Clinical Profile and Outcome of Primary Membranous Nephropathy

Clinical Profile and Outcome of Primary Membranous Nephropathy | 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 Research Article Clinical Profile and Outcome of Primary Membranous Nephropathy Muzamil Ahmad Wani, Imran Khan, Jawad Iqbal Rather, Mohammad Ashraf Bhat, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6930835/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: Primary membranous nephropathy (MN) is a major cause of nephrotic syndrome in adults, characterized by immune complex formation on the outer side of the glomerular basement membrane. Primary MN accounts for 80% of the cases and 20% cases are associated with a secondary etiology. While immunosuppressive therapy has improved patient outcomes in MN, the clinical profile and treatment outcomes of MN in our patient population have not been previously studied. Methods: This two-year retrospective and prospective observational study, approved by the Institutional Ethics Committee, was conducted at the Department of Nephrology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India. The primary objective was to investigate the clinicopathological profile and outcomes of primary MN patients. We included consenting patients aged ≥ 18 years with primary MN and excluded those with end-stage kidney disease, pregnancy, or secondary MN. Detailed history, physical examination, laboratory investigations (including 24-hour urinary protein, kidney and liver function tests, and anti-PLA2R antibody levels), and screening for secondary etiologies were performed. Renal biopsy tissues were examined using light microscopy, immunofluorescence, immunohistochemistry for PLA2R, THSD7A, NELL-1, EXT1, EXT2, and electron microscopy. Patients were risk-stratified based on proteinuria, kidney function, and serum anti-PLA2R antibody levels. Remission, relapse, and resistant disease were defined by specific proteinuria and albumin criteria Results: Of 46 patients, 60.9% were female, with a mean age of 43.8 ± 13.7 years. The mean proteinuria was 5.8 ± 3.2 g/day, mean serum albumin was 2.5 ± 0.39 g/dL, and mean eGFR was 99.8 ± 26.6 mL/min/1.73 2 . Edema was the most common symptom (100%), and hypertension was the most frequent comorbidity (37%). Serum anti-PLA2R antibodies were positive in 39.1% of patients. On immunohistochemistry, 58.7% were tissue PLA2R positive and 17.4% were NELL-1 positive. At baseline, 71.1% of patients were in the high-risk category. Initial non-immunosuppressive supportive care was given to 84.8% of patients, with 23.08% achieving remission. Among those receiving immunosuppressive therapy, 72.2% on modified Ponticelli regimen and 85.7% on other regimens achieved remission at 6 months (p=0.432). At 12 months, 82.9% of patients on immunosuppressive therapy achieved remission. Both modified Ponticelli and other immunosuppressive regimens significantly improved proteinuria and serum albumin at 12 months (p<0.0001). Conclusion: PLA2R associated MN was the most common form of MN, followed by NELL-1. Primary MN prevalence was highest in the fifth and sixth decades of life, with a slight female preponderance observed in this study. Most patients presented in the high-risk group. Immunosuppression led to complete remission in over 80% of patients, with no significant difference in remission rates between different immunosuppressive agents. This study provides initial insights into MN in the local patient population, despite its limitations of being a single-center observational study with a relatively small sample size and short follow-up. Membranous Nephropathy PLA2R NELL-1 Modified Ponticelli Rituximab Figures Figure 1 Introduction The term membranous nephropathy (MN) indicates a pathological condition characterized by diffuse thickening of the glomerular basement membrane (GBM) and involves the whole glomerulus [ 1 ]. It occurs due to immune complex formation on the outer side of the glomerular basement membrane. MN is a pathological diagnosis on the renal biopsy. MN can be primary MN where the disease is limited to the kidneys without systemic involvement or secondary MN which is associated with other diseases like autoimmune diseases, infections, malignancy, and drugs. Primary MN accounts for 80% of cases and 20% are associated with other systemic diseases or exposures [ 2 ]. Primary MN represents the commonest cause of idiopathic nephrotic syndrome in adult non-diabetics worldwide, representing between 20% and 37% in many series and rising to as high as 40% in adults over 60 [ 3 ]. Antibodies to PLA2R are found in 70% of patients and are specific for MN [ 4 ]. Other podocyte antigens have been found implicated like thrombospondin type 1 domain-containing 7A (THSD7A) in < 5% of primary MN [ 5 ], exostosin 1 (EXT1) and EXT2, semaphorin 3B (SEMA3B), protein kinase C-binding protein NELL1 (also known as neural epidermal growth factor-like 1 protein), protocadherin 7 (PCDH7), neural cell adhesion molecule 1 (NCAM1) and serine protease HTRA1 [ 6 ]. Progression of MN is variable, one-third of the patients have spontaneous remission, one-third have variable levels of proteinuria, and the remaining third progress to advanced kidney failure. Immunosuppressive therapy has substantially reduced the rate of kidney replacement therapy [ 2 ]. In untreated MN, complete remission rates of 20–30% with 60–80% of 10–year renal survival rates are reported in many studies [ 7 ]. In patients who have persistent nephrotic syndrome, renal failure develops over the period of 10 – years in 40–50% [ 8 ]. Therapy of MN included supportive care and immunomodulatory therapies. Patients with MN need intensive monitoring to identify the estimated risk of progression of renal function deterioration. Patients at high risk of progression of kidney disease are considered for immunosuppressive therapies [ 9 ]. The clinical profile and treatment outcome of MN is unknown in our patient population. Materials and Methods This was a retrospective cum prospective observational study conducted in the Department of Nephrology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India. The duration of the study was 2 years. The study was approved by the Institutional Ethics Committee of Sher-I-Kashmir Institute of Medical Sciences (319/2022). The primary objective of this study was to study the clinicopathological profile and outcome of the patients with primary MN. All the consenting patients aged ≥ 18 years with primary MN were included in the study. Patients with end-stage kidney disease, pregnancy, and secondary MN were excluded from the study. Patients who were diagnosed with primary membranous nephropathy during the study period and those patients who were already diagnosed and were on follow-up and had required data available were studied. A detailed history including any history of current illness, past history or comorbidity, as well as personal and drug history was taken. A detailed general physical and systemic examination was done. History of any potential clue for secondary membranous nephropathy was sought. Laboratory investigations included a complete hemogram, kidney, and liver function tests, 24-hour urinary protein excretion or urine protein – creatinine ratio, and a basic metabolic panel including blood glucose, lipid profile, and electrolytes. Patients were screened for any secondary etiology of membranous nephropathy by viral serology for hepatitis B virus, hepatitis C virus, and Human immunodeficiency virus. Appropriate patients with suspicion of autoimmune disease were screened for anti-nuclear antibody (ANA), anti-double-stranded DNA, and complement levels. Age-appropriate screening for malignancy with chest X-ray, stool for occult blood, gastrointestinal endoscopy, imaging like Computed Tomography and/or magnetic resonance imaging, mammography, PAP smear, tumor markers like CA-125, CEA, CA 19 − 9, AFP, PSA was done. Serum anti-phospholipase A2 receptor antibody levels were done at baseline and during monitoring of disease activity. Patients were classified based on the risk of progression of renal disease which helped in management decisions. Treatment medications including immunosuppressive agents received by patients were recorded. All patients were followed periodically, and disease status was noted. Renal biopsy tissue was examined in detail using light microscopy, immunofluorescence microscopy for IgA, IgM, IgG and its subtypes, C3, C1q, kappa, and lambda light chains, immunohistochemistry for PLA2R, THSD7A, NELL-1, EXT1, EXT2 and electron microscopy and detailed histopathological findings were noted. Patients were risk stratified on the basis of proteinuria, kidney function, and serum anti-PLA2R antibody levels as per Table 1 . Table 1 Risk stratification of patients of Membranous nephropathy [ 10 ]. Very high risk High risk Moderate risk Low risk Presence