NDT Advance Access originally published online on May 3, 2005
Nephrology Dialysis Transplantation 2005 20(10):2113-2119; doi:10.1093/ndt/gfh873
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Salt-sensitive blood pressure—an intermediate phenotype predisposing to diabetic nephropathy?
1 Department of Internal Diseases, Diabetology and Nephrology, Silesian Medical Academy, Zabrze, Poland, 2 Division of Nephrology and Hypertension, University Hospital Berne, Switzerland and 3 Department of Internal Medicine, Ruperto Carola University, Heidelberg, Germany
Correspondence and offprint requests to: Krzysztof Strojek, Department of Internal Diseases, Diabetology and Nephrology, Silesian Medical Academy, 3-go Maja 13/15, Zabrze 41-800, Poland. Email: kstrojek{at}slam.katowice.pl
Background. Family studies point to important genetic determinants of diabetic nephropathy (DN). Blood pressure (BP) is higher in offspring of patients with type 2 diabetes and DN, but the pathomechanisms involved have not been elucidated.
Methods. We examined the salt sensitivity of BP after 5 days equilibration on a low (20 mmol/day) vs high salt diet (220 mmol/day) in three matched groups of 15 subjects each: (i) control individuals; (ii) offspring of type 2 diabetic parents without DN (DN–); and (iii) offspring of type 2 diabetic parents with DN (DN+). Ambulatory BP and hormones involved in sodium homeostasis [plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP)] as well as the tetrahydrocortisol + 5-allotetrahydrocortisol/tetrahydrocortisone (THF + 5
THF)/THE) ratio in the urine as an index of 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2) activity were analysed.
Results. In offspring of DN+ patients on a high salt diet, systolic and diastolic BP was 137/82±10/8 mmHg vs 125/77±12/8 mmHg in offspring of DN– patients (P<0.01 for systolic BP). The salt-induced difference in mean BP between high and low salt diet was 5.2±3.3 mmHg in offspring of DN+ patients vs 0.7±4.7 mmHg in offspring of DN– patients (P<0.002). The proportion of ‘salt-sensitive’ individuals was 67% in offspring of DN+ patients vs 20% in offspring of DN– patients (P<0.05). In all groups, a high salt diet caused a comparable decrease of PRA and p-aldosterone accompanied by an increase in ANP. The urinary (THF + 5THF)/THE ratio was 1.23±0.36 in salt-sensitive individuals and 0.99±0.33 (P<0.03) in salt-resistant subjects, consistent with increased activity of 11ßHSD2.
Conclusions. BP is more salt sensitive in offspring of type 2 diabetic patients with diabetic nephropathy. The salt sensitivity of BP may be an intermediate phenotype in individuals with a high risk of future diabetic nephropathy.
Keywords: diabetic nephropathy; hypertension; intermediate phenotype; salt sensitivity
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