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Updated: Jun 17, 2025
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
C3 Glomerulopathy Recurs Early after Kidney Transplantation in Serial Biopsies Performed within the First 2 Years
Blanca Tarragón1, Yonatan Peleg1, Geetha Jagannathan2
1Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, New York.
Insights
C3 glomerulopathy (C3G) frequently recurs early after kidney transplantation, often with subtle histologic changes. Immunofluorescence and electron microscopy are key for diagnosing subclinical C3G recurrence in kidney allografts.
Area of Science:
- Nephrology
- Complement System Biology
- Transplantation Immunology
Background:
- C3 glomerulopathy (C3G), encompassing C3GN and DDD, arises from alternative complement pathway dysregulation.
- Limited data exist on C3G recurrence post-kidney transplant, particularly regarding histologic features.
- Understanding C3G recurrence is crucial for managing kidney transplant recipients.
Purpose of the Study:
- To evaluate C3G recurrence in kidney allografts.
- To characterize the histologic presentation and progression of recurrent C3G.
- To assess the role of transcriptomics in detecting recurrence.
Main Methods:
- Retrospective analysis of 18 C3G patients undergoing kidney transplantation (2016-2023).
- Evaluation of demographic, genetic, clinical, and histologic data.
- Transcriptomic analysis using NanoString 770 genes PanCancer Immune Profiling Panel.
Main Results:
- C3G recurrence occurred in 89% of patients within a median of 33 days post-transplant.
- 38% of recurrences were detected in protocol biopsies, often with minimal proteinuria (<300 mg/g).
- Recurrence showed subtle histologic alterations and overlapping immunofluorescence/electron microscopy findings between C3GN and DDD.
Conclusions:
- C3G recurrence is common and early after kidney transplantation, frequently presenting with minimal proteinuria and mild histologic changes.
- Immunofluorescence and electron microscopy are vital for detecting early, subclinical C3G recurrence.
- Allografts showed favorable short-term survival despite early recurrence.
Background:
C3 glomerulopathy (C3G), which encompasses C3GN and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation are limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression.
Methods:
We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and six DDD), who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The NanoString 770 genes PanCancer Immune Profiling Panel was used for transcriptomic analysis. Disease recurrence was the primary outcome.
Results:
During a median (interquartile range) follow-up period of 37 (18–56) months, C3G recurrence occurred in 16 (89%) patients (11 with C3GN and five with DDD) at a median (interquartile range) of 33 (13–141) days after transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all the allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence.
Conclusions:
Most of the patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played a crucial role in detecting early, subclinical recurrence of C3GN and DDD, which showed significant overlapping features.
