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Apelin is a vasoactive peptide isolated as a selective endogenous ligand of orphan receptor, APJ, which was genetically identified to have closest identity to the angiotensin II type 1 (AT-1) receptor. Subsequent studies elucidated the roles of the apelin–APJ system in human physiology, including the regulation of cardiovascular function and fluid homeostasis. In spite of the high homology between APJ receptor and AT-1 receptor, the apelin–APJ system has been found to exert opposing actions to angiotensin II (Ang II)-AT-1. Recent reports have also shown the roles of apelin–APJ in renal physiology, including the maintenance of water balance in the kidney. In addition, the renoprotective effect of the apelin–APJ system in renal diseases has been reported in the context of renal fibrosis, renal ischemia/reperfusion (I/R) injury and diabetic nephropathy, suggesting that the apelin–APJ system may become a new therapeutic target for renal diseases. The aim of this critical review is to discuss the apelin–APJ system, its role in renal physiology and potential therapeutic applications for renal diseases. Conclusion The functional counter-regulatory role of apelin–APJ in Ang II-AT1 and AVP action is critically important when considering the action of the apelin–APJ system in the regulation of human physiology. Regarding kidney function, recent reports have shown the direct action of apelin– APJ to the kidney in the context of fluid homeostasis, and also its roles in renal fibrosis, renal I/R injury and diabetic nephropathy, along with its potential use as a therapeutic target.

The Apelin-APJ system: its role in renal physiology and potential therapeutic applications for renal disease