Dapagliflozin in IgA Nephropathy-associated CKD: What is the Evidence?

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has an estimated incidence of 0.2-5 per 100,000 persons annually and accounts for approximately 16.5% of biopsy-proven primary glomerular diseases in India. ^{1, 2} Despite its heterogeneous clinical course, IgAN remains a major cause of chronic kidney disease (CKD), with nearly 30–40% of patients progressing to kidney failure within 20–30 years. ³ Given the substantial risk of progressive kidney function loss despite optimized supportive care, effective kidney-protective therapies are needed to improve long-term renal outcomes. We examine the current evidence on dapagliflozin, a widely used kidney disease-modifying therapy in CKD, in the context of IgA nephropathy-associated CKD.

Mechanistic Rationale for Dapagliflozin in IgA Nephropathy-Associated CKD: Beyond Glycemic Effects

The pathogenesis of CKD progression in IgA nephropathy (IgAN) is driven by persistent proteinuria, glomerular hypertension, tubulointerstitial inflammation, and progressive fibrosis. Dapagliflozin targets several of these pathways through mechanisms independent of glycaemic control. By inhibiting proximal tubular sodium-glucose reabsorption, it restores tubuloglomerular feedback, resulting in afferent arteriolar vasoconstriction and a reduction in intraglomerular pressure. In addition to its haemodynamic effects, SGLT2 inhibition has been associated with attenuation of inflammatory and profibrotic signalling pathways, improved tubular energy metabolism, and reduced albuminuria. These pleiotropic renal effects provide a prudent mechanistic rationale for the consideration of dapagliflozin as an adjunct to standard therapy in IgAN-associated CKD. ^4-6 (Figure 1)

Dapagliflozin in IgA Nephropathy–Associated CKD: Landmark and Real-World Evidence

Dapagliflozin Slows Kidney Function Decline in Patients with IgA Nephropathy associated CKD: The most robust evidence for dapagliflozin in IgA nephropathy (IgAN) comes from a prespecified subgroup analysis of the DAPA-CKD trial, which included 270 patients, 94% of whom had biopsy-confirmed disease. Over a median follow-up of 2.4 years, dapagliflozin, when added to standard care, was associated with a 71% relative risk reduction in the primary composite outcome of sustained ≥50% decline in eGFR, end-stage kidney disease (ESKD), or kidney/cardiovascular death compared with placebo (HR 0.29; 95% CI 0.12–0.73). The treatment also reduced albuminuria by 26% and slowed the rate of eGFR decline, while maintaining a safety profile comparable to placebo. These findings demonstrate that dapagliflozin provides clinically meaningful renoprotection in patients with IgAN and support its use as an adjunct to optimized standard therapy in those at risk of CKD progression. ⁵

Dapagliflozin in Treatment-Experienced IgA Nephropathy-Associated CKD Patients: A 2025 study in Renal Failure evaluated dapagliflozin 10mg once daily in 105 biopsy-proven IgAN patients with persistent proteinuria >0.5 g/day despite three months of low-dose steroids, with or without mycophenolate mofetil, and renin–angiotensin–aldosterone system inhibition Patients had high-risk histological features based on the Oxford MEST-C classification, including frequent M1, E1, S1, C1/C2, and T1 lesions. Among them, 49 received dapagliflozin and 56 served as controls. At six months, total remission was significantly higher with dapagliflozin than control therapy (55.1% vs 33.9%; OR 2.39; 95% CI 1.09–5.26), suggesting added antiproteinuric benefit in high-risk IgAN. The study concluded that dapagliflozin may provide additional proteinuria reduction in high-risk IgAN patients receiving immunosuppressive therapy. ⁴

Reno-protective Benefits of Dapagliflozin in IgA Nephropathy-Associated CKD: Indian Real-World Case Series Experience: A 2026 real-world case series from India evaluated dapagliflozin 10 mg once daily in six non-diabetic CKD patients with autoimmune glomerular disorders, including five with IgA nephropathy and one with membranous nephropathy. Over six months, dapagliflozin therapy was associated with progressive reductions in proteinuria. Although an initial eGFR decline was observed two weeks after initiation, kidney function subsequently improved, with mean eGFR increasing from 38.83 ± 9.21 mL/min/1.73 m² at Day 14 to 44.83 ± 9.78 mL/min/1.73 m² at six months (P=0.0052). No adverse events were reported. These findings highlight that dapagliflozin was well tolerated and associated with improvements in renal function and proteinuria in non-diabetic CKD patients with autoimmune glomerular disorders. ⁷

Practice Pearls for Clinicians

The available evidence supports the consideration of dapagliflozin as an adjunct to optimized standard care in patients with proteinuric IgAN-associated CKD. The potential of dapagliflozin is relevant as its benefits appear to extend beyond glycaemic control, with consistent reductions in proteinuria and slower kidney function decline observed across clinical trials and real-world studies. Importantly, efficacy has been demonstrated in both diabetic and non-diabetic CKD populations. Clinicians may anticipate a modest initial eGFR dip following treatment initiation and continue routine monitoring of kidney function, proteinuria, and volume status during therapy. ^{5, 6}

Key Takeaways

• Dapagliflozin addresses multiple drivers of CKD progression in IgAN, including glomerular hypertension, persistent proteinuria, tubulointerstitial inflammation, and fibrosis, providing renoprotection potential beyond glycaemic control. ⁴
• Evidence from the DAPA-CKD IgAN subgroup demonstrates a clinically meaningful reduction in the risk of CKD progression and kidney failure when dapagliflozin is added to standard care. ⁵
• Emerging data suggest that dapagliflozin may provide additional antiproteinuric benefits even in patients receiving immunosuppressive therapy, supporting its role as a complementary treatment strategy in high-risk IgAN. ⁴
• The findings across randomized trials and Indian real-world experience reinforces the potential of dapagliflozin as a clinically relevant consideration, aimed at preserving long-term kidney function in IgAN-associated CKD, when indicated. More robust long-term studies are needed in this direction. ^5-7

** Abbreviations: CKD: Chronic Kidney Disease, IgAN: IgA Nephropathy, eGFR: Estimated Glomerular Filtration Rate, SGLT2: Sodium-Glucose Cotransporter-2, AMPK: AMP-Activated Protein Kinase, HIF-1α: Hypoxia-Inducible Factor-1 Alpha, TGF-β: Transforming Growth Factor-Beta, NF-κB: Nuclear Factor-Kappa B, RAAS: Renin–Angiotensin–Aldosterone System, ESKD: End-Stage Kidney Disease, HR: Hazard Ratio, CI: Confidence Interval, MEST-C: Mesangial Hypercellularity, Endocapillary Hypercellularity, Segmental Sclerosis, Tubular Atrophy/Interstitial Fibrosis, and Crescents.