#2012 Long term outcomes in patients with primary membranous nephropathy: a retrospective cohort study from a single center
Authors: Georgopoulos Christos , Duni Anila , Gkika-Zervou Luiza , Kitsos Athanasios , Theodorou Ioanna , Liapis George , Pappas Charalampos , Stamellou Eleni , Ntounousi Evangelia 
Published: May 2024

Abstract

Background and Aims
Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in non-diabetic adults, accounting for almost 30% of biopsy-diagnoses. The degree of proteinuria varies widely from sub-nephrotic (less than 3.5 g/day) to more than 20 g/day. Patients with primary MN who attain either spontaneous or treatment-induced remission, generally, have a good long-term prognosis. Those who reach partial remission fare better than those with stable or progressive disease, while duration of remission- whether spontaneous or due to treatment is linked to better renal outcomes. This study aims to study long-term outcomes in MN patients, identifying risk factors of relapse and treatment non-responsiveness.

Method
The retrospective cohort study included 40 patients, with available data, diagnosed with primary MN between 2013 and 2023. Data on urinary protein to creatinine ratio (UPCR), serum albumin, estimated glomerular filtration rate (e-GFR), anti-PLA2R-Antibodies (PLA2R-Ab), CD19+ subpopulations, and lipid profile were collected, alongside treatment types over five years. Baseline date was defined as the date of renal biopsy, primary renal diagnosis, or symptom onset. We defined complete remission, partial remission, and relapse based on UPCR: complete remission as a UPCR of less than 300 mg/g, partial remission as a UPCR of less than 3.5 g/g provided there is also a 50% or greater reduction from the baseline UPCR, and relapse as a UPCR greater than 3.5 g/g after a period in which complete or partial remission was achieved. We monitored patients for clinical signs of remission, relapse, and non-response to treatment. Logistic regression was used to identify risk factors for remission and relapse. Additionally, a survival analysis was conducted with the primary endpoint being time to a 40% reduction in e-GFR.

Results
The mean age at baseline was 55.5 ± 13.2 years, with 70% being men. Mean proteinuria was 11 ± 7.5 g/g, with 75% presenting with nephrotic syndrome, while 34% of them had positive anti-PLA2R Ab. Baseline e-GFR was 75 ± 30.5 ml/min/1.73 m2. 15% (6/40) of patients did not require immunosuppressive treatment and experienced spontaneous remission. 44% (18/40) of total patients received treatment with Rituximab, 35% (14/40) received treatment with modified ponticelli regimen, while the remaining 2 patients required more than 2 different treatments to achieve remission. Complete remission was achieved by 42% of the patients, 41% achieved only partial remission, while the rest 17% did not attain remission. Relapse occurred in 32% of the patients, requiring further immunosuppressive therapy. Positive anti-PLA2R Ab (exp (B) = 15.1 p-value = 0.031) and male gender (exp (B) = 2, =.3 p-value = 0.01) were associated with higher risk of non-response to treatment. Over a follow-up of 5 years, patients with partial remission had a 26-fold times increased risk of relapse (p-value = 0.023,) compared to those with complete remission. Higher baseline UPCR also correlated with an increased relapse risk; a 1g/g increase in UPCR raised relapse risk by 17% (p-value = 0.016, exp (B) = 1.174). Kaplan-Meier survival curves demonstrated that patients achieving any form of remission did not experience the endpoint of 40% reduction in e-GFR (log-rank p-value = 0.007).

Conclusion
These analyses indicate that achieving and maintaining remission in primary MN is key for preserving e-GFR and preventing kidney progression. Risk factors like male gender, initial heavy proteinuria, and positive PLA2R antibodies need special attention and careful management to optimize patient outcomes.