6/30/23, 12:10 AM VA-NEPHRON D Pathway Feedback Search Clinical Topics Home Studies VA NEPHRON D VA NEPHRON D Disease Disease Diabetes mellitus type 2 Diabetic nephropathy Trial question What is the role of combined therapy with ACEIs and angiotensin-receptor blockers in patients with T2DM who have diabetic nephropathy? Study design Multi-center Double blinded RCT Population Characteristics of study participants 1.1% female N = 1648 98.9% male 1648 patients (12 female, 1436 male) Inclusion criteria: patients with T2DM, a urinary albumin-to-creatinine ratio of at least 300, and an eGFR of 30.0 to 89.9 mL/min/1.73 m of body-surface area Key exclusion criteria: known nondiabetic kidney disease, a serum potassium level > 5.5 mmol/L, treatment with sodium polystyrene sulfonate, or an inability to stop prescribed medications that increase the risk of hyperkalemia Interventions N=724 combined angiotensin inhibition (losartan at a dose of 100 mg/day plus lisinopril at a dose of 10 to 40 mg/day) N=724 monotherapy (losartan at a dose of 100 mg/day plus placebo) Primary outcome https://web.pathway.md/studies/rec4o5msKPuuICw4l 1/2 6/30/23, 12:10 AM VA-NEPHRON D Pathway Decline in eGFR (by 30 mL/min if eGFR 60-90 at baseline, or by 50% eGFR 30-60 at baseline), ESRD, or death 21.0 % 21 18.2 15.8 % 10.5 % 5.3 % No significant difference 0.0 % Combined angiotensin inhibition Monotherapy No significant difference in decline in eGFR (by 30 mL/min if eGFR 60-90 at baseline, or by 50% eGFR 30-60 at baseline), ESRD, or death (18.2% vs. 21%; HR 0.88, 95% CI 0.7 to 1.12) Secondary outcomes No significant difference in decline in eGFR or end-stage renal disease (10.6% vs. 14%; HR 0.78, 95% CI 0.58 to 1.05) No significant difference in death (8.7% vs. 8.3%; HR 1.04, 95% CI 0.73 to 1.49) No significant difference in cardiovascular events (18.5% vs. 18.8%; HR 0.97, 95% CI 0.76 to 1.23) Safety outcomes Significant differences in serious adverse events (57.5% vs. 52.5%, p = 0.06), including hyperkalemia (9.9% vs. 4.4%, p < 0.001) and AKI (18.0% vs. 11.0%, p < 0.001). Conclusion In patients with T2DM, a urinary albumin-to-creatinine ratio of at least 300, and an eGFR of 30.0 to 89.9 mL/min/1.73 m of body-surface area, combined angiotensin inhibition was not superior to monotherapy with respect to decline in eGFR (by 30 mL/min if eGFR 60-90 at baseline, or by 50% eGFR 30-60 at baseline), ESRD, or death. Reference Fried LF, Emanuele N, Zhang JH et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013 Nov 14;369(20):1892-903. Open reference URL https://web.pathway.md/studies/rec4o5msKPuuICw4l 2/2