Clinicopathological characterization of subgroups in anti-glomerular basement membrane nephritis patients From a Single Center in China: A 12-Year observational study

Clinicopathological characterization of subgroups in anti-glomerular basement membrane nephritis patients From a Single Center in China: A 12-Year observational study | 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 Article Clinicopathological characterization of subgroups in anti-glomerular basement membrane nephritis patients From a Single Center in China: A 12-Year observational study Kun Fang, Rui Wang, Yan Ding, Wenxv Zhou, Zheren Zhou, Ting Wei, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4251504/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Despite the previous reports of patients with combined anti-glomerular basement membrane (anti-GBM) disease occurring sequentially or simultaneously with other nephropathies, most of them have been reported seperately. The complication of these diseases is rare and the mechanism is not clear, and their immuno-antibodies, microscopic picture, clinical presentation, treatment and prognosis are different, therefore, we presented the collection of anti-GBM with combined disease such as membranous nephropathy (MN), anti-neutrophil cytoplasmic antibody (ANCA), IgA nephropathy and atypical anti-GBM to systematically characterized the epidemiological features, clinical manifestations, pathological features and herapeutic outcomes through a summative review. Method We retrospectively a case series of 39 anti-GBM diseases from a single center in Northwest China from 2011–2023. Results A total of 39 patients with anti-GBM disease including 19 males and 20 females were collected with a mean age of 50.0 ± 14.6 years. Among them there were 22 cases (22/39,56.4%) of anti-GBM alone, 6 cases (6/39,15.4%) of combined ANCA, 6 cases (6/39,15.4%) of combined MN, 2 cases (2/39,5.1%) of combined IgAN, and 3 cases (3/39,7.7%) of atypical anti-GBM nephropathy. The mean duration of the disease was 2.6 ± 6.2 months. Clinical symptoms were dominated by fever 68.2% (15/22), oliguria/anuria 63.6% (14/22), and microscopic haematuria 88.9% (16/22,) in the anti-GBM alone group, and nausea and vomiting 50% (3/6) in the anti-GBM + MN group, and edema 83.3% (5/6) in the anti-GBM + MN group. The proportion of patients requiring hemodialysis (HD) at the first visit was 79.5% (31/39) in all patients, 56.4% (22/39) in the anti-GBM alone group, 66.7% (4/6) in the anti-GBM + ANCA group, 66.7% (4/6) in the anti-GBM + MN group, and 100% (2/2) in the anti-GBM + IgAN group. Among them, 56.4% had more than 85% glomerular involvement. The proportion of sclerotic glomeruli was higher in the anti-GBM and anti-GBM + ANCA groups. The highest percentage of cellular crescents was found in the anti-GBM group as long with fibrous crescents in the anti-GBM + ANCA group. Immunofluorescence staining demonstrated positive IgG and C3 staining in all subgroups. Conclusions We concluded that the complication of other nephritis is another potential risk factor for anti-GBM, which is directly attributable to the adverse effects of the different immune depositions and pathological features on renal function, as timely intervention in patients with different pathological features is crucial. Anti-glomerular basement membrane disease Nephropathology Crescentic glomerulonephritis Figures Figure 1 Introduction Anti-glomerular basement membrane disease (Anti-GBM) refers to a group of autoimmune diseases in which pathogenic anti-GBM antibodies are present in the circulation and deposited in the kidney and lung as the main organs involved. Crescentic glomerulonephritis and linear deposition of immunoglobulin G (IgG) along GBM are the hallmarks of anti-GBM glomerulonephritis [ 1 ] . The key to the development of this disease is a conformational change in the collagen molecule, resulting in the exposure of hidden epitopes to which antibodies bind to produce a series of immune-inflammatory reactions, ultimately causing basement membrane destruction in kidney and/or lung tissue [ 2 – 3 ] . The target antigen has been identified as the non-collagenous structural domain (NC1) of the α3 strand of type IV collagen on the GBM [α3(IV)NC1] ༻4༽ . Different immune deposits and pathological features of Anti-GBM have diverse adverse effects on renal function, and prompt intervention is crucial for the prognosis of patients with different renal pathologies. Although Anti-GBM has been reported to be associated with other nephropathies, such as antineutrophil cytoplasmic antibody (ANCA) ༻5༽ , membranous nephropathy (MN) ༻6༽ , and immunoglobulin A nephropathy (IgAN) ༻7༽ . However, it is rare and mostly reported as a combination of one nephropathy alone. To the best of our knowledge, no summarized data on the combination of Anti-GBM nephropathy with other nephropathies has been reported. Therefore, in this paper, we retrospectively summarized and analyzed the clinical and pathological features of 39 cases of anti-GBM nephropathy to better characterize the epidemiological features, clinical presentation and therapeutic outcomes of these patients through a systematic review as timely intervention in patients with different pathological features are crucial, which is of great significance to clinical practice. Materials and Methods We conducted a retrospective case series study of all patients with anti-GBM nephropathy who underwent renal biopsy between January 2011 and November 2023 at the Department of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University. Variables collected included demographics, history of renal disease, renal biopsy report, history of chronic disease, clinical presentation, laboratory tests, renal biopsy results, treatment, and prognosis, and follow-up information were obtained through outpatient follow-ups, chart review, and telephone follow-ups. This retrospective study was in accordance with the Declaration of Helsinki. All data was collected retrospectively, the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University approved this study with a waiver of informed consent. Diagnostic criteria [ 8 ] Anti-GBM is defined as: linear deposition of IgG along GBM and positive serum anti-GBM antibodies with renal damage only; Anti-GBM + ANCA is defined as: In line with the diagnostic conditions of Anti-GBM, patients who tested positive for ANCAs were enrolled in the anti-GBM + ANCA group; Anti-GBM + MN is defined as: In line with the diagnostic conditions of Anti-GBM, renal pathology light microscopy shows deposition of immune complexes on the epithelial side of GBM, which may include spike formation. Additionally, electron microscopy shows deposition of electron dense material on the epithelial side of the GBM. This definition also excludes secondary MNs caused by viruses and autoimmune diseases; Anti-GBM + IgAN is defined as: In line with the diagnostic conditions of Anti-GBM, immunopathology showed IgA-based immune complex deposits in the glomerular mesangial area, and electron microscopy showed electron-dense material deposits in the mesangial area or paramedian area, while secondary IgAN such as anaphylactic purpura and autoimmune diseases were excluded from the clinical picture; Results 1. Clinical manifestation: A total of 39 patients with anti-GBM diagnosis through renal biopsy in our nephrology department from January 2011 to December 2023 were considered in this retrospective study, accounting for 0.36% (39 of 10872) of the total non-transplant kidney biopsies in this period. The patients included 19 males and 20 females with a mean age of 50.0 ± 14.6 years. Among them were 22 cases (22/39,56.4%) of anti-GBM alone, 6 cases (6/39,15.4%) of combined ANCA, 6 cases (6/39,15.4%) of combined MN, 2 cases (2/39,5.1%) of combined IgAN, and atypical anti-GBM nephropathy in 3 cases (3/39,7.7%). The mean duration of the disease was 2.6 ± 6.2 months. Clinical symptoms were dominated by fever 68.2% (15/22), oliguria/anuria 63.6% (14/22), and microscopic hematuria 88.9% (16/22), in the anti-GBM alone group, and nausea and vomiting 50% (3/6) in the anti-GBM + MN group, and oedema 83.3% (5/6) in the anti-GBM + MN group. The proportion of patients requiring haemodialysis (HD) at the first visit was 79.5% (31/39) in all patients, 56.4% (22/39) in the anti-GBM alone group, 66.7% (4/6) in the anti-GBM + ANCA group, 66.7% (4/6) in the anti-GBM + MN group, and 100% (2/2) in the anti-GBM + IgAN group. None have hepatitis B/hepatitis C virus infection, lupus, malignant tumors and heavy metal toxicity, kidney stones or have undergone extracorporeal shock wave lithotripsy (ESWL), history of exposure to organic solvents. (Table 1 ) 2. Laboratory examinations: Urinary protein quantification was higher and hypoalbuminemia was more pronounced in the anti-GBM + MN group, urinary RBC count was higher in the anti-GBM + IgAN group, and the anti-GBM alone group had the worst anemia serum creatinine, BUN and anti-GBM antibody titers at admission. (Table 1 ) Table 1 Clinical and laboratory features of subgroups in anti-GBM disease patients All (n = 39) anti-GBM (n = 22) anti-GBM + ANCA (n = 6) anti-GBM + MN (n = 6) anti-GBM + IgA (n = 2) atypical anti-GBM (n = 3) Age (years) 50.0 ± 14.6 43.8 ± 13.2 58.2 ± 5.4 61.3 ± 13.2 59.5 ± 13.5 50.7 ± 7.9 Sex, % (male) 48.7(19/39) 31.8 (7/22) 66.7(4/6) 100(6/6) 0(0/2) 66.7(2/3) Onset to Diagnosis, months 2.6 ± 6.2 0.7 ± 0.3 1.6 ± 1.4 5.5 ± 6.8 19.0 ± 17.0 2.0 ± 1.4 Fever(%, n/n) 43.6(17/39) 68.2(15/22) 16.7(1/6) 16.7(1/6) N/A N/A Edema(%, n/n) 33.3(13/39) 22.7(5/22) 16.7(1/6) 83.8(5/6) N/A 66.7(2/3) Nausea/vomiting (%, n/n) 23.1(9/39) 22.7(5/22) 50(3/6) 16.7(1/6) N/A N/A Hypertension (%, n/n) 43.6(17/39) 27.3(6/22) 66.7(4/6) 83.8(5/6) 50(1/2) 33.3(1/3) ANCA(%, n/n) 15.4(6/39) N/A 100(6/6) N/A N/A N/A Pulmonary involvement (%, n/n) 5.1(2/39) 4.5(1/22) 16.7(1/6) N/A N/A N/A Oliguria/anuria, (%, n/n) 23.1 (9/39) 63.6(14/22) N/A 4/6 N/A N/A Gross hematuria, (%, n/n) 12.8(5/39) 88.9(16/22) 83.8(5/6) 3/6 N/A 100(3/3) Hb 80.4 ± 20.6 77.1 ± 14.2 79.2 ± 6.9 92.5 ± 18.6 88.5 ± 7.5 116.3 ± 40.1 Urine RBC count, /uL 1035.3 ± 781.2 1317.4 ± 763.6 587.0 ± 475.4 N/A N/A 277.8 ± 251.3 Urinary protein (g/24h) 2.5 ± 2.3 0.57 ± 0.45 1.8 ± 0.7 5.4 ± 2.2 3.3 ± 0.7 4.5 ± 1.1 Serum creatinine on diagnosis (umol/l) 726.5 ± 316.1 819.6 ± 262.3 601.7 ± 275.0 695.7 ± 342.0 563.5 ± 4.5 463.3 ± 475.6 Bun 24.0 ± 10.8 24.2 ± 10.3 26.9 ± 8.3 25.5 ± 13.2 22.8 ± 5.0 15.1 ± 11.3 Serum albumin (g/L) 28.2 ± 5.3 27.1 ± 4.8 28.5 ± 3.8 27.4 ± 3.8 35.2 ± 0.9 33.9 ± 4.8 Levels of anti-GBM antibodies (RU/ml) 163.6 ± 109.1 196.8 ± 95.9 49.4 ± 1.2 129.3 ± 68.7 84.9 ± 64.7 N/A Anti-glomerular basement membrane disease; MN: membranous nephropathy; ANCA: antineutrophil cytoplasmic antibody; IgAN: immunoglobulin A nephropathy; NA: not available. 3. Renal pathology biopsy In this study, 39 patients underwent ultrasound-guided renal puncture pathology biopsy, and all renal biopsy tissue specimens were routinely examined by light microscopy (HE, PAS, PASM, Masson staining) and immunofluorescence (IgA, IgG1, IgG2, IgG3, IgG4, IgM, C3, C1q). Crescents were present in all pathological specimens, with cellular crescents and fibrous cellular crescents predominating. Among them, 22 cases (22/39, 56.4%) had more than 85% glomerular involvement. Among the 5 subgroups, the proportion of sclerotic glomeruli was higher in the anti-GBM and anti-GBM + ANCA groups than in the other groups. The highest proportion of cellular crescents was in the anti-GBM group as well as fibrous crescents in the anti-GBM + ANCA group. Immunofluorescence staining showed positive IgG and C3 staining in all subgroups, with 2 cases (2/39,5.1%) staining positive for IgA, 16 cases (16/38,42.1%) staining positive for IgM with the highest proportion in the anti-GBM + MN group, 31 cases (31/39, 79.5%) staining positive for C3 and 4 cases (4/38, 10.5%) staining positive for C1q. PLA2R positivity was (5/6, 83.3%). 28 cases were stained for IgG subtypes and all cases stained positive for IgG4 in anti-GBM + MN group. 