Optimal Conservative Therapy Use among Adult Cure Glomerulonephropathy Participants with IgA Nephropathy

Introduction IgA nephropathy is the most common primary glomerulonephritis, affecting approximately 2.5 per 100,000 persons worldwide, and is a leading cause of CKD. Up to 40% of patients with IgA nephropathy progress to kidney failure within 20 years of diagnostic biopsy.¹ Furthermore, a diagnosis of IgA nephropathy reduces the expected life span by about a decade. Importantly, this increased mortality risk seems to be mediated by the occurrence of kidney failure, suggesting that measures to slow disease progression may mitigate this mortality risk.² Adverse patient outcomes, including initiation of dialysis or death, have been correlated with the presence of clinical risk factors at the time of biopsy diagnosis, including proteinuria .1 g/d, sustained hypertension, and severity of pathologic findings on the basis of the revised Oxford classification—a structured and reproducible scoring system for evaluating the light microscopy features of IgA nephropathy.³ Clinical outcomes significantly improve if proteinuria #1 g/d is maintained with therapeutic interventions⁴; thus, reduction of proteinuria has been accepted as a surrogate end point to assess the efficacy of treatment in delaying disease progression.^4,5 The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, published in 2012 and updated in 2021, emphasized robust supportive measures in patients with proteinuric IgA nephropathy at high risk of disease progression. Recommended interventions include optimal BP control; preferential use of maximal tolerated or allowed doses of a renin-angiotensin-aldosterone system inhibitor (RAASI); addressing cardiovascular risk, including hyperlipidemia; and adopting a healthy lifestyle. For patients with persistent proteinuria .1 g/d, the 2021 guidelines recommend consideration of clinical trials.⁶ In line with these recommendations, all ongoing clinical trials require these conservative measures to be in place before assessing patient eligibility. We sought to ascertain the prevalence of the recommended robust conservative therapy at enrollment and longitudinally across 6 years after the initial kidney biopsy among well-characterized adults with IgA nephropathy in the National Institutes of Health–sponsored Cure Glomerulonephropathy Network (CureGN) study. We anticipated that the findings would identify the proportion of adults in this population who would benefit from more intensive conservative treatment and consideration for clinical trial enrollment.