Kidney transplantation outcomes in patients with IgA nephropathy and other glomerular and non-glomerular primary diseases in the new era of immunosuppression.

Frank Jmf Dor,Smaragdi Marinaki,Konstantinos Panagiotellis,Ioannis Bokos,Ioannis Boletis,Ioannis Gavalas,Ilias Makropoulos,George Liapis,George Vlachopanos,Sophia Lionaki,Ioannis Michelakis

doi:10.1371/journal.pone.0253337

Abstract

ObjectivesKidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes.MethodsNinety-nine KTx recipients with end-stage kidney disease (ESKD) due to IgAN, were retrospectively compared to; i/ a matched case-control group of patients with non-glomerular causes of ESKD, and ii/ four control groups with ESKD due to glomerular diseases; 44 patients with primary focal segmental glomerulosclerosis (FSGS), 19 with idiopathic membranous nephropathy (IMN), 22 with lupus nephritis (LN) and 21 with pauci-immune glomerulonephritis (PIGN).ResultsAt end of the observation period, graft function and survival, were similar between KTx recipients with IgAN and all other groups, but the rate of disease recurrence in the graft differed significantly across groups. The rate of IgAN recurrence in the graft was 23.2%, compared to 59.1% (p<0.0001) in the FSGS group, 42.1% (p = 0.17) in the IMN group, and 0% in the LN and PIGN groups (p = 0.01). IgAN recipients, who were maintained with a regimen containing tacrolimus, experienced recurrence less frequently, compared to those maintained with cyclosporine (p = 0.01). Graft loss attributed to recurrence was significantly higher in patients with FSGS versus all others.ConclusionRecipients with IgAN as primary disease, experienced outcomes comparable to those of recipients with other causes of ESKD. The rate of IgAN recurrence in the graft was significantly lower than the rate of FSGS recurrence, but higher than the one recorded in recipients with LN or PIGN. Tacrolimus, as part of the KTx maintenance therapy, was associated with lower rates of IgAN recurrence in the graft, compared to the rate cyclosporine.

Highlights

IgA nephropathy (IgAN) is the most common type of primary glomerular disease worldwide [1], with 30% of cases reaching end-stage kidney disease (ESKD) two decades after the initial diagnosis
IgAN recipients, who were maintained with a regimen containing tacrolimus, experienced recurrence less frequently, compared to those maintained with cyclosporine (p = 0.01)
The rate of IgAN recurrence in the graft was significantly lower than the rate of focal segmental glomerulosclerosis (FSGS) recurrence, but higher than the one recorded in recipients with lupus nephritis (LN) or pauci-immune glomerulonephritis (PIGN)

Summary

Introduction

IgA nephropathy (IgAN) is the most common type of primary glomerular disease worldwide [1], with 30% of cases reaching end-stage kidney disease (ESKD) two decades after the initial diagnosis. Kidney transplantation (KTx) is the treatment of choice for these patients [2,3,4], but IgAN recurrence in the graft remains a threat to graft survival [5]. The optimal maintenance immunosuppressive therapy for KTx is still not established, but important advances in the field have been developed during the past two decades, including the introduction of agents such as mycophenolate mofetil, tacrolimus, and mammalian target of rapamycin inhibitors for maintenance therapy, and monoclonal antibodies that bind to the α-chain of the interleukin-2 receptor for induction therapy. Previous studies in recipients with a history of IgAN have revealed contrasting results regarding graft survival, depending on the methodology and the length of observation, while the probability of disease recurrence in the graft was significantly higher in the years before 2000 [7]

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