Clinical course and outcome after kidney transplantation in patients with C3 glomerulonephritis due to CFHR5 nephropathy

Abstract

Background Complement factor H-related protein 5 (CFHR5) nephropathy is an inherited renal disease characterized by microscopic and synpharyngitic macroscopic haematuria, C3 glomerulonephritis and renal failure. It is caused by an internal duplication of exons 2–3 within the CFHR5 gene resulting in dysregulation of the alternative complement pathway. The clinical characteristics and outcomes of transplanted patients with this rare familial nephropathy remain unknown. Methods This is a retrospective case series study of 17 kidney transplant patients with the established founder mutation, followed-up over a span of 30 years. Results The mean (±SD) age of patients at the time of the study and at transplantation was 58.6 ± 9.9 and 46.7 ± 8.8 years, respectively. The 10- and 15-year patient survival rates were 100 and 77.8%, respectively. Proteinuria was present in 33.3% and microscopic haematuria in 58.3% of patients with a functional graft. Serum complement levels were normal in all. ‘Confirmed’ and ‘likely’ recurrence of CFHR5 nephropathy were 16.6 and 52.9%, respectively; however, 76.5% of patients had a functional graft after a median of 120 months post-transplantation. Total recurrence was not associated with graft loss (P = 0.171), but was associated with the presence of microscopic haematuria (P = 0.001) and proteinuria (P = 0.018). Graft loss was associated with the presence of proteinuria (P = 0.025). Conclusions We describe for the first time the clinical characteristics and outcome of patients with CFHR5 nephropathy post-transplantation. Despite the recurrence of CFHR5 nephropathy, we provide evidence for a long-term favourable outcome and support the continued provision of kidney transplantation as a renal replacement option in patients with CFHR5 nephropathy.

C3 glomerulopathy: Understanding an ultra‐rare complement‐mediated renal disease

“…The presence of pathogenic variants increased the risk for recurrent disease in the transplant due to continued complement dysregulation in the recipient. In a study by Frangou et al, of 17 transplanted patients with CFHR5 nephropathy, a form of C3GN caused by an internal duplication of exons 2–3 within CFHR5 , five patients lost their grafts due to disease recurrence, and in the remaining patients, the recurrence rate was 50% (Frangou et al, 2019). Graft loss with confirmed recurrence of CFHR5 nephropathy was likely in 62% of patients.…”

Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review

“…A total of 207 potentially relevant articles were identified and screened. Twenty-three articles were assessed in detail, of which 12 studies (7 cohort studies and 5 case series) [32,48,50,[71][72][73][74][75][76][77][78][79] consisting of 122 KTx patients with C3G (73 C3GN ( Table 1) and 49 DDD (Table 2)) were included in our systematic review ( Figure 1).…”

Recurrent C3 Glomerulonephritis along with BK-Virus-Associated Nephropathy after Kidney Transplantation: A Case Report

“…C3GN is a highly recurrent type of glomerulonephritis following KT, with a recurrence rate of 67–83% [ 5 , 17 , 18 , 19 ]. The time to recurrence was median 28 months (range, 9 days to 11 years) in C3GN [ 5 ] and 164 months (range, 9 to 207 months) in C3GN with CFHR5 nephropathy [ 19 ]. However, there is no evidence to support serum complement monitoring for predicting the risk of recurrent C3GN following KT, and there are no known strategies for reducing the risk of C3GN recurrence [ 20 , 21 ].…”