The risk of recurrent IgA nephropathy in a steroid‐free protocol and other modifying immunosuppression

Abstract

Recurrent glomerulonephritis is an important cause of kidney allograft failure. The effect of immunosuppression on recurrent IgA nephropathy (IgAN) is unclear. We analyzed the impact of steroids and other immunosuppression on the risk of recurrent IgAN post-kidney transplantation. Between June 1989 and November 2008, 3311 kidney transplants were performed at our center. IgAN was the primary disease in 124 patients; of these, 75 (60.5%) patients received steroid-based immunosuppression (15 undergoing late steroid withdrawal), and 49 (39.5%) were maintained on steroid-free immunosuppression. Recurrent IgAN was diagnosed in 27 of 124 (22%) patients in clinically indicated kidney allograft biopsies over a median follow-up of 6.86 ± 5.4 yr. On cox proportional hazards model multivariate analysis, the hazard risk (HR) of IgAN recurrence was significantly higher in patients managed with steroid-free (HR 8.59: 3.03, 24.38, p < 0.001) and sirolimus-based (HR = 3.00:1.16, 7.75, p = 0.024) immunosuppression without antilymphocyte globulin induction (HR = 4.5: 1.77, 11.73, p = 0.002). Mycophenolate use was associated with a lower risk (HR = 0.42: 0.19, 0.95, p = 0.036), whereas cyclosporine did not have a significant impact on the risk of IgAN recurrence (p = 0.61). These results warrant future prospective studies regarding the role of steroids and other immunosuppression drugs in reducing recurrence of IgAN and other glomerulonephritis post-transplant.

Recurrence of IgA nephropathy after kidney transplantation in steroid continuation versus early steroid-withdrawal regimens: a retrospective analysis of the UNOS/OPTN database

“…The use of ESW increased from 5% in 1998 to 34% in 2006 . However, existing literature suggests that recurrent IgAN may be more common with these regimens .…”

“…Similarly, Visger et al . observed a significantly higher risk of histologic IgAN recurrence with ESW regimens when compared to steroid continuation regimens (HR 8.59, 95% CI 3.03–24.38; P < 0.001).…”

“… and Visger et al . observed a lower risk of recurrent IgAN with steroid maintenance. Both studies were from single centers; therefore, small sample sizes were their major limitations.…”

Defining a Steroid Withdrawal Protocol in a newly established Kidney Transplantation Unit

“…Patient and graft survival was not affected in patients inducted on rATG and maintained on TAC and MMF [44,52]. In a study comprising 124 kidney transplant recipients, of whom 91% were on rATG induction Visger et al, also had the same results as shown by Kuklan [44,53]. Generally in patients where the initial cause of kidney disease is IgA nephropathy, steroid avoidance is not recommended.…”

Corticosteroids in the treatment of IgA nephropathy: any light beyond the clouds of confusion?

“…The immunosuppressive and anti-inflammatory actions of corticosteroids appear pertinent to the pathogenic mechanisms in IgAN. Based on data from 27 subjects with biopsy-proven IgAN affecting the transplanted kidney, steroid-free immunosuppression after kidney transplantation was associated with an eightfold increase in the risk of recurrent IgAN 6. Corticosteroids, alone or combined with cytotoxic agents, have been reported to confer renal benefit, although the evidence was not sufficiently robust due to issues related to sample size and/or follow-up duration 7.…”