The past, presence and future of ADMA in nephrology.
Kakimoto and Akazawa, first isolated and identified asymmetric dimethylarginine (ADMA) from human urine in 1970. They speculated that ADMA, and its structural isomer symmetrical dimethylarginine (SDMA), "may be important for the study of various pathological states". It took 22 years before this hypothesis materialized in form of the seminal paper by Vallance et al. who advanced the idea that ADMA accumulation may be a cardiovascular risk factor in chronic kidney disease (CKD). In the last 15 years the relationship between ADMA and adverse cardiovascular outcomes has been thoroughly investigated in more than 600 published reports. These studies have shown that ADMA does not only correlate with traditional and non-traditional risk factors but also, independently of other risk factors, is strongly associated with clinical measures of cardiovascular burden such as intima-media thickness (IMT) of the carotid artery and left ventricular mass. Furthermore, cohort studies in both the general population and the dialysis population demonstrated a strong and independent link between ADMA, all-cause mortality and cardiovascular events. Last but not least, ADMA predicts the progression of CKD. This burgeoning body experimental and clinical studies form a fairly coherent framework indicating that ADMA is not only a marker but also a potent mediator of endothelial dysfunction and atherosclerosis as well as a solid predictor of mortality in selected patient populations. This article reviews the role of ADMA as a marker and mediator in cardiovascular disease in the setting of CKD and summarizes the effect of different renal replacement therapies as well as the effect on ADMA levels of commonly used drugs in nephrology. We conclude with remarks on the usefulness of ADMA as a marker in the clinical setting as well as for emerging therapeutic strategies.
Kielstein
Jan T
JT
Division of Nephrology, Department of Internal Medicine, Medical School Hannover, 1, Carl-Neuberg-Strasse, 30625 Hannover, Germany. Kielstein@yahoo.com
Fliser
Danilo
D
D001120:Arginine / Q000031:analogs & derivatives* / Q000652:urine; D002318:Cardiovascular Diseases / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology* / Q000652:urine; D007677:Kidney Function Tests; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012307:Risk Factors
D004791:Enzyme Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase