left vein was recanalized, with minor sequelae of previous thrombosis, both kidneys enlarged and that irregular opacified wall thickening of the proximal part of the ureter and part of the pyelon, as well as the distal part of the ureter on the left side was now described without ureterohydronephrosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe kidney biopsy was performed under ultrasound guidance. PH examination indicated the presence of MN. Immunofluorescence analysis was performed on a fresh frozen tissue section containing eight glomeruli and revealed intense fine granular deposits along the glomerular basement membranes (GBM). IgG showed strong granular capillary wall staining, accompanied by granular C3 positivity, while IgA, IgM, C1q, kappa and lambda light chains, and fibrinogen were negative. On light microscopy, the biopsy consisted of a renal cortical core measuring approximately 10 mm in length and containing up to 20 glomeruli on serial sections, two of which were globally sclerotic (Fig.\u0026nbsp;4A and 4B). The remaining glomeruli demonstrated mild to moderate, diffuse and uniform thickening of the GBM, consistent with a membranous pattern of injury. Segmental mesangial expansion with mild mesangial hypercellularity and increased mesangial matrix was observed in a minority of glomeruli. The tubulointerstitial compartment showed diffuse chronic changes, including interstitial fibrosis involving approximately 50% of the cortical parenchyma and associated tubular atrophy affecting around 40% of tubules. A mild focal mononuclear inflammatory infiltrate was present (Fig.\u0026nbsp;4C and 4D). Immunohistochemistry demonstrated diffuse granular C4d (Fig.\u0026nbsp;4E) and PLA2R (Fig.\u0026nbsp;4F) positivity along the GBM. IgG4 showed segmental granular staining (Fig.\u0026nbsp;4G). NELL1 (Fig.\u0026nbsp;4H ) and Netrin G1 (Fig.\u0026nbsp;4I) were focally positive along the GBM, while EXT1, EXT2, NCAM, SEMA3B, and PACE4 were negative.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 4 Renal biopsy findings - membranous nephropathy\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eA\u003c/b\u003e and \u003cb\u003eB\u003c/b\u003e, periodic acid-Schiff, 200x, \u003cb\u003eC\u003c/b\u003e Jines methenamine silver staining, 200x and \u003cb\u003eD\u003c/b\u003e massin trichrome staining, 100x, \u003cb\u003eE\u003c/b\u003e, \u003cb\u003eF\u003c/b\u003e, \u003cb\u003eG\u003c/b\u003e, \u003cb\u003eH\u003c/b\u003e and \u003cb\u003eI\u003c/b\u003e immunohistochemical staining\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eImmunofluorescence analysis was performed on a fresh frozen tissue section containing eight glomeruli and revealed intense fine granular deposits along the glomerular basement membranes (GBM). IgG showed strong granular capillary wall staining, accompanied by granular C3 positivity, while IgA, IgM, C1q, kappa and lambda light chains, and fibrinogen were negative. On light microscopy, the biopsy consisted of a renal cortical core measuring approximately 10 mm in length and containing up to 20 glomeruli on serial sections, two of which were globally sclerotic. The remaining glomeruli demonstrated mild to moderate, diffuse and uniform thickening of the GBM, consistent with a membranous pattern of injury. Segmental mesangial expansion with mild mesangial hypercellularity and increased mesangial matrix was observed in a minority of glomeruli. The tubulointerstitial compartment showed diffuse chronic changes, including interstitial fibrosis involving approximately 50% of the cortical parenchyma and associated tubular atrophy affecting around 40% of tubules. A mild focal mononuclear inflammatory infiltrate was present. Immunohistochemistry demonstrated diffuse granular C4d (\u003cb\u003eE\u003c/b\u003e, 200x) and PLA2R (\u003cb\u003eF\u003c/b\u003e, 200x) positivity along the GBM. IgG4 showed segmental granular staining (\u003cb\u003eG\u003c/b\u003e, 200x). NELL1 (\u003cb\u003eH\u003c/b\u003e, 200x) and Netrin G1 (\u003cb\u003eI\u003c/b\u003e, 200x) were focally positive along the GBM, while EXT1, EXT2, NCAM, SEMA3B, and PACE4 were negative.\u003c/p\u003e \u003cp\u003eOff-label* use of Rituximab (Rtx), as the first line therapy for treatment of idiopathic membranous glomerulonephritis, is indicated according to the KDIGO guidelines [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Patient has received the first dose of Rtx (375 mg/m\u003csup\u003e2\u003c/sup\u003e or 750 mg intravenously). After two weeks the same dose was repeated. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the laboratory data at the time patient received the therapy. At the time of discharge from our department, the patient's body weight was reduced by 6 kg compared to his weight upon admission to the hospital.\u003c/p\u003e \u003cp\u003e*In Serbia, Rituximab is not registered for the indication of treatment of primary glomerulonephritis and systemic diseases, but only for the treatment of B lymphomas.