of the any 2 of the following is considered to be at very high risk of disease progression: Serum creatinine > 1.5 mg/dl, considered to be due to MN. Progressive decline in kidney function, > 25% decline in eGFR from the baseline over the prior 2 years. Severe, disabling, or life-threatening nephrotic syndrome defined by serum albumin < 2.5 g/dl and a refractory edema, or a thromboembolic event. Presence of ≥ 2 of the following is considered to be high risk: Decrease in eGFR ≥ 25% not explained by other causes any time during observation period. Proteinuria > 8 g/day at the end of observation period or persistent nephrotic syndrome. Patient is anti – PLA2R antibody positive, serial anti – PLA2R antibody titres are high ( ≥ 150 RU/ml by ELISA) and not decreasing or are increasing to ≥ 150 RU/ml. Presence of ≥ 2 of the following: Normal or stable eGFR (< 25% decrease) over 3 to 6 months period. Persistent proteinuria between 4 g/day and 8 g/day at the end of observation period. P atient is anti – PLA2R antibody positive, serial anti – PLA2R antibody titres are < 150 RU/ml by ELISA and stable or increasing by < 25% over 6 months period. Normal or stable eGFR (< 25% decrease) over 3 to 6 months period. Proteinuria < 4 g/day at the end of observation period Patient is anti – PLA2R antibody positive, serial anti – PLA2R antibody titres are persistently low < 50 RU/ml by ELISA or are decreasing ≥ 25% at 3 to 6 months period. Complete remission (CR) was defined as a reduction in proteinuria to 50% from the baseline to > 300 mg/day and 3.5 g/day after an initial complete or partial response. Patients with a relapse after partial remission should have > 50% increase in proteinuria from the nadir in addition to proteinuria > 3.5 g/day. Resistant disease was defined as the persistent or worsening of proteinuria and hypoalbuminemia which prompted addition or change in immunosuppressive therapy in the absence of intolerance or adverse effects of the immunosuppressive regimen. Statistical analysis : The data obtained was compiled in Microsoft Excel and subjected to analysis using SPSS Software. Values were expressed as mean (± SD). Between-group comparisons for continuous variables were done using the Independent t -test and Mann–Whitney test for normal and non-normal (distribution) data, respectively. P value < 0.05 was considered to indicate statistical significance. The chi-square test was utilized for categorical variables. Results A total of 46 patients were included in the study out of which 28(60.9%) were females and 18(39.1%) were males. The average age of our patients was 43.8 + 13.7 years. 19 (41.3%) patients fell in the age group of 45-60 years. This was followed by the age group of 30-45 years, which accounted for 14 (30.4%) patients. Only 4 (8.7%) of patients were above 60 years of age. The mean proteinuria of our patients was 5.8 + 3.2 grams per day. The mean serum albumin and creatinine were respectively 2.5 + 0.39 g/dl and 0.8 + 0.3 mg/dl. The mean estimated glomerular filtration rate (eGFR) was 99.8 + 26.6 ml/min/1.73m 2 . The mean anti-PLA2R titer was 81.6 + 148.5 RU/ml. The baseline characteristics are shown in Table 2. Table 2: Baseline characteristics of the study population. PARAMETER MEAN SD BMI (Kg/m 2 ) 24.8 3.4 Systolic BP (mmHg) 126 12.7 Diastolic BP (mmHg) 75.7 8.7 Cholesterol (mg/dL) 253.1 84.4 Triglycerides (mg/dL) 297 89.5 LDL (mg/dL) 148 54.1 HDL (mg/dL) 52.3 14.2 Hemoglobin (g/dL) 12.3 1.7 Total serum protein (g/dL) 6.1 0.85 Proteinuria (g/dL) 5.8 3.2 Serum albumin (g/dL) 2.5 0.39 Urea (mg/dL) 30.8 22.4 Creatinine (mg/dL) 0.8 0.3 eGFR (ml/min/1.73m 2 ) 99.83 26.6 Anti-PLA2R titre (RU/ml) 81.6 148.5 Edema was the most common symptom seen in all patients. The clinical features are shown in table 2. Table 3: Clinical features of the study population. Clinical Features Yes No Nephrotic Syndrome 73.9 26.1 Edema 100 0 Foamy Urine 82.6 17.4 Microscopic Hematuria 26.1 73.9 The most common comorbidity was hypertension which was present in 17 (37%) patients. The comorbidity status is shown in table 4. Table 4: Comorbidities in the study population. Comorbidity Number Percent Hypertension 17 37 Smoker 12 26.1 Hypothyroidism 6 13 Obese 6 13 Diabetes Mellitus 3 6.5 18 (39.1%) of our patients had positive serum anti-PLA2R antibodies and 17 (37%) of patients had negative serum anti-PLA2R antibodies. However, in 11 (23.9%) patients, serum anti-PLA2R antibodies were not available. On immunohistochemistry of the kidney biopsies, 27 (58.7%) of patients were tissue PLA2R positive and 8 (17.4%) of patients were tissue NELL-1 positive. 11 (23.9%) of patients had no identifiable antigen on immunohistochemistry. 33 (71.1%) of our patients were in the high-risk category at the baseline, remaining 13 (28.3%) were in the low to moderate-risk category. 39 (84.8%) patients received initial non-immunosuppressive supportive care while as 7 (15.2%) received upfront immunosuppression. Among patients who received initial supportive care, 9 (23.08%) patients achieved remission while 30 (76.92%) had no remission. In terms of risk category, there was no difference in the outcome with supportive care as shown in Table 5. Table 5: Comparison of remission with baseline risk category after supportive care (Fisher’s Exact Test). Risk Remission No Remission Total Low or Moderate 5 (38.5%) 8 (61.5%) 13 (100%) P value - 0.129 High 4 (15.4%) 22 (84.6%) 26 (100%) Total 9 (23.08%) 30 (76.92%) 39 (100%) Among patients who received immunosuppressive therapy 18(46.2%) received a modified Ponticelli regimen and 21(53.8%) received other immunosuppressive regimens. 15 (83.3%) patients who received a modified Ponticelli regimen had baseline proteinuria greater than 6 grams per day compared to 12 (57.1%) patients who received another immunosuppressive regimen; however, the difference was not statistically significant (p-value 0.096, Fischer’s exact test). In our study baseline mean 24-hour urinary protein was higher in the modified Ponticelli group compared to other immunosuppressive groups, however, it was not statistically significant (8.77 + 3.12 vs 7.22 + 2.69 g/day, P -0.109). Patients who received modified Ponticelli had significantly higher serum creatinine at baseline compared with the other immunosuppressive group (0.99 + 0.44 vs 0.74 + 0.14 mg/dl, P -0.02), Table 6. Table 6: Comparison of baseline parameters between modified Ponticelli regimen versus other immunosuppression. Parameter Modified Ponticelli Others P Value Proteinuria(g/day) 8.77 + 3.12 7.22 + 2.69 0.109 Serum Albumin(g/dl) 2.07 + 0.52 2.16 + 0.54 0.6 Serum Creatinine(mg/dl) 0.99 + 0.44 0.74 + 0.14 0.02 At 6 months,13 (72.2%) patients who received a modified Ponticelli regimen had remission and 18 (85.7%) who received other immunosuppressive therapies achieved remission (p value 0.432). In patients with positive serum anti-PLA2R, there was a significant decline at 6 months with immunosuppression, Figure 1. Discussion This was an observational study conducted in the Department of Nephrology at SKIMS Srinagar over a period of 2 years. Primary membranous nephropathy is a specific pathological disorder of the glomerulus characterized by thickening of the capillary glomerular wall due to subepithelial immune complex deposition where a secondary cause of glomerular lesion is excluded [ 2 ]. It is one of the most common causes of nephrotic syndrome in adult non-diabetic patients. Around 30% of cases of adult nephrotic syndrome are due to membranous nephropathy only surpassed by non-diabetic podocytopathy with focal segmental glomerulosclerosis lesions in African and Hispanic Americans [ 9 ]. There is a paucity of data on the primary membranous nephropathy from our population, so this study was contemplated to study the primary MN. We studied 46 patients with primary membranous nephropathy during the study period. The mean age at diagnosis of primary membranous nephropathy was 43.8 years. Our result was comparable to a study by Hemanth Kumar et al who studied the profile and outcomes of PMN in a tertiary hospital in North India, in their study mean age of participants was 43 years [ 11 ]. In our study, 28 (60.9%) patients were females and 39.1% (18) were males. For unknown reasons, there is a slight male preponderance in PMN [ 12 ]. However, our study did not demonstrate the same probably because of a small number of participants. This needs to be confirmed with larger studies from our population. The most common clinical presentation was edema seen in all patients. 