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NDT Advance Access published online on May 3, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh873
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received November 17, 2004
Accepted April 8, 2005

Original Articles

Salt-sensitive blood pressure--an intermediate phenotype predisposing to diabetic nephropathy?

Krzysztof Strojek 1*, Jerome Nicod 2, Paolo Ferrari 2, Wladyslaw Grzeszczak 1, Juta Gorska 1, Bernard Dick 2, Felix Frey 1, and Eberhard Ritz 3

1 Department of Internal Diseases, Diabetology and Nephrology, Silesian Medical Academy, Zabrze, Poland
2 Division of Nephrology and Hypertension, University Hospital Berne, Switzerland
3 Department of Internal Medicine, Ruperto Carola University, Heidelberg, Germany

* To whom correspondence should be addressed.
Krzysztof Strojek, E-mail: kstrojek{at}slam.katowice.pl



  Abstract

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{alpha}THF)/THE) ratio in the urine as an index of 11{beta}-hydroxysteroid dehydrogenase type 2 (11{beta}HSD2) 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 + 5{alpha}THF)/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 11{beta}HSD2.

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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