Effect of keto amino acids on asymmetric dimethyl arginine, muscle and fat tissue in chronic kidney disease

Levels of 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 CKD patients by long-term administration of low-protein diet (LPD) supplemented with keto amino acids (KA). In a long-term prospective double blind placebo controlled randomized trial, we evaluated a total of 120 CKD patients (62/58F) aged 22-76 yrs with creatinine clearance 22-40mL/min/1.73m2 for a period of 36 months. All patients were on low-protein diet containing 0.6 protein/kg/IBW/day and 120-125/kJ/kg/IBW/day. LPD was randomly supplemented with KA at dosage of 100 mg/kg/IBW/day (61 patients, Group I) while 59 patients (Group II) received placebo. During the study period, glomerular filtration rate (GFR) slightly decreased (Ccr from 34.2±11.6 to 29.9±9.2 mL/min and 33.5±11.6 to 22.2±10.4 mL/min in Group I and II, respectively); this however was more marked in Group II (p<0.01). Fat in muscle measured by MR spectroscopy (MRS, m.tibialis anterior) significantly decreased in Group I and was linked to reduced volume of visceral fat measured by MRI (p<0.01). Reduction of fat in Group II was not significant. In Group I, there was a significant decrease in the plasma level of ADMA (from 2.4±0.4 to 1.2±0.3 μmol/L, p<0.01), but ADMA remained unchanged in Group II. A further remarkable finding was reduction in the plasma concentration of pentosidine (from 486±168 to 325±127 μg/L, p<0.01) and decrease of proteinuria (from 3.7±2.20 to 1.6±1.2 g/24hrs, p<0.01) in Group I. Plasma adiponectin (ADPN) in Group I rose (p<0.01). Analysis of lipid spectrum revealed a mild yet significant decrease in total cholesterol and LPD-cholesterol (p<0.01), more pronounced in Group I. In Group I, there was a decrease in plasma triglycerides (from 3.8±1.5 down to 2.3±0.5 mmol/L, p<0.01), whereas glycated hemoglobin (HbAc1) decreased from 7.0±1.3 to 4.1±0.9 %, (p<0.01) nIn conclusion,comparing to placebo group long term co-administration of LPD and KA in CKD patients led to decrease of ADMA,fat in muscle and visceral body fat, and proteinuria. Concomitant decreases of glycated haemoglobin, LDL-c and pentosidine may also contribute to the delay in progression of renal failure and decrease of cardiovascular risk factors..The study was supported by Research Project MZO 00023001 awarded by Ministry of Health of the Czech Republi