82.6% of patients had frothuria (as reported by patients). Microscopic haematuria was observed in 26.1% of patients. Nephrotic syndrome was seen in 73.9% of patients. Pierre Ronco et al. reported microscopic haematuria in < 25% of patients and nephrotic syndrome in two-thirds of patients [ 9 ]; and William G. Couser reported edema in 60–75%, 80% of patients with primary MN present with nephrotic syndrome and haematuria in 50–60% of patients during the course of primary membranous nephropathy [ 2 ]. In our study, Serum anti-PLA2R antibody was available in 35 patients. Of the 11 patients where anti-PLA2R antibody was not available, 8 patients were NELL-1 related MN and in 3 patients anti-PLA2R antibody was not performed. Of the remaining 35 patients 3 had qualitative anti-PLA2R antibodies done by immunofluorescence assay which were positive and 32 had quantitative anti-PLA2R antibodies performed by ELISA. On immunohistochemistry 27(58.7%) patients were positive for Phospholipase A2 Receptor (PLA2R) and 8(17.4%) were positive for Neural Epidermal Growth Factor –like 1 (NELL-1), 11(23.9%) had no identifiable antigens on IHC. Mcdonell et al reported 70% of primary MN associated with PLA2R [ 13 ], and Sethi S et al reported NELL-1 to be associated with approximately 10% of primary MN [ 14 ]. 33(71.7%) patients were in the high/very high-risk category at baseline. 7 (15.2%) patients had received upfront immunosuppression along with supportive care. Of the remaining 39 patients, 7 (15.2%) patients received non-immunosuppressive antiproteinuric therapy only while 32 (69.6%) patients received immunosuppressive therapy after the variable duration of non-immunosuppressive antiproteinuric therapy. Among 39 patients who received non-immunosuppressive antiproteinuric therapy (NIAT), 9 (23.08%) patients had remission [3 (7.69%) had complete remission and 6 (15.39%) had partial remission] with supportive care only without immunosuppression and 30(76.92%) patients had no remission with supportive care. Dahan K et al [ 15 ] reported 21.1% remission with non-immunosuppressive anti-proteinuric therapy at 1 year. There was no significant difference between the baseline risk category and the rate of remission with supportive care. The mean duration of supportive care in patients who didn’t receive any immunosuppressive therapy (n-7) was 24.7 ± 8.17 months while the mean duration of supportive care in patients who received immunosuppressive therapy after supportive care (n-32) was 5.3 ± 4.02 months. Among patients who achieved remission with non-immunosuppressive antiproteinuric therapy 3 (7.69%) patients had relapse after 11.3 ± 2.08 months of NIAT. All three patients had partial remission with NIAT which is a known risk factor for relapse [ 16 ]. Of the 46 patients, 39(84.8%) received immunosuppressive therapy out of which 7(17.9%) patients received upfront immunosuppression. At 6 months of therapy, compared from baseline there was significant improvement in proteinuria (7.93 ± 2.96 to 1.96 ± 2.66 g/day, p < 0.001) and serum albumin (2.12 ± 0.53 to 3.48 ± 0.83 mg/dl, p < 0.001). 31 (79.5%) had remission- 14(35.9%) had complete remission and 17(43.6%) had partial remission and 8(20.5%) patients no remission. Our results were comparable with the study of Hemanth Kumar et al [ 11 ] who found an 87.5% remission rate with immunosuppressive therapy. Shankar Prasad Nagaraju et al [ 16 ] found at the end of 6 months complete remission was seen in 25.9% and 62.9% had partial remission. The mean anti-PLA2R antibody level at baseline was 81.6 ± 148.5 RU/ml. After 6 months of immunosuppressive therapy serum anti-PLA2R antibody titres were significantly decreased to a mean 27.78 ± 82.81 RU/ml ( p – 0.001 ). 4 of 8 patients who did not undergo remission at 6 months were resistant to initial immunosuppressive therapy and were excluded from analysis at 12 months. At 12 months 29 (82.9%) patients had remission- 18(51.4%) had complete remission and 11(31.5%) had partial remission, and 6(17.1%) patients had no remission. Our results are comparable with the study of Hemanth Kumar et al who found an 87.5% remission rate with immunosuppressive therapy [ 11 ]. Gema Fernandez-Juarez et al reported 79% overall remission at 12 months and 33% and 60% complete remission at 1 year and 2 years respectively [ 17 ]. There was a significant improvement in proteinuria and serum albumin concentration at 12 months with a decrease in mean 24-hour urinary protein from 7.93 ± 2.96 g/day to 1.29 ± 1.67 g/day and an increase in serum albumin from 2.12 ± 0.53mg/dl to 3.84 ± 0.53 mg/dl. Out of 39 patients who received immunosuppressive therapy, 18(46.2%) received modified Ponticelli, and 21 (53.8%) received other immunosuppressive agents. In the other immunosuppressive group,15 patients received prednisolone and tacrolimus, 3 patients received prednisolone, tacrolimus, and rituximab, 2 patients received rituximab alone and 1 patient received tacrolimus alone). The rate of remission with the modified Ponticelli regimen was not significantly different compared to other immunosuppressive therapy at 6 months (72% vs 85%; p -0.432) or at 12 months (68.8% vs 94.7%; p -0.073). This non-significant higher remission rates with other immunosuppressive groups compared to the modified Ponticelli regimen could be because of higher baseline proteinuria and serum creatinine in the modified Ponticelli group (8.77 + 3.12 g/day vs 7.22 + 2.69 g/day, p -0.109; 0.99 + 0.44 vs 0.74 + 0.14 mg/dl, p -0.02). We found that there is a significant decrease in proteinuria and an increase in serum albumin with both immunosuppressive groups at 6 months and 12 months. The limitations of our study are that it was a single-center observational study with a relatively small sample size and the follow-up period was short. However, this study provides useful insight into the previously unstudied realm of MN in our patient population. In conclusion, PLA2R-associated MN was the most common form of MN followed by NELL-1 in our study population. The prevalence of primary MN was highest in the 5th and 6th decade of life with a slight female preponderance. Most of the patients were in the high-risk group. With immunosuppression, more than 80% of patients achieved complete remission. There was no significant difference in remission among different immunosuppressive agents. Abbreviations MN: Membranous nephropathy NIAT: Non-immunosuppressive antiproteinuric therapy IFTA: Interstitial fibrosis and tubular atrophy eGFR: Estimated glomerular filtration rate PLA2R: Phospholipase A2 receptor NELL-1: Neural epidermal growth factor like-1 THSD7A: Thrombospondin type 1 domain containing 7A CR: Complete remission PR: Partial remission NR: No remission ACEI: Angiotensin converting enzyme inhibitors ARB: Angiotensin receptor blockers Declarations Ethics Approval and consent to Participate : This study was approved by IEC SKIMS with Protocol ID 319/2022. Each participant gave an informed written consent for participation. The research was conducted according to the Declaration of Helsinki. Consent for Publication : Not applicable Availability of data and materials : The datasets are available from the corresponding author on reasonable request. Competing interests : None Funding : None Author’s contributions : M.A.W, I.k and J.I.R were involved in the design, data collection, data analysis and writing of this manuscript. J.I.R is the corresponding author. M.A.B, M.M.W, I.A.W, R.Y.S, M.A.P were involved in conceptualization, data analysis and critically reviewing the manuscript Acknowledgements : Not applicable References Moroni G, Ponticelli C. Secondary Membranous Nephropathy. A Narrative Review. Front Med (Lausanne). 2020 Dec 3;7:611317. doi: 10.3389/fmed.2020.611317 Couser, W. G. Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 2017 Jun 7;12(6):983-997. doi: 10.2215/CJN.11761116. Epub 2017 May 26. Erratum in: Clin J Am Soc Nephrol. 2017 Sep 7;12 (9):1528. Salant DJ, Cattran DC. Membranous nephropathy. Chapter 20. In: Comprehensive Clinical Nephrology, 5th Ed., edited by Floege J, Johnson RJ, Feehally J, St. Louis, MI, Saunders, an imprint of Elsevier Inc., 2015, pp 239– 251 6. Beck LH Beck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009 Jul 2;361(1):11-21. doi: 10.1056/NEJMoa0810457. Tomas NM, Beck LH Jr, Meyer-Schwesinger C, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014 Dec 11;371(24):2277-2287. doi: 10.1056/NEJMoa1409354. Sethi S. New ‘antigens’ in membranous nephropathy. J. Am. Soc. Nephrol. 2021; 32: 268–278. Maisonneuve P, Agodoa L, Gellert R, et al. Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study. Am J Kidney Dis. 2000 Jan;35(1):157-65. doi: 10.1016/S0272-6386(00)70316-7. De Vriese AS, Glassock RJ, Nath KA, et al. A Proposal for a Serology-Based Approach to Membranous Nephropathy. J Am Soc Nephrol. 2017 Feb;28(2):421-430. doi: 10.1681/ASN.2016070776. Ronco P, Beck L, Debiec H, et al. Membranous nephropathy. Nat Rev Dis Primers. 