Low salt diet and weight loss have additive effects on the anti-proteinuric effects of angiotensin II receptor blockers in hypertensive patients with chronic kidney disease
고혈압성 만성 신장병 환자에서 저염식과 체중감량이 안지오텐신 수용체차단제에 의한 단백뇨 감소 효과에 미치는 영향

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의과대학 의학과
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서울대학교 대학원
low salt dietweight lossalbuminuriaangitensin ll receptor blockerchronic kidney diseasehypertension
학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2017. 2. 진호준.
Efforts to delay progression to end stage renal disease (ESRD) are mainly based on the control of hypertension and diabetes. However, chronic kidney disease (CKD) is a complex and life-long disease, and physicians should integrate pharmacological and non-pharmacological therapies for the management of CKD.

Investigator explore the additive anti-proteinuric effects of reduced salt intake and weight on the usage of an angiotensin II receptor blocker and the potential mechanisms of the beneficial effects in hypertensive CKD patients.

This study is a subanalysis of data from an open-label, randomized, controlled clinical trial (NCT01552954). Among the 235 participants, the body weight of 227 participants was measured and 24h urine samples were collected at baseline and after 16 weeks. The participants were assigned to each subgroup according to changes in their salt intake and body weight. Urinary cytokines as well as urine creatinine, sodium, urea nitrogen, and albumin excretion were measured over the 16-week study period.

Adherence to ARB treatment over the 16 weeks was 95% (71.5 - 100%). The mean 24h urinary sodium and albumin excretions at enrollment were 170 ± 74 mEq/day and 1041 ± 1094 mg/day, respectively. Over the study period, a low salt diet and unintentional weight loss independently increased the probability of reduced albuminuria (low salt group: with a ≥ 25% decrease in the estimated urine sodium excretion rate after 16 weeks, RR 3.583, 95% CI 1.448 - 8.865, p=0.006
weight reduction group: with a ≥ 1.5% decrease in body weight after 16 weeks, RR 6.234, 95% CI 1.913 - 20.315, p=0.002). The relationship between weight loss and a decrease in albuminuria was even more significant in several subgroups, including participants who were female, younger (< 65 yrs), non-obese and obese (BMI ≥ 18.5 kg/m2), as well as those who had a CKD stage ≥ 3a (≥ 45 ml/min/1.73m2), consumed a low salt diet (urinary sodium excretion < 200 mEq/day), consumed a low protein diet (< 1.2 g/kg/day), and had a low baseline level of albuminuria (< 2000 mg/day). Among the urinary cytokines, angiotensinogen was significantly decreased in the participants who reduced their salt intake and podocalyxin was noticeably decreased in the participants who lost weight (p=0.017 and p=0.013, respectively).

Investigator observed that the low salt diet and unintentional weight loss have additive effects on the anti-proteinuric effects of treatment with ARBs in hypertensive CKD patients, which are possibly related to the reduced intrarenal renin-angiotensin-aldosteron activation and damaged podocytes, respectively.
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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