Renin receptor blockade: a better strategy for renal protection than renin-angiotensin system inhibition?

Prorenin and renin bind to a 350-amino acid protein called the (pro)renin receptor, which is present on the surface and functions intracellularly. When the receptor's N terminus binds either prorenin or renin, intracellular signaling occurs via extracellular-regulated kinases, which can result in plasminogen activator inhibitor and transforming growth factor-beta production. Investigators have developed a novel decoy peptide, called the handle-region peptide (HRP), which obviates binding of prorenin to the receptor. HRP has successfully inhibited diabetic nephropathy in rats and in angiotensin receptor-deleted mice, and has blocked fibrosis in the hearts of spontaneously hypertensive rats. The same researchers developed a transgenic (pro)renin receptor-expressing rat with glomerulosclerosis that responded dramatically to HRP treatment. However, groups in Paris, Rotterdam, and Berlin have not been able to confirm the findings, and the precise role of the (pro)renin receptor remains imperfectly defined.