2021 Sep 30;7(1):69 Neil turner, Norbert Lameire, David J. goldsmith, et al. Oxford Textbook of Clinical Nephrology (Vol. 1), pp. 492.Glasgow: University Oxford Press Hemanth Kumar MK, Sandhu J, Sandhu JS. Profile and primary treatment outcomes in membranous nephropathy. Saudi Med J. 2022 Sep; 43(9): 10511056. Hogan SL, Muller KE, Jennette JC, et al. A review of therapeutic studies of idiopathic membranous glomerulopathy. Am. J. Kidney Dis. 1995; 25: 862– 875 McDonnell T, Wu HHL, Sinha S, et al. The Role of PLA2R in Primary Membranous Nephropathy: Do We Still Need a Kidney Biopsy? Genes (Basel). 2023 Jun 26;14(7):1343. Sethi S, Beck LH Jr, Glassock RJ, et al. Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification. Kidney Int. 2023 Dec;104(6):1092-1102 Dahan K, Debiec H, Plaisier E, et al. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up. J Am Soc Nephrol. 2017 Jan;28(1):348-358. doi: 10.1681/ASN.2016040449. Nagaraju SP, Parthasarathy R, Prabhu RA,et al. Modified-‘Modified ponticelli regimen’-for idiopathic membranous nephropathy. Nephrology Dialysis Transplantation. 2015; 30(Supl-3): iii420-39. Fernández-Juárez G, Rojas-Rivera J, Logt AV, et al. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy. Kidney Int. 2021 Apr; 99(4): 986-998. 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. 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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-6930835","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":477777856,"identity":"a6874384-13f3-4f6c-829a-93b6fe3b37c4","order_by":0,"name":"Muzamil Ahmad Wani","email":"","orcid":"","institution":"Sher-I-Kashmir Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Muzamil","middleName":"Ahmad","lastName":"Wani","suffix":""},{"id":477777857,"identity":"985c2476-d35a-4c0b-8f25-387c5fd069db","order_by":1,"name":"Imran Khan","email":"","orcid":"","institution":"Sher-I-Kashmir Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Imran","middleName":"","lastName":"Khan","suffix":""},{"id":477777858,"identity":"d5ada98e-96f9-45c9-942b-8cc064253e1b","order_by":2,"name":"Jawad Iqbal Rather","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYBACxgYgwWPAkMDAznz4wQcgh42daC3MbGmGM0BamImxiocBpIXHQJoHxCOkhbn9jOGHNwXWefzNPAbGNr+2yfMxMzB++JiDx2E9OcaScwzSiyUOsxU8zu27bdjGzMAsOXMbPr/kbpDmMTic2HCYeYNxbs9tRqAWNmZefFr6327+DdIy/zCDgbRlz217wlpm5G4D27LhMIuBNMOP24lEaHn/zRLkF8PDwEDubbid3MbM2IzXL4b9ack33vyxzpM73nz4wY8/t23ntzcf/PARn5YGMAWNC8Y2MNmAWz0QyDMga2H4g1fxKBgFo2AUjFAAAF5GUei3t0xiAAAAAElFTkSuQmCC","orcid":"","institution":"Government Medical College, Anantnag","correspondingAuthor":true,"prefix":"","firstName":"Jawad","middleName":"Iqbal","lastName":"Rather","suffix":""},{"id":477777859,"identity":"9580cecb-ae18-4938-ad5a-c77dcbaa5b0f","order_by":3,"name":"Mohammad Ashraf Bhat","email":"","orcid":"","institution":"Sher-I-Kashmir Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Ashraf","lastName":"Bhat","suffix":""},{"id":477777860,"identity":"80daff22-486f-4961-9c4f-c8ad1178ec77","order_by":4,"name":"Muzafar Maqsood Wani","email":"","orcid":"","institution":"Sher-I-Kashmir Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Muzafar","middleName":"Maqsood","lastName":"Wani","suffix":""},{"id":477777861,"identity":"d338557c-7d36-4d02-857c-fef6dfbe6429","order_by":5,"name":"Imtiyaz Ahmad Wani","email":"","orcid":"","institution":"Sher-I-Kashmir Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Imtiyaz","middleName":"Ahmad","lastName":"Wani","suffix":""},{"id":477777862,"identity":"a3774d4d-0955-4d17-87cd-f65dfd92521f","order_by":6,"name":"Manzoor Ahmad Parry","email":"","orcid":"","institution":"Sher-I-Kashmir Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Manzoor","middleName":"Ahmad","lastName":"Parry","suffix":""},{"id":477777863,"identity":"4242bb87-c608-4b71-afab-1d1e1e9d04a7","order_by":7,"name":"Rayees Yousuf sheikh","email":"","orcid":"","institution":"Sher-I-Kashmir Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Rayees","middleName":"Yousuf","lastName":"sheikh","suffix":""}],"badges":[],"createdAt":"2025-06-19 11:38:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6930835/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6930835/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85747029,"identity":"d4ad1833-b4b8-4691-b6ff-3408e4812331","added_by":"auto","created_at":"2025-07-01 09:37:43","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":35776,"visible":true,"origin":"","legend":"\u003cp\u003eAt 6 months serum Anti-PLA2R (RU/ml) levels declined significantly with immunosuppression (p-value 0.001, Wilcoxon Rank Test).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6930835/v1/f820609cdc4a4f4cc6467e6e.jpg"},{"id":89265411,"identity":"f19955aa-6ff4-4188-a6ad-289bea7bc5ea","added_by":"auto","created_at":"2025-08-18 08:02:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":581731,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6930835/v1/387ab638-71f9-42db-a9fb-1d8486f8cf0d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Profile and Outcome of Primary Membranous Nephropathy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe term membranous nephropathy (MN) indicates a pathological condition characterized by diffuse thickening of the glomerular basement membrane (GBM) and involves the whole glomerulus [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It occurs due to immune complex formation on the outer side of the glomerular basement membrane. MN is a pathological diagnosis on the renal biopsy. MN can be primary MN where the disease is limited to the kidneys without systemic involvement or secondary MN which is associated with other diseases like autoimmune diseases, infections, malignancy, and drugs. Primary MN accounts for 80% of cases and 20% are associated with other systemic diseases or exposures [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Primary MN represents the commonest cause of idiopathic nephrotic syndrome in adult non-diabetics worldwide, representing between 20% and 37% in many series and rising to as high as 40% in adults over 60 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Antibodies to PLA2R are found in 70% of patients and are specific for MN [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Other podocyte antigens have been found implicated like thrombospondin type 1 domain-containing 7A (THSD7A) in \u0026lt;\u0026thinsp;5% of primary MN [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], exostosin 1 (EXT1) and EXT2, semaphorin 3B (SEMA3B), protein kinase C-binding protein NELL1 (also known as neural epidermal growth factor-like 1 protein), protocadherin 7 (PCDH7), neural cell adhesion molecule 1 (NCAM1) and serine protease HTRA1 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Progression of MN is variable, one-third of the patients have spontaneous remission, one-third have variable levels of proteinuria, and the remaining third progress to advanced kidney failure. Immunosuppressive therapy has substantially reduced the rate of kidney replacement therapy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In untreated MN, complete remission rates of 20\u0026ndash;30% with 60\u0026ndash;80% of 10\u0026ndash;year renal survival rates are reported in many studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In patients who have persistent nephrotic syndrome, renal failure develops over the period of 10 \u0026ndash; years in 40\u0026ndash;50% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTherapy of MN included supportive care and immunomodulatory therapies. Patients with MN need intensive monitoring to identify the estimated risk of progression of renal function deterioration. Patients at high risk of progression of kidney disease are considered for immunosuppressive therapies [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe clinical profile and treatment outcome of MN is unknown in our patient population.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis was a retrospective cum prospective observational study conducted in the Department of Nephrology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India. The duration of the study was 2 years. The study was approved by the Institutional Ethics Committee of Sher-I-Kashmir Institute of Medical Sciences (319/2022).\u003c/p\u003e \u003cp\u003eThe primary objective of this study was to study the clinicopathological profile and outcome of the patients with primary MN.\u003c/p\u003e \u003cp\u003eAll the consenting patients aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years with primary MN were included in the study. Patients with end-stage kidney disease, pregnancy, and secondary MN were excluded from the study.\u003c/p\u003e \u003cp\u003ePatients who were diagnosed with primary membranous nephropathy during the study period and those patients who were already diagnosed and were on follow-up and had required data available were studied. A detailed history including any history of current illness, past history or comorbidity, as well as personal and drug history was taken. A detailed general physical and systemic examination was done. History of any potential clue for secondary membranous nephropathy was sought.