Removal of asymmetric dimethylarginine during artificial liver support using fractionated plasma separation and adsorption

Abstract

This study shows for the first time that plasma levels of ADMA can be effectively lowered by an artificial liver support system (Prometheus). Effective elimination of ADMA might explain some of the beneficial clinical effects of these systems in patients with liver failure.

Renal biomarkers in domestic species

“…Currently, SDMA's rate of production is thought to be relatively constant, although in theory, altered arginine methylation and/or protein breakdown could contribute to increased or decreased serum concentrations. Furthermore, SDMA does not appear to be highly protein bound, and its clearance is similar to that of creatinine, supporting that it is freely filtered through the glomerulus . It is largely renally excreted; however, hepatic clearance of SDMA was observed in people, and a small degree of uptake by the gut was observed in rats .…”

Dimethylarginines ADMA and SDMA: The Real Water-Soluble Small Toxins?

“…32 The liver support system Prometheus, a tool that effectively removes protein-bound substances, was able to reduce SDMA levels by only 22%. 21 This suggests that protein binding should not hamper SDMA removal by dialysis. Interestingly, in patients with liver failure, SDMA (but not ADMA) correlated with ammonia levels.…”

“…Interestingly, in patients with liver failure, SDMA (but not ADMA) correlated with ammonia levels. 21 Aside from ADMA and SDMA there is a third methylarginine residue produced in mammals, NG monomethyl-l-arginine (l-NMMA), which has been the standard nitric oxide synthase inhibitor used to evaluate the role of the l-arginine:nitric oxide pathway. 33 Because the l-NMMA concentrations in plasma are about an order of magnitude lower than those of ADMA and SDMA, 5 l-NMMA has not been the focus of many preclinical and clinical studies.…”

The effect of fractionated plasma separation and adsorption on cerebral amino acid metabolism and oxidative metabolism during acute liver failure

“…A beneficial effect of MARS and FPSA on plasma proinflammatory cytokine levels in acute liver failure and on substances such as phenols and dimethylarginine, all of which contribute to the development of HE and brain edema, has been demonstrated [10][11][12]. Whether the effect of these blood purification systems is favorable to brain metabolism has not been studied in patients with ALF.…”