Many patients with IgA nephropathy (IgAN) progress to end-stage kidney disease (ESKD) and require a kidney transplant, and these patients experience a range of outcomes that include IgAN recurrence and transplant rejection. This important topic was presented at the National Kidney Foundation (NKF) 2024 Spring Clinical Meetings (SCM24).

Following these proceedings, featured expert Jai Radhakrishnan, MD, MS, was interviewed by Conference Reporter Associate Editor-in-Chief Rick Davis. Dr Radhakrishnan’s clinical perspectives are presented here.

There are data on the disease course and kidney transplant outcomes of patients with IgAN, mostly from single-center observational trials and patient cohorts that were followed for varying lengths of time. The good news is that the overall survival of patients with IgAN who undergo kidney transplants is very similar to that of patients without IgAN. A large part of the success is attributed to the dramatic improvements in immunosuppressants and post-transplant care over the last 20 years.

Since IgAN is an immune-mediated disease, it stands to reason that the disease tends to be quiescent while patients are receiving immunosuppressants. Unfortunately, IgAN does recur, and you will find IgA deposits in a significant number of patients over time. Despite having IgA deposits, proteinuria and hematuria may not be observed in these patients, especially early on. One major risk factor for IgAN recurrence after kidney transplant is the patient’s age at transplant. If kidney failure occurs at a young age, the risk of recurrence is correspondingly higher. The amount of time from onset to ESKD is also an important factor. In her presentation at SCM24 on the recurrence of IgAN following kidney transplant from the session titled “Evaluation and Management of IgA Nephropathy,” Rowena Delos Santos, MD, discussed the treatment of patients who undergo transplant and considerations for recurrent IgAN.

Very little is known about how to treat recurrent IgAN in patients with kidney transplants. There are no randomized trials to assess the optimal therapy, but we consider optimal conservative management with good blood pressure control, blockers of the renin-angiotensin system, and, perhaps, SGLT2 inhibitors as forming the backbone of therapy. Further treatment strategies could include immunomodulation, immunosuppression, and, ultimately, the goal of graft preservation in all patients with recurrent IgAN. I think that newer therapies, including the B-cell–targeting therapies, complement inhibitors, and targeted-release anti-inflammatory agents, will have a role in this setting. There may not be any trials to assess these agents in patients with clinically significant IgA recurrence—so how things play out remains to be determined—but we are lucky to be in a situation where we will be having significantly more therapies to offer patients.

Over time, the risk of graft loss from IgAN recurrence increases. The rule of thumb is that the risk of graft loss is roughly equal to the number of years of follow-up. So, graft loss is approximately 5% at 5 years, 10% at 10 years, and 15% at 15 years. As discussed at SCM24, social deprivation and economic disadvantage are also associated with poor outcomes after kidney transplant and in other disease states (poster 509). There are several other factors that are associated with poor outcomes, including poor biological response, poor treatment adherence, and problems with getting medication, so it is very difficult to know with certainty what the reason is. But what is clear is that close follow-up and, perhaps, more intensive follow-up are very important for patients who are at risk of rejection.

Of note, socioeconomic factors do play a significant role in kidney graft outcomes. Patients may miss clinic appointments or may not take medications for reasons that might include a family emergency or work-related stress. I think that the key is to have a multidisciplinary approach with social workers, psychiatrists, nephrologists, and financial coordinators all working together to closely follow high-risk patients through the course of their transplant. That has worked well in some of the kidney transplant centers that do this routinely.