Hong Kong Study Using Valsartan in IgA Nephropathy (HKVIN): A Double-Blind, Randomized, Placebo-Controlled Study

Background: Previous studies showed that angiotensin-receptor blocker (ARB) therapy decreased proteinuria and possibly slowed the rate of renal function decline in patients with chronic proteinuric nephropathies. We performed a double-blind, randomized, placebo-controlled, multicenter study on the ARB valsartan in the treatment of patients with immunoglobulin A (IgA) nephropathy. Methods: From 6 centers, we recruited 109 patients with IgA nephropathy who had either: (1) proteinuria with protein greater than 1 g/d and serum creatinine level less than 2.8 mg/dL (<250 μmol/L), or (2) serum creatinine level of 1.4 to 2.8 mg/dL (120 to 250 μmol/L) regardless of degree of proteinuria. Patients were randomly assigned to administration of either valsartan, 80 mg/d (titrated up to 160 mg/d for blood pressure control), or placebo for 104 weeks. Additional antihypertensive therapy was allowed to achieve a target blood pressure of 140/90 mm Hg. The primary end point was doubling of serum creatinine level or dialysis-dependent renal failure. Secondary outcomes included change in proteinuria and decrease in glomerular filtration rate (GFR). Results: There were 54 patients in the treatment group and 55 patients in the placebo group. Baseline clinical characteristics were similar between groups, although the treatment group had a marginally greater baseline GFR (87 ± 36 versus 78 ± 38 mL/min/1.73 m2 [1.45 ± 0.60 versus 1.30 ± 0.63 mL/s/1.73 m2];P = 0.29) and less proteinuria (protein, 1.8 ± 1.2 versus 2.3 ± 1.7 g/d; P = 0.21) than the placebo group. Average blood pressures during the study were 92.7 ± 10.6 mm Hg in the treatment group and 100.9 ± 9.1 mm Hg in the placebo group (P < 0.001). During the study period, 4 patients in the placebo group and 1 patient in the treatment group reached the primary end point (log-rank test, P = 0.18). Proteinuria decreased significantly in the treatment group (protein, 1.8 ± 1.2 to 1.2 ± 1.2 g/d; P = 0.03), but did not change in the placebo group. With multiple linear regression models, valsartan treatment resulted in a 33.0% decrease in proteinuria (95% confidence interval, 10.9 to 55.1) after adjusting for other confounding factors. There was a significant decrease in mean rate of GFR decrease in the valsartan-treated group (−5.62 ± 6.79 mL/min/y [−0.09 ± 0.11 mL/s/y]) compared with the placebo group (−6.98 ± 6.17 mL/min/y [−0.12 ± 0.10 mL/s/y]) throughout the study period after adjustment for average blood pressure and proteinuria (P = 0.014). Conclusion: Valsartan significantly decreases proteinuria and slows renal deterioration in patients with IgA nephropathy after adjustment for confounding factors, notably blood pressure. The long-term benefit of valsartan needs to be confirmed with additional studies. Background: Previous studies showed that angiotensin-receptor blocker (ARB) therapy decreased proteinuria and possibly slowed the rate of renal function decline in patients with chronic proteinuric nephropathies. We performed a double-blind, randomized, placebo-controlled, multicenter study on the ARB valsartan in the treatment of patients with immunoglobulin A (IgA) nephropathy. Methods: From 6 centers, we recruited 109 patients with IgA nephropathy who had either: (1) proteinuria with protein greater than 1 g/d and serum creatinine level less than 2.8 mg/dL (<250 μmol/L), or (2) serum creatinine level of 1.4 to 2.8 mg/dL (120 to 250 μmol/L) regardless of degree of proteinuria. Patients were randomly assigned to administration of either valsartan, 80 mg/d (titrated up to 160 mg/d for blood pressure control), or placebo for 104 weeks. Additional antihypertensive therapy was allowed to achieve a target blood pressure of 140/90 mm Hg. The primary end point was doubling of serum creatinine level or dialysis-dependent renal failure. Secondary outcomes included change in proteinuria and decrease in glomerular filtration rate (GFR). Results: There were 54 patients in the treatment group and 55 patients in the placebo group. Baseline clinical characteristics were similar between groups, although the treatment group had a marginally greater baseline GFR (87 ± 36 versus 78 ± 38 mL/min/1.73 m2 [1.45 ± 0.60 versus 1.30 ± 0.63 mL/s/1.73 m2];P = 0.29) and less proteinuria (protein, 1.8 ± 1.2 versus 2.3 ± 1.7 g/d; P = 0.21) than the placebo group. Average blood pressures during the study were 92.7 ± 10.6 mm Hg in the treatment group and 100.9 ± 9.1 mm Hg in the placebo group (P < 0.001). During the study period, 4 patients in the placebo group and 1 patient in the treatment group reached the primary end point (log-rank test, P = 0.18). Proteinuria decreased significantly in the treatment group (protein, 1.8 ± 1.2 to 1.2 ± 1.2 g/d; P = 0.03), but did not change in the placebo group. With multiple linear regression models, valsartan treatment resulted in a 33.0% decrease in proteinuria (95% confidence interval, 10.9 to 55.1) after adjusting for other confounding factors. There was a significant decrease in mean rate of GFR decrease in the valsartan-treated group (−5.62 ± 6.79 mL/min/y [−0.09 ± 0.11 mL/s/y]) compared with the placebo group (−6.98 ± 6.17 mL/min/y [−0.12 ± 0.10 mL/s/y]) throughout the study period after adjustment for average blood pressure and proteinuria (P = 0.014). Conclusion: Valsartan significantly decreases proteinuria and slows renal deterioration in patients with IgA nephropathy after adjustment for confounding factors, notably blood pressure. The long-term benefit of valsartan needs to be confirmed with additional studies.