Immunoglobulin A nephropathy is a commonly occurring type of glomerulonephritis. The condition often progresses to kidney failure even with renin-angiotensin-aldosterone-system (RAAS) blockers and immunosuppressants.

In the DAPA trial (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial), it was reported that dapagliflozin significantly reduced the risk of kidney failure and prolonged survival in study participants with chronic kidney disease with or without diabetes, including patients with Immunoglobulin A nephropathy. In the study in patients with IgA nephropathy (254 [94%] confirmed by the previous biopsy), 137 were randomly assigned to dapagliflozin, and 133 were assigned to receive placebo and followed for a median of 2.1 years. The results showed that the primary outcome occurred in six (4%) participants on dapagliflozin and 20 (15%) on placebo (hazard ratio, 0.29; 95% confidence interval, 0.12, 0.73). Mean rates of the decline of eGFR were -3.5 mL/min/1.73m² with dapagliflozin and -4.7mL/min/1.73m² with placebo. In addition, there was no significant difference in adverse events with dapagliflozin vs. placebo. 

The authors concluded that in patients with IgA nephropathy, dapagliflozin lowered the risk of chronic kidney disease progression and a favorable safety profile. Similar results were seen in a small, crossover study including patients with proteinuric CKD without diabetes, of whom 50% had IgA nephropathy. The study showed that the use of 10 mg of dapagliflozin caused a short-term but reversible decrease in the estimated glomerular filtration rate. The results were suggestive of the fact that dapagliflozin reduces intraglomerular pressure even in patients without diabetes. Additionally, dapagliflozin also reduced body weight and increased hematocrit. 

Based on the study results, it is recommended that in patients with IgA nephropathy, dapagliflozin added to ACE inhibitors or ARB therapy significantly reduces the risk of CKD progression with an established safety profile. 

Reference: Wheeler DC, Toto RD, Stefansson BV, Jongs N, et al. A pre-specified analysis of the DAPA-CKD trial demonstrated the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. 2021; 100: 215-224.