#1913 Fifteen-year follow-up of outcomes of patients treated for membranous nephropathy

Abstract Background and Aims Membranous nephropathy (MN) is a glomerular disease that can occur at all ages but is more frequently encountered in adults than children. In White adults, it is the leading cause of nephrotic syndrome. In ∼80% of patients, there is no underlying cause of MN (primary MN), and the remaining cases are associated with medications or other diseases such as systemic lupus erythematosus, hepatitis virus infection, or malignancies. MN is characterized by the deposition of immune complexes leading to diffuse thickening of glomerular basement membranes. Disease outcomes are difficult to predict; around one-third of patients will undergo spontaneous remission. In those at high risk of progression, immunosuppressive therapy with cyclophosphamide plus corticosteroids has substantially reduced the need for kidney replacement therapy. Nevertheless, up to 30% of patients fail to respond to standard therapy. This study aims to study long-term outcomes in MN patients, identifying risk factors for developing chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Method The retrospective cohort study included 94 patients with kidney biopsy diagnosed MN between 2008 and 2023. Demographic, clinical, and laboratory data were obtained from medical histories and data on applied therapeutic protocols. All patients with proteinuria (PRT) were treated with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), and patients with nephrotic range proteinuria were treated with a modified Ponticelli regimen. We monitored patients for clinical signs of remission and developing CKD and ESKD. Logistic regression was used to identify risk factors for developing CKD and ESKD. Definition: remission: reduction of PRT to <0.5 g/day and with creatinine clearance (Ccr) of >60 ml/min/1.73 m2. CKD: (Ccr) of <60 ml/min/1.73 m2 and/or PRT ≥0.5 g/day. ESKD <15 ml/min/1.73 m2. A p-value of <0.05 was considered significant. Results The study included 94 patients. At the time of diagnosis, the mean age was 45.83 ± 16.40 years, with 54.3% being men. The mean PRT, serum creatinine (sCr), serum uric acid (sUA), and (Ccr) was 9.05 ± 6.23 g/day, 114.71 ± 89.38 μmol/L, 378.34 ± 107.05 μmol/L and 95.91 ± 44.36 ml/min/1.73 m2, respectively. On histology, 27.7% of patients had immunoglobulin (Ig) G deposits, 10.6% IgM deposits, 2.1% IgA deposits, 38.3% mix deposits, and 21.3% were with no deposits. The median follow-up was 24 months. Statistical significance of lower baseline sCr and higher Ccr was observed in the remission group than in the CKD and ESKD group of patients (P < 0.001). Significantly higher baseline sUA was observed in the CKD (P = 0.009) and ESKD (P = 0.034) groups than in the remission group of patients. A statistically significant difference was observed in outcomes according to the histology stage of MN; 22% of patients with stage I and stage II developed ESKD and 55.6% of patients with stage III (P = 0.046). Significant predictors for outcome were Ccr (χ2 = 12.74, P = 0.002) and sUA (χ2 = 12.20, P = 0.002). Furthermore, the type of Ig deposits also contributed significantly (χ2 = 23.96, P = 0.002) to differentiating outcome categories, although its individual parameter estimates were not statistically significant. Examination of parameter estimates showed that Ccr was negatively associated with being in the CKD group relative to the remission group (Exp (B) = −0.038, P = 0.003). In contrast, sUA was positively associated with both CKD (Exp (B) = 0.012, P = 0.010) and ESKD (Exp (B) = 0.025, P = 0.019), suggesting that higher sUA levels increased the odds of more severe outcomes. Other variables did not reach statistical significance. Conclusion These analyses indicate that lower Ccr and higher sUA levels at the time of diagnosis are risk factors for developing CKD and ESKD in MN.