Acute Estimated Glomerular Filtration Rate Decline after Initiation of Therapies That Slow Kidney Disease Progression: Clinical Practice Implications

A comprehensive treatment strategy including renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, and finerenone is recommended to reduce the risk of adverse kidney outcomes in people with chronic kidney disease (CKD) and type 2 diabetes. These therapies, along with glucagon-like peptide-1 receptor agonists, slow the progression of CKD, reflected in long-term decline in estimated glomerular filtration rate (eGFR); however, they may also reduce eGFR within the first 3 months of treatment initiation. The initial eGFR decline observed with renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, and finerenone is linked to beneficial hemodynamic changes that lead to reduction in maladaptive glomerular hypertension and hyperfiltration. These beneficial hemodynamic changes ultimately protect against loss of nephron function and mitigate the risk of end-stage kidney disease. This review presents evidence from randomized controlled trials with these therapies demonstrating that this initial decline in eGFR is usually reversible and generally does not reflect an adverse effect on the kidney. An acute eGFR decline less than 30% does not usually reduce the efficacy of these therapies in people with CKD, type 2 diabetes, or heart failure. The clinical implications of this eGFR decline are discussed, including recommendations for initiating therapies and monitoring kidney function. When considering use of these therapies, an initial eGFR decline less than 30% without significant hyperkalemia or acute adverse kidney events should, in general, not be a barrier to continuation of treatment as it may predict a greater long-term benefit on CKD progression.