\u003c/p\u003e \u003cp\u003eLaboratory investigations included a complete hemogram, kidney, and liver function tests, 24-hour urinary protein excretion or urine protein \u0026ndash; creatinine ratio, and a basic metabolic panel including blood glucose, lipid profile, and electrolytes. Patients were screened for any secondary etiology of membranous nephropathy by viral serology for hepatitis B virus, hepatitis C virus, and Human immunodeficiency virus. Appropriate patients with suspicion of autoimmune disease were screened for anti-nuclear antibody (ANA), anti-double-stranded DNA, and complement levels. Age-appropriate screening for malignancy with chest X-ray, stool for occult blood, gastrointestinal endoscopy, imaging like Computed Tomography and/or magnetic resonance imaging, mammography, PAP smear, tumor markers like CA-125, CEA, CA 19\u0026thinsp;\u0026minus;\u0026thinsp;9, AFP, PSA was done. Serum anti-phospholipase A2 receptor antibody levels were done at baseline and during monitoring of disease activity. Patients were classified based on the risk of progression of renal disease which helped in management decisions. Treatment medications including immunosuppressive agents received by patients were recorded. All patients were followed periodically, and disease status was noted.\u003c/p\u003e \u003cp\u003eRenal biopsy tissue was examined in detail using light microscopy, immunofluorescence microscopy for IgA, IgM, IgG and its subtypes, C3, C1q, kappa, and lambda light chains, immunohistochemistry for PLA2R, THSD7A, NELL-1, EXT1, EXT2 and electron microscopy and detailed histopathological findings were noted.\u003c/p\u003e \u003cp\u003ePatients were risk stratified on the basis of proteinuria, kidney function, and serum anti-PLA2R antibody levels as per 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\u003eRisk stratification of patients of Membranous nephropathy [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVery high risk\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh risk\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerate risk\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLow risk\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of the any 2 of the following is considered to be at very high risk of disease progression:\u003c/p\u003e \u003cp\u003eSerum creatinine\u0026thinsp;\u0026gt;\u0026thinsp;1.5 mg/dl, considered to be due to MN.\u003c/p\u003e \u003cp\u003eProgressive decline in kidney function, \u0026gt; 25% decline in eGFR from the baseline over the prior 2 years.\u003c/p\u003e \u003cp\u003eSevere, disabling, or life-threatening nephrotic syndrome defined by serum albumin\u0026thinsp;\u0026lt;\u0026thinsp;2.5 g/dl and a refractory edema, or a thromboembolic event.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresence of \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;2 of the following is considered to be high risk:\u003c/p\u003e \u003cp\u003eDecrease in eGFR\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;25% not explained by other causes any time during observation period.\u003c/p\u003e \u003cp\u003eProteinuria\u0026thinsp;\u0026gt;\u0026thinsp;8 g/day at the end of observation period or persistent nephrotic syndrome.\u003c/p\u003e \u003cp\u003ePatient is anti \u0026ndash; PLA2R antibody positive, serial anti \u0026ndash; PLA2R antibody titres are high (\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;150 RU/ml by ELISA) and not decreasing or are increasing to \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;150 RU/ml.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePresence of \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;2 of the following:\u003c/p\u003e \u003cp\u003eNormal or stable eGFR (\u0026lt;\u0026thinsp;25% decrease) over 3 to 6 months period.\u003c/p\u003e \u003cp\u003ePersistent proteinuria between 4 g/day and 8 g/day at the end of observation period.\u003c/p\u003e \u003cp\u003eP atient is anti \u0026ndash; PLA2R antibody positive, serial anti \u0026ndash; PLA2R antibody titres are \u0026lt;\u0026thinsp;150 RU/ml by ELISA and stable or increasing by \u0026lt;\u0026thinsp;25% over 6 months period.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNormal or stable eGFR (\u0026lt;\u0026thinsp;25% decrease) over 3 to 6 months period.\u003c/p\u003e \u003cp\u003eProteinuria\u0026thinsp;\u0026lt;\u0026thinsp;4 g/day at the end of observation period\u003c/p\u003e \u003cp\u003ePatient is anti \u0026ndash; PLA2R antibody positive, serial anti \u0026ndash; PLA2R antibody titres are persistently low\u0026thinsp;\u0026lt;\u0026thinsp;50 RU/ml by ELISA or are decreasing\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;25% at 3 to 6 months period.\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\u003eComplete remission (CR) was defined as a reduction in proteinuria to \u0026lt;\u0026thinsp;300 mg/day with normal serum albumin and renal function. Partial remission (PR) was defined as a reduction of proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;50% from the baseline to \u0026gt;\u0026thinsp;300 mg/day and \u0026lt;\u0026thinsp;3.5 g/day accompanied by normalization of serum albumin and stable renal function\u003c/p\u003e \u003cp\u003eRelapse was defined as the return of proteinuria to \u0026gt;\u0026thinsp;3.5 g/day after an initial complete or partial response. Patients with a relapse after partial remission should have \u0026gt;\u0026thinsp;50% increase in proteinuria from the nadir in addition to proteinuria\u0026thinsp;\u0026gt;\u0026thinsp;3.5 g/day.\u003c/p\u003e \u003cp\u003eResistant disease was defined as the persistent or worsening of proteinuria and hypoalbuminemia which prompted addition or change in immunosuppressive therapy in the absence of intolerance or adverse effects of the immunosuppressive regimen.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis :\u003c/h2\u003e \u003cp\u003eThe data obtained was compiled in Microsoft Excel and subjected to analysis using SPSS Software. Values were expressed as mean (\u0026plusmn;\u0026thinsp;SD). Between-group comparisons for continuous variables were done using the Independent \u003cem\u003et\u003c/em\u003e-test and Mann\u0026ndash;Whitney test for normal and non-normal (distribution) data, respectively. \u003cem\u003eP value\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate statistical significance. The chi-square test was utilized for categorical variables.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 46 patients were included in the study out of which\u0026nbsp;28(60.9%) were females and 18(39.1%) were males. The average age of our patients was 43.8\u003cu\u003e+\u003c/u\u003e13.7 years. 19 (41.3%) patients fell in the age group of 45-60 years. This was followed by the age group of 30-45 years, which accounted for 14 (30.4%) patients. Only 4 (8.7%) of patients were above 60 years of age. The mean proteinuria of our patients was 5.8 \u003cu\u003e+\u003c/u\u003e3.2 grams per day. \u0026nbsp;The mean serum albumin and creatinine were respectively 2.5\u003cu\u003e+\u003c/u\u003e0.39 g/dl and 0.8\u003cu\u003e+\u003c/u\u003e0.3 mg/dl. The mean estimated glomerular filtration rate (eGFR) was 99.8\u003cu\u003e+\u003c/u\u003e26.6 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e. The mean anti-PLA2R titer was 81.6\u003cu\u003e+\u003c/u\u003e148.5 RU/ml. The baseline characteristics are shown in Table 2.\u003c/p\u003e\n\u003cp\u003eTable 2: Baseline characteristics of the study population.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003ePARAMETER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003eMEAN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eBMI (Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e24.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eSystolic BP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eDiastolic BP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e75.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e8.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eCholesterol (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e253.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e84.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eTriglycerides (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e89.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eLDL (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e54.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eHDL (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e52.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e14.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e12.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eTotal serum protein (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eProteinuria (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eSerum albumin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eUrea (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e30.