NIV Congres

Introduction: Reduction in sodium intake has proven an efficient non-pharmacological intervention to optimize treatment response to RAAS-blockade in non-diabetic chronic kidney disease. Whether this holds true for diabetic kidney disease is however unknown. We therefore investigated the potentiating effects of dietary sodium restriction (SR) and hydrochlorothiazide (HCT) and their combination, in subjects with type II diabetes and nephropathy.

Methods: Multicentre, randomized, double-blind, placebo-controlled, cross-over trial, with 6-week treatment periods in a rotation design, testing the separate and combined effects of SR and HCT (50 mg daily) in addition to standardized maximal ACE-inhibition (ACEi; lisinopril 40 mg daily) on proteinuria (Up) and blood pressure in 45 patients with type II diabetes and nephropathy (84% male, age 65 ± 9 yrs, BMI 32 ± 5 kg/m²).

Results: Urinary sodium excretion, as a measure of dietary sodium intake, decreased from 224 ± 76 mmol/d during regular sodium to 150 ± 66 mmol/day upon SR (p < 0.001). Median Up during baseline treatment (ACEi and regular sodium diet) was 1.1 (0.5-3.2) gr/day; it decreased to 0.7 (0.4-1.2) and 0.7 (0.5-1.7) gr/day during SR and HCT, resp. (both < 0.001 vs. baseline). The combination of HCT and SR further reduced up to 0.5 (0.3-1.4) gr/day (p < 0.001 vs. baseline). Mean arterial blood pressure (MAP) at baseline was 104 ± 11 mmHg; it was reduced to 100 ± 11 and 96 ± 9 mmHg in response to SR and HCT, respectively (both < 0.02). MAP was more reduced by HCT than by SR (p = 0.017). Creatinine clearance at baseline was 101 ± 47 ml/min; it remained unaffected by SR (99 ± 48 ml/min, p = 0.5) and HCT (97 ± 48 ml/min, p = 0.4), however, was significantly reduced by their combination (86 ± 42 ml/min, p < 0.001 vs. baseline).

Conclusion: In this population with very high regular sodium intake, both moderate SR and HCT, added to RAAS-blockade, reduced proteinuria and blood pressure, without affecting creatinine clearance. Combination of SR and HCT reduced proteinuria and blood pressure even further, however, at the expense of a decrease in creatinine clearance. Intervention in sodium status is an effective measure to increase efficacy of RAAS-blockade in type II diabetic subjects with nephropathy.