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. It occurs due to immune complex formation on the outer side of glomerular basement membrane. MN can be primary MN where 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.
Antibodies to PLA2R is found in 70% of patients and are specific for MN. Other podocyte antigens have been found implicated like thrombospondin type 1 domain-containing 7A (THSD7A) in <5% of primary MN, 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.
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.
Methods:
Aims and objectives
1. To study the clinicopathological profile of patients with primary membranous nephropathy.
2. To estimate the response of treatment in patients with primary membranous nephropathy at 12 months.
Material and methods
This was a retrospective cum prospective observational study conducted at the, Department of Nephrology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, over a period of two years, after approval by the Institutional Ethics Committee.
Patients aged > 18 years with biopsy-proven primary membranous nephropathy were included in the study. Patient who were unwilling for renal biopsy, patients who were pregnant, end-stage kidney disease and patients with secondary MN were excluded from the study.
Clinical assessment:
The data of patients with a diagnosis of primary membranous nephropathy was retrieved. 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 and systemic examination was done.
Laboratory investigations included a complete hemogram, renal 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. The glomerular filtration rate was estimated by CKD – EPI creatinine equation. Patients were screened for any secondary etiology of membranous nephropathy.
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.
Complete remission (CR) was defined as a reduction in proteinuria to <300 mg/day with normal serum albumin and renal function. Partial remission (PR) was defined as reduction of proteinuria >50% from the baseline to >300 mg/day and < 3.5 g/day accompanied by normalization of serum albumin and stable renal function. No remission was defined as <50% reduction of proteinuria from baseline or proteinuria > 3.5 g/day. Relapse was defined as the return of proteinuria to > 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 prompts 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. 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.
Values of P<0.05 are considered to indicate statistical significance. Values are expressed as mean (±SD). The chi-square test was utilized for categorical variables.
Results:
A total of 46 patients were included in this study out of which 28(60.9%) were females and 18(39.1%) were males. The mean age of our patients was 43.8+13.7 years. The largest proportion of patients, comprising 41.3% of the total fell in the age group of 45-60 years. The rest of the baseline parameters are shown in Table 1.
Table 1: Baseline parameters.
58.7% of patients were PLA2R positive and 17.4% of patients were tissue NELL-1 positive. 23.9% of patients had no identifiable antigen on immunohistochemistry.
All patients at presentation had edema and nephrotic syndrome was seen in 73.9% of patients. Frothy urine was seen in 82.6% of patients 26.1% of patients had microscopic hematuria.
71.1% of our patients were in the high-risk category at the baseline, remaining 28.3% were in the low to moderate-risk category.
9(23.08%) of patients had remission with supportive care while 30(76.92%) had no remission (Table 2).
Table 2: Comparision of remission with baseline risk category after supportive care. The intergroup rate of remission was not statistically significant (p-0.129).
With immunosuppressive therapy 29(82.9%) patients had remission while 6(17.1%) patients had no remission at 12 months.
Our patients had a significant decline in the mean Anti-PLA2R titers (81.62 + 148.47 to 27.78 + 82.81 RU/ml, p-0.001) with immunosuppressive therapy at 6 months. Patients who received either modified ponticielli or other immunosuppression had a significant improvement in 24-hour urinary proteinuria and serum albumin concentration at 12 months of therapy.
Table 3: Comparision of clinical parameters at baseline and 12 months of immunosuppressive therapy
11 (68.8%) patients who received a modified ponticelli regimen achieved remission and 18(94.7%) who received other immunosuppressive therapies achieved remission and the intergroup difference wasn’t statistically significant (p-Value 0.073).
Conclusions:
Membranous nephropathy is one of the most common cause of nephrotic syndrome in adults. We found PLA2R antigen to be most commonly associated with primary membranous nephropathy. The prevalence of primary membranous nephropathy was highest in the fifth and sixth decade of life with female preponderance. Most of the patients in our cohort were in the high-risk group at the time of presentation. Three-quarters of our patients presented with nephrotic syndrome More than 80% of our patients achieved remission with immunosuppressive therapy. There was no significant difference in remission among various immunosuppressive agents.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.