Asymmetric dimethylarginine in hemodialysis, hemodiafiltration, and peritoneal dialysis.

Asymmetric dimethylarginine (ADMA) is a mediator of endothelial dysfunction. Production and elimination of ADMA may be affected by the type of renal replacement therapy used and oxidative stress. Plasma ADMA, advanced glycation end products (AGE), and homocysteine were assessed in 59 subjects: 20 hemodialysis (HD) patients, 19 patients undergoing peritoneal dialysis (PD), and 20 controls. Results were compared between the groups. The effect of 8 weeks of HD and high-volume predilution hemodiafiltration (HDF) was compared in a randomized study. HD patients showed higher ADMA (1.20 [0.90-1.39 micromol/L]) compared to controls (0.89 [0.77-0.98], P < 0.01), while ADMA in PD did not differ from controls (0.96 [0.88-1.28]). AGE and homocysteine were highest in HD, lower in PD (P < 0.01 vs. HD), and lowest in controls (P < 0.001 vs. HD and PD). PD patients had higher residual renal function than HD (P < 0.01). The decrease in ADMA at the end of HD (from 1.25 [0.97-1.33] to 0.66 [0.57-0.73], P < 0.001) was comparable to that of HDF. Switching from HD to HDF led to a decrease in predialysis homocysteine level in 8 weeks (P < 0.05), while ADMA and AGE did not change. Increased ADMA levels in patients undergoing HD, as compared to PD, may be caused by higher oxidative stress and lower residual renal function in HD. Other factors, such as diabetes and statin therapy, may also be at play. The decrease in ADMA at the end of HD and HDF is comparable. Switching from HD to HDF decreases in 8 weeks the predialysis levels of homocysteine without affecting ADMA.

Asymmetric dimethylarginine and adiponectin after renal transplantation: role of obesity.

BACKGROUND: In obese renal transplant recipients, we assessed the course of selected proinflammatory factors liable to influence long-term outcomes of transplant patients and kidney grafts. METHODS: In a prospective cohort study, we examined a total of 140 renal transplant recipients for a period of 12 months. Based on body mass index (BMI), patients were divided into Group I (BMI > or = 30 kg/m2, 68 patients) and Group II (BMI < or = 30 kg/m2, 72 patients). RESULTS: Twelve months after renal transplantation, significant differences were found between Group I versus Group II in plasma levels of asymmetric dimethylarginine (ADMA) (3.65 [SD +/- 0.47 micromol/L] versus 2.01 [SD +/- 0.36 micromol/L], P < .01), adiponectin (ADPN) (15.4 [SD +/- 6.6 microg/mL] versus 22.3 [SD +/- 8.2 microg/mL], P < .01), leptin (51.3 [SD +/- 11.2 ng/L] versus 21.3 [SD +/- 9.2 ng/L], P < .01), soluble leptin receptor (24.6 [SD +/- 8.4 U/mL] versus 46.1 [SD +/- 11.4 U/mL], P < .01), resistin (20.8 [SD +/- 10.1 microg/mL] versus 14.6 [SD +/- 6.4 microg/mL], P < .025), and triglycerides (3.9 [SD +/- 1.6] versus mmol/L 2.8 [SD +/- 1.6 mmol/L], P < .01). There were significant correlations between ADMA and BMI (r = 0.520; P < .001), and ADPN and BMI (r = -0.570, P < .001). The correlation between ADMA and inulin clearance (Cin) was weak (r = -0.185, P < .05). CONCLUSIONS: Obesity after renal transplantation is associated with increased ADMA and decreased ADPN in plasma, and this may represent a risk factor for renal transplant recipients.

Effect of L-carnitine supplementation on secondary hyperparathyroidism and bone metabolism in hemodialyzed patients.

