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

Is Proteinuria Reduction by Angiotensin-Converting Enzyme Inhibition Enough to Prove Its Role in Renal Protection in IgA Nephropathy?

“…An RCT of adult patients with IgAN recently confirmed an independent renal protective effect of ACE inhibition (enalapril) and confirmed by multivariate analysis the independent value of proteinuria reduction over the course of the trial (but not the presenting proteinuria) (15). The importance of renin-angiotensin-aldosterone system blockade on proteinuria, although not on GFR, is also supported by the results of a recent RCT in Asian patients with IgA using the angiotensin II receptor blocker valsartan (16).…”

Cardiovascular and Renal Outcomes With Telmisartan, Ramipril, or Both in People at High Renal Risk

“…[32][33][34] Previous trials of ARB against placebo in nondiabetic renal disease are limited to 2 randomized studies of 165 patients and are unable to examine clinically important outcomes. 35,36 In patients with diabetic nephropathy, a meta-analysis of 3 trials of 3251 patients found a reduction in end-stage renal disease with ARBs compared with placebo by 22%. 37 TRANSCEND, with an exclusion criterion for macroalbuminuria, would have excluded most of these patients and found no benefit overall for an ARB to prevent doubling of creatinine or dialysis.…”

IgA Nephropathy: Insights into Genetic Basis and Treatment Options

“…Praga et al in their randomized trial in 44 IgAN patients with proteinuria (≥0.5 g/day, mean 1.9 g/day) and a serum creatinine concentration ≤1.5 mg/dL at baseline, found a significant decrease in proteinuria in the enalapril group (1.9 g/day at baseline to 0.9 g/day at the last visit) and a significantly higher renal survival, defined as less than a 50 percent increase in the serum creatinine concentration, at 6 years of follow up [Praga et al, 2003]. More recently, Li et al in their double-blind randomized placebocontrolled HKVIN trial in 109 Chinese patients with protein excretion ≥1 g/day (mean ~2.0 g/day), found a better renal survival, defined as doubling of serum creatinine or ESRD, a significant improvement in proteinuria (33 % reduction in proteinuria) and a slower rate of decline in GFR (4.6 versus 6.9 mL/min per year) in the valsartan group compared to placebo [Li PK et al, 2006]. Similarly, the IgACE trial in 65 young patients with moderate proteinuria (between 1 and 3.5 grams/day per 1.73 m 2 ) and creatinine clearance >50 mL/min per 1.73 m 2 revealed a better renal survival (fewer patients with >30% decline in renal function) and significant improvement in proteinuria at 38 months of follow-up in the benazepril group compared to the placebo group [Coppo, 2007].…”

“…ACE inhibitors and ARBs act by reducing the intraglomerular pressure and by directly improving the size-selective properties of the glomerular capillary wall, both of which contribute to reducing protein excretion [Remuzzi et al, 1991;Maschio et al, 1994]. Both observational studies [Cattran et al, 1994;Kanno et al, 2005] and small randomized trials [Maschio et al, 1994;Praga et al, 2003;Li PK et al, 2006] have provided suggestive evidence that ACE inhibitors or ARBs are more effective than other antihypertensive drugs in slowing the progressive decline in GFR in IgAN as they are in other forms of chronic proteinuric kidney disease. Praga et al in their randomized trial in 44 IgAN patients with proteinuria (≥0.5 g/day, mean 1.9 g/day) and a serum creatinine concentration ≤1.5 mg/dL at baseline, found a significant decrease in proteinuria in the enalapril group (1.9 g/day at baseline to 0.9 g/day at the last visit) and a significantly higher renal survival, defined as less than a 50 percent increase in the serum creatinine concentration, at 6 years of follow up [Praga et al, 2003].…”