Effects of valsartan on progression of kidney disease in Japanese hypertensive patients with advanced, predialysis, chronic kidney disease: Kanagawa Valsartan Trial (KVT)

Abstract

Suppression of the renin-angiotensin system is known to slow progression of chronic kidney disease (CKD). However, few trials have been performed with Japanese patients. This study investigated whether the angiotensin receptor blocker (ARB) valsartan would delay the progression of kidney disease more effectively than conventional treatment in Japanese hypertensive patients with advanced, predialysis CKD. In a multicenter, randomized, open-label trial, 303 patients with hypertension and CKD with serum creatinine levels 2.0 mg dl(-1) were assigned to receive either conventional therapy plus valsartan (valsartan add-on group) or conventional therapy without ARB (control group). The primary outcome was a change in serum creatinine levels. Changes in urinary protein levels and time to onset of renal events were analyzed as secondary end points. There were no between-group differences in blood pressure during the study. Changes in serum creatinine and urinary protein levels did not differ between the groups. However, the rate of renal events, including doubling of serum creatinine levels or end-stage renal disease, was significantly lower in the valsartan add-on group than in the control group. The addition of valsartan decreased the risk by 42.6% after adjustment for baseline variables. The addition of valsartan to conventional therapy significantly slowed the rate of renal function decline and delayed the need for renal replacement therapy in Japanese hypertensive patients with advanced CKD.

Assessing the Validity of Surrogate Outcomes for ESRD

“…Twenty trials (10 trials assessing the effects of BP lowering, 12,13,19,[21][22][23][24][25][26]32 2 trials in lipid lowering, 11,15 4 trials comparing the effects of intensive glucose lowering to standard glucose lowering, 16,20,27,30 2 trials in anemia therapy, 14,18 and 2 trials each assessing the effects of a dietary intervention and chelation therapy 8,10 ) comprising 95,457 participants reported treatment effects on doubling of serum creatinine (3893 events) and ESRD (3850 events) ( Figure 3). Overall, the treatment effect on doubling of serum creatinine was consistent with the treatment effect on ESRD (treatment effect ratio, 0.98; 95% CI, 0.85 to 1.14).…”

“…Studies were conducted in some or all of the United States, Canada, Europe, Asia, and Oceania, with trial results published between 1992 and 2013. A variety of interventions were assessed, including BP lowering (16 trials 12,13,17,19,[21][22][23][24][25][26]28,29,[31][32][33][34] ), lipid-lowering therapy (3 trials 9,11,15 ), intensive glucose-lowering therapy (4 trials 16,20,27,30 ), anemia therapy (2 trials 14,18 ), dietary intervention (1 trial 10 ), and chelation therapy (1 trial 8 ).The mean age of study participants ranged between 34.5 and 68.3 years, with the proportion of men between 48.8% and 97.1%. Eighteen trials specified the presence of diabetes as part of their inclusion criteria.…”

Estimated Glomerular Filtration Rate Variability Independently Predicts Renal Prognosis in Advanced Chronic Kidney Disease Patients

“…The Kanagawa Valsartan Trial (KVT) was designed to evaluate the effect of add-on treatment with the angiotensin II receptor blocker, valsartan, on the rate of CKD progression in Japanese hypertensive patients with advanced CKD with a sCr level of ≥2.0 mg/dl [11]. The overall objective of this post hoc analysis was to verify our hypothesis that advanced CKD patients with higher eGFR variability would have poorer renal prognosis than those with lower eGFR variability.…”

Renal and metabolic effects of valsartan

“…In the multicenter, randomized, open-label Kanagawa Valsartan Trial (KVT) performed by Yasuda et al (29), 303 patients with chronic renal failure associated both diabetic and nondiabetic causes were enrolled. Patients were randomized into a control group (144 patients) that received antihypertensive drugs but not angiotensin receptor blockers and a valsartan group (149 patients) that received valsartan and the conventional therapy.…”