Role of Transport Proteins for the Renal Handling of L-Arginine and Related Derivatives.

L-arginine and its derivatives L-homoarginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) show distinct (patho-) physiological properties as well as a differential renal handling. L-arginine and L-homoarginine have a lower renal clearance and are largely retained (i.e., reabsorbed) as compared to ADMA and SDMA, which are relatively enriched in the urine and excreted. To obtain a more complete picture of what is known regarding transport proteins involved in renal reabsorption and secretion of these substances, a comprehensive literature review and search of cell-specific gene expression databases were performed. Five transport proteins known to transport L-arginine and its derivatives were included, and the data available regarding their tubular expression pattern and their transport characteristics, as well as experimental and clinical data regarding their possible impact on the renal handling of L-arginine and its derivatives, are presented and discussed in a structured narrative review. Based on their transport properties and links to clinical phenotypes, bAT-rBAT and yLAT1-4F2hc were identified as the most promising candidates to explain a significant part of the observed differential renal handling. This also makes them promising candidates for further investigations as mediators of possible adverse and beneficial drug effects involving L-arginine, L-homoarginine, ADMA, and SDMA.