Comparison of regular versus low sodium diet on the effects of Losartan in hypertensive subjects with Type II diabetes

Houlihan, C.A.; Allen, T.; Hovey, A.; Jenkins, M.; Cooper, M.; Jerums, G.

Journal of the American Society of Nephrology 11(Program and Abstract Issue): 116A

2000


ISSN/ISBN: 1046-6673
Accession: 034621952

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Abstract
ACE inhibitors (ACEi) are recommended as first line therapy for diabetic nephropathy (DN) to slow progression and prevent/delay the onset of overt DN. Whether angiotensin II receptor blocking (ATRB) agents confer the same benefits remains to be established. Dietary sodium has been shown to influence the actions of ACEi in non-diabetic renal disease and experimental diabetes. This study assesses the effect of dietary sodium on the systemic and renal hemodynamic and anti-proteinuric actions of the ATRB Losartan in subjects with Type II diabetes. Twenty diabetic patients with hypertension (SBPgtoreq135 and/or DBPgtoreq80) and albumin excretion rates (AER) between 10-200ug/min were randomised to treatment with Losartan (LOS) 50mg daily (n=10) or matching placebo (PL) (n=10). Drug therapy was given in two 4 week phases separated by a 4 week washout. In the last 2 weeks of each phase patients were assigned to low (ls) (target 50mmol/d) or regular sodium (rs) diet in random order. Before and after each 2 week period of dietary intervention 24h urinary sodium (UNa), AER, 24h ambulatory blood pressure, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured. Paired t-test was used to compare DELTAw4-w2rs versus DELTAw4-w2ls diet within each treatment group. No change in any parameter was found on ls diet in the PL group. In the LOS group on ls, UNa fell from 226+-25 to 85+-14mmol/d (mean+-SEM) and this significantly reduced 24h SBP (0+-2.1 vs -9.7+-2.7mmHg, p<0.05), 24h DBP (0.4+-0.9 vs -5.1+-1.4mmHg, p<0.01) and AER (+11% vs -31%, p<0.05, % change in geometric mean). No significant changes in GFR or ERPF were found. This study shows that a low sodium diet promotes the anti-hypertensive and antiproteinuric effects of losartan in diabetic patients. The favourable reduction in the surrogate endpoint of microalbuminuria raises the possibility that a ls diet in diabetic subjects on ATRB treatment may be useful adjunctive therapy for preventing onset and progression of diabetic renal disease.