Weight loss has an additive effect on the proteinuria reduction of angiotensin II receptor blockers in hypertensive patients with chronic kidney disease

Abstract

Background: Weight reduction is a lifestyle intervention that has been introduced for prevention and management of chronic kidney disease (CKD). We investigate the additive anti-proteinuric effect of weight reduction on the usage of angiotensin II receptor blockers (ARBs) and its potential mechanisms in hypertensive CKD patients.

Methods: This study is a subanalysis of data from an open-label, randomized, controlled clinical trial. Among the 235 participants, 227 were assigned to subgroups according to changes in body weight.

Results: Fifty-eight participants (25.6%) were assigned to group 1 (≥1.5% decrease in body weight after 16 weeks), 32 participants (14.1%) were assigned to group 2 (1.5-0.1% decrease in body weight), and 136 participants (59.9%) were assigned to group 3 (≥ 0.0% increase in body weight). Characteristics at enrollment were not different among the three groups, but mean differences in weight and percent changes in urinary sodium excretion over the period were statistically different (P < 0.001 and P = 0.017). Over the study period, unintentional weight loss independently increased the probability of reduced albuminuria (group 1, relative risk 6.234, 95% confidence interval 1.913-20.315, P = 0.002). Among urinary cytokines, only podocalyxin level decreased significantly in participants who lost weight (P = 0.013).

Conclusion: We observed that weight loss had an additive effect on the anti-proteinuric effects of ARBs in nondiabetic hypertensive CKD patients, although it was minimal. An additive effect was shown in both obese and non-obese participants, and its possible mechanism is related to reduction of podocyte damage.

Keywords: Angiotensin type II receptor blocker; Chronic renal insufficiency; Hypertension; Proteinuria; Weight loss.

Figure 1. Study flow chart

ARB, angiotensin II receptor blocker.

Figure 2. Decreased albuminuria according to change in body weight during the 16-week study period

(A) Percent change in albuminuria over 16 weeks. (B) Percentage of participants who achieved > 25% decrease in albuminuria. Group 1 (≥ 1.5% decrease in body weight), group 2 (1.5–0.1% decrease in body weight), and group 3 (≥ 0.0% increase in body weight). The bar represents the 95% confidence interval of the mean value. P values were estimated by *Kruskal–Wallis test and ^†Pearson’s chi-square test.

Figure 3. Changes in urinary cytokines according to change in body weight over 16 weeks

Frequency of decrease in cytokine level: The frequency of a 25% or greater reduction in 24-hour urinary cytokine to creatinine ratio at 16 weeks compared to 0 weeks. Group 1 (≥ 1.5% decrease in body weight), group 2 (1.5–0.1% decrease in body weight), and group 3 (≥ 0.0% increase in body weight). AGT, angiotensinogen; APN, adiponectin; Cr, creatinine; MCP-1, monocyte chemoattractant protein-1; MDA, malondialdehyde; PCX, podocalyxin; u-, urine.