Are oral prostaglandins effective in preventing nephrotoxicity from NSAIDs and cyclosporin?

Abstract

Prostaglandins are modulators of renal excretory function via alterations of intrarenal perfusion pressures and the distribution of blood flow. The predominant renal prostaglandins are prostacyclin (PGI2), prostaglandin E2 (PGE2) and PGF2α Medullary synthesis exceeds cortical synthesis five to ten fold, although PGI2 appears to be maximally produced in the cortex [1-3]. The regulation of basal prostaglandin production is still poorly understood, but renal injury readily augments output. This appears to be true independent of the mechanism of injury, whether by ischaemia, obstructive uropathy, toxic exposure or immunological disturbance [4,5]. Renal vasoconstriction markedly accelerates prostaglandin synthesis and release, and chronic renal damage is usually characterized by an elevation in renal vascular resistance. In addition, the infusion of exogenous vasoconstrictors such as angiotensin II or norepinephrine elicits release of the vasodilator PGE2 [4]. Under normal volume replete conditions renal function is to a very limited, if any extent dependent on endogenous prostaglandin synthesis. When maintenance of renal circulation is stressed by vasoconstricting hormones or by diminished circulating volume, then endogenous prostaglandin production becomes critically important in the maintenance of a normal renal blood flow (RBF) and glomerular filtration rate (GFR).