Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in patients with chronic kidney diseases.
BACKGROUND
NO synthesis is inhibited by the dimethylarginine (DMA) ADMA, which accumulates, similar to SDMA, in the plasma of patients suffering from chronic renal failure (CRF). ADMA and possibly SDMA contribute to hypertension and atherosclerosis in patients with chronic renal disease: ADMA inhibits directly eNOS, whereas SDMA competes with the NO precursor arginine for uptake into the cells.


METHODS
In 26 control persons and 221 patients with kidney diseases of different stage as were CRF, end stage renal disease (ESRD), and patients after renal transplantation (RT), the plasma concentrations of ADMA (c(ADMA)), SDMA (c(SDMA)) and 20 endogenous amino acids (AA) were measured by HPLC and correlated to blood pressure, cardiac events, endothelial dysfunction, and diabetes mellitus.


RESULTS
Both ADMA (1.04+/-0.04 vs. 0.66+/-0.04 microM) and SDMA (2.69+/-0.12 vs. 0.49+/-0.03 microM) were significantly (p<0.001) elevated in all patients compared to healthy controls, whereas arginine concentration (51.4+/-2.3 vs. 76.0+/-5.2 microM) was decreased in dependence on the degree of kidney disease. In RT patients, SDMA levels were significantly decreased, but c(ADMA) remained enhanced. A strong correlation was found between SDMA and both serum urea and creatinine in CRF and RT patients. A linear correlation was found between ADMA and cholesterol concentrations in RT patients. Hypertension in CRF was accompanied by a further increase in the concentration of DMAs. There was no relation between DMAs and the occurrence of peripheral arterial occlusive disease or cerebrovascular diseases. In patients with cardiac diseases, c(SDMA) was additionally increased only in the CRF group.


CONCLUSIONS
In patients with chronic kidney disease, c(ADMA) and c(SDMA) are significantly increased but cardiovascular diseases are evidently not correlated to changes in DMA concentrations in this group of patients.
D000596:Amino Acids / Q000097:blood; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D006331:Heart Diseases / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D016030:Kidney Transplantation; D012044:Regression Analysis; D006435:Renal Dialysis
D000596:Amino Acids; C018524:N,N-dimethylarginine; D001120:Arginine; D003404:Creatinine