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e22.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eeGFR (ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e99.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e26.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 295px;\"\u003e\n \u003cp\u003eAnti-PLA2R titre (RU/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e81.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e148.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Edema was the most common symptom seen in all patients. The clinical features are shown in table 2.\u003c/p\u003e\n\u003cp\u003eTable 3: Clinical features of the study population.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"622\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 280px;\"\u003e\n \u003cp\u003eClinical Features\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 171px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 280px;\"\u003e\n \u003cp\u003eNephrotic Syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 171px;\"\u003e\n \u003cp\u003e73.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e26.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 280px;\"\u003e\n \u003cp\u003eEdema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 171px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 280px;\"\u003e\n \u003cp\u003eFoamy Urine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 171px;\"\u003e\n \u003cp\u003e82.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e17.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 280px;\"\u003e\n \u003cp\u003eMicroscopic Hematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 171px;\"\u003e\n \u003cp\u003e26.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e73.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe most common comorbidity was hypertension which was present in 17 (37%) patients. The comorbidity status is shown in table 4.\u003c/p\u003e\n\u003cp\u003eTable 4: Comorbidities in the study population.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eComorbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003ePercent\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eSmoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e26.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eHypothyroidism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eObese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 277px;\"\u003e\n \u003cp\u003eDiabetes Mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003e6.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e18 (39.1%) of our patients had positive serum anti-PLA2R antibodies and 17 (37%) of patients had negative serum anti-PLA2R antibodies. However, in 11 (23.9%) patients, serum anti-PLA2R antibodies were not available. On immunohistochemistry of the kidney biopsies, 27 (58.7%) of patients were tissue PLA2R positive and 8 (17.4%) of patients were tissue NELL-1 positive. 11 (23.9%) of patients had no identifiable antigen on immunohistochemistry.\u003c/p\u003e\n\u003cp\u003e33 (71.1%) of our patients were in the high-risk category at the baseline, remaining 13 (28.3%) were in the low to moderate-risk category.\u003c/p\u003e\n\u003cp\u003e39 (84.8%) patients received initial non-immunosuppressive supportive care while as 7 (15.2%) received upfront immunosuppression. Among patients who received initial supportive care, 9 (23.08%) patients achieved remission while 30 (76.92%) had no remission. In terms of risk category, there was no difference in the outcome with supportive care as shown in Table 5.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Table 5: Comparison of remission with baseline risk category after supportive care (Fisher\u0026rsquo;s Exact Test).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"632\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eRisk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 122px;\"\u003e\n \u003cp\u003eRemission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003eNo Remission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eLow or Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 122px;\"\u003e\n \u003cp\u003e5 (38.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e8 (61.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 124px;\"\u003e\n \u003cp\u003eP value - 0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 122px;\"\u003e\n \u003cp\u003e4 (15.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e22 (84.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 122px;\"\u003e\n \u003cp\u003e9 (23.08%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\n \u003cp\u003e30 (76.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e39 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAmong patients who received immunosuppressive therapy 18(46.2%) received a modified Ponticelli regimen and 21(53.8%) received other immunosuppressive regimens. 15 (83.3%) patients who received a modified Ponticelli regimen had baseline proteinuria greater than 6 grams per day compared to 12 (57.1%) patients who received another immunosuppressive regimen; however, the difference was not statistically significant (p-value 0.096, Fischer\u0026rsquo;s exact test). In our study baseline mean 24-hour urinary protein was higher in the modified Ponticelli group compared to other immunosuppressive groups, however, it was not statistically significant (8.77 \u003cu\u003e+\u003c/u\u003e 3.12 vs 7.22 \u003cu\u003e+\u003c/u\u003e 2.69 g/day,\u003cem\u003e\u0026nbsp;P\u003c/em\u003e-0.109). Patients who received modified Ponticelli had significantly higher serum creatinine at baseline compared with the other immunosuppressive group (0.99 \u003cu\u003e+\u003c/u\u003e 0.44 vs 0.74 \u003cu\u003e+\u003c/u\u003e 0.14 mg/dl, \u003cem\u003eP\u003c/em\u003e-0.02), Table 6.\u003c/p\u003e\n\u003cp\u003eTable 6: Comparison of baseline parameters between modified Ponticelli regimen versus other immunosuppression.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"635\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 209px;\"\u003e\n \u003cp\u003eModified Ponticelli\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eProteinuria(g/day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 209px;\"\u003e\n \u003cp\u003e8.77 \u003cu\u003e+\u003c/u\u003e 3.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e7.22 \u003cu\u003e+\u003c/u\u003e 2.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eSerum Albumin(g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 209px;\"\u003e\n \u003cp\u003e2.07 \u003cu\u003e+\u003c/u\u003e 0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e2.16 \u003cu\u003e+\u003c/u\u003e 0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eSerum Creatinine(mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 209px;\"\u003e\n \u003cp\u003e0.99 \u003cu\u003e+\u003c/u\u003e 0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e0.74 \u003cu\u003e+\u003c/u\u003e 0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;At 6 months,13 (72.2%) patients who received a modified Ponticelli regimen had remission and 18 (85.7%) who received other immunosuppressive therapies achieved remission (p value 0.432). In patients with positive serum anti-PLA2R, there was a significant decline at 6 months with immunosuppression, Figure 1.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis was an observational study conducted in the Department of Nephrology at SKIMS Srinagar over a period of 2 years.\u003c/p\u003e \u003cp\u003ePrimary membranous nephropathy is a specific pathological disorder of the glomerulus characterized by thickening of the capillary glomerular wall due to subepithelial immune complex deposition where a secondary cause of glomerular lesion is excluded [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It is one of the most common causes of nephrotic syndrome in adult non-diabetic patients. Around 30% of cases of adult nephrotic syndrome are due to membranous nephropathy only surpassed by non-diabetic podocytopathy with focal segmental glomerulosclerosis lesions in African and Hispanic Americans [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. There is a paucity of data on the primary membranous nephropathy from our population, so this study was contemplated to study the primary MN.\u003c/p\u003e \u003cp\u003eWe studied 46 patients with primary membranous nephropathy during the study period. The mean age at diagnosis of primary membranous nephropathy was 43.8 years. Our result was comparable to a study by Hemanth Kumar et al who studied the profile and outcomes of PMN in a tertiary hospital in North India, in their study mean age of participants was 43 years [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In our study, 28 (60.9%) patients were females and 39.1% (18) were males. For unknown reasons, there is a slight male preponderance in PMN [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, our study did not demonstrate the same probably because of a small number of participants. This needs to be confirmed with larger studies from our population.