Salt-sensitive blood pressure--an intermediate phenotype predisposing to diabetic nephropathy?
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 + 5alphaTHF)/THE) ratio in the urine as an index of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) 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 + 5alphaTHF)/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 11betaHSD2.


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.
Strojek
Krzysztof
K
Department of Internal Diseases, Diabetology and Nephrology, Silesian Medical Academy, 3-go Maja 13/15, Zabrze 41-800, Poland. kstrojek@slam.katowice.pl
Nicod
Jerome
J
Ferrari
Paolo
P
Grzeszczak
Wladyslaw
W
Gorska
Juta
J
Dick
Bernard
B
Frey
Felix
F
Ritz
Eberhard
E
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D004039:Diet, Sodium-Restricted; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000009:adverse effects*
D012982:Sodium, Dietary