14 cases (14/28, 50%) stained positive for IgG1, with the highest proportion in the anti-GBM + ANCA and atypical anti-GBM groups; 14 cases (14/28, 50%) stained positive for IgG2, with the highest proportion in the anti-GBM group; 7 cases (7/28, 25%) stained positive for IgG3, with the highest proportion in the anti-GBM + IgAN group. (Table 2 ) Table 2 The pathological features of subgroups in anti-GBM disease patients anti-GBM (n = 22) anti-GBM + ANCA (n = 6) anti-GBM + MN (n = 6) anti-GBM + IgA (n = 2) Atypical anti-GBM (n = 3) Light microscopy Number of glomeruli 16(7 ~ 26) 18(13 ~ 28) 18(15 ~ 25) 19 ~ 22 16 ~ 23 Sclerosis/TG, % 11(4 ~ 23) 10(5 ~ 15) 6(5 ~ 13) 5 ~ 9 4 ~ 12 CGC/TG, % 56(22 ~ 85) 36(11 ~ 53) 44(17 ~ 60) 53 ~ 55 27(12 ~ 56) FCGC/TG, % 15(0 ~ 36) 20(11 ~ 36) 21(12 ~ 44) 14 ~ 21 10(5 ~ 19) Immunofluorescence IgG1, (%, n/n) 28.6(4/14) 83.3(5/6) 50.0(2/4) 50.0(1/2) 100(2/2) IgG2, (%, n/n) 57.1(8/14) 50.0(3/6) 25.0(1/4) 50.0(1/2) 50.0(1/2) IgG3, (%, n/n) 21.4(3/14) 33.3(2/6) 25.0(1/4) 50.0(1/2) 0(0/2) IgG4, (%, n/n) 28.6(4/14) 33.3(2/6) 100.0(4/4) 50.0(1/2) 100.0(2/2) IgA(%, n/n) 0(0/14) 0(0/6) 0(0/4) 100.0(2/2) 0(0/2) IgM, (%, n/n) 38.1(8/21) 50.0(3/6) 66.7(4/6) 0(0/2) 33.3(1/3) C1q 9.5(2/21) 16.7(1/6) 16.7(1/6) 0(0/2) 0(0/3) C3 72.7(16/22) 66.7(4/6) 100.0(6/6) 100.0(2/2) 100.0(3/3) GBM: glomerular basement membrane; MN: membranous nephropathy; ATN: acute tubular necrosis; NA: not available; K: Kappa; λ:Lambda; CGC, cellular glomerular crescent; FCGC: fibrous-cellular glomerular crescent; TG, total number of glomeruli; 4.Treatment and prognosis 37 cases received immunosuppressive therapy, most commonly (30/39,76.9%) cyclophosphamide and steroids; cases (32/39,82.1%) underwent plasmapheresis; 4 cases (4/39, 10.3%) underwent renal transplantation. Monthly follow-up after discharge for 1 consecutive year, 3 cases (3/39, 7.7%) recovered renal function, all of them were simple anti-GBM patients; 1 case progressed to end-stage renal disease (ESRD); 25 cases (25/39, 64.1%) were on maintenance dialysis treatment. (Table 3 and Fig. 1 ) Table 3 Treatment and prognosis of subgroups in anti-GBM disease patients Anti-GBM (n = 22) Anti-GBM +ANCA (n = 6) Anti-GBM +MN (n = 6) Anti-GBM +IgAN (n = 2) Atypical anti-GBM (n = 3) Treatment (n, %) Steroids alone 27.3(6/22) 16.7(1/6) 0(0/6) 0(0/2) 0 (0/3) Cyclophosphamide +steroids 72.7(16/22) 50(3/6) 100(6/6) 100(2/2) 100 (3/3) Plasmapheresis 100(22/22) 50(3/6) 83.3(5/6) 100(2/2) 0 (0/3) Kidney outcome (n, %) Renal survival at 1 year 22.7(5/22) 33.3(2/6) 33.3(2/6) 0(0/2) 33.3 (1/3) Discussion The current study presented a case series of 39 anti-GBM diseases from a single center in Northwest China, with defined clinical and pathological data, which enabled us to summarize the study of the clinical features and immunological characteristics of these patients. Previous studies have shown that anti-GBM + MN is more rare [ 9 ] , but in our study, there was no significant difference in the number of cases of anti-GBM + MN compared to other nephropathies, which may be related to the smaller number of cases. Our study showed a bimodal presentation of the age of prevalence of simple anti-GBM, with a high incidence around 20–30 years of age and a second peak at 50–60 years of age, with a trend towards younger age compared with previous reports [ 10 ] . Combined IgAN occurs predominantly in young adults, and combined MN onset is common in middle-aged and elderly individuals. Anti-GBM + ANCA: In this study, the mean age of onset was (58.2 ± 5.4) years in anti-GBM + ANCA group, with male patients accounting for 4/6 (66.7%), and nausea and vomiting were found in 3 cases (3/6, 50%). These findings suggest that there were more extra-renal manifestations in patients with anti-GBM + ANCA, which is in line with previous studies [ 8 ] . Additionally, myeloperoxidase-ANCA (MPO-ANCA) was positive in all anti-GBM + ANCA patients (100%), which is consistent with previous reports [ 11 ] . It is suggested that the prevalence of MPO as the target antigen may be one of the characteristics of anti-GBM + ANCA patients. Renal pathology showed crescentic nephritis in 5 cases, chronic sclerosing nephritis in 1 case, and immunofluorescence was atypical in all of them. 5 cases showed granular deposition of IgG1 along the mesangial area and capillary wall, and the other case was negative. The latest study showed that the release of ANCA can damage the kidney and then result in the revelation of a3(IV)NC1, leading to infiltration of CD11c + macrophages, subsequently the exposed GBM epitope can induce the formation of anti-GBM antibodies [ 12 ] . Furthermore, there are data showing that the target antigen of anti-GBM in anti-GBM positive patients is the NC1 region of the α3 chain of type IV collagen, irrespective of whether they are combined with ANCA or not [ 13 ] . The prognosis of patients with anti-GBM + ANCA has been reported to be variable, Srivastava ༻14༽ reported that the prognosis of anti-GBM + ANCA was poorer than that of anti-GBM alone, whereas Segelmark ༻15༽ reported a better outcome than anti-GBM alone. In our study, after 1 year of follow-up, 4 patients with anti-GBM + ANCA were being maintained on dialysis, and the prognosis was not significantly improved, ANCA did not seem to have a positive role in anti-GBM nephritis, which is in line with another report. [ 16 ] This may also be related to the small number of cases and the short follow-up time. Anti-GBM + MN: In this study, the mean age of onset was (61.3 ± 17.3) years in the anti-GBM + MN group. All participants were male with 3 cases (3/6, 50%) experiencing hematuria, and 5 cases (5/6, 83.3%) experiencing hypoproteinemia. The level of proteinuria was 5.4 ± 2.2 g/24h, which is basically consistent with previous studies showing that showed 85.7% of anti-GBM + MN cases also had hypoproteinemia [ 6 ] . Pathological results revealed both subepithelial and intra-basement membrane electron density deposits in 1 patient (1/6, 16.7%). Previous studies have shown that the genetic susceptibility DRB1*1501 of the HLA alleles of anti-GBM and MN are the same, suggesting that there is a link between the pathogenesis of the two diseases [ 17 ] . In our study, the pathology showed that the IgG class of pathological gene antibodies mainly consisted of IgG4 [ 18 ] . 3 cases with pre-existing MN had an average age of (74.7 ± 5.0) years, and the clinical manifestation was mainly proteinuria, with creatinine level at the time of consultation (844.7 ± 355.0) µmol/L. Two of the cases (2/3, 66.7%) were on dialysis at the time of consultation and continued with on dialysis after treatment. 3 patients with simultaneous anti-GBM and MN had an average age of (48.0 ± 13.9) years. Clinical manifestations were predominantly hematuria or oedema, with a creatinine level at the time of consultation of (546.7 ± 396.7) µmol/L, 2 out of 3 cases (2/3, 66.7%) were on dialysis at the time of consultation, and remained on dialysis after treatment. The poor prognosis is consistent with previous findings which suggest almost all cases of simultaneous anti-GBM and MN have a poor renal prognosis [ 19 – 22 ] . However, a good renal prognosis has been reported in some cases ༻23༽ . The different natural course of the patient's illness at the time of admission may also have contributed to this phenomenon. Basford's study also showed that the prognosis for MN secondary to anti-GBM glomerulonephritis was generally better [ 24 ] . It is hypothesized that either disease in the first place can cause GBM damage, leading to the exposure of hidden antigenic determinants, which stimulates anti-GBM antibodies related to it [ 25 ] . Our results also showed that after 1 year of follow-up, the number of maintenance dialysis patients in this group was still 4 (4/6, 66.7%), which may be due to the fact that 4 of the 6 cases of anti-GBM + MN in our group had blood creatinine greater than 500µmol/L and the presence of oliguria and anuria at the time of diagnosis, and their renal function had been severely impaired, so that they could not be released from dialysis ultimately, even with the treatment of aggressive immunosuppression and plasma exchange. Some studies have concluded that the serum creatinine (Scr) on diagnosis is an independent risk factor for the prognosis of renal function in patients with anti-GBM disease, and for prediction of dialysis dependency at 1 year was 536.4µmol/L [ 26 ] , so early and clear diagnosis and active treatment are the key to improving the prognosis. Although our study could not confirm that the prognosis of the anti-GBM + MN group was milder than that of anti-GBM alone, previous studies have shown that the prognosis of the former group was generally better than that of the latter group [ 27 ] , which may be attributed to the fact that autoantibodies in the former group are mainly IgG4, which recognize mainly α3(IV) NC1, and has limited recognition of the other α-chains, resulting in a much narrower spectrum of antibodies [ 28 ] , whereas in anti-GBM alone, the antibodies are mainly composed of IgG1 and IgG3 [ 29 ] , recognizing more α chains, therefore, IgG4 dominant anti-GBM has a good prognosis, while IgG1 and IgG3 anti-GBM are associated with severe renal insufficiency [ 30 ] .In this study, two of the four patients were positive for IgG1 and one was positive for IgG3, which may also explain the poorer renal prognosis. The different natural course of the patient's illness at the time of admission may also have contributed to this phenomenon. Anti-GBM + IgAN: The pathogenesis of anti-GBM + IgAN is unknown. 3 patients in this study had no history of renal disease and were diagnosed with anti-GBM + IgAN for the first time, and it was hypothesized that these patients might have had cryptogenic IgAN in the past. Some studies have shown that DRB1 * 15 and DRB1* 04 genes are common susceptibility genes for anti-GBM disease and tethered membrane aplasia IgAN, while HLA-DRB1*15 is more commonly linked with anti-GBM disease in Asian ethnicity [ 31 – 32 ] . Some experiments have also found that inflammatory cells infiltrating the glomerulus in IgAN can produce eicosanoids and oxygen free radicals, which further induce inflammatory and immune responses, causing GBM damage, exposure of hidden antigenic epitopes, and then production of antibodies that mediate anti-GBM disease [ 33 ] . Atypical anti-GBM: In this study, the average age of onset of atypical anti-GBM for patients was (50.7 ± 7.9) years, with males being predominant (2/3,66.7%), The main symptoms were proteinuria and renal function was either basically normal or mildly abnormal. The quantitative amount of 24-hour urinary protein was significantly higher than that of the anti-GBM, measuring at 4.5 ± 1.1 versus 0.57 ± 0.45. The initial serum creatinine was 463.3 ± 475.6µmol/L, only 1 case required dialysis, the impairment of renal function was significantly milder than that of the anti-GBM patients, whose initial serum creatinine was 819.6 ± 262.3µmol/L, and 20 (20/22,90.9%) patients needed dialysis at the time of consultation. Under a light microscope, the primary feature of atypical anti-GBM was membranoproliferative-like alterations, formation of nodules, segmental sclerosis and crescent formation. The patient had an increased urinary light chain, which suggests crescentic nephritis or light chain deposition disease. Immunofluorescence staining showed linear deposition of IgG, κ and λ chains along glomerular capillary collaterals, which is consistent with previous reports, Nasr [34] reported that 20 cases of atypical anti-GBM disease lacked the typical electron dense material deposition under electron microscopy. Only immunofluorescent deposition was present, 17 cases of IgG were linearly deposited along the GBM line, 2 cases of IgM were linearly deposited along the GBM line and 1 case of IgA was linearly deposited along the GBM line. Unlike the pathogenesis of anti-GBM, in patients with atypical anti-GBM, although antibodies against GBM were present in the circulation and deposited in the GBM, these antibodies might be directed against other epitopes of type IV collagen (other than the α3NC1 antigen) [ 35 ] , the antibody titer was low [ 36 ] or transient, the antibody activated complement or had low ability to bind to the FC receptor (e.g., IgG4 subtype) [ 29 , 37 – 38 ] . Regarding the mechanism of these atypical changes in immunofluorescence, which is still unclear, it may be related to the formation of new antigens after anti-GBM antibodies bind to antigens on the glomerular basement membrane, or lead to the emergence of some new antigenic determinants, or subsequent pathological manifestations lead to the exposure of some hidden antigenic determinants, which results in the production of secondary antibodies, which may be related to the fact that some of the patients have pre-existing IgG, C3 along the This may be related to the fact that in some patients, the original IgG and C3 were deposited in a linear pattern along the glomerular capillary collaterals, which changed into fine particle-like immune complexes and were deposited along the glomerular capillary collaterals [39–40] , and it has also been suggested to be the early stage of monoclonal immunoglobulin deposition disease [ 41 ] . Although crescent formation can be seen in the pathological findings of the patients in this study, their conditions improved after hormone and rituximab treatment, and their long-term efficacy and prognosis still need to be further observed. Atypical anti-GBM progresses slowly, symptoms of pulmonary involvement such as hemoptysis are rare [ 42 ] , and most of them have a better prognosis than patients with classical anti-GBM, but the prognosis is poor when atypical anti-GBM is combined with crescent bodies. There is no standard treatment regimen, and usually the vast majority of patients are treated conservatively (e.g., angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) and/or immune suppressively [ 43 – 49 ] , with the addition of plasma exchange therapy in a few patients when other types of antibodies are detected [ 50 ] , and in a few patients with the addition of rituximab in the event of a poor conventional outcome or in the presence of a rapid deterioration in renal function [ 51 – 52 ] . In conclusion, the coexistence of anti-GBM disease and other nephropathy is rare and not well described in literature. Even though it has been clarified that anti-GBM glomerulonephritis combined with other nephritis is significantly different from anti-GBM alone in terms of pathophysiology, the clinical course, ideal treatment regimen, and prognosis of patients with the combined disease could not be determined due to the low prevalence and small sample size. In addition, because our study was still retrospective, it is difficult to draw accurate conclusions regarding the association between the two diseases, and further follow-up and a larger sample size are needed to explore the impact of immunosuppressive treatment regimens on patient prognosis. Declarations Author contributions The authors’ contributions were as follows—conception and design of the research: KF,WR, JF. Analysis and interpretation of data: YY、TW and DY. Assistant in data analysis: WX Z and ZR Z. Draft the manuscript: KF, RW. Assistant in the manuscript preparation: YD. Supervision or mentorship: JF. All the authors read and approved the final manuscript. Funding This study was supported by the National Natural Science Foundation of China, Grant/Award Number: 82100718; Key R&D Program of Shaanxi Province, Grant/Award Number: 2022SF-116 Data availability The data that support the results of this research are available from the corresponding author upon reasonable request. Conflict of interest None to declare. Informed consent All the participants provided written informed consent. References Reggiani F, L'Imperio V, Calatroni M, Pagni F, Sinico RA. Goodpasture syndrome and anti-glomerular basement membrane disease. Clin Exp Rheumatol. 2023 Apr;41(4):964-974. L'Imperio V, Ajello E, Pieruzzi F, Nebuloni M, Tosoni A, Ferrario F, Pagni F. Clinicopathological characteristics of typical and atypical anti-glomerular basement membrane nephritis. J Nephrol. 2017 Aug;30(4):503-509. Kant S, Kronbichler A, Sharma P, Geetha D. Advances in Understanding of Pathogenesis and Treatment of Immune-Mediated Kidney Disease: A Review. Am J Kidney Dis. 2022 Apr;79(4):582-600. Pedchenko V, Bondar O, Fogo AB, Vanacore R, Voziyan P, Kitching AR, Wieslander J, Kashtan C, Borza DB, Neilson EG, Wilson CB, Hudson BG. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med. 2010 Jul 22;363(4):343-54. Hu X, Shen C, Meng T, Ooi JD, Eggenhuizen PJ, Zhou YO, Luo H, Chen JB, Lin W, Gong Y, Xiong Q, Xu J, Liu N, Xiao X, Tang R, Zhong Y. Clinical features and prognosis of MPO-ANCA and anti-GBM double-seropositive patients. Front Immunol. 2022 Oct 27;13:991469. Zhang S, Li C, Huang J, Zhou Y, Gao C, Sun M, Wang R, Chen B. Clinical and pathological features of anti-glomerular basement membrane disease associated with membranous nephropathy: an observational study. Ren Fail. 2022 Dec;44(1):1904-1914. Shen CR, Jia XY, Cui Z, Yu XJ, Zhao MH. Clinical and immunological characteristics of patients with combined anti-glomerular basement membrane disease and IgA nephropathy. Clin Kidney J. 2023 Mar 31;16(9):1480-1488. Chen S, Tang Z, Xiang H, Li X, Chen H, Zhang H, Hu W, Zeng C, Liu Z. Etiology and Outcome of Crescentic Glomerulonephritis From a Single Center in China: A 10-Year Review. Am J Kidney Dis. 2016 Mar;67(3):376-83. Bu L, Said SM, Herrera Hernandez L, Taheri Z, Spry L, Rosenthal BS, Das A, Madden B, Larsen CP, Kim Y, Sethi S, Nasr SH. The Characteristics of Concurrent Anti-Glomerular Basement Membrane Nephritis and Membranous Nephropathy. Kidney Int Rep. 2023 Aug 11;8(10):2164-2167. Gulati K, McAdoo SP. Anti-Glomerular Basement Membrane Disease. Rheum Dis Clin North Am. 2018 Nov;44(4):651-673. Philip R, Dumont A, Martin Silva N, de Boysson H, Aouba A, Deshayes S. ANCA and anti-glomerular basement membrane double-positive patients: A systematic review of the literature. Autoimmun Rev. 2021 Sep;20(9):102885. Nishibata Y, Nonokawa M, Tamura Y, Higashi R, Suzuki K, Hayashi H, Masuda S, Nakazawa D, Tanaka S, Tomaru U, Ishizu A. Possible implication of intermolecular epitope spreading in the production of anti-glomerular basement membrane antibody in anti-neutrophil cytoplasmic antibody-associated vasculitis. Clin Exp Rheumatol. 2022 May;40(4):691-704. Hellmark T, Niles JL, Collins AB, McCluskey RT, Brunmark C. Comparison of anti-GBM antibodies in sera with or without ANCA. J Am Soc Nephrol. 1997 Mar;8(3):376-85. Srivastava A, Rao GK, Segal PE, Shah M, Geetha D. Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody. Clin Rheumatol. 2013 Sep;32(9):1317-22. Segelmark M, Hellmark T, Wieslander J. The prognostic significance in Goodpasture's disease of specificity, titre and affinity of anti-glomerular-basement-membrane antibodies. Nephron Clin Pract. 2003;94(3):c59-68. Van Daalen EE, Jennette JC, McAdoo SP, Pusey CD, Alba MA, Poulton CJ, Wolterbeek R, Nguyen TQ, Goldschmeding R, Alchi B, Griffiths M, de Zoysa JR, Vincent B, Bruijn JA, Bajema IM. Predicting Outcome in Patients with Anti-GBM Glomerulonephritis. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):63-72. Ahmad SB, Santoriello D, Canetta P, Bomback AS, D'Agati VD, Markowitz G, Ahn W, Radhakrishnan J, Appel GB. Concurrent Anti-Glomerular Basement Membrane Antibody Disease and Membranous Nephropathy: A Case Series. Am J Kidney Dis. 2021 Aug;78(2):219-225.e1. Couser WG. Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 2017 Jun 7;12(6):983-997. Sano T, Kamata K, Shigematsu H, Kobayashi Y. A case of anti-glomerular basement membrane glomerulonephritis superimposed on membranous nephropathy. Nephrol Dial Transplant. 2000 Aug;15(8):1238-41. Singh A, Arif F, Mangat S, Ames R, Douglas C. Quiz page. Acute cellular crescentic glomerulonephritis in association with anti-glomerular basement membrane disease and superimposed membranous nephropathy. Am J Kidney Dis. 2004 Mar;43(3):A48, e1. Hoshino J, Hara S, Ubara Y, Takaya H, Suwabe T, Sawa N, Tagami T, Katori H, Takemoto F, Hara S, Takaichi K. Distribution of IgG subclasses in a biopsy specimen showing membranous nephropathy with anti-glomerular basement membrane glomerulonephritis: an uncharacteristically good outcome with corticosteroid therapy. Am J Kidney Dis. 2005 Apr;45(4):e67-72. Patel D, Nivera N, Tunkel AR. Anti-glomerular basement membrane disease superimposed on membranous nephropathy: a case report and review of the literature. J Med Case Rep. 2010 Aug 2;4:237. Troxell ML, Saxena AB, Kambham N. Concurrent anti-glomerular basement membrane disease and membranous glomerulonephritis: a case report and literature review. Clin Nephrol. 2006 Aug;66(2):120-7. Basford AW, Lewis J, Dwyer JP, Fogo AB. Membranous nephropathy with crescents. J Am Soc Nephrol. 2011 Oct;22(10):1804-8. Klassen J, Elwood C, Grossberg AL, Milgrom F, Montes M, Sepulveda M, Andres GA. Evolution of membranous nephropathy into anti-glomerular-basement-membrane glomerulonephritis. N Engl J Med. 1974 Jun 13;290(24):1340-4. Jia XY, Xu HY, Jia XY, Cui Z, Zhao MH. Predictors of Kidney Outcomes of Anti-Glomerular Basement Membrane Disease in a Large Chinese Cohort. Am J Nephrol. 2022;53(5):397-406. Holmes D. Glomerular disease: MN linked to improved prognosis in anti-GBM disease. Nat Rev Nephrol. 2013 Nov;9(11):626. Jia XY, Hu SY, Chen JL, Qu Z, Liu G, Cui Z, Zhao MH. The clinical and immunological features of patients with combined anti-glomerular basement membrane disease and membranous nephropathy. Kidney Int. 2014 Apr;85(4):945-52. Zhao J, Yan Y, Cui Z, Yang R, Zhao MH. The immunoglobulin G subclass distribution of anti-GBM autoantibodies against rHalpha3(IV)NC1 is associated with disease severity. Hum Immunol. 2009 Jun;70(6):425-9. Ohlsson S, Herlitz H, Lundberg S, Selga D, Mölne J, Wieslander J, Segelmark M. Circulating anti-glomerular basement membrane antibodies with predominance of subclass IgG4 and false-negative immunoassay test results in anti-glomerular basement membrane disease. Am J Kidney Dis. 2014 Feb;63(2):289-93. Fisher M, Pusey CD, Vaughan RW, Rees AJ. Susceptibility to anti-glomerular basement membrane disease is strongly associated with HLA-DRB1 genes. Kidney Int. 1997 Jan;51(1):222-9. McAdoo SP, Pusey CD. Anti-Glomerular Basement Membrane Disease. Clin J Am Soc Nephrol. 2017 Jul 7;12(7):1162-1172. Khor C, Wong MG, Reagh J. Anti-glomerular basement membrane disease and IgA nephropathy in a patient with previous renal cell carcinoma. BMJ Case Rep. 2021 Jul 27;14(7):e236555. Nasr SH, Collins AB, Alexander MP, Schraith DF, Herrera Hernandez L, Fidler ME, Sethi S, Leung N, Fervenza FC, Cornell LD. The clinicopathologic characteristics and outcome of atypical anti-glomerular basement membrane nephritis. Kidney Int. 2016 Apr;89(4):897-908. Olaru F, Wang XP, Luo W, Ge L, Miner JH, Kleinau S, Geiger XJ, Wasiluk A, Heidet L, Kitching AR, Borza DB. Proteolysis breaks tolerance toward intact α345(IV) collagen, eliciting novel anti-glomerular basement membrane autoantibodies specific for α345NC1 hexamers. J Immunol. 2013 Feb 15;190(4):1424-32. Bazari H, Guimaraes AR, Kushner YB. Case records of the Massachusetts General Hospital. Case 20-2012. A 77-year-old man with leg edema, hematuria, and acute renal failure. N Engl J Med. 2012 Jun 28;366(26):2503-15. Qu Z, Cui Z, Liu G, Zhao MH. The distribution of IgG subclass deposition on renal tissues from patients with anti-glomerular basement membrane disease. BMC Immunol. 2013 Apr 15;14:19. Yang R, Hellmark T, Zhao J, Cui Z, Segelmark M, Zhao MH, Wang HY. Levels of epitope-specific autoantibodies correlate with renal damage in anti-GBM disease. Nephrol Dial Transplant. 2009 Jun;24(6):1838-44. Shibata Y, Fukuoka K, Yokota R, Lee H, Sayo H, Ikegaya N, Mori K, Yamamoto J, Isomura A, Nagahama K, Shimoyamada H, Kawakami T, Komagata Y, Kaname S. Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report. BMC Nephrol. 2020 Jul 17;21(1):283. Savige JA, Dowling J, Kincaid-Smith P. Superimposed glomerular immune complexes in anti-glomerular basement membrane disease. Am J Kidney Dis. 1989 Aug;14(2):145-53. Rosales IA, Colvin RB. Glomerular disease with idiopathic linear immunoglobulin deposition: a rose by any other name would be atypical. Kidney Int. 2016 Apr;89(4):750-2. Shen CR, Jia XY, Cui Z, Yu XJ, Zhao MH. Clinical-Pathological Features and Outcome of Atypical Anti-glomerular Basement Membrane Disease in a Large Single Cohort. Front Immunol. 2020 Sep 3;11:2035. Liang D, Liang S, Xu F, Zhang M, Li X, Tu Y, Liu Z, Zeng C. Clinicopathological features and outcome of antibody-negative anti-glomerular basement membrane disease. J Clin Pathol. 2019 Jan;72(1):31-37. Tsuji T, Ohashi N, Sato T, Goto D, Nagata S, Matsuyama T, Naito Y, Tsuji N, Isobe S, Fujikura T, Kato A, Fujigaki Y, Shimizu A, Yasuda H. Monoclonal immunoglobulin G1 κ-type atypical antiglomerular basement membrane disease accompanied by necrotizing glomerulonephritis . Clin Nephrol. 2020 Mar;93(3):152-157. Zhuo N, Wang G, Song P, Liu Y, Li S, Liu Y. A case of seronegative anti-glomerular basement membrane disease with linear IgG deposition. Ren Fail. 2022 Dec;44(1):2006-2009. Elshirbeny M, Alkadi MM, Mujeeb I, Fituri O. Atypical Anti-Glomerular Basement Membrane Disease With Diffuse Crescentic Membranoproliferative Glomerulonephritis: Case Report and Review of Literature. Qatar Med J. 2020 May 5;2020(1):16. Adapa S, Konala VM, Hou J, Naramala S, Agrawal N, Dhingra H, Aronow WS. Seronegative atypical anti-glomerular basement membrane crescentic glomerulonephritis. Ann Transl Med. 2019 Jun;7(11):246. Olivier M, Watson H, Lee D, Mohanlal V, Madruga M, Carlan S. Monotypic IgG1-kappa Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Report. Case Rep Nephrol Dial. 2019 Feb 28;9(1):8-14. Le Flecher A, Viallet N, Hebmann D, Chauveau B, Vacher Coponat H. Atypical anti-glomerular basement membrane disease presenting as macroscopic haematuria, loin pain and acute kidney injury after intensive exercise. Clin Kidney J. 2019 Apr 23;12(6):801-802. Guo N, Yin Q, Lei S, He Y, Fu P. Atypical anti-glomerular basement membrane disease with anti-GBM antibody negativity and ANCA positivity: a case report. BMC Nephrol. 2021 Feb 5;22(1):53. Sporinova B, McRae SA, Muruve DA, Fritzler MJ, Nasr SH, Chin AC, Benediktsson H. A case of aggressive atypical anti-GBM disease complicated by CMV pneumonitis. BMC Nephrol. 2019 Jan 31;20(1):29. Isobe S, Tomosugi T, Futamura K, Okada M, Hiramitsu T, Tsujita M, Narumi S, Goto N, Takeda A, Watarai Y. A Case of Recurrent Atypical Anti-Glomerular Basement Membrane Nephritis Suspicion after Renal Transplantation. Nephron. 2020;144 Suppl 1:49-53. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies 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-4251504","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":292596394,"identity":"07b18018-652b-49ab-88c9-e1641ca7c2dc","order_by":0,"name":"Kun Fang","email":"","orcid":"","institution":"The First Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Kun","middleName":"","lastName":"Fang","suffix":""},{"id":292596395,"identity":"b7f72e8e-7c91-41ab-9470-3ef58b3126fc","order_by":1,"name":"Rui Wang","email":"","orcid":"","institution":"Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Rui","middleName":"","lastName":"Wang","suffix":""},{"id":292596396,"identity":"6e59de0e-a281-41d2-9eb8-b116afa8ffba","order_by":2,"name":"Yan Ding","email":"","orcid":"","institution":"Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Ding","suffix":""},{"id":292596397,"identity":"c766aeba-46f9-493f-ac0e-a8daf989cb37","order_by":3,"name":"Wenxv Zhou","email":"","orcid":"","institution":"hospital of Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Wenxv","middleName":"","lastName":"Zhou","suffix":""},{"id":292596398,"identity":"00bbacc1-4927-4248-a1e0-b6828653c9ca","order_by":4,"name":"Zheren Zhou","email":"","orcid":"","institution":"hospital of Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Zheren","middleName":"","lastName":"Zhou","suffix":""},{"id":292596399,"identity":"6f48999a-5325-4fa5-8ba0-fb8c8e89fc43","order_by":5,"name":"Ting Wei","email":"","orcid":"","institution":"hospital of Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Ting","middleName":"","lastName":"Wei","suffix":""},{"id":292596400,"identity":"66b58794-b8a5-422c-8204-5b2c729d9ddb","order_by":6,"name":"Yi Yang","email":"","orcid":"","institution":"The First Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Yang","suffix":""},{"id":292596401,"identity":"d4a27e29-05c1-4cfe-9e4f-371568c96b79","order_by":7,"name":"Jie Feng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIie2RsWrDMBCG/2CQF+GsZwz2KzgYTAqFvopCIVkS6NhONRS0hazNW2TsaGFIF7VdNTZbhw4NfoBWKpnljIXqA90huI/j7oBA4A8SNzZQyXKgBe7crx1QuCug26QCOuDlbAU6nzWIzlXidfdxIevFTr3tST0hT4wY9Tc+hb/Op6mcr7ZNx0hpVKkRUfboUa5oWZep3K826Fh2lJjtjGAR93UpPp3yvWBwXSTuhxXi1TtpJsYnRZSDCl/WdslsYmeppkrSZKsPD5lXiXXV21MWpVEHo+RlkTxfq96nWFhGLlH7G+0bNX4BiI5fLo0HCwOBQOC/8gN2ME5B6H4TXgAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":true,"prefix":"","firstName":"Jie","middleName":"","lastName":"Feng","suffix":""}],"badges":[],"createdAt":"2024-04-11 09:23:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4251504/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4251504/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55175181,"identity":"0111e165-377d-4ef0-803b-a9e68da8f433","added_by":"auto","created_at":"2024-04-23 16:11:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":123887,"visible":true,"origin":"","legend":"\u003cp\u003ePrognosis of subgroups in anti-GBM disease patients\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4251504/v1/f04977233845b434978824ce.png"},{"id":60801516,"identity":"cff4dda8-3629-4b93-ad71-371a9d90cbdb","added_by":"auto","created_at":"2024-07-22 09:06:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":695625,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4251504/v1/e3b78860-7343-42c3-8487-5b5af4e7af70.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinicopathological characterization of subgroups in anti-glomerular basement membrane nephritis patients From a Single Center in China: A 12-Year observational study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnti-glomerular basement membrane disease (Anti-GBM) refers to a group of autoimmune diseases in which pathogenic anti-GBM antibodies are present in the circulation and deposited in the kidney and lung as the main organs involved. Crescentic glomerulonephritis and linear deposition of immunoglobulin G (IgG) along GBM are the hallmarks of anti-GBM glomerulonephritis \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The key to the development of this disease is a conformational change in the collagen molecule, resulting in the exposure of hidden epitopes to which antibodies bind to produce a series of immune-inflammatory reactions, ultimately causing basement membrane destruction in kidney and/or lung tissue \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. The target antigen has been identified as the non-collagenous structural domain (NC1) of the α3 strand of type IV collagen on the GBM [α3(IV)NC1]\u003csup\u003e༻4༽\u003c/sup\u003e. Different immune deposits and pathological features of Anti-GBM have diverse adverse effects on renal function, and prompt intervention is crucial for the prognosis of patients with different renal pathologies. Although Anti-GBM has been reported to be associated with other nephropathies, such as antineutrophil cytoplasmic antibody (ANCA) \u003csup\u003e༻5༽\u003c/sup\u003e, membranous nephropathy (MN) \u003csup\u003e༻6༽\u003c/sup\u003e, and immunoglobulin A nephropathy (IgAN) \u003csup\u003e༻7༽\u003c/sup\u003e. However, it is rare and mostly reported as a combination of one nephropathy alone. To the best of our knowledge, no summarized data on the combination of Anti-GBM nephropathy with other nephropathies has been reported. Therefore, in this paper, we retrospectively summarized and analyzed the clinical and pathological features of 39 cases of anti-GBM nephropathy to better characterize the epidemiological features, clinical presentation and therapeutic outcomes of these patients through a systematic review as timely intervention in patients with different pathological features are crucial, which is of great significance to clinical practice.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eWe conducted a retrospective case series study of all patients with anti-GBM nephropathy who underwent renal biopsy between January 2011 and November 2023 at the Department of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University. Variables collected included demographics, history of renal disease, renal biopsy report, history of chronic disease, clinical presentation, laboratory tests, renal biopsy results, treatment, and prognosis, and follow-up information were obtained through outpatient follow-ups, chart review, and telephone follow-ups. This retrospective study was in accordance with the Declaration of Helsinki. All data was collected retrospectively, the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University approved this study with a waiver of informed consent.\u003c/p\u003e \u003cp\u003e \u003cb\u003eDiagnostic criteria\u003c/b\u003e \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAnti-GBM is defined as: linear deposition of IgG along GBM and positive serum anti-GBM antibodies with renal damage only;\u003c/p\u003e \u003cp\u003eAnti-GBM\u0026thinsp;+\u0026thinsp;ANCA is defined as: In line with the diagnostic conditions of Anti-GBM, patients who tested positive for ANCAs were enrolled in the anti-GBM\u0026thinsp;+\u0026thinsp;ANCA group;\u003c/p\u003e \u003cp\u003eAnti-GBM\u0026thinsp;+\u0026thinsp;MN is defined as: In line with the diagnostic conditions of Anti-GBM, renal pathology light microscopy shows deposition of immune complexes on the epithelial side of GBM, which may include spike formation. Additionally, electron microscopy shows deposition of electron dense material on the epithelial side of the GBM. This definition also excludes secondary MNs caused by viruses and autoimmune diseases;\u003c/p\u003e \u003cp\u003eAnti-GBM\u0026thinsp;+\u0026thinsp;IgAN is defined as: In line with the diagnostic conditions of Anti-GBM, immunopathology showed IgA-based immune complex deposits in the glomerular mesangial area, and electron microscopy showed electron-dense material deposits in the mesangial area or paramedian area, while secondary IgAN such as anaphylactic purpura and autoimmune diseases were excluded from the clinical picture;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e1. Clinical manifestation:\u003c/p\u003e \u003cp\u003eA total of 39 patients with anti-GBM diagnosis through renal biopsy in our nephrology department from January 2011 to December 2023 were considered in this retrospective study, accounting for 0.36% (39 of 10872) of the total non-transplant kidney biopsies in this period. The patients included 19 males and 20 females with a mean age of 50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6 years. Among them were 22 cases (22/39,56.4%) of anti-GBM alone, 6 cases (6/39,15.4%) of combined ANCA, 6 cases (6/39,15.4%) of combined MN, 2 cases (2/39,5.1%) of combined IgAN, and atypical anti-GBM nephropathy in 3 cases (3/39,7.7%). The mean duration of the disease was 2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 months. Clinical symptoms were dominated by fever 68.2% (15/22), oliguria/anuria 63.6% (14/22), and microscopic hematuria 88.9% (16/22), in the anti-GBM alone group, and nausea and vomiting 50% (3/6) in the anti-GBM\u0026thinsp;+\u0026thinsp;MN group, and oedema 83.3% (5/6) in the anti-GBM\u0026thinsp;+\u0026thinsp;MN group. The proportion of patients requiring haemodialysis (HD) at the first visit was 79.5% (31/39) in all patients, 56.4% (22/39) in the anti-GBM alone group, 66.7% (4/6) in the anti-GBM\u0026thinsp;+\u0026thinsp;ANCA group, 66.7% (4/6) in the anti-GBM\u0026thinsp;+\u0026thinsp;MN group, and 100% (2/2) in the anti-GBM\u0026thinsp;+\u0026thinsp;IgAN group. None have hepatitis B/hepatitis C virus infection, lupus, malignant tumors and heavy metal toxicity, kidney stones or have undergone extracorporeal shock wave lithotripsy (ESWL), history of exposure to organic solvents. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e2. Laboratory examinations:\u003c/p\u003e \u003cp\u003eUrinary protein quantification was higher and hypoalbuminemia was more pronounced in the anti-GBM\u0026thinsp;+\u0026thinsp;MN group, urinary RBC count was higher in the anti-GBM\u0026thinsp;+\u0026thinsp;IgAN group, and the anti-GBM alone group had the worst anemia serum creatinine, BUN and anti-GBM antibody titers at admission. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\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\u003eClinical and laboratory features of subgroups in anti-GBM disease patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eanti-GBM\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eanti-GBM\u0026thinsp;+\u0026thinsp;ANCA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-GBM\u0026thinsp;+\u0026thinsp;MN\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eanti-GBM\u0026thinsp;+\u0026thinsp;IgA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eatypical anti-GBM\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e59.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e50.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, % (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.7(19/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.8 (7/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.7(4/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100(6/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e66.7(2/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnset to Diagnosis, months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever(%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.6(17/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.2(15/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.7(1/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.7(1/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEdema(%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.3(13/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.7(5/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.7(1/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e83.8(5/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e66.7(2/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea/vomiting (%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.1(9/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.7(5/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50(3/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.7(1/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003cp\u003e(%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.6(17/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.3(6/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.7(4/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e83.8(5/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50(1/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33.3(1/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eANCA(%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.4(6/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100(6/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary involvement\u003c/p\u003e \u003cp\u003e(%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.1(2/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5(1/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.7(1/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOliguria/anuria, (%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.1 (9/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.6(14/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4/6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGross hematuria, (%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.8(5/39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88.9(16/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83.8(5/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3/6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e100(3/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.4\u0026thinsp;\u0026plusmn;\u0026thinsp;20.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e92.5\u0026thinsp;\u0026plusmn;\u0026thinsp;18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e88.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e116.3\u0026thinsp;\u0026plusmn;\u0026thinsp;40.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine RBC count, /uL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1035.3\u0026thinsp;\u0026plusmn;\u0026thinsp;781.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1317.4\u0026thinsp;\u0026plusmn;\u0026thinsp;763.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e587.0\u0026thinsp;\u0026plusmn;\u0026thinsp;475.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e277.8\u0026thinsp;\u0026plusmn;\u0026thinsp;251.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary protein\u003c/p\u003e \u003cp\u003e(g/24h)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum creatinine on diagnosis (umol/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e726.5\u0026thinsp;\u0026plusmn;\u0026thinsp;316.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e819.6\u0026thinsp;\u0026plusmn;\u0026thinsp;262.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e601.7\u0026thinsp;\u0026plusmn;\u0026thinsp;275.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e695.7\u0026thinsp;\u0026plusmn;\u0026thinsp;342.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e563.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e463.3\u0026thinsp;\u0026plusmn;\u0026thinsp;475.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBun\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.5\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\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\u003e28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevels of anti-GBM antibodies (RU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e163.6\u0026thinsp;\u0026plusmn;\u0026thinsp;109.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e196.8\u0026thinsp;\u0026plusmn;\u0026thinsp;95.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e129.3\u0026thinsp;\u0026plusmn;\u0026thinsp;68.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e84.9\u0026thinsp;\u0026plusmn;\u0026thinsp;64.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eN/A\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\u003eAnti-glomerular basement membrane disease; MN: membranous nephropathy; ANCA: antineutrophil cytoplasmic antibody; IgAN: immunoglobulin A nephropathy; NA: not available.\u003c/p\u003e \u003cp\u003e3. Renal pathology biopsy\u003c/p\u003e \u003cp\u003eIn this study, 39 patients underwent ultrasound-guided renal puncture pathology biopsy, and all renal biopsy tissue specimens were routinely examined by light microscopy (HE, PAS, PASM, Masson staining) and immunofluorescence (IgA, IgG1, IgG2, IgG3, IgG4, IgM, C3, C1q). Crescents were present in all pathological specimens, with cellular crescents and fibrous cellular crescents predominating. Among them, 22 cases (22/39, 56.4%) had more than 85% glomerular involvement. Among the 5 subgroups, the proportion of sclerotic glomeruli was higher in the anti-GBM and anti-GBM\u0026thinsp;+\u0026thinsp;ANCA groups than in the other groups. The highest proportion of cellular crescents was in the anti-GBM group as well as fibrous crescents in the anti-GBM\u0026thinsp;+\u0026thinsp;ANCA group. Immunofluorescence staining showed positive IgG and C3 staining in all subgroups, with 2 cases (2/39,5.1%) staining positive for IgA, 16 cases (16/38,42.1%) staining positive for IgM with the highest proportion in the anti-GBM\u0026thinsp;+\u0026thinsp;MN group, 31 cases (31/39, 79.5%) staining positive for C3 and 4 cases (4/38, 10.5%) staining positive for C1q. PLA2R positivity was (5/6, 83.3%). 28 cases were stained for IgG subtypes and all cases stained positive for IgG4 in anti-GBM\u0026thinsp;+\u0026thinsp;MN group. 14 cases (14/28, 50%) stained positive for IgG1, with the highest proportion in the anti-GBM\u0026thinsp;+\u0026thinsp;ANCA and atypical anti-GBM groups; 14 cases (14/28, 50%) stained positive for IgG2, with the highest proportion in the anti-GBM group; 7 cases (7/28, 25%) stained positive for IgG3, with the highest proportion in the anti-GBM\u0026thinsp;+\u0026thinsp;IgAN group. (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\u003eThe pathological features of subgroups in anti-GBM disease patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eanti-GBM\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eanti-GBM\u0026thinsp;+\u0026thinsp;ANCA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eanti-GBM\u0026thinsp;+\u0026thinsp;MN\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-GBM\u0026thinsp;+\u0026thinsp;IgA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAtypical anti-GBM\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLight microscopy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of glomeruli\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(7\u0026thinsp;~\u0026thinsp;26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(13\u0026thinsp;~\u0026thinsp;28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18(15\u0026thinsp;~\u0026thinsp;25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19\u0026thinsp;~\u0026thinsp;22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16\u0026thinsp;~\u0026thinsp;23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSclerosis/TG, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(4\u0026thinsp;~\u0026thinsp;23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(5\u0026thinsp;~\u0026thinsp;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(5\u0026thinsp;~\u0026thinsp;13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u0026thinsp;~\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u0026thinsp;~\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCGC/TG, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56(22\u0026thinsp;~\u0026thinsp;85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(11\u0026thinsp;~\u0026thinsp;53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44(17\u0026thinsp;~\u0026thinsp;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53\u0026thinsp;~\u0026thinsp;55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27(12\u0026thinsp;~\u0026thinsp;56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFCGC/TG, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(0\u0026thinsp;~\u0026thinsp;36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(11\u0026thinsp;~\u0026thinsp;36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(12\u0026thinsp;~\u0026thinsp;44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u0026thinsp;~\u0026thinsp;21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10(5\u0026thinsp;~\u0026thinsp;19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImmunofluorescence\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgG1, (%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.6(4/14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.3(5/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.0(2/4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50.0(1/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100(2/2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgG2, (%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.1(8/14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.0(3/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.0(1/4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50.0(1/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50.0(1/2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgG3, (%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.4(3/14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.3(2/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.0(1/4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50.0(1/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0(0/2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgG4, (%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.6(4/14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.3(2/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100.0(4/4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50.0(1/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100.0(2/2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgA(%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0/14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0/4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100.0(2/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0(0/2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgM, (%, n/n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.1(8/21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.0(3/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.7(4/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33.3(1/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC1q\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.5(2/21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7(1/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.7(1/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0(0/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.7(16/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.7(4/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100.0(6/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100.0(2/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100.0(3/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eGBM: glomerular basement membrane; MN: membranous nephropathy; ATN: acute tubular necrosis; NA: not available; K: Kappa; λ:Lambda; CGC, cellular glomerular crescent; FCGC: fibrous-cellular glomerular crescent; TG, total number of glomeruli;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e4.Treatment and prognosis \u003c/p\u003e\u003cp\u003e37 cases received immunosuppressive therapy, most commonly (30/39,76.9%) cyclophosphamide and steroids; cases (32/39,82.1%) underwent plasmapheresis; 4 cases (4/39, 10.3%) underwent renal transplantation. Monthly follow-up after discharge for 1 consecutive year, 3 cases (3/39, 7.7%) recovered renal function, all of them were simple anti-GBM patients; 1 case progressed to end-stage renal disease (ESRD); 25 cases (25/39, 64.1%) were on maintenance dialysis treatment. (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment and prognosis of subgroups in anti-GBM disease patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnti-GBM\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-GBM\u003c/p\u003e \u003cp\u003e+ANCA\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnti-GBM\u003c/p\u003e \u003cp\u003e+MN\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAnti-GBM\u003c/p\u003e \u003cp\u003e+IgAN\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAtypical\u003c/p\u003e \u003cp\u003eanti-GBM\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment\u003c/b\u003e(n, %)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSteroids alone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.3(6/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7(1/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCyclophosphamide\u003c/p\u003e \u003cp\u003e+steroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.7(16/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50(3/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100(6/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100(2/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100 (3/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlasmapheresis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100(22/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50(3/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83.3(5/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100(2/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0/3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKidney outcome\u003c/b\u003e(n, %)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal survival at 1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.7(5/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.3(2/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33.3(2/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33.3 (1/3)\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\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe current study presented a case series of 39 anti-GBM diseases from a single center in Northwest China, with defined clinical and pathological data, which enabled us to summarize the study of the clinical features and immunological characteristics of these patients. Previous studies have shown that anti-GBM\u0026thinsp;+\u0026thinsp;MN is more rare\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, but in our study, there was no significant difference in the number of cases of anti-GBM\u0026thinsp;+\u0026thinsp;MN compared to other nephropathies, which may be related to the smaller number of cases. Our study showed a bimodal presentation of the age of prevalence of simple anti-GBM, with a high incidence around 20\u0026ndash;30 years of age and a second peak at 50\u0026ndash;60 years of age, with a trend towards younger age compared with previous reports \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Combined IgAN occurs predominantly in young adults, and combined MN onset is common in middle-aged and elderly individuals.\u003c/p\u003e\n\u003ch3\u003eAnti-GBM + ANCA:\u003c/h3\u003e\n\u003cp\u003eIn this study, the mean age of onset was (58.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4) years in anti-GBM\u0026thinsp;+\u0026thinsp;ANCA group, with male patients accounting for 4/6 (66.7%), and nausea and vomiting were found in 3 cases (3/6, 50%). These findings suggest that there were more extra-renal manifestations in patients with anti-GBM\u0026thinsp;+\u0026thinsp;ANCA, which is in line with previous studies \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Additionally, myeloperoxidase-ANCA (MPO-ANCA) was positive in all anti-GBM\u0026thinsp;+\u0026thinsp;ANCA patients (100%), which is consistent with previous reports \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. It is suggested that the prevalence of MPO as the target antigen may be one of the characteristics of anti-GBM\u0026thinsp;+\u0026thinsp;ANCA patients. Renal pathology showed crescentic nephritis in 5 cases, chronic sclerosing nephritis in 1 case, and immunofluorescence was atypical in all of them. 5 cases showed granular deposition of IgG1 along the mesangial area and capillary wall, and the other case was negative. The latest study showed that the release of ANCA can damage the kidney and then result in the revelation of a3(IV)NC1, leading to infiltration of CD11c\u0026thinsp;+\u0026thinsp;macrophages, subsequently the exposed GBM epitope can induce the formation of anti-GBM antibodies \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Furthermore, there are data showing that the target antigen of anti-GBM in anti-GBM positive patients is the NC1 region of the α3 chain of type IV collagen, irrespective of whether they are combined with ANCA or not \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. The prognosis of patients with anti-GBM\u0026thinsp;+\u0026thinsp;ANCA has been reported to be variable, Srivastava\u003csup\u003e༻14༽\u003c/sup\u003ereported that the prognosis of anti-GBM\u0026thinsp;+\u0026thinsp;ANCA was poorer than that of anti-GBM alone, whereas Segelmark\u003csup\u003e༻15༽\u003c/sup\u003ereported a better outcome than anti-GBM alone. In our study, after 1 year of follow-up, 4 patients with anti-GBM\u0026thinsp;+\u0026thinsp;ANCA were being maintained on dialysis, and the prognosis was not significantly improved, ANCA did not seem to have a positive role in anti-GBM nephritis, which is in line with another report. \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e This may also be related to the small number of cases and the short follow-up time.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eAnti-GBM\u0026thinsp;+\u0026thinsp;MN:\u003c/h2\u003e \u003cp\u003eIn this study, the mean age of onset was (61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.3) years in the anti-GBM\u0026thinsp;+\u0026thinsp;MN group. All participants were male with 3 cases (3/6, 50%) experiencing hematuria, and 5 cases (5/6, 83.3%) experiencing hypoproteinemia. The level of proteinuria was 5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2 g/24h, which is basically consistent with previous studies showing that showed 85.7% of anti-GBM\u0026thinsp;+\u0026thinsp;MN cases also had hypoproteinemia \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Pathological results revealed both subepithelial and intra-basement membrane electron density deposits in 1 patient (1/6, 16.7%).\u003c/p\u003e \u003cp\u003ePrevious studies have shown that the genetic susceptibility DRB1*1501 of the HLA alleles of anti-GBM and MN are the same, suggesting that there is a link between the pathogenesis of the two diseases \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. In our study, the pathology showed that the IgG class of pathological gene antibodies mainly consisted of IgG4 \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. 3 cases with pre-existing MN had an average age of (74.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0) years, and the clinical manifestation was mainly proteinuria, with creatinine level at the time of consultation (844.7\u0026thinsp;\u0026plusmn;\u0026thinsp;355.0) \u0026micro;mol/L. Two of the cases (2/3, 66.7%) were on dialysis at the time of consultation and continued with on dialysis after treatment. 3 patients with simultaneous anti-GBM and MN had an average age of (48.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9) years. Clinical manifestations were predominantly hematuria or oedema, with a creatinine level at the time of consultation of (546.7\u0026thinsp;\u0026plusmn;\u0026thinsp;396.7) \u0026micro;mol/L, 2 out of 3 cases (2/3, 66.7%) were on dialysis at the time of consultation, and remained on dialysis after treatment. The poor prognosis is consistent with previous findings which suggest almost all cases of simultaneous anti-GBM and MN have a poor renal prognosis \u003csup\u003e[\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. However, a good renal prognosis has been reported in some cases\u003csup\u003e༻23༽\u003c/sup\u003e. The different natural course of the patient's illness at the time of admission may also have contributed to this phenomenon. Basford's study also showed that the prognosis for MN secondary to anti-GBM glomerulonephritis was generally better \u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. It is hypothesized that either disease in the first place can cause GBM damage, leading to the exposure of hidden antigenic determinants, which stimulates anti-GBM antibodies related to it \u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Our results also showed that after 1 year of follow-up, the number of maintenance dialysis patients in this group was still 4 (4/6, 66.7%), which may be due to the fact that 4 of the 6 cases of anti-GBM\u0026thinsp;+\u0026thinsp;MN in our group had blood creatinine greater than 500\u0026micro;mol/L and the presence of oliguria and anuria at the time of diagnosis, and their renal function had been severely impaired, so that they could not be released from dialysis ultimately, even with the treatment of aggressive immunosuppression and plasma exchange. Some studies have concluded that the serum creatinine (Scr) on diagnosis is an independent risk factor for the prognosis of renal function in patients with anti-GBM disease, and for prediction of dialysis dependency at 1 year was 536.4\u0026micro;mol/L\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e, so early and clear diagnosis and active treatment are the key to improving the prognosis.\u003c/p\u003e \u003cp\u003eAlthough our study could not confirm that the prognosis of the anti-GBM\u0026thinsp;+\u0026thinsp;MN group was milder than that of anti-GBM alone, previous studies have shown that the prognosis of the former group was generally better than that of the latter group \u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e, which may be attributed to the fact that autoantibodies in the former group are mainly IgG4, which recognize mainly α3(IV) NC1, and has limited recognition of the other α-chains, resulting in a much narrower spectrum of antibodies \u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, whereas in anti-GBM alone, the antibodies are mainly composed of IgG1 and IgG3\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e, recognizing more α chains, therefore, IgG4 dominant anti-GBM has a good prognosis, while IgG1 and IgG3 anti-GBM are associated with severe renal insufficiency \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e.In this study, two of the four patients were positive for IgG1 and one was positive for IgG3, which may also explain the poorer renal prognosis. The different natural course of the patient's illness at the time of admission may also have contributed to this phenomenon.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eAnti-GBM\u0026thinsp;+\u0026thinsp;IgAN:\u003c/h2\u003e \u003cp\u003eThe pathogenesis of anti-GBM\u0026thinsp;+\u0026thinsp;IgAN is unknown. 