\u003c/p\u003e \u003cp\u003eThe most common clinical presentation was edema seen in all patients. 82.6% of patients had frothuria (as reported by patients). Microscopic haematuria was observed in 26.1% of patients. Nephrotic syndrome was seen in 73.9% of patients. Pierre Ronco et al. reported microscopic haematuria in \u0026lt;\u0026thinsp;25% of patients and nephrotic syndrome in two-thirds of patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]; and William G. Couser reported edema in 60\u0026ndash;75%, 80% of patients with primary MN present with nephrotic syndrome and haematuria in 50\u0026ndash;60% of patients during the course of primary membranous nephropathy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, Serum anti-PLA2R antibody was available in 35 patients. Of the 11 patients where anti-PLA2R antibody was not available, 8 patients were NELL-1 related MN and in 3 patients anti-PLA2R antibody was not performed. Of the remaining 35 patients 3 had qualitative anti-PLA2R antibodies done by immunofluorescence assay which were positive and 32 had quantitative anti-PLA2R antibodies performed by ELISA. On immunohistochemistry 27(58.7%) patients were positive for Phospholipase A2 Receptor (PLA2R) and 8(17.4%) were positive for Neural Epidermal Growth Factor \u0026ndash;like 1 (NELL-1), 11(23.9%) had no identifiable antigens on IHC. Mcdonell et al reported 70% of primary MN associated with PLA2R [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and Sethi S et al reported NELL-1 to be associated with approximately 10% of primary MN [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e33(71.7%) patients were in the high/very high-risk category at baseline. 7 (15.2%) patients had received upfront immunosuppression along with supportive care. Of the remaining 39 patients, 7 (15.2%) patients received non-immunosuppressive antiproteinuric therapy only while 32 (69.6%) patients received immunosuppressive therapy after the variable duration of non-immunosuppressive antiproteinuric therapy. Among 39 patients who received non-immunosuppressive antiproteinuric therapy (NIAT), 9 (23.08%) patients had remission [3 (7.69%) had complete remission and 6 (15.39%) had partial remission] with supportive care only without immunosuppression and 30(76.92%) patients had no remission with supportive care. Dahan K et al [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] reported 21.1% remission with non-immunosuppressive anti-proteinuric therapy at 1 year. There was no significant difference between the baseline risk category and the rate of remission with supportive care. The mean duration of supportive care in patients who didn\u0026rsquo;t receive any immunosuppressive therapy (n-7) was 24.7\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;8.17 months while the mean duration of supportive care in patients who received immunosuppressive therapy after supportive care (n-32) was 5.3\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;4.02 months. Among patients who achieved remission with non-immunosuppressive antiproteinuric therapy 3 (7.69%) patients had relapse after 11.3\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.08 months of NIAT. All three patients had partial remission with NIAT which is a known risk factor for relapse [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOf the 46 patients, 39(84.8%) received immunosuppressive therapy out of which 7(17.9%) patients received upfront immunosuppression. At 6 months of therapy, compared from baseline there was significant improvement in proteinuria (7.93\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.96 to 1.96\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.66 g/day, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and serum albumin (2.12\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.53 to 3.48\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.83 mg/dl, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). 31 (79.5%) had remission- 14(35.9%) had complete remission and 17(43.6%) had partial remission and 8(20.5%) patients no remission. Our results were comparable with the study of Hemanth Kumar et al [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] who found an 87.5% remission rate with immunosuppressive therapy. Shankar Prasad Nagaraju et al [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] found at the end of 6 months complete remission was seen in 25.9% and 62.9% had partial remission. The mean anti-PLA2R antibody level at baseline was 81.6\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;148.5 RU/ml. After 6 months of immunosuppressive therapy serum anti-PLA2R antibody titres were significantly decreased to a mean 27.78\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;82.81 RU/ml (\u003cem\u003ep \u0026ndash; 0.001\u003c/em\u003e). 4 of 8 patients who did not undergo remission at 6 months were resistant to initial immunosuppressive therapy and were excluded from analysis at 12 months.\u003c/p\u003e \u003cp\u003eAt 12 months 29 (82.9%) patients had remission- 18(51.4%) had complete remission and 11(31.5%) had partial remission, and 6(17.1%) patients had no remission. Our results are comparable with the study of Hemanth Kumar et al who found an 87.5% remission rate with immunosuppressive therapy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Gema Fernandez-Juarez et al reported 79% overall remission at 12 months and 33% and 60% complete remission at 1 year and 2 years respectively [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. There was a significant improvement in proteinuria and serum albumin concentration at 12 months with a decrease in mean 24-hour urinary protein from 7.93\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;2.96 g/day to 1.29\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;1.67 g/day and an increase in serum albumin from 2.12\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.53mg/dl to 3.84\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026plusmn;\u003c/span\u003e\u0026thinsp;0.53 mg/dl.\u003c/p\u003e \u003cp\u003eOut of 39 patients who received immunosuppressive therapy, 18(46.2%) received modified Ponticelli, and 21 (53.8%) received other immunosuppressive agents. In the other immunosuppressive group,15 patients received prednisolone and tacrolimus, 3 patients received prednisolone, tacrolimus, and rituximab, 2 patients received rituximab alone and 1 patient received tacrolimus alone). The rate of remission with the modified Ponticelli regimen was not significantly different compared to other immunosuppressive therapy at 6 months (72% vs 85%; \u003cem\u003ep\u003c/em\u003e-0.432) or at 12 months (68.8% vs 94.7%; \u003cem\u003ep\u003c/em\u003e-0.073). This non-significant higher remission rates with other immunosuppressive groups compared to the modified Ponticelli regimen could be because of higher baseline proteinuria and serum creatinine in the modified Ponticelli group (8.77\u0026thinsp;+\u0026thinsp;3.12 g/day vs 7.22\u0026thinsp;+\u0026thinsp;2.69 g/day, \u003cem\u003ep\u003c/em\u003e-0.109; 0.99\u0026thinsp;+\u0026thinsp;0.44 vs 0.74\u0026thinsp;+\u0026thinsp;0.14 mg/dl, \u003cem\u003ep\u003c/em\u003e-0.02). We found that there is a significant decrease in proteinuria and an increase in serum albumin with both immunosuppressive groups at 6 months and 12 months.\u003c/p\u003e \u003cp\u003eThe limitations of our study are that it was a single-center observational study with a relatively small sample size and the follow-up period was short. However, this study provides useful insight into the previously unstudied realm of MN in our patient population.\u003c/p\u003e \u003cp\u003eIn conclusion, PLA2R-associated MN was the most common form of MN followed by NELL-1 in our study population. The prevalence of primary MN was highest in the 5th and 6th decade of life with a slight female preponderance. Most of the patients were in the high-risk group. With immunosuppression, more than 80% of patients achieved complete remission. There was no significant difference in remission among different immunosuppressive agents.