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Tonsillectomy for the Management of Immunoglobulin A Nephropathy.

Considering the global burden of disease associated with IgA nephropathy, it is striking how little data are available about effective therapies for patients. Originally, IgA was seen as a benign entity and the mesangial deposits of IgA that characterize the disease were considered an immunological curiosity. But extended clinical observation confirmed that nearly 30% of affected patients will progress to end-stage kidney disease over 20 to 25 years of follow-up. Immunoglobulin A nephropathy initially requires a genetic predisposition toward the synthesis of IgA 1 molecules with deficient galactosylation of the hinge region of the antibody. This triggers production of autoantibodies, formation of immune complexes, deposition in the glomerular mesangium, and initiation of inflammation.1 Based on this understanding of disease pathogenesis, immunosuppressive medications have been a staple in the treatment of patients with IgA nephropathy. However, despite numerous attempts to address the question, the efficacy of corticosteroids and other immunosuppressive drugs remains unproven.1 Tonsillectomy has lurked in the background as a potential treatment to reduce mucosal production of the aberrant IgA 1. There have been trials and a meta-analysis that support the value of this operation.2 However, there were flaws in all these studies and the role of tonsillectomy in the management of IgA nephropathy remains an unsettled question. Hirano et al3 report a retrospective analysis of outcomes in Japanese adults with IgA nephropathy who underwent a tonsillectomy within a year of the renal diagnosis and compared the course of disease to patients who did not undergo surgery. They took advantage of a national retrospective cohort study of IgA nephropathy and the remarkably high rate of tonsillectomy in Japan. The primary outcome was a combination of either a 1.5-fold increase in serum creatinine level or the initiation of renal replacement therapy. There were 1065 patients in the registry with IgA nephropathy with a diagnostic biopsy performed between 2002 and 2004, of whom 252 underwent tonsillectomy. The median follow-up period was 5.8 years. Several matching protocols were used to achieve balanced clinical features among those who did and did not undergo tonsillectomy. The main finding was that the hazard ratio for the primary outcome, progression of kidney disease, was 0.37 in the tonsillectomy group. In addition, there was a significantly reduced likelihood of prescribing a new renin-angiotensin aldosterone system inhibitor (RASi) or corticosteroid therapy to patients who underwent the procedure. The benefit of tonsillectomy was confirmed in the complete cohort and was independent of baseline characteristics, including estimated glomerular filtration rate (eGFR), proteinuria, degree of hematuria, or prior use of RASi therapy. A key strength of the study was the detailed accounting for administration of corticosteroid use and confirmation of the benefit associated with the procedure regardless of whether patients were treated with oral or intravenous corticosteroids during the follow-up period. This well-conceived study makes optimal use of a comprehensive registry to assess the benefits associated with a therapeutic intervention. It is not a randomized clinical trial, but the results are clear cut and clinically meaningful. There are some concerns that readers should keep in mind. The primary end point is composed of 2 vastly different events, namely, a modest change in eGFR and initiation of renal replacement therapy. To be sure, in a subgroup analysis, the benefits of tonsillectomy were confirmed in a smaller group of patients (n = 56) who progressed to end-stage kidney disease. The authors do not describe the analytic method(s) used to measure serum creatinine and the procedures that they used to verify the accuracy of the 1.5-fold increment in serum creatinine + Related article