Prostaglandins and the side effects of anti-inflammatory drugs--the kidney

The most important renal side effect of non-steroidal anti-inflammatory therapy in man is analgesic nephropathy. One possible mechanism for this effect is inhibition of renal prostaglandin synthesis. However, an understanding of the regional biosynthesis of renal prostaglandins, of their pharmacological, physiological and pathological properties in the kidney and an understanding of the consequences of their inhibition by drugs is required in order to assess whether such a mechanism is involved. These aspects are reviewed, using much of the early work of the author as a basis for the discussion. The following conclusions can be drawn form a review of published work. "The consequences of the inhbiition of renal prostaglandin synthesis do not seem to bear much relationship to the renal side effects of anti-inflammatory therapy in man". It is further suggested that impaired renomedullary blood flow arising from decreased renomedullary PGE2 synthesis results in increased accumulation of drug in the renal medulla leading to direct toxic damage. Finally, examples of diseases associated with increased or decreased renal PGE2 synthesis are discussed and some examples of drug interactions are presented.