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMN: Membranous nephropathy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNIAT: Non-immunosuppressive antiproteinuric therapy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIFTA: Interstitial fibrosis and tubular atrophy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eeGFR: Estimated glomerular filtration rate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePLA2R: Phospholipase A2 receptor\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNELL-1: Neural epidermal growth factor like-1\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTHSD7A: Thrombospondin type 1 domain containing 7A\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;CR: Complete remission\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePR: Partial remission\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNR: No remission\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eACEI: Angiotensin converting enzyme inhibitors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eARB: Angiotensin receptor blockers\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and consent to Participate\u003c/strong\u003e: This study was approved by IEC SKIMS with Protocol ID 319/2022.\u003c/p\u003e\n\u003cp\u003eEach participant gave an informed written consent for participation. The research was conducted according to the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e: The datasets are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions\u003c/strong\u003e: M.A.W, I.k and J.I.R were involved in the design, data collection, data analysis and writing of this manuscript. J.I.R is the corresponding author. M.A.B, M.M.W, I.A.W, R.Y.S, M.A.P were involved in conceptualization, data analysis and critically reviewing the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: Not applicable\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMoroni G, Ponticelli C. Secondary Membranous Nephropathy. A Narrative Review. Front Med (Lausanne). 2020 Dec 3;7:611317. doi: 10.3389/fmed.2020.611317\u003c/li\u003e\n\u003cli\u003eCouser, W. G. Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 2017 Jun 7;12(6):983-997. doi: 10.2215/CJN.11761116. Epub 2017 May 26. Erratum in: Clin J Am Soc Nephrol. 2017 Sep 7;12 (9):1528.\u003c/li\u003e\n\u003cli\u003eSalant DJ, Cattran DC. Membranous nephropathy. Chapter 20. In: Comprehensive Clinical Nephrology, 5th Ed., edited by Floege J, Johnson RJ, Feehally J, St. Louis, MI, Saunders, an imprint of Elsevier Inc., 2015, pp 239\u0026ndash; 251 6. Beck LH\u003c/li\u003e\n\u003cli\u003eBeck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009 Jul 2;361(1):11-21. doi: 10.1056/NEJMoa0810457.\u003c/li\u003e\n\u003cli\u003eTomas NM, Beck LH Jr, Meyer-Schwesinger C, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014 Dec 11;371(24):2277-2287. doi: 10.1056/NEJMoa1409354. \u003c/li\u003e\n\u003cli\u003eSethi S. New \u0026lsquo;antigens\u0026rsquo; in membranous nephropathy. J. Am. Soc. Nephrol. 2021; 32: 268\u0026ndash;278.\u003c/li\u003e\n\u003cli\u003eMaisonneuve P, Agodoa L, Gellert R, et al. Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study. Am J Kidney Dis. 2000 Jan;35(1):157-65. doi: 10.1016/S0272-6386(00)70316-7. \u003c/li\u003e\n\u003cli\u003eDe Vriese AS, Glassock RJ, Nath KA, et al. A Proposal for a Serology-Based Approach to Membranous Nephropathy. J Am Soc Nephrol. 2017 Feb;28(2):421-430. doi: 10.1681/ASN.2016070776. \u003c/li\u003e\n\u003cli\u003eRonco P, Beck L, Debiec H, et al. Membranous nephropathy. Nat Rev Dis Primers. 2021 Sep 30;7(1):69\u003c/li\u003e\n\u003cli\u003eNeil turner, Norbert Lameire, David J. goldsmith, et al. Oxford Textbook of Clinical Nephrology (Vol. 1), pp. 492.Glasgow: University Oxford Press\u003c/li\u003e\n\u003cli\u003eHemanth Kumar MK, Sandhu J, Sandhu JS. Profile and primary treatment outcomes in membranous nephropathy. Saudi Med J. 2022 Sep; 43(9): 10511056.\u003c/li\u003e\n\u003cli\u003eHogan SL, Muller KE, Jennette JC, et al. A review of therapeutic studies of idiopathic membranous glomerulopathy. Am. J. Kidney Dis. 1995; 25: 862\u0026ndash; 875\u003c/li\u003e\n\u003cli\u003eMcDonnell T, Wu HHL, Sinha S, et al. The Role of PLA2R in Primary Membranous Nephropathy: Do We Still Need a Kidney Biopsy? Genes (Basel). 2023 Jun 26;14(7):1343.\u003c/li\u003e\n\u003cli\u003eSethi S, Beck LH Jr, Glassock RJ, et al. Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification. Kidney Int. 2023 Dec;104(6):1092-1102\u003c/li\u003e\n\u003cli\u003eDahan K, Debiec H, Plaisier E, et al. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up. J Am Soc Nephrol. 2017 Jan;28(1):348-358. doi: 10.1681/ASN.2016040449. \u003c/li\u003e\n\u003cli\u003eNagaraju SP, Parthasarathy R, Prabhu RA,et al. Modified-\u0026lsquo;Modified ponticelli regimen\u0026rsquo;-for idiopathic membranous nephropathy. Nephrology Dialysis Transplantation. 2015; 30(Supl-3): iii420-39.\u003c/li\u003e\n\u003cli\u003eFern\u0026aacute;ndez-Ju\u0026aacute;rez G, Rojas-Rivera J, Logt AV, et al. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy. Kidney Int. 2021 Apr; 99(4): 986-998.\u003c/li\u003e\n\u003c/ol\u003e"}],"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":"Membranous Nephropathy, PLA2R, NELL-1, Modified Ponticelli, Rituximab","lastPublishedDoi":"10.21203/rs.3.rs-6930835/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6930835/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Primary membranous nephropathy (MN) is a major cause of nephrotic syndrome in adults, characterized by immune complex formation on the outer side of the glomerular basement membrane. Primary MN accounts for 80% of the cases and 20% cases are associated with a secondary etiology. While immunosuppressive therapy has improved patient outcomes in MN, the clinical profile and treatment outcomes of MN in our patient population have not been previously studied.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This two-year retrospective and prospective observational study, approved by the Institutional Ethics Committee, was conducted at the Department of Nephrology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India. The primary objective was to investigate the clinicopathological profile and outcomes of primary MN patients. We included consenting patients aged ≥ 18 years with primary MN and excluded those with end-stage kidney disease, pregnancy, or secondary MN. Detailed history, physical examination, laboratory investigations (including 24-hour urinary protein, kidney and liver function tests, and anti-PLA2R antibody levels), and screening for secondary etiologies were performed. Renal biopsy tissues were examined using light microscopy, immunofluorescence, immunohistochemistry for PLA2R, THSD7A, NELL-1, EXT1, EXT2, and electron microscopy. Patients were risk-stratified based on proteinuria, kidney function, and serum anti-PLA2R antibody levels. Remission, relapse, and resistant disease were defined by specific proteinuria and albumin criteria\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Of 46 patients, 60.9% were female, with a mean age of 43.8 ± 13.7 years. The mean proteinuria was 5.8 ± 3.2 g/day, mean serum albumin was 2.5 ± 0.39 g/dL, and mean eGFR was 99.8 ± 26.6 mL/min/1.73\u003csup\u003e2\u003c/sup\u003e. Edema was the most common symptom (100%), and hypertension was the most frequent comorbidity (37%). Serum anti-PLA2R antibodies were positive in 39.1% of patients. On immunohistochemistry, 58.7% were tissue PLA2R positive and 17.4% were NELL-1 positive. At baseline, 71.1% of patients were in the high-risk category. Initial non-immunosuppressive supportive care was given to 84.8% of patients, with 23.08% achieving remission. Among those receiving immunosuppressive therapy, 72.2% on modified Ponticelli regimen and 85.7% on other regimens achieved remission at 6 months (p=0.432). At 12 months, 82.9% of patients on immunosuppressive therapy achieved remission. Both modified Ponticelli and other immunosuppressive regimens significantly improved proteinuria and serum albumin at 12 months (p\u0026lt;0.0001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e PLA2R associated MN was the most common form of MN, followed by NELL-1. Primary MN prevalence was highest in the fifth and sixth decades of life, with a slight female preponderance observed in this study. Most patients presented in the high-risk group. Immunosuppression led to complete remission in over 80% of patients, with no significant difference in remission rates between different immunosuppressive agents. This study provides initial insights into MN in the local patient population, despite its limitations of being a single-center observational study with a relatively small sample size and short follow-up.\u003c/p\u003e","manuscriptTitle":"Clinical Profile and Outcome of Primary Membranous Nephropathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-01 09:37:39","doi":"10.21203/rs.3.rs-6930835/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":"63b0ed29-3096-4123-975f-dd26c68f031b","owner":[],"postedDate":"July 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-18T07:54:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-01 09:37:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6930835","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6930835","identity":"rs-6930835","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}