Abstract: SA-PO629
Trending Complement C3 in C3 Glomerulopathy Patients Before and After Renal Transplant
Session Information
- Glomerular Diseases: Immunology, Inflammation - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Hall, Monica D., University of Iowa, Iowa, Iowa, United States
- Ghiringhelli Borsa, Nicolò, University of Iowa, Iowa, Iowa, United States
- Taylor, Amanda O., University of Iowa, Iowa City, Iowa, United States
- Martin, Bertha, University of Iowa, Iowa City, Iowa, United States
- Goodfellow, Renee X., University of Iowa, Iowa, Iowa, United States
- Hauer, Jill Johanna, University of Iowa, Iowa, Iowa, United States
- Weaver, Amy E., University of Iowa, Iowa, Iowa, United States
- Zhang, Yuzhou, University of Iowa, Iowa, Iowa, United States
- Smith, Richard J., University of Iowa, Iowa, Iowa, United States
- Nester, Carla Marie, University of Iowa, Iowa, Iowa, United States
Background
C3 Glomerulopathy (C3G) is characterized by dysregulation of the alternative pathway of complement. Most patients will approach ESRD within 10 years of diagnosis. Recurrence in renal transplants is as high as 84%. Little is known about the natural history of transplant recurrence or predictors of poor renal outcome. The degree of C3 consumption (represented by a low C3) has been postulated as a predictor of disease activity in the setting of native kidney disease. Whether C3 abnormality plays a similar role in the transplant setting is unknown. Similarly, the predictive value of other complement biomarkers is unknown.
Methods
We studied a sub-cohort of the University of Iowa’s C3G Natural History Study. All patients met biopsy criteria for C3G. Reviewed patients had at least 3 pre-transplant and 3 post-transplant C3 values. Using our standard assays, we tested all patients in the cohort for complement gene abnormalities and for longitudinal nephritic factor trend. Phenotypic results were correlated with recurrence of C3G in a renal allograft.
Results
Average age at diagnosis was 24 years. Average time to ESRD was 2 years. Drivers of disease included nephritic factors (NF, n=5), gene mutations (n=2), and a monoclonal protein (n=1). Median follow-up time post-transplant was 5 years. At transplantation, 6 patients had a low C3 level. In the five patients with a NF at the time of transplant, the NF remained positive at follow-up. Disease recurrence was noted in 2 patients (both within the first year of transplant). One was positive for a nephritic factor, one has a C3 mutation. One patient had histologic recurrence. This patient was both nephritic factor negative and with normal genetics. All patients with recurrence had a low C3 at the time of recurrence. All nonrecurring patients have a normal C3.
Conclusion
Considering this preliminary data, having a low C3 appears to predict risk for C3G recurrence. It remains unclear what role a persistent nephritic factor titer may have. Our data suggest the impact of this titer may change over time. We have extended the collection of the clinical parameters and the complement biomarker evaluation for each subject in this cohort - with the express goal of creating a predictive model for C3G recurrence.
Funding
- NIDDK Support – Novartis