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAt the time of diagnosis, a third of newly diagnosed T2DM patients already have one or more late complications: ischemic heart disease, diabetic foot, retinopathy, neuropathy or nephropathy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. GN is the most common renal complication in T2DM patients with co-existing DN and NDRD. Chines researcher Li Zho summarized studies that have been published between 1983 and 2012 year and found that in T2DM patients could also be find GN: IgAN (14.1%), mesangial proliferative GN (10%), and post-infectious GN (10%) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In 1973 year the first case report of kidney biopsy findings of MN and DN was reported by Warms et al. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In the period of next 20 years, other authors also showed the connection between the appearance of DN and MN [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Different studies have described different percentage of NDRD in T2DM patients: Prakash et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] showed 12.3%, Zhuo et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] 7.8%, and even more than 60% in study of Grujicic et al. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Authors showed that in T2DM patients for whom kidney biopsy was performed, significantly lower duration of T2DM was found in NDRD patients compared to DN patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe suspicion that our patient did not have DN arose from several factors. These included significant nephrotic proteinuria that appered after a shorter duration of T2DM than is typical for DN, as well as the absence of retinopathy and hypertension. Additionally, the presence of erythrocyte casts and dysmorphic erythrocytes in the urine sediment, suggested GN rather than DN.\u003c/p\u003e \u003cp\u003eKidney biopsy is not typically conducted in T2DM patients who show abnormal urine sediment findings or renal failure. However, our case report, along with other studies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], confirm that kidney biopsy can be beneficial for T2DM patients who exhibit clinical and laboratory abnormalities that are not characteristic of DN.\u003c/p\u003e \u003cp\u003eThromboembolic complications are not rare in patients with MN. Reported literature indicate incidence of about 15% of deep vein thrombosis (DVT), up to 30% of pulmonary thromboembolism (PTE), and 25\u0026ndash;37% of renal vein thrombosis (RVT) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Anti PLA2R antibody is found to correlate with development of venous thromboembolism (VTE) (most often PTE, RVT and DVT) in MN. But, there are also PLA2R antibody seronegative patients who are in high risk of developing VTE despite seronegativity [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Jeyalan et al. in their study found that PLA2R seronegative patients had higher mean values of proteinuria and serum albumin in MN patients. In this study anti PLA2R positive patients had higher thrombosis risk despite lower mean proteinuria and higher values of serum albumin compared to seronegative group, but both groups showed significant thrombosis risk [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn study by Henry HLW et al. is shown that patients with anti PLA2R seronegative MN who had VTE event, have lower serum albumin values, higher cholesterol level, increased daily proteinuria and proteinuria-albumin ratio. Serum cholesterol was also associated with higher risk for VTE, in both anti PLA2R seropositive and seronegative group. They also showed that in anti PLA2R seronegative group of patients low serum albumin and higher proteinuria were significant risk factors for VTE [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment of primary MN involves the application of symptomatic therapy and immunosuppressive therapy only in certain patients. Considering that literature data suggest 1/3 of patients achieve spontaneous remission within 6 months, initially therapy should be based on the \"watch-and-wait\" principle [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The main goal of therapy is to reduce proteinuria, as one of the most important factors in the progression of kidney disease due to the direct toxic effect on the tubules and the resulting interstitial fibrosis and tubular atrophy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Conservative treatment measures such as restricting dietary sodium to less than 2g/day, protein intake (0.8-1g/kg/day) and BP control (systolic BP\u0026thinsp;\u0026lt;\u0026thinsp;120mmHg), hyperlipidemia are of crucial importance. Medicaments that reduced proteinuria are renin angiotensin system (RAS) blockers, which effect was