3 patients in this study had no history of renal disease and were diagnosed with anti-GBM\u0026thinsp;+\u0026thinsp;IgAN for the first time, and it was hypothesized that these patients might have had cryptogenic IgAN in the past. Some studies have shown that DRB1 * 15 and DRB1* 04 genes are common susceptibility genes for anti-GBM disease and tethered membrane aplasia IgAN, while HLA-DRB1*15 is more commonly linked with anti-GBM disease in Asian ethnicity \u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. Some experiments have also found that inflammatory cells infiltrating the glomerulus in IgAN can produce eicosanoids and oxygen free radicals, which further induce inflammatory and immune responses, causing GBM damage, exposure of hidden antigenic epitopes, and then production of antibodies that mediate anti-GBM disease\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAtypical anti-GBM:\u003c/h2\u003e \u003cp\u003eIn this study, the average age of onset of atypical anti-GBM for patients was (50.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9) years, with males being predominant (2/3,66.7%), The main symptoms were proteinuria and renal function was either basically normal or mildly abnormal. The quantitative amount of 24-hour urinary protein was significantly higher than that of the anti-GBM, measuring at 4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 versus 0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45. The initial serum creatinine was 463.3\u0026thinsp;\u0026plusmn;\u0026thinsp;475.6\u0026micro;mol/L, only 1 case required dialysis, the impairment of renal function was significantly milder than that of the anti-GBM patients, whose initial serum creatinine was 819.6\u0026thinsp;\u0026plusmn;\u0026thinsp;262.3\u0026micro;mol/L, and 20 (20/22,90.9%) patients needed dialysis at the time of consultation. Under a light microscope, the primary feature of atypical anti-GBM was membranoproliferative-like alterations, formation of nodules, segmental sclerosis and crescent formation. The patient had an increased urinary light chain, which suggests crescentic nephritis or light chain deposition disease. Immunofluorescence staining showed linear deposition of IgG, κ and λ chains along glomerular capillary collaterals, which is consistent with previous reports, Nasr\u003csup\u003e[34]\u003c/sup\u003e reported that 20 cases of atypical anti-GBM disease lacked the typical electron dense material deposition under electron microscopy. Only immunofluorescent deposition was present, 17 cases of IgG were linearly deposited along the GBM line, 2 cases of IgM were linearly deposited along the GBM line and 1 case of IgA was linearly deposited along the GBM line. Unlike the pathogenesis of anti-GBM, in patients with atypical anti-GBM, although antibodies against GBM were present in the circulation and deposited in the GBM, these antibodies might be directed against other epitopes of type IV collagen (other than the α3NC1 antigen) \u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e, the antibody titer was low \u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e or transient, the antibody activated complement or had low ability to bind to the FC receptor (e.g., IgG4 subtype) \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e. Regarding the mechanism of these atypical changes in immunofluorescence, which is still unclear, it may be related to the formation of new antigens after anti-GBM antibodies bind to antigens on the glomerular basement membrane, or lead to the emergence of some new antigenic determinants, or subsequent pathological manifestations lead to the exposure of some hidden antigenic determinants, which results in the production of secondary antibodies, which may be related to the fact that some of the patients have pre-existing IgG, C3 along the This may be related to the fact that in some patients, the original IgG and C3 were deposited in a linear pattern along the glomerular capillary collaterals, which changed into fine particle-like immune complexes and were deposited along the glomerular capillary collaterals \u003csup\u003e[39\u0026ndash;40]\u003c/sup\u003e, and it has also been suggested to be the early stage of monoclonal immunoglobulin deposition disease \u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/sup\u003e. Although crescent formation can be seen in the pathological findings of the patients in this study, their conditions improved after hormone and rituximab treatment, and their long-term efficacy and prognosis still need to be further observed.\u003c/p\u003e \u003cp\u003eAtypical anti-GBM progresses slowly, symptoms of pulmonary involvement such as hemoptysis are rare \u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e, and most of them have a better prognosis than patients with classical anti-GBM, but the prognosis is poor when atypical anti-GBM is combined with crescent bodies. There is no standard treatment regimen, and usually the vast majority of patients are treated conservatively (e.g., angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) and/or immune suppressively \u003csup\u003e[\u003cspan additionalcitationids=\"CR44 CR45 CR46 CR47 CR48\" citationid=\"CR41\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/sup\u003e, with the addition of plasma exchange therapy in a few patients when other types of antibodies are detected \u003csup\u003e[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/sup\u003e, and in a few patients with the addition of rituximab in the event of a poor conventional outcome or in the presence of a rapid deterioration in renal function \u003csup\u003e[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e52\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn conclusion, the coexistence of anti-GBM disease and other nephropathy is rare and not well described in literature. Even though it has been clarified that anti-GBM glomerulonephritis combined with other nephritis is significantly different from anti-GBM alone in terms of pathophysiology, the clinical course, ideal treatment regimen, and prognosis of patients with the combined disease could not be determined due to the low prevalence and small sample size. In addition, because our study was still retrospective, it is difficult to draw accurate conclusions regarding the association between the two diseases, and further follow-up and a larger sample size are needed to explore the impact of immunosuppressive treatment regimens on patient prognosis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor\u0026nbsp;contributions\u003c/strong\u003e The authors\u0026rsquo; contributions were as follows\u0026mdash;conception\u0026nbsp;and\u0026nbsp;design\u0026nbsp;of\u0026nbsp;the\u0026nbsp;research:\u0026nbsp;KF,WR, JF.\u0026nbsp;Analysis\u0026nbsp;and\u0026nbsp;interpretation\u0026nbsp;of\u0026nbsp;data:\u0026nbsp;YY、TW and DY.\u0026nbsp;Assistant\u0026nbsp;in\u0026nbsp;data\u0026nbsp;analysis:\u0026nbsp;WX Z\u0026nbsp;and\u0026nbsp;ZR\u0026nbsp;Z. Draft\u0026nbsp;the\u0026nbsp;manuscript:\u0026nbsp;KF, RW.\u0026nbsp;Assistant\u0026nbsp;in\u0026nbsp;the\u0026nbsp;manuscript\u0026nbsp;preparation:\u0026nbsp;YD.\u0026nbsp;Supervision or mentorship: JF. All the authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThis study was supported by the National\u0026nbsp;Natural Science Foundation of China, Grant/Award Number: 82100718; Key R\u0026amp;D Program of Shaanxi Province, Grant/Award Number: 2022SF-116\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData\u0026nbsp;availability\u0026nbsp;\u003c/strong\u003eThe\u0026nbsp;data\u0026nbsp;that\u0026nbsp;support\u0026nbsp;the\u0026nbsp;results\u0026nbsp;of\u0026nbsp;this\u0026nbsp;research\u0026nbsp;are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict\u0026nbsp;of\u0026nbsp;interest\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNone to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed\u0026nbsp;consent\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAll the participants provided written informed consent.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eReggiani F, L\u0026apos;Imperio V, Calatroni M, Pagni F, Sinico RA. Goodpasture syndrome and anti-glomerular basement membrane disease. Clin Exp Rheumatol. 2023 Apr;41(4):964-974. \u003c/li\u003e\n\u003cli\u003eL\u0026apos;Imperio V, Ajello E, Pieruzzi F, Nebuloni M, Tosoni A, Ferrario F, Pagni F. Clinicopathological characteristics of typical and atypical anti-glomerular basement membrane nephritis. J Nephrol. 2017 Aug;30(4):503-509.\u003c/li\u003e\n\u003cli\u003eKant S, Kronbichler A, Sharma P, Geetha D. Advances in Understanding of Pathogenesis and Treatment of Immune-Mediated Kidney Disease: A Review. Am J Kidney Dis. 2022 Apr;79(4):582-600.\u003c/li\u003e\n\u003cli\u003ePedchenko V, Bondar O, Fogo AB, Vanacore R, Voziyan P, Kitching AR, Wieslander J, Kashtan C, Borza DB, Neilson EG, Wilson CB, Hudson BG. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Engl J Med. 2010 Jul 22;363(4):343-54. \u003c/li\u003e\n\u003cli\u003eHu X, Shen C, Meng T, Ooi JD, Eggenhuizen PJ, Zhou YO, Luo H, Chen JB, Lin W, Gong Y, Xiong Q, Xu J, Liu N, Xiao X, Tang R, Zhong Y. Clinical features and prognosis of MPO-ANCA and anti-GBM double-seropositive patients. Front Immunol. 2022 Oct 27;13:991469.\u003c/li\u003e\n\u003cli\u003eZhang S, Li C, Huang J, Zhou Y, Gao C, Sun M, Wang R, Chen B. Clinical and pathological features of anti-glomerular basement membrane disease associated with membranous nephropathy: an observational study. Ren Fail. 2022 Dec;44(1):1904-1914.\u003c/li\u003e\n\u003cli\u003eShen CR, Jia XY, Cui Z, Yu XJ, Zhao MH. Clinical and immunological characteristics of patients with combined anti-glomerular basement membrane disease and IgA nephropathy. Clin Kidney J. 2023 Mar 31;16(9):1480-1488. \u003c/li\u003e\n\u003cli\u003eChen S, Tang Z, Xiang H, Li X, Chen H, Zhang H, Hu W, Zeng C, Liu Z. Etiology and Outcome of Crescentic Glomerulonephritis From a Single Center in China: A 10-Year Review. Am J Kidney Dis. 2016 Mar;67(3):376-83. \u003c/li\u003e\n\u003cli\u003eBu L, Said SM, Herrera Hernandez L, Taheri Z, Spry L, Rosenthal BS, Das A, Madden B, Larsen CP, Kim Y, Sethi S, Nasr SH. The Characteristics of Concurrent Anti-Glomerular Basement Membrane Nephritis and Membranous Nephropathy. Kidney Int Rep. 2023 Aug 11;8(10):2164-2167.\u003c/li\u003e\n\u003cli\u003eGulati K, McAdoo SP. Anti-Glomerular Basement Membrane Disease. Rheum Dis Clin North Am. 2018 Nov;44(4):651-673. \u003c/li\u003e\n\u003cli\u003ePhilip R, Dumont A, Martin Silva N, de Boysson H, Aouba A, Deshayes S. ANCA and anti-glomerular basement membrane double-positive patients: A systematic review of the literature. Autoimmun Rev. 2021 Sep;20(9):102885.\u003c/li\u003e\n\u003cli\u003eNishibata Y, Nonokawa M, Tamura Y, Higashi R, Suzuki K, Hayashi H, Masuda S, Nakazawa D, Tanaka S, Tomaru U, Ishizu A. Possible implication of intermolecular epitope spreading in the production of anti-glomerular basement membrane antibody in anti-neutrophil cytoplasmic antibody-associated vasculitis. Clin Exp Rheumatol. 2022 May;40(4):691-704. \u003c/li\u003e\n\u003cli\u003eHellmark T, Niles JL, Collins AB, McCluskey RT, Brunmark C. Comparison of anti-GBM antibodies in sera with or without ANCA. J Am Soc Nephrol. 1997 Mar;8(3):376-85.\u003c/li\u003e\n\u003cli\u003eSrivastava A, Rao GK, Segal PE, Shah M, Geetha D. Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody. Clin Rheumatol. 2013 Sep;32(9):1317-22.\u003c/li\u003e\n\u003cli\u003eSegelmark M, Hellmark T, Wieslander J. The prognostic significance in Goodpasture\u0026apos;s disease of specificity, titre and affinity of anti-glomerular-basement-membrane antibodies. Nephron Clin Pract. 2003;94(3):c59-68.\u003c/li\u003e\n\u003cli\u003eVan Daalen EE, Jennette JC, McAdoo SP, Pusey CD, Alba MA, Poulton CJ, Wolterbeek R, Nguyen TQ, Goldschmeding R, Alchi B, Griffiths M, de Zoysa JR, Vincent B, Bruijn JA, Bajema IM. Predicting Outcome in Patients with Anti-GBM Glomerulonephritis. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):63-72. \u003c/li\u003e\n\u003cli\u003eAhmad SB, Santoriello D, Canetta P, Bomback AS, D\u0026apos;Agati VD, Markowitz G, Ahn W, Radhakrishnan J, Appel GB. Concurrent Anti-Glomerular Basement Membrane Antibody Disease and Membranous Nephropathy: A Case Series. Am J Kidney Dis. 2021 Aug;78(2):219-225.e1. \u003c/li\u003e\n\u003cli\u003eCouser WG. Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 2017 Jun 7;12(6):983-997. \u003c/li\u003e\n\u003cli\u003eSano T, Kamata K, Shigematsu H, Kobayashi Y. A case of anti-glomerular basement membrane glomerulonephritis superimposed on membranous nephropathy. Nephrol Dial Transplant. 2000 Aug;15(8):1238-41.\u003c/li\u003e\n\u003cli\u003eSingh A, Arif F, Mangat S, Ames R, Douglas C. Quiz page. Acute cellular crescentic glomerulonephritis in association with anti-glomerular basement membrane disease and superimposed membranous nephropathy. Am J Kidney Dis. 2004 Mar;43(3):A48, e1. \u003c/li\u003e\n\u003cli\u003eHoshino J, Hara S, Ubara Y, Takaya H, Suwabe T, Sawa N, Tagami T, Katori H, Takemoto F, Hara S, Takaichi K. Distribution of IgG subclasses in a biopsy specimen showing membranous nephropathy with anti-glomerular basement membrane glomerulonephritis: an uncharacteristically good outcome with corticosteroid therapy. Am J Kidney Dis. 2005 Apr;45(4):e67-72.\u003c/li\u003e\n\u003cli\u003ePatel D, Nivera N, Tunkel AR. Anti-glomerular basement membrane disease superimposed on membranous nephropathy: a case report and review of the literature. J Med Case Rep. 2010 Aug 2;4:237. \u003c/li\u003e\n\u003cli\u003eTroxell ML, Saxena AB, Kambham N. Concurrent anti-glomerular basement membrane disease and membranous glomerulonephritis: a case report and literature review. Clin Nephrol. 2006 Aug;66(2):120-7.\u003c/li\u003e\n\u003cli\u003eBasford AW, Lewis J, Dwyer JP, Fogo AB. Membranous nephropathy with crescents. J Am Soc Nephrol. 2011 Oct;22(10):1804-8. \u003c/li\u003e\n\u003cli\u003eKlassen J, Elwood C, Grossberg AL, Milgrom F, Montes M, Sepulveda M, Andres GA. Evolution of membranous nephropathy into anti-glomerular-basement-membrane glomerulonephritis. N Engl J Med. 1974 Jun 13;290(24):1340-4. \u003c/li\u003e\n\u003cli\u003eJia XY, Xu HY, Jia XY, Cui Z, Zhao MH. Predictors of Kidney Outcomes of Anti-Glomerular Basement Membrane Disease in a Large Chinese Cohort. Am J Nephrol. 2022;53(5):397-406. \u003c/li\u003e\n\u003cli\u003eHolmes D. Glomerular disease: MN linked to improved prognosis in anti-GBM disease. Nat Rev Nephrol. 2013 Nov;9(11):626. \u003c/li\u003e\n\u003cli\u003eJia XY, Hu SY, Chen JL, Qu Z, Liu G, Cui Z, Zhao MH. The clinical and immunological features of patients with combined anti-glomerular basement membrane disease and membranous nephropathy. Kidney Int. 2014 Apr;85(4):945-52.\u003c/li\u003e\n\u003cli\u003eZhao J, Yan Y, Cui Z, Yang R, Zhao MH. The immunoglobulin G subclass distribution of anti-GBM autoantibodies against rHalpha3(IV)NC1 is associated with disease severity. Hum Immunol. 2009 Jun;70(6):425-9.\u003c/li\u003e\n\u003cli\u003eOhlsson S, Herlitz H, Lundberg S, Selga D, M\u0026ouml;lne J, Wieslander J, Segelmark M. Circulating anti-glomerular basement membrane antibodies with predominance of subclass IgG4 and false-negative immunoassay test results in anti-glomerular basement membrane disease. Am J Kidney Dis. 2014 Feb;63(2):289-93. \u003c/li\u003e\n\u003cli\u003eFisher M, Pusey CD, Vaughan RW, Rees AJ. Susceptibility to anti-glomerular basement membrane disease is strongly associated with HLA-DRB1 genes. Kidney Int. 1997 Jan;51(1):222-9. \u003c/li\u003e\n\u003cli\u003eMcAdoo SP, Pusey CD. Anti-Glomerular Basement Membrane Disease. Clin J Am Soc Nephrol. 2017 Jul 7;12(7):1162-1172. \u003c/li\u003e\n\u003cli\u003eKhor C, Wong MG, Reagh J. Anti-glomerular basement membrane disease and IgA nephropathy in a patient with previous renal cell carcinoma. BMJ Case Rep. 2021 Jul 27;14(7):e236555.\u003c/li\u003e\n\u003cli\u003eNasr SH, Collins AB, Alexander MP, Schraith DF, Herrera Hernandez L, Fidler ME, Sethi S, Leung N, Fervenza FC, Cornell LD. The clinicopathologic characteristics and outcome of atypical anti-glomerular basement membrane nephritis. Kidney Int. 2016 Apr;89(4):897-908.\u003c/li\u003e\n\u003cli\u003eOlaru F, Wang XP, Luo W, Ge L, Miner JH, Kleinau S, Geiger XJ, Wasiluk A, Heidet L, Kitching AR, Borza DB. Proteolysis breaks tolerance toward intact \u0026alpha;345(IV) collagen, eliciting novel anti-glomerular basement membrane autoantibodies specific for \u0026alpha;345NC1 hexamers. J Immunol. 2013 Feb 15;190(4):1424-32. \u003c/li\u003e\n\u003cli\u003eBazari H, Guimaraes AR, Kushner YB. Case records of the Massachusetts General Hospital. Case 20-2012. A 77-year-old man with leg edema, hematuria, and acute renal failure. N Engl J Med. 2012 Jun 28;366(26):2503-15. \u003c/li\u003e\n\u003cli\u003eQu Z, Cui Z, Liu G, Zhao MH. The distribution of IgG subclass deposition on renal tissues from patients with anti-glomerular basement membrane disease. BMC Immunol. 2013 Apr 15;14:19. \u003c/li\u003e\n\u003cli\u003eYang R, Hellmark T, Zhao J, Cui Z, Segelmark M, Zhao MH, Wang HY. Levels of epitope-specific autoantibodies correlate with renal damage in anti-GBM disease. Nephrol Dial Transplant. 2009 Jun;24(6):1838-44. \u003c/li\u003e\n\u003cli\u003eShibata Y, Fukuoka K, Yokota R, Lee H, Sayo H, Ikegaya N, Mori K, Yamamoto J, Isomura A, Nagahama K, Shimoyamada H, Kawakami T, Komagata Y, Kaname S. Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report. BMC Nephrol. 2020 Jul 17;21(1):283. \u003c/li\u003e\n\u003cli\u003eSavige JA, Dowling J, Kincaid-Smith P. Superimposed glomerular immune complexes in anti-glomerular basement membrane disease. Am J Kidney Dis. 1989 Aug;14(2):145-53. \u003c/li\u003e\n\u003cli\u003eRosales IA, Colvin RB. Glomerular disease with idiopathic linear immunoglobulin deposition: a rose by any other name would be atypical. Kidney Int. 2016 Apr;89(4):750-2. \u003c/li\u003e\n\u003cli\u003eShen CR, Jia XY, Cui Z, Yu XJ, Zhao MH. Clinical-Pathological Features and Outcome of Atypical Anti-glomerular Basement Membrane Disease in a Large Single Cohort. Front Immunol. 2020 Sep 3;11:2035.\u003c/li\u003e\n\u003cli\u003eLiang D, Liang S, Xu F, Zhang M, Li X, Tu Y, Liu Z, Zeng C. Clinicopathological features and outcome of antibody-negative anti-glomerular basement membrane disease. J Clin Pathol. 2019 Jan;72(1):31-37.\u003c/li\u003e\n\u003cli\u003eTsuji T, Ohashi N, Sato T, Goto D, Nagata S, Matsuyama T, Naito Y, Tsuji N, Isobe S, Fujikura T, Kato A, Fujigaki Y, Shimizu A, Yasuda H. Monoclonal immunoglobulin G1 \u0026kappa;-type atypical antiglomerular basement membrane disease accompanied by necrotizing glomerulonephritis\u2029. Clin Nephrol. 2020 Mar;93(3):152-157. \u003c/li\u003e\n\u003cli\u003eZhuo N, Wang G, Song P, Liu Y, Li S, Liu Y. A case of seronegative anti-glomerular basement membrane disease with linear IgG deposition. Ren Fail. 2022 Dec;44(1):2006-2009.\u003c/li\u003e\n\u003cli\u003eElshirbeny M, Alkadi MM, Mujeeb I, Fituri O. Atypical Anti-Glomerular Basement Membrane Disease With Diffuse Crescentic Membranoproliferative Glomerulonephritis: Case Report and Review of Literature. Qatar Med J. 2020 May 5;2020(1):16. \u003c/li\u003e\n\u003cli\u003eAdapa S, Konala VM, Hou J, Naramala S, Agrawal N, Dhingra H, Aronow WS. Seronegative atypical anti-glomerular basement membrane crescentic glomerulonephritis. Ann Transl Med. 2019 Jun;7(11):246. \u003c/li\u003e\n\u003cli\u003eOlivier M, Watson H, Lee D, Mohanlal V, Madruga M, Carlan S. Monotypic IgG1-kappa Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Report. Case Rep Nephrol Dial. 2019 Feb 28;9(1):8-14.\u003c/li\u003e\n\u003cli\u003eLe Flecher A, Viallet N, Hebmann D, Chauveau B, Vacher Coponat H. Atypical anti-glomerular basement membrane disease presenting as macroscopic haematuria, loin pain and acute kidney injury after intensive exercise. Clin Kidney J. 2019 Apr 23;12(6):801-802. \u003c/li\u003e\n\u003cli\u003eGuo N, Yin Q, Lei S, He Y, Fu P. Atypical anti-glomerular basement membrane disease with anti-GBM antibody negativity and ANCA positivity: a case report. BMC Nephrol. 2021 Feb 5;22(1):53. \u003c/li\u003e\n\u003cli\u003eSporinova B, McRae SA, Muruve DA, Fritzler MJ, Nasr SH, Chin AC, Benediktsson H. A case of aggressive atypical anti-GBM disease complicated by CMV pneumonitis. BMC Nephrol. 2019 Jan 31;20(1):29. \u003c/li\u003e\n\u003cli\u003eIsobe S, Tomosugi T, Futamura K, Okada M, Hiramitsu T, Tsujita M, Narumi S, Goto N, Takeda A, Watarai Y. A Case of Recurrent Atypical Anti-Glomerular Basement Membrane Nephritis Suspicion after Renal Transplantation. Nephron. 2020;144 Suppl 1:49-53. \u003c/li\u003e\n\u003c/ol\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Anti-glomerular basement membrane disease, Nephropathology, Crescentic glomerulonephritis","lastPublishedDoi":"10.21203/rs.3.rs-4251504/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4251504/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDespite the previous reports of patients with combined anti-glomerular basement membrane (anti-GBM) disease occurring sequentially or simultaneously with other nephropathies, most of them have been reported seperately. The complication of these diseases is rare and the mechanism is not clear, and their immuno-antibodies, microscopic picture, clinical presentation, treatment and prognosis are different, therefore, we presented the collection of anti-GBM with combined disease such as membranous nephropathy (MN), anti-neutrophil cytoplasmic antibody (ANCA), IgA nephropathy and atypical anti-GBM to systematically characterized the epidemiological features, clinical manifestations, pathological features and herapeutic outcomes through a summative review.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eWe retrospectively a case series of 39 anti-GBM diseases from a single center in Northwest China from 2011\u0026ndash;2023.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 39 patients with anti-GBM disease including 19 males and 20 females were collected with a mean age of 50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6 years. Among them there were 22 cases (22/39,56.4%) of anti-GBM alone, 6 cases (6/39,15.4%) of combined ANCA, 6 cases (6/39,15.4%) of combined MN, 2 cases (2/39,5.1%) of combined IgAN, and 3 cases (3/39,7.7%) of atypical anti-GBM nephropathy. The mean duration of the disease was 2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 months. Clinical symptoms were dominated by fever 68.2% (15/22), oliguria/anuria 63.6% (14/22), and microscopic haematuria 88.9% (16/22,) in the anti-GBM alone group, and nausea and vomiting 50% (3/6) in the anti-GBM\u0026thinsp;+\u0026thinsp;MN group, and edema 83.3% (5/6) in the anti-GBM\u0026thinsp;+\u0026thinsp;MN group. The proportion of patients requiring hemodialysis (HD) at the first visit was 79.5% (31/39) in all patients, 56.4% (22/39) in the anti-GBM alone group, 66.7% (4/6) in the anti-GBM\u0026thinsp;+\u0026thinsp;ANCA group, 66.7% (4/6) in the anti-GBM\u0026thinsp;+\u0026thinsp;MN group, and 100% (2/2) in the anti-GBM\u0026thinsp;+\u0026thinsp;IgAN group. Among them, 56.4% had more than 85% glomerular involvement. The proportion of sclerotic glomeruli was higher in the anti-GBM and anti-GBM\u0026thinsp;+\u0026thinsp;ANCA groups. The highest percentage of cellular crescents was found in the anti-GBM group as long with fibrous crescents in the anti-GBM\u0026thinsp;+\u0026thinsp;ANCA group. Immunofluorescence staining demonstrated positive IgG and C3 staining in all subgroups.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eWe concluded that the complication of other nephritis is another potential risk factor for anti-GBM, which is directly attributable to the adverse effects of the different immune depositions and pathological features on renal function, as timely intervention in patients with different pathological features is crucial.\u003c/p\u003e","manuscriptTitle":"Clinicopathological characterization of subgroups in anti-glomerular basement membrane nephritis patients From a Single Center in China: A 12-Year observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-23 16:11:14","doi":"10.21203/rs.3.rs-4251504/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c6af8dd2-6d9a-4407-a359-613ca3853aae","owner":[],"postedDate":"April 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-22T09:06:33+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-23 16:11:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4251504","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4251504","identity":"rs-4251504","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}