Recurrent, Nonrecurrent, and De Novo Membranous Nephropathy After Kidney Transplantation: A Systematic Review and Meta-Analysis

TL;DR

This study reviews and analyzes the recurrence and new onset of membranous nephropathy after kidney transplants, finding that protocol biopsies help detect recurrence and rituximab improves remission rates.

Contribution

The first comprehensive meta-analysis of post-transplant membranous nephropathy, linking protocol biopsies and rituximab to better outcomes.

Findings

Recurrence prevalence is higher with protocol biopsies (39%) than without (25%).

Rituximab increases remission odds by nearly fivefold in recurrent membranous nephropathy.

De novo MN is associated with higher rejection rates compared to recurrent MN.

Abstract

Recurrent and de novo membranous nephropathy (MN) are significant complications after kidney transplantation, yet prevalence, risk determinants, and treatment outcomes have not been comprehensively quantified.

Systematic review and meta-analysis.

Kidney transplant recipients with native-kidney MN (recurrent or nonrecurrent) and recipients with de novo MN.

PubMed, Scopus, and the Cochrane Library were searched through June 30, 2025; studies comparing risk factors and outcomes among these groups were eligible for meta-analyses.

Study characteristics, demographics, transplant features, outcomes including remission and allograft loss.

Random-effects meta-analyses calculated weighted mean differences or pooled ORs for comparisons between recurrent versus nonrecurrent or de novo MN, allograft outcomes, and response to rituximab.

The included studies comprised a total of 2,259 kidney transplant recipients with recurrent (28%), nonrecurrent (61%), or de novo MN (11%). Recurrence prevalence was 39% (95% CI, 28%-50%) in studies with protocol biopsies versus 25% (95% CI, 20%-29%) without protocol biopsies (P = 0.046). Compared with nonrecurrence, recurrent MN was linked to older recipient age, shorter dialysis vintage and interval from native MN to dialysis, living-donor grafts, and higher pretransplant antiphospholipase A2 receptor antibody titer. Mycophenolic acid and prednisolone use was protective against recurrent MN. De novo MN carried a higher associated rejection than recurrent MN (OR, 2.30; 95% CI, 1.16-4.58). Rituximab increased remission odds (OR, 4.90; 95% CI, 1.70-14.13). Meta-regression demonstrated a significant decline in allograft loss rates over time following MN recurrence.

Substantial heterogeneity and small-study effects in some variables; magnitudes should be interpreted cautiously.

MN recurs in approximately one-third of recipients. Protocol biopsy should be utilized in recipients with history of native MN. Rituximab emerges as the preferred first-line treatment for recurrent MN.

Recurrent glomerular disease after kidney transplantation is a challenging posttransplant complication, and recurrent membranous nephropathy (MN) is among the most common entities. Prior evidence has established pretransplant antiphospholipase A2 receptor antibodies as a risk factor for recurrence; however, other risk factors and treatment outcomes have not been comprehensively assessed. This study is the first to include all available evidence on posttransplant MN and shows that protocol biopsy increases detection of recurrent MN and is associated with a lower risk of allograft loss. In addition to identifying several risk factors for recurrence, the analysis demonstrates that rituximab therapy yields a significantly higher remission rate than non-rituximab treatment in recurrent MN.

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