Immunosuppression in IgA Nephropathy: Guideline Medicine Versus Personalized Medicine

Abstract

The role of immunosuppression in IgAN remains controversial despite a growing evidence base of randomized controlled trials (RCTs). In IgAN with nephrotic syndrome the role for corticosteroids is limited to cases with minimal change on light microscopy. In crescentic IgAN, the use of immunosuppression is supported only by anecdotal data, and outcome may be poor especially when glomerular filtration rate is impaired severely at presentation or there are pathologic features of chronic injury. In slowly progressive IgAN, prediction of outcome now is based both on clinical and pathologic features. Most RCTs have studied patients with urine protein levels greater than 1 g/24 h and only a minority have enrolled patients with a glomerular filtration rate less than 60 mL/min. The Supportive versus immunosuppressive Therapy of Progressive IgA nephropathy (STOP) IgAN study emphasized the efficacy of supportive therapy (including blood pressure control and renin-angiotensin system blockade) in decreasing proteinuria to less than the usually accepted threshold for the use of corticosteroids. Earlier RCTs of corticosteroids usually did not deploy supportive therapy optimally. The recent Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study closed prematurely because of excess toxicity, but the high dose of corticosteroids seemed to provide benefit. Guidelines provide valuable information about the quality and limitations of available evidence that needs to be personalized in application to the individual patient's medical and nonmedical circumstances to ensure wise clinical decision making.

Keywords: Corticosteroids; IgA nephropathy; RAS blockade; immunosuppression; nephrotic syndrome; proteinuria.