Gender-related determinants of advanced subclinical atherosclerosis in patients undergoing kidney transplantation.

BACKGROUND: Cardiovascular disease caused by atherosclerosis remains a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). We evaluated the potential association of cardiovascular risk factors including asymmetric dimethyl L-arginine (ADMA) and the soluble receptor for advanced glycation end products (sRAGE) with preclinical atherosclerosis in patients undergoing kidney transplantation. PATIENTS AND METHODS: In 92 males and 47 females undergoing the first cadaveric renal transplantation, ADMA, sRAGE and common risk factors including lipid parameters were evaluated as potential predictors of preclinical atherosclerosis defined as the Belcaro score (focused on advanced atherosclerotic changes) measured by ultrasound. RESULTS: The prevalence of atherosclerotic changes was approximately 70% in men and women. In logistic regression, age, history of smoking, presence of diabetes mellitus, and plasma triglycerides were the strongest independent predictors for advanced atherosclerosis in the whole group. In unadjusted analyses advanced atherosclerosis was also associated with sRAGE in men and with the atherogenic index of plasma in women. CONCLUSION: Apart from traditional cardiovascular risk factors, plasma triglycerides were found to be strong and independent predictors of advanced atherosclerosis in patients with ESRD. In addition, sRAGE was associated with atherosclerosis in men and the atherogenic index of plasma in women.

Reduction of plasma asymmetric dimethylarginine in obese patients with chronic kidney disease after three years of a low-protein diet supplemented with keto-amino acids: a randomized controlled trial.

BACKGROUND: Levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are elevated in chronic kidney disease (CKD) and may contribute to vascular complications. In this study we tested the hypothesis that elevated ADMA can be reduced in obese CKD patients by long-term administration of a low-protein diet supplemented with keto-amino acids. PATIENTS AND METHODS: In a long-term prospective double-blind placebo-controlled randomized trial, we evaluated for a period of 36 months a total of 111 CKD patients (54 men, 57 women) aged 22-76 years with obesity (BMI >or= 30 kg/m(2)) and an inulin clearance rate (C(in)) of 22-40 ml/min/1.73 m(2). All patients were on a low-protein diet containing 0.6 g protein/kg BW per day and 120-125 kJ/kg BW per day. The diet was randomly supplemented with keto-amino acids at a dosage of 100 mg/kg BW per day (66 patients, Group I); 65 patients received placebo (Group II). RESULTS: During the study period, the glomerular filtration rate decreased slightly in Group I (C(in) from 32.4 +/- 12.6 to 29.8 +/- 8.6 ml/min/1.73 m(2)) and more markedly in Group II (from 33.2 +/- 12.6 to 23.2 +/- 98.4 ml/min/1.73 m(2), P < 0.01). BMI decreased significantly in Group I (from 32.0 +/- 3.3 to 26.1 +/- 4.0 kg/m(2), P < 0.01) and was linked to reduced volume of visceral fat measured by MRI (P < 0.01). Reduction of BMI in Group II was not significant. In Group I, there was a significant decrease in the plasma level of ADMA (from 2.5 +/- 0.5 to 1.3 +/- 0.4 micromol/l, P < 0.01), but ADMA remained unchanged in Group II. A further remarkable finding in Group I was reduction in the plasma concentration of pentosidine (from 480 +/- 170 to 320 +/- 120 microg/l, P < 0.01) and decrease of proteinuria (from 3.8 +/- 2.24 to 1.6 +/- 1.0 g/24 h, P < 0.02). Plasma adiponectin rose in Group I (P < 0.01). Analysis of the lipid spectrum revealed a mild but significant decrease in total cholesterol and LPD-cholesterol (P < 0.02), more pronounced in Group I. There was also a decrease in plasma triglycerides in Group I (from 3.9 +/- 1.6 down to 2.2 +/- 0.6 mmol/l, P < 0.01) and a decrease in glycated hemoglobin (from 7.2 +/- 1.4% to 4.2 +/- 0.8%, P < 0.02). CONCLUSION: Compared with the placebo group, long term co-administration of a low-protein diet and keto-amino acids in CKD patients with obesity led to decreases of ADMA, visceral body fat and proteinuria. Concomitant decreases of glycated hemoglobin, LDL-cholesterol and pentosidine may also contribute to the delay in progression of renal failure.

Estimation of glomerular filtration rate based on the modification of diet in renal disease equation in patients with chronic renal failure.

The list of indications for initiating regular dialysis treatment includes residual glomerular filtration rate (GFR). Under the current European Best Practice Guidelines for Hemodialysis, residual GFR (and the presence of one or more symptoms of uremia) should not decrease below 15 ml/min. The present article seeks to determine to what extent the modification of diet in renal disease (MDRD) equation enables the detection of this decrease in GFR. We tried to answer this question using a more detailed analysis of the relationship between MDRD and renal inulin clearance (C in). Residual GFR based on C in (under conditions of stable plasma levels and water loading) and GFR calculated using the MDRD equation was measured in 79 individuals with chronic renal failure (with mean C in = 19.1 +/- 10.1 ml/min/1.73 m2). Statistical evaluation was performed using regression analysis, the interchangeability of both methods (Bland-Altman) and receiver-operating characteristic (ROC) curve analysis. Regression analysis demonstrated a significant correlation between MDRD and C in (r = 0.892; p < 0.001). However, the regression equation line for the correlation differs significantly from the identity line (p < 0.001). The value of the regression coefficient (0.722) is significantly lower than 1.0 (CI50 0.63; 0.81). The mean MDRD -C in difference was 3.26 +/- 4.46 ml/min/1.73 m2 and the value was significantly different from zero (p < 0.001). The mean difference +2 SD was 12.2 ml/min/1.73 m2, and the mean - 2 SD was -5.7 ml/min/1.73 m2. ROC curve analysis (for a cutoff C in = 15 ml/min/1.73 m2) indicates an area under the curve (AUC) of 0.954 +/- 0.023. The best combination of sensitivity and specificity was obtained for a MDRD of 19.7 ml/min/1.73 m2, with a sensitivity of 90.5% and specificity of 87.5%. For cutoff value of C in = 10 ml/min/1.73 m2, the AUC was 0.939 +/- 0.026 (CI95 0.863-0.890). A combination of maximum sensitivity and specificity was obtained with an MDRD of 16.5 ml/min/1.73 m2. With this value, MDRD sensitivity was 100% and specificity 81.5%. A significant correlation between the MDRD equation and the measured creatinine clearance (C cr) was found (r = 0.883, p < 0.001). The mean difference of MDRD-C cr was -7.2 +/- 6.5 ml/min/1.73 m2. This is significantly different from that of MDRD-C in (p < 0.001). Our results suggest that MDRD and C in in individuals with chronic renal failure are not interchangeable methods for a GFR <15 ml/min/1.73 m2 determination. However, MDRD may furnish valuable information in terms of detecting a critical decrease in GFR; but, the MDRD equation for this decrease in GFR (15 ml/min/1.73 m2) will provide a somewhat higher value (19.7 ml/min/1.73 m2).