The aim of our work was to test the influence of L-carnitine supplementation on secondary hyperparathyroidism and bone metabolism in hemodialyzed patients in a randomized study. Eighty-three chronically hemodialyzed patients were observed; 44 were supplemented with L-carnitine (15 mg/kg intravenously after each hemodialysis for 6 months), while 39 took placebo. Levels of free carnitine (CAR), calcium (Ca), inorganic phosphate (P), Ca x P product, parathormone (PTH), bone-specific alkaline phosphatase (b-ALP), osteocalcin (OC), and osteoprotegerin (OPG) were monitored. In comparison with pretreatment values, changes of some selected parameters occurred in the supplemented patients after 6 months (data are expressed as medians; NS, nonsignificant change): PTH, 186.0 vs. 135.5 ng/L (NS); b-ALP, 13.9 vs. 13.2 microg/L (P < 0.05); OC, 78.3 vs. 68.8 microg/L (NS); OPG, 144.0 vs. 182.0 ng/L (P < 0.05). In the controls, there were the following changes: PTH, 148.0 vs. 207.0 ng/L (NS); b-ALP, 15.2 vs. 13.2 microg/L (P < 0.05); OC, 62.7 vs. 79.8 microg/L (P < 0.05); OPG, 140.0 vs. 164.0 ng/L (NS). A significant correlation was found between CAR and OPG changes (r = 0.51, P < 0.001) in the supplemented patients. The supplementation led to a significant increase of serum OPG concentration. Nevertheless, we observed only nonsignificant tendencies to correction of secondary hyperparathyroidism and reduction of bone turnover in hemodialyzed patients supplemented with L-carnitine in contrast to controls. At this point, the use of L-carnitine does not seem to be justified.

Measurement of carnitine in hemodialysis patients - adaptation of an enzymatic photometric method for an automatic analyzer.

BACKGROUND: The main goal of this work was to describe the analytical characteristics of an enzymatic photometric test for carnitine determination and its automation using an Olympus analyzer. METHODS: We used a test from Roche intended for manual processing and tried to apply it for use on an Olympus AU 400 analyzer. The analytical parameters of our modified technique were determined using external quality controls and kit controls, and by measurements in venous blood samples from 85 chronically hemodialyzed patients (before and after hemodialysis) and from 68 healthy blood donors serving as controls. RESULTS: A reference value for free carnitine was estimated parametrically as 40.1+/-17.8 micromol/L. The mean bias for eight control measurements was 5.1%. Sensitivity was calculated as the limit of quantification at 2.6 micromol/L. The intra-assay coefficient of variation was 2.4%. The inter-assay coefficient of variation was 8.3%. Analytical recovery was 101.8%, 99.5% and 95.4%. CONCLUSIONS: The main advantages of our automated method in comparison to the original manual method are the smaller amounts of samples, reagents and diluents required and the shorter analysis time. As hemodialysis patients often suffer from carnitine deficiency, we conclude that its determination may be helpful for diagnostic verification.

Asymmetric dimethylarginine, homocysteine and renal function--is there a relation?

The adverse effect of hyperhomocysteinemia on the vascular wall can be partially explained by increasing plasma concentration of asymmetric dimethylarginine (ADMA), a potent inhibitor of nitric oxide synthase. The aim of the study was to compare ADMA and homocysteine levels in three groups of subjects: blood donors with normal homocysteine concentration (group A), patients with hyperhomocysteinemia and normal kidney function (group B) and hemodialysis patients who are known to be hyperhomocysteinemic (group C). Concentrations of homocysteine (enzymatic method), ADMA (enzyme-linked immunoassay) and creatinine (Jaffe method) in EDTA plasma were measured. Plasma ADMA levels were significantly higher in both groups with hyperhomocysteinemia (1.60+/-0.56 micromol/L in group B, 1.81+/-0.57 micromol/L in group C) when compared with those in blood donors (0.82+/-0.29 micromol/L, p<0.001 in both cases). Significant positive correlations were found between concentrations of ADMA and homocysteine (r=0.42, p<0.0001), ADMA and creatinine (r=0.39 p<0.001), homocysteine and creatinine (r=0.69, p<0.0001), age and homocysteine (r=0.47, p<0.001), age and ADMA (r=0.57, p<0.001) and age and creatinine (r=0.37, p<0.001). Increased ADMA concentrations in hyperhomocysteinemic patients were confirmed, but multiple linear regression analysis showed that this significant correlation is only apparent due the dependence of both parameters on age.