Geovanni Faddoul, MD: IgAN Recurrence After Kidney Transplantation

Geovanni Faddoul, MD

Credit: Albany Med Health System

Findings from a recent study are highlighting the impact of induction and maintenance immunosuppression on immunoglobulin A nephropathy (IgAN) recurrence, graft survival, and mortality in living and deceased donor kidney transplants.

Results suggest steroid maintenance may increase the rate of recipient mortality, although investigators were careful to note a stratified risk approach is still necessary to determine which patients can benefit from a more aggressive induction and maintenance regimen due to lingering uncertainties regarding the pathology of IgAN.

Geovani Faddoul, MD, assistant professor of medicine at Albany Medical College, and a team of investigators sought to assess the impact of induction and maintenance therapy on IgAN recurrence, graft survival, and mortality following kidney transplantation. To do so, they retrospectively examined data from the UNOS database for adults with end-stage kidney disease secondary to IgAN who received a kidney transplant between January 2000 and June 30, 2022.

A total of 11,341 patients with thymoglobulin, alemtuzumab, or basiliximab/daclizumab induction with calcineurin inhibitor and mycophenolate mofetil with or without prednisone maintenance were included in the analysis. Investigators compared the presence of IgAN recurrence, graft failure, and patient mortality between induction and immunosuppressive maintenance therapy groups.

Among the cohort, 10,731 (95%) transplant recipients did not experience recurrence and the remaining 610 (5%) recipients did. Time to recurrence ranged from 70 to 4379 days, with a mean duration of 794 (Standard deviation [SD], 561.4) days.

Investigators pointed out compared to the nonrecurrence group, patients who experienced recurrence were generally younger at the time of transplant (40.53 vs 45.43 years; P <.001), male (71.97% vs 64.19%; P <.001), White (68.69% vs 59.26%; P <.001), and spent fewer days on the waitlist (258 vs 371 days; P <.001).

Further analysis revealed compared to thymoglobulin with steroid maintenance, patients receiving alemtuzumab with steroid maintenance had greater odds of IgAN recurrence in deceased donor transplants (Odds ratio [OR], 1.90; 95% Confidence interval [CI], 1.169–3.101; P <.010). Alemtuzumab with and without steroid maintenance increased the odds of recurrence by 52% (P = .036) and 56% (P = .005), respectively, in living donor transplants.

Thymoglobulin without steroids was associated with less risk of IgAN recurrence (Hazard ratio [HR], 0.665; 95% CI, 0.447–0.989; P = .044), graft failure (HR, 0.758; 95% CI, 0.633– .907; P = .002), and death (HR, 0.619; 95% CI, 0.490–0.783; P <.001) in deceased donor transplants. Investigators also pointed out recurrence was strongly associated with risks of graft failure in deceased donor transplants and living donor transplants as well as death in living donor transplants.

The editorial team of HCPLive Nephrology reached out to Faddoul for further insight into the pathology of IgAN, the burden of recurrence post-kidney transplant, and the main takeaways from the study as well as their clinical significance.

HCPLive Nephrology: Can you describe the progression from IgAN to kidney failure and why kidney transplantation is the most effective treatment option for these patients?

Faddoul: IgA nephropathy is the most common glomerulonephritis and has a variable progression to kidney failure necessitating dialysis. Various study populations see patients progress toward end-stage kidney disease in 20 to 50% of the cases. The disease can be intermittent and benign in certain cases, or aggressive and leading to kidney failure rapidly in other cases. There are also patients on all the spectrum of how aggressive this disease can be. With a relatively low rate of recurrence and transplantation being the best treatment of kidney failure in both quality of life and absolute years of life added to a patient's lifespan, kidney transplantation is de facto the better solution for patients with ESKD due to IgA nephropathy.

HCPLive Nephrology: What do we know about the burden of IgAN recurrence post-transplantation? Why is it important that we have a comprehensive understanding of the factors influencing recurrence and other outcomes in these patients?

Faddoul: Our study shows that IgA recurrence significantly increases the risk of graft loss over a 5-year follow-up period. Transplantation being an extensive procedure, and since every organ donated is precious, we should persevere to prevent the failure of these organs with any opportunity we can. Understanding the risk factors helps us intervene early on when we can modify these factors. When the factors cannot be modified, our patients can be given at least enough information to make an informed decision and manage expectations on the long run.

HCPLive Nephrology: Can you break down some of the main/most important findings from the study?

Faddoul: This study shows data from the US collected over two decades. The recurrence rate is close to 5%, and we know with certainty that IgA nephropathy recurrence affects negatively the life of a kidney transplant. It also shows us that in general, thymoglobulin without prednisone is probably the best option when it comes to outcomes of the kidney graft. Alemtuzumab, a different induction immunosuppressive medication than thymoglobulin, was not better in outcomes of graft failure.

HCPLive Nephrology: What is the clinical significance of these findings?

Faddoul: There are currently multiple medications being approved, or in the pipeline to be approved, for the treatment of IgA nephropathy. While there are new techniques to prevent rejection that do not rely on thymoglobulin or on induction as we know it, induction remains the gold standard for kidney transplants. Knowing the best choice for induction in IgA nephropathy is the first step in tailoring the most successful therapy plan. New therapies in IgA nephropathy will be incorporated in the most successful therapy plan. The study also gives validation to programs that use thymoglobulin and rapid steroid withdrawal protocols. It remains however the responsibility of the transplant team to determine if some patients need specifically tailored treatments to their patients that are not necessarily part of the mainstream findings in the literature. This study remains a retrospective study and causality cannot be ascertained.

Reference

Aydin-Ghormoz EA, Perlmutter J, Koizumi N, et al. Outcomes of kidney transplantation in patients with IgA nephropathy based on induction: A UNOS data analysis. Clin Transplant. doi:10.1111/ctr.15225