Research Viewpoints Recurrent IgA Nephropathy – Prediction and Prognosis

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Kavanagh C.R., Zanoni F., Leal R., Jain N.G., Stack M.N., Vasilescu E.-R., Serban G., Shaut C., Kamal J., Kudose S., Martinho A., Alves R., Santoriello D., Canetta P.A., Cohen D., Radhakrishnan J., Appel G.B., Stokes M.B., Markowitz G.S., D’Agati V.D., Kiryluk K., Andeen N.K., Batal I.: Clinical Predictors and Prognosis of Recurrent IgA Nephropathy in the Kidney Allograft. Glomerular Disease DOI 10.1159/000519834

It is well known that IgA nephropathy (IgAN) in a recipient of a kidney allograft (or isograft) has high propensity to redevelop in the kidney graft. This recurrence is believed to disadvantage the kidney graft in terms of long-term functional survival in the recipient.

Kavanagh and coworkers sought to determine predictive and prognostic factors for such recurrent IgAN. They examined cohorts (two from the USA and one from Europe) consisting of 282 patients with IgAN receiving kidney allografts. After a follow-up of 92 months (median), 80 patients (28%) had developed a recurrence of IgAN and 202 were free of recurrence after a follow-up of 74 months (median). Recurrence of IgAN was detected on clinical grounds and a transplant biopsy (n = 73) or according to protocol (non-clinical) transplant biopsy findings (n = 7).

Ninety percent were first kidney transplants, and 47% were deceased donor transplants. Fifty percent of patients received induction therapy, and 41% received steroid-free regimens of immunosuppression. Recurrences were discovered at a median of 43 months post-transplantation (range 13–121 months).

Recurrences developed more frequently in younger recipients, better HLA matching, lower use of induction therapy, and possibly in association with the frequency of HLA-DQ05 in recipients. Higher HLA matching frequency only had an impact on recurrence in living related donor kidneys. Steroid-free immunosuppressive therapy had no impact on recurrence rates. HLA matching was not independently associated with protection from recurrent IgAN, and individual HLA antigen in donor or recipient did not affect overall IgAN recurrence rates.

Recurrent IgAN was associated with poorer long-term graft survival. Treatment of recurrent IgAN was highly variable and not determined by a pre-defined protocol. High-dose steroids were used in 45% of those with a recurrence. Allograft failure was associated with a long post-transplant interval (no surprise), a higher serum creatinine level, greater magnitude of proteinuria, concomitant acute rejection episodes, and higher Oxford-MEST scores.

While this observational study is largely confirmatory, the studies on the impact of HLA matching and steroid-free immunosuppression are valuable additions to our understanding of how to best predict recurrence risk. Treatment of IgAN recurrence remains highly uncertain, and the design of this study precludes making any statement on efficacy of any particular regimen.