Effects of Salt Supplementation on the Albuminuric Response to Telmisartan With or Without Hydrochlorothiazide Therapy in Hypertensive Patients With Type 2 Diabetes Are Modulated by Habitual Dietary Salt Intake

Abstract

OBJECTIVEThis prospective randomized double-blind placebo-controlled crossover study examined the effects of sodium chloride (NaCl) supplementation on the antialbuminuric action of telmisartan with or without hydrochlorothiazide (HCT) in hypertensive patients with type 2 diabetes, increased albumin excretion rate (AER), and habitual low dietary salt intake (LDS; <100 mmol sodium/24 h on two of three consecutive occasions) or high dietary salt intake (HDS; >200 mmol sodium/24 h on two of three consecutive occasions).RESEARCH DESIGN AND METHODSFollowing a washout period, subjects (n = 32) received 40 mg/day telmisartan for 4 weeks followed by 40 mg telmisartan plus 12.5 mg/day HCT for 4 weeks. For the last 2 weeks of each treatment period, patients received either 100 mmol/day NaCl or placebo capsules. After a second washout, the regimen was repeated with supplements in reverse order. AER and ambulatory blood pressure were measured at weeks 0, 4, 8, 14, 18, and 22.RESULTSIn LDS, NaCl supplementation reduced the anti-albuminuric effect of telmisartan with or without HCT from 42.3% (placebo) to 9.5% (P = 0.004). By contrast, in HDS, NaCl supplementation did not reduce the AER response to telmisartan with or without HCT (placebo 30.9%, NaCl 28.1%, P = 0.7). Changes in AER were independent of changes in blood pressure.CONCLUSIONSThe AER response to telmisartan with or without HCT under habitual low salt intake can be blunted by NaCl supplementation. By contrast, when there is already a suppressed renin angiotensin aldosterone system under habitual high dietary salt intake, the additional NaCl does not alter the AER response.

Effects of Intensive Low-Salt Diet Education on Albuminuria among Nondiabetic Patients with Hypertension Treated with Olmesartan

“…There were several short-term studies on the effect of restricting salt intake on BP and albuminuria reduction during RAAS blockade (6,9,10). Enhanced treatment effects of LSD education on albuminuria were observed in our study.…”

“…Several studies revealed an additive effect of dietary salt restriction with RAAS blockade on BP and proteinuria. However, most of these studies include a small number of patients (6,(9)(10)(11)20), and there has been no randomized, controlled study in Korean populations. Most importantly, the methods for implementing LSDs or high-salt diets used in previous studies offered strongly controlled or modulated diets (6,11), or they provided salt tablets (9), which are not suitable for application in typical clinical practice.…”

“…Blockade of the reninangiotensin-aldosterone system (RAAS) is well known to reduce urinary albumin excretion, and it is considered a mainstay of therapy in the prevention of ESRD (4,5). The antiproteinuric effect of the RAAS blockade can be magnified or reduced depending on the amount of dietary salt intake (6)(7)(8)(9)(10)(11).…”

Salt supplementation blunts the blood pressure response to telmisartan with or without hydrochlorothiazide in hypertensive patients with type 2 diabetes

“…We therefore performed a double blind, prospective, randomised crossover study of the effects of NaCl supplementation on the response to telmisartan with or without HCT, in subjects with type 2 diabetes, hypertension, raised albumin excretion rate (AER) and habitual high or low salt intake. In this study we found that the AER response was blunted by NaCl supplementation only in subjects with habitual low salt intake [10]. Here we describe in detail the blood pressure response to telmisartan with or without HCT in the same group of patients and show that the effect of NaCl supplementation on blood pressure is independent of habitual salt intake.…”

N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) predicts the cardio‐renal response to aliskiren in patients with type 2 diabetes at high renal and cardiovascular risk

“…People with type 2 diabetes are susceptible to retaining sodium and fluid as a result of disturbed insulin homeostasis 3. Previous studies have shown that sodium retention and subsequent volume overload are the main determinants of poor response to RAAS therapy 4, 5. Accordingly, volume restriction by means of co‐diuretic treatment or a low sodium diet enhances the blood pressure‐lowering and albuminuria‐reducing effects of RAAS inhibition 6.…”