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 + 5αTHF)/THE) ratio in the urine as an index of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) 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 + 5αTHF)/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 11βHSD2. 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 nephropath

Inverse associations between androgens and renal function : The Young Men Cardiovascular Association (YMCA) study

Background: Men exhibit higher risk of nondiabetic renal diseases than women. This male susceptibility to renal disease may be mediated by gender-specific factors such as sex hormones. Methods: We have undertaken a cross-sectional examination of associations between renal function (creatinine clearance estimated based on Cockcroft-Gault equation) and circulating levels of sex steroids (total testosterone, total estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and dihydrotestosterone) in 928 young (mean age: 18.5 ± 1.2 years) men. Results: Both androstenedione and DHEA-S showed inverse linear associations with renal function in the crude analysis of lean men (those with body mass index (BMI) less than median). However, only DHEA-S retained its association with renal function in lean subjects after adjustment - assuming no changes in other independent variables 1 s.d. increase in DHEA-S was associated with 13%-s.d. decrease in creatinine clearance (P = 0.004). Testosterone decreased across tertiles of creatinine clearance only in the crude analysis of nonlean (BMI greater than median) subjects (P < 0.001). The adjusted regression analysis that assumed no changes in other independent variables showed that 1 s.d. increase in total testosterone was associated with 11%-s.d. decrease in creatinine clearance of nonlean men (P = 0.006). Factor analysis confirmed an inverse association of renal function with both sex steroids and a different pattern of their loadings on glomerular filtration-related factors in lean (DHEA-S) and nonlean (testosterone) subjects. Conclusions: Our data may suggest that androgens are inversely associated with estimated renal function in apparently healthy men without history of cardiovascular disease. © 2009 American Journal of Hypertension, Ltd.C