Changes in kidney function in a population with essential hypertension in real life settings

Introduction. Hypertension has been identified as one of the commonest modifiable determinants for chronic kidney disease progression. A variety of antihypertensive drugs are available and their effect on kidney function has been investigated by a large number of randomized controlled trials. Observational studies, although scarcely been used, outpatient can reflect everyday practice, where drug exposures vary over time, and may provide an alternative for detecting longitudinal changes in kidney function. Materials and Methods. We applied mixed model repeated measures analysis to investigate the effect of antihypertensive drug categories and their combinations on kidney function change over time in a cohort of 779 patients with essential hypertension, using the data from a Greek hypertension outpatient clinic. Antihypertensive drugs were grouped in 5 categories. Their effect was evaluated and their combinations with and without renin-angiotensin-system inhibitors (RASI) to each other. In addition, the combination of RASI with calcium channel blockers (CCBs) was studied. Results. Diuretics, RASI, CCBs, and beta-blockers had a significant renoprotective and blood pressure lowering effect. Combinations with RASI had a smaller beneficial effect on kidney function compared to CCBs (0.75 mL/min/1.73 m2 per year of drug use versus 0.97 mL/min/1.73 m2). There was no additional effect when combining RASI with CCBs. However, the lowering effect on systolic blood pressure was greater (-0.83 mm Hg per year of drug use, P < .001). Conclusions. RASI were found to have a smaller, although significant, renoprotective effect. There was no additional effect on kidney function when combining RASI with CCBs

Validity and reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and McAuley's indices in patients with hypertension and type II diabetes

The aim of this study was to evaluate the validity and reliability of homeostasis model assessment-insulin resistance (HOMA-IR) index, its reciprocal (1/HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and McAuley's index in hypertensive diabetic patients. In 78 patients with hypertension and type II diabetes glucose, insulin and triglyceride levels were determined after a 12-h fast to calculate these indices, and insulin sensitivity (IS) was measured with the hyperinsulinemic euglycemic clamp technique. Two weeks later, subjects had again their glucose, insulin and triglycerides measured. Simple and multiple linear regression analysis were applied to assess the validity of these indices compared to clamp IS and coefficients of variation between the two visits were estimated to assess their reproducibility. HOMA-IR index was strongly and inversely correlated with the basic IS clamp index, the M-value (r = 0.572, P < 0.001), M- value normalized with subjects' body weight or fat-free mass and every other clamp-derived index. 1/HOMA-IR and QUICKI indices were positively correlated with the M- value (r = 0.342, P < 0.05 and r = 0.456, P < 0.01, respectively) and the rest clamp indices. McAuley's index generally presented less strong correlations ( r = 0.317, P < 0.05 with M- value). In multivariate analysis, HOMA-IR was the best fit of clampderived IS. Coefficients of variation between the two visits were 23.5% for HOMA-IR, 19.2% for 1/HOMA-IR, 7.8% for QUICKI and 15.1% for McAuley's index. In conclusion, HOMA- IR, 1/HOMA-IR and QUICKI are valid estimates of clamp-derived IS in patients with hypertension and type II diabetes, whereas the validity of McAuley's index needs further evaluation. QUICKI displayed better reproducibility than the other indices

Oral Calcium Supplementation Ambulatory Blood Pressure and Relation to Changes in Intracellular Ions and Sodium-Hydrogen Exchange

BACKGROUND Calcium (Ca2+) supplementation has been shown paradoxically to reduce intracellular Ca2+ and induce vascular relaxation. The aim of the study was to assess 24-h blood pressure (BP) change after Ca2+ supplementation and to investigate its relation to changes in intracellular ions and the activity of the first isoform of sodium-hydrogen exchange (NHE-1) in subjects with hypertension and type 2 diabetes. METHODS This parallel, randomized controlled, single-blinded trial, consisted of 31 patients with type 2 diabetes, and hypertension who were allocated to receive 1,500 mg of Ca2+ per day (n = 15) or no treatment (n = 16) for 8 weeks. RESULTS In the Ca2+ group a decrease of 1.7 +/- 2.7 mm Hg (mean +/- SE) P = 0.52 for mean 24-h systolic BP (SBP) and 2.1 +/- 1.5 mm Hg, P = 0.19 for mean 24-h diastolic BP (DBP) was recorded. Whereas in the control group an increase of 1.4 +/- 2.7 mm Hg, P = 0.59 for mean 24-h SBP and 1.2 +/- 2.8 mm Hg, P = 0.83 for mean 24-h DBP was observed. Intraplatelet Ca2+ decreased whereas intraplatelet magnesium (Mg2+) and erythrocyte K+ increased in the intervention group. Change in mean 24-h SBP in the pooled group correlated with both change in intraplatelet Ca2+ (r = 0.49, P < 0.05) and NHE-1 activity (r = 0.6, P < 0.001). The contribution of intraplatelet Ca2+ was attenuated when both parameters were entered in a multivariate regression model. CONCLUSIONS The present study shows a weak, statistically nonsignificant trend towards association of Ca2+ supplementation on 24-h BP in hypertensive subjects with type 2 diabetes. However, our results indicated an interrelation of [Ca2+], levels and NHE-1 activity on BP in patients with hypertension and type 2 diabetes

Insulin sensitivity increase after calcium supplementation and change in intraplatelet calcium and sodium-hydrogen exchange in hypertensive patients with Type 2 diabetes

To investigate the effect of oral calcium (Ca2+) supplementation on insulin sensitivity measured by the euglycaemic hyperinsulinaemic clamp, intraplatelet cationic concentration of Ca2+ ([Ca2+](i)) and the transmembrane sodium-hydrogen exchanger (NHE) activity in erythrocytes in subjects with Type 2 diabetes and hypertension. In this parallel randomized controlled single-blinded trial, 31 patients were allocated to receive either 1500 mg of Ca2+ orally, daily (n = 15) or no treatment (n = 16) for 8 weeks. At baseline and at the end of the 8-week period insulin sensitivity, [Ca2+](i) and the first isoform of NHE (NHE-1) activity were measured. At the end of the study, subjects who received Ca2+ supplementation showed higher insulin sensitivity (Delta M-value 0.32 +/- 0.5 mmol/min P < 0.05) and lower [Ca2+](i) (125.0 +/- 24.7 to 80.4 +/- 10.6 nmol/l, P < 0.05, mean +/- sem) and NHE-1 activity (79.5 +/- 10.0 to 52.1 +/- 6.4 mmol Na/l red cell/h, P < 0.05). None of the above parameters were changed in the control group. Simple regression analysis demonstrated the change in [Ca2+](i) significantly determined insulin sensitivity change (beta = -0.36, P < 0.05). Oral Ca2+ supplementation improves insulin sensitivity in patients with Type 2 diabetes and hypertension. These changes are likely to be mediated by changes in intracellular ionic Ca2+. NHE-1 activity was also reduced after Ca2+ supplementation but its role in insulin sensitivity requires further investigation