Recurrence of IgA Nephropathy after Kidney Transplantation in Adults

Abstract

Background and objectives: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small.

Design, setting, participants, & measurements: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America.

Results: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence.

Conclusions: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

Keywords: IgA deposition; IgA nephropathy; glomerular disease; graft survival; kidney transplantation; recurrence.

Graphical abstract

Figure 1.

Recurrent IgA postkidney transplantation. Cumulative incidence curve of IgA recurrence in kidney transplant recipients with biopsy-proven IgA nephropathy. Cumulative incidence of recurrence of IgA deposits was 19% at 10 years and 23% at 15 years. Among patients with IgA nephropathy recurrence, median time to recurrence was 3.4 years. Shaded area around the curve represents the 95% confidence interval.

Figure 2.

Graft survival in patients with recurrent IgA nephropathy post-transplantation. Kaplan–Meier graft survival curve of patients with IgA nephropathy recurrence after diagnosis. Area around the curve represents 95% confidence intervals.

Figure 3.

Clinical signs at time of IgA nephropathy recurrence and graft survival. Death-censored Kaplan–Meier analysis to graft survival in patients with IgA nephropathy recurrence, stratified by the presence of proteinuria and/or rise in creatinine.