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Recurrence of Glomerular Diseases (GN) After Kidney Transplantation: A Narrative Review
Abbal Koirala1, Aditi Singh1, Duvuru Geetha1
1Division of Nephrology, Johns Hopkins School of Medicine, 5501 Hopkins Bayview Circle, Floor 1, Baltimore, MD 21224, USA.
Insights
Kidney transplant recipients face a risk of original glomerular disease recurrence, particularly C3 glomerulopathy and FSGS. Early diagnosis and targeted therapies like rituximab and complement inhibitors improve outcomes, moving beyond standard immunosuppression.
Area of Science:
- Nephrology
- Transplantation Immunology
- Glomerular Diseases
Background:
- Recurrence of original glomerular disease (GN) significantly threatens kidney transplant success.
- Certain GNs, like C3 glomerulopathy and FSGS, have high recurrence rates post-transplant.
- Standard immunosuppression shows limited efficacy in preventing GN recurrence.
Purpose of the Study:
- To review the incidence, predictors, diagnostic strategies, and therapeutic options for recurrent GN post-kidney transplant.
- To provide practical monitoring algorithms for post-transplant GN management.
- To synthesize current evidence on managing various glomerular disease subtypes after transplantation.
Main Methods:
- Narrative literature review of MEDLINE, Embase, and Cochrane databases (1996-2025).
- Prioritization of systematic reviews, cohort studies, registries, and interventional reports.
- Inclusion of adult transplant recipients with recurrent glomerular disease outcomes.
Main Results:
- Recurrence risk depends on initial GN characteristics, genetics, recipient/donor factors, and proteinuria.
- Diagnosis requires clinical evaluation, labs (proteinuria, hematuria, biomarkers), and allograft biopsy (light, immunofluorescence, electron microscopy).
- Evolving treatments include targeted therapies (rituximab, complement inhibitors) instead of broad immunosuppression.
Conclusions:
- Effective management of recurrent GN necessitates a comprehensive diagnostic approach and tailored therapeutic strategies.
- Targeted therapies show promise in improving outcomes for specific recurrent glomerular diseases.
- Future research should focus on predictive biomarkers, standardized criteria, and robust clinical trials.
Abstract:
Recurrence of the original glomerular disease (GN) poses a significant threat to kidney transplant function and longevity. The probability and severity of this recurrence vary, with C3 glomerulopathy and certain forms of FSGS exhibiting particularly high rates. Kidney transplant GN recurrence risk hinges on the characteristics of the initial GN, recipient/donor genetics, recipient age, donor type, end-stage kidney disease (ESRD) progression rate, and proteinuria levels. Standard immunosuppression has limited efficacy in preventing primary disease recurrence; however, agent selection and induction therapy can influence the risk for specific GNs. Diagnosing recurrent GN involves a comprehensive approach, including clinical evaluation, laboratory tests (such as proteinuria, hematuria, and specific biomarkers like anti-PLA2R for membranous nephropathy or complement for C3G), and, critically, an allograft biopsy analyzed with light, immunofluorescence, and electron microscopy. Treatment strategies are evolving towards targeted therapies, such as rituximab for antibody-mediated GN and complement inhibitors for C3G, moving away from broad immunosuppression. This narrative literature review provides practical monitoring algorithms for post-transplant settings, synthesizing information on the incidence, predictors, diagnostic strategies, and therapeutic options for various glomerular disease subtypes. The methodology involved searching MEDLINE, Embase, and Cochrane databases from 1996 to 2025, prioritizing systematic reviews, cohort studies, registries, and interventional reports. Eligibility criteria included adult transplant recipients and English-language reports on recurrent glomerular disease outcomes, excluding most single-patient case reports. Limitations include potential selection bias, omission of relevant studies, and the absence of a formal risk-of-bias assessment or meta-analysis. The evidence base is heterogeneous, with inconsistent outcome reporting and scarce randomized controlled trials. Future efforts should focus on developing predictive biomarkers, standardizing diagnostic and response criteria, conducting multicenter prospective cohorts and pragmatic trials, and creating shared registries with harmonized data.
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