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Recurrent, Nonrecurrent, and De Novo Membranous Nephropathy After Kidney Transplantation: A Systematic Review and
Thanyarat Phumthian1,2, Veerapat Wattanasatja1,3, Aschariya Wipattanakitcharoen1
1Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand.
Rationale & Objective:
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.
Study Design:
Systematic review and meta-analysis.
Setting & Participants:
Kidney transplant recipients with native-kidney MN (recurrent or nonrecurrent) and recipients with de novo MN.
Selection Criteria For Studies:
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.
Data Extraction:
Study characteristics, demographics, transplant features, outcomes including remission and allograft loss.
Analytic Approach:
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.
Results:
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.
Limitations:
Substantial heterogeneity and small-study effects in some variables; magnitudes should be interpreted cautiously.
Conclusions:
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.
Insights
Membranous nephropathy (MN) recurs in about one-third of kidney transplant recipients. Rituximab is the preferred treatment for recurrent MN, improving remission rates and reducing allograft loss over time.
Area of Science:
- Nephrology
- Transplantation Immunology
- Clinical Epidemiology
Background:
- Membranous nephropathy (MN) is a significant complication following kidney transplantation, with both recurrent and de novo forms impacting graft survival.
- Quantifying the prevalence, risk factors, and treatment outcomes of MN post-transplantation is crucial for improving patient care.
Purpose of the Study:
- To systematically review and meta-analyze the prevalence, risk determinants, and treatment outcomes of recurrent and de novo membranous nephropathy in kidney transplant recipients.
- To compare outcomes between recurrent and de novo MN and evaluate the efficacy of rituximab.
Main Methods:
- A systematic review and meta-analysis of studies identified through PubMed, Scopus, and Cochrane Library up to June 30, 2025.
- Included studies compared risk factors and outcomes in kidney transplant recipients with recurrent, nonrecurrent, or de novo MN.
- Random-effects meta-analyses were used to pool data on outcomes and treatment response, including remission and allograft loss.
Main Results:
- The analysis included 2,259 kidney transplant recipients: 28% recurrent MN, 61% nonrecurrent MN, and 11% de novo MN.
- Recurrence prevalence was higher with protocol biopsies (39%) compared to those without (25%).
- Recurrent MN was associated with older recipient age, shorter dialysis vintage, living-donor grafts, and higher pre-transplant anti-PLA2R antibody titers. De novo MN showed higher rejection rates than recurrent MN. Rituximab significantly increased remission odds.
Conclusions:
- Membranous nephropathy recurs in approximately one-third of kidney transplant recipients.
- Protocol biopsies are recommended for recipients with a history of native MN.
- Rituximab is the preferred first-line treatment for recurrent MN, demonstrating improved remission rates and a decline in allograft loss over time.
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