confirmed in the Athavale A. \u003cb\u003es\u003c/b\u003etudy [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Additionally, it is recommended to use diuretics of the loop of Henle and recently SGLT2 inhibitors might also be of significant benefit [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. High risk of thromboembolic events in patients with nephrotic syndrome can be prevented by oral anticoagulant therapy [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrent recommendations for treating MN highlight the importance of recognizing disease progression risks [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Immunosuppressive therapy should begin for patients with persistent nephrotic syndrome or significant proteinuria despite RAS blockers, especially those with reduced kidney function or high anti-PLA2R autoantibodies. Rtx, a chimeric monoclonal antibody that targets the extracellular domain of the CD20 molecule, on the surface of B lymphocytes, has been increasingly used in the last fifteen years. It's positive effect on remission has been proven in several studies [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to the clinical course, our patient was at high risk for progressive loss of renal function (complete nephrotic syndrome, daily proteinuria 13g, eGFR CKD-EPI 84.7ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e). The use of Rtx, as the treatment of idiopathic MN, was indicated according to the KDIGO guidelines [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Patient has received two doses of Rtx two weeks apart. Pneumococcal vaccination was performed six weeks before the first dose of Rtx. In the coming weeks, we anticipate seeing the effects of the treatment that has been applied.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePatients with type 2 diabetes mellitus, nephrotic syndrome, and rapidly declining renal function are diagnostic challenges due to the potential presence of associated NDRD. The presence of complications further complicates the differentiation between primary and secondary NDRD. Anti-PLA2R serology is highly specific for MN; however, a negative result does not rule out the disease. A kidney biopsy is essential for the definitive diagnosis and, along with clinical presentation, helps determine the appropriate treatment. Understanding the different types of NDRD in T2DM patients is necessary to improve future patient's outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eanti- PLA2R phospholipase A2 receptor antibodies\u003c/p\u003e\n\u003cp\u003eBP blod pressure\u003c/p\u003e\n\u003cp\u003eDN diabetic nephropathy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDVT deep vein thrombosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eeGFR estimated glomerular filtration rate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eESRD end stage renal disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGN glomerulonephritis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIgAN Ig A nephropathy\u003c/p\u003e\n\u003cp\u003eMN membranous nephropathy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNDRD non diabetic renal disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePH pathohystological\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePTE pulmonary thromboembolism\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRAS renin angiotensin system\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRVT renal vein thrombosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRx Rituximab\u003c/p\u003e\n\u003cp\u003eT2DM type 2 diabetes mellitus\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eURS ureterorenoscopy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVTE venous thromboembolism\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe case report was written and conceived in accordance with the Declaration of Helsinki.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSince in Serbia, Rituximab is not registered for the indication of treatment of primary glomerulonephritis and systemic diseases, the Ethical Committee of Clinical Hospital Centre Zemun approved off-label use of drug (number of ethical approval 86/1). Patient provided written informed consent before administration of the drug (number of informed consent 61/1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient provided written informed consent for publication of his anonymous and confidential information to be used in our case report (number of informed consent 120/1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funds, grants or other support were received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization E.J.; design of the work: E.J.,T.J.,R.M.; data curation E.J., M.K; writing original draft preparation E.J.; writing- review and editing T.J.; visualisation M.K.,R.M.,M.Z.,P.P.; supervision: T.J. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u0026quot;Not applicable\u0026quot;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKidney Disease. Improving Global Outcomes (KDIGO). Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int Suppl. 2022;102(55):S1\u0026ndash;127. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003c/span\u003e\u003cspan address=\"http://www.kidney-international.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTarrass F, Anabi A, Zamb A, Ramdani B, Benghanem MG, Zaid D, et al. Idiopathic membranous glomerulonephritis in patients with type 2 diabetes mellitus. Hong Kong J Nephrol. 2005;7(1):34\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1561-5413(09)60178-2\u003c/span\u003e\u003cspan address=\"10.1016/s1561-5413(09)60178-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrujicic M, Salapura A, Basta-Jovanovic G, Figurek A, Micic-Zrnic D, Grbic A. Non-Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus-11-Year Experience from a Single Center. Med Arch. 2019;73(2):87\u0026ndash;91. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.5455/medarh.2019.73.87-91\u003c/span\u003e\u003cspan address=\"10.5455/medarh.2019.73.87-91\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePonticelli C. Membranous nephropathy. J Clin Med. 2025;14(3):761. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003edoi.org/10.3390/jcm14030761\u003c/span\u003e\u003cspan address=\"10.3390/jcm14030761\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePonticelli C, Glassock RJ. Glomerular diseases: Membranous nephropathy- A modern view. Clin J Am Soc Nephrol. 2014;9(3):609\u0026ndash;16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2215/CJN.04160413\u003c/span\u003e\u003cspan address=\"10.2215/CJN.04160413\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group KDIGO Clinical Practice Guideline for Management of Glomerular Diseases. Kidney Int Suppl. 2021;100(45):S1\u0026ndash;276. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.kint.2021.05.021\u003c/span\u003e\u003cspan address=\"10.1016/j.kint.2021.05.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhuo L, Zou G, Li W, Lu J, Ren W. Prevalence of diabetic nephropathy complicating non-diabetic renal disease among Chinese patients with type 2 diabetes mellitus. Eur J Med Res. 2013;18(4):1\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003edoi.org/10.1186/2047-783X-18-4\u003c/span\u003e\u003cspan address=\"10.1186/2047-783X-18-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWarms PC, Rosenbaum BJ, Michelis MF, Haas JE. Idiopathic membranous glomerulonephritis occurring with diabetes mellitus. Arch Intern Med. 1973;132:735\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmoah E, Glickman JL, Malchoff C, Sturgill BC, Kaiser DL, Bolton WK. Clinical identification of nondiabetic renal disease in diabetic patients with type I and type II disease presenting with renal dysfunction. Am J Nephrol. 1988;8:204\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000167584\u003c/span\u003e\u003cspan address=\"10.1159/000167584\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoshikawa Y, Truong LD, Mattioli CA, Ordonez NG, Balsaver AM. Membranous glomerulonephritis in diabetic patients: a study of 15 cases and review of the literature. Mod Pathol. 1990;3:36\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrakash J, Lodha M, Singh SK, Vohra R, Raja R. Diabetic retinopathy is a poor predictor of type of nephropathy in proteinuric type 2 diabetic patients. J Assoc Physicians India. 2007;55:412\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhuo L, Zou G, Li W, Lu J, Ren W. Prevalence of diabetic nephropathy complicating non-diabetic renal disease among Chinese patients with type 2 diabetes mellitus. Eur J Med Res. 2013;18(4):2047\u0026ndash;58. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/2047-783X-18-4\u003c/span\u003e\u003cspan address=\"10.1186/2047-783X-18-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYaqub S, Kashi W, Hussain SA. Non-diabetic renal disease in patients with type-2 diabetes mellitus. Saudi J Kidney Dis Transpl. 2012;23(5):1000\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/1319-2442.100882\u003c/span\u003e\u003cspan address=\"10.4103/1319-2442.100882\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChong YB, Keng TC, Tan LP, Ng KP, Kong WY, Wong CM, et al. Clinical predictors of non diabetic renal disease and role of renal biopsy in diabetic patients with renal involvement: a single centre review. Ren Fail. 2012;34:323\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/0886022X.2011.647302\u003c/span\u003e\u003cspan address=\"10.3109/0886022X.2011.647302\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasey D, Romero K, Patel R, Ouelle T, Anasseri Sh. Bilateral Renal Vein Thrombosis in Membranous Nephropathy: Hypoalbuminemia Predictive of Venous Thromboembolism in Nephrotic Syndrome. Cureus. 2022;14(10):e30032. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/cureus.30032\u003c/span\u003e\u003cspan address=\"10.7759/cureus.30032\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu H, Xu L, Liu X, Liu B, Zhai C, Wang R, et al. Anti-PLA2R antibody measured by ELISA predicts the risk of vein, thrombosis in patients with primary membranous nephropathy. Ren Fail. 2022;44(1):594\u0026ndash;600. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/0886022X.2022.2057861\u003c/span\u003e\u003cspan address=\"10.1080/0886022X.2022.2057861\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeyalan V, Straus M, Liew Kang S, Ponnusamy A. A retrospective analysis of venous thromboembolism incidence among patients with membranous nephropathy: a single centre experience. Is anti-PLA2R an accessory or an accomplice? Kidney Int Rep. 2022;7(2):S209. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003edoi.org/10.1016/j.rpth.2023.102162\u003c/span\u003e\u003cspan address=\"10.1016/j.rpth.2023.102162\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu H, Alozai A, Li J, Elmowafy A, Ponnusamy A, Woywodt A, et al. Risk factors of venous thromboembolism in anti-PLA2R-positive and - negative primary membranous nephropathy. Clin Kidney J. 2022;15(8):1636\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ckj/sfac052\u003c/span\u003e\u003cspan address=\"10.1093/ckj/sfac052\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJobson C, Krishnan N. Thrombotic Risks in Primary Membranous Nephropathy. Kidney 360. 2025;6(6):886\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003edoi.org/10.34067/KID.0000000807\u003c/span\u003e\u003cspan address=\"10.34067/KID.0000000807\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTroyanov S, Wall AC, Scholey JW, Miller Cattran D. Idiopathic membranous nephropathy: Definition and relevance of a partial remission. Kidney Int. 2004;66(3):1199\u0026ndash;205. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1523-1755.2004.00873.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1523-1755.2004.00873.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZucchelli P, Ponticelli C, Cagnoli L, Passerini P. Long-term outcome of idiopathic membranous nephropathy with nephrotic syndrome. Nephrol Dial Transpl. 1987;2(2):73\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma S, Smyth B. From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options. Kidney Blood Press Res. 2021;46(4):411\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000516911\u003c/span\u003e\u003cspan address=\"10.1159/000516911\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAthavale A, Roberts DM. Management of proteinuria: blockade of the renin-angiotensin-aldosterone system. Aust Prescr. 2020;43(4):121\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.18773/austprescr.2020.021\u003c/span\u003e\u003cspan address=\"10.18773/austprescr.2020.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists\u0026rsquo; Consortium. The Nuffield Department of Population Health Renal Studies Group; SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists\u0026rsquo; Consortium Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials Lancet. 2022; 400:1788-1801.36351458.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu X, Kan C, Zhang R. Phospholipase A2 receptor is associated with hypercoagulable status in membranous nephropathy: A narrative review. Ann Transl Med. 2022;10(17):938. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.21037/atm-22-3572\u003c/span\u003e\u003cspan address=\"10.21037/atm-22-3572\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParker K, Ragy O, Hamilton P, Thachil J, Kanigicherla D. Thromboembolism in nephrotic syndrome: Controversies and uncertainties. Res Pract Thromb Haemost. 2023;7(6):102162. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.rpth.2023.102162\u003c/span\u003e\u003cspan address=\"10.1016/j.rpth.2023.102162\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePonticelli C. Membranous nephropathy: an endless story. J Nephrol. 2023;36(2):563\u0026ndash;74. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40620-022-01461-3\u003c/span\u003e\u003cspan address=\"10.1007/s40620-022-01461-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, et al. GEMRITUX Study Group. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up. J Am Soc Nephrol. 2017;28(1):348\u0026ndash;58. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1681/ASN.2016040449\u003c/span\u003e\u003cspan address=\"10.1681/ASN.2016040449\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGauckler P, Shin JI, Alberici F, Audard V, Bruchfeld A, Busch M, et al. Rituximab in Membranous Nephropathy. Kidney Int Rep. 2021;6(4):881\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1681/ASN.2016040449\u003c/span\u003e\u003cspan address=\"10.1681/ASN.2016040449\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRonco P, Plaisier E, Debiec H. Advances in Membranous Nephropathy. J Clin Med. 2021;10(4):607. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003edoi.org/10.3390/,jcm1004060\u003c/span\u003e\u003cspan address=\"10.3390/,jcm1004060\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"type 2 diabetes mellitus, diabetic nephopathy, non diabetic renal disease, kidney biopsy, membranous nephropathy","lastPublishedDoi":"10.21203/rs.3.rs-8484421/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8484421/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eWe report a type 2 diabetes mellitus (T2DM) patient with clinical and laboratory features of nephrotic syndrome. Pathohystological findings (PH) of the biopsy performed idiopathic membranous nephropathy (MN).\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eThe 54 years old male patient was admitted to the hospital with clinical and laboratory features of nephrotic syndrome (initial value of serume creatinine was 1.87 mg/dl, creatinine clearance was 57 ml/ min, daily proteinuria was 16 g). Immunological analyses (ANA-Hep2(IgG), ANCA, anti GBM At(IgG), antiPLA2R(IgG) antibodies) and tumour markers were negative. Abdominal ultrasound examination showed both kidneys to be normal diameter with parenchyma thickness of 17\u0026ndash;18 mm, emphasized pyramids on both sides, without stasis or calculosis. Then macrohematuria appeared (value sCr 4.38 mg/dl) and CT urography was done- thrombosis of the left renal vein along it\u0026rsquo;s entire length, venous stasis and edema of the left kidney, ureterohydronephrosis stage I/ II left; signs of ureteritis on the left side and subsequent tumour of the proximal part of the ureter - focally thickened wall of the ureter in that part. The urethritis was treated with quinolones. After 7 days CT scan was repeated and confirmed the high suspicion of a tumour of the ureteropelvic junction and the proximal part of the ureter; stage II ureterohydronephrosis remained on the left side. An exploratory retrograde ureterorenoscopy was performed. The procedure revealed no evidence of tumour, and JJ stent has been placed in the left ureter. Daily proteinuria was still nephrotic range (13.45 g). After one month, the JJ stent was removed. Two months later, a control CT scan of the abdomen and pelvis was conducted, and a kidney biopsy was performed. The PH findings showed MN. The patient received the first dose of Rituximab at 375 mg/m\u003csup\u003e2\u003c/sup\u003e (750 mg intravenously). This same dose was administered again after two weeks.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePatients with T2DM, nephrotic syndrome and rapidly declining renal function present diagnostic challenges due to the potential presence of associated non diabetic renal disease. Kidney biopsy is essential for PH diagnosis. Understanding of different types non diabetic renal disease in T2DM patients is necessary to improve future patient's outcomes.\u003c/p\u003e","manuscriptTitle":"Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patient- a Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 09:16:06","doi":"10.21203/rs.3.rs-8484421/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-26T16:46:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-25T04:36:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"271979489599168277881539420938641776364","date":"2026-01-16T15:26:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-15T08:59:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"150110007715470410570539094792207995311","date":"2026-01-14T16:43:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-13T02:23:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-12T22:16:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"699591015652674231841107705792580975","date":"2026-01-12T21:39:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"107369555372439219354535266371940760903","date":"2026-01-12T21:05:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-12T15:38:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-11T10:47:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2026-01-11T10:41:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7eb6affa-fc3d-4364-9d46-082f57b240a4","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T16:11:59+00:00","versionOfRecord":{"articleIdentity":"rs-8484421","link":"https://doi.org/10.1186/s12882-026-04919-9","journal":{"identity":"bmc-nephrology","isVorOnly":false,"title":"BMC Nephrology"},"publishedOn":"2026-03-21 15:59:48","publishedOnDateReadable":"March 21st, 2026"},"versionCreatedAt":"2026-01-16 09:16:06","video":"","vorDoi":"10.1186/s12882-026-04919-9","vorDoiUrl":"https://doi.org/10.1186/s12882-026-04919-9","workflowStages":[]},"version":"v1","identity":"rs-8484421","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8484421","identity":"rs-8484421","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}