The Adverse Renal Effects of Nonsteroidal Anti-inflammatory Drugs: Increasing Problems or Overrated Risk

I N the past few years the pharmaceutic"al industry has provided the clinician with a host of new nonsteroidal anti-inflammatory medications which are effective in the treatment of many chronic disorders such as rheumatoid arthritis, degenerative joint disease, gout, and spondyloarthritis. Their mechanism of action is at least in part achieved by prostaglandin inhibition. The market for these drugs is large and there are estimates that over 5 million individuals are exposed daily. This figure may be conservative if one considers individuals exposed to older nonsteroidal anti-inflammatory compounds such as aspirin. The growth in the number of available drugs has been paralleled by an explosion of information regarding the critical role of prostaglandins in normal and abnormal renal function. Since there appears to be a divergence of opinion regarding the prevalence and significance of renal dysfunction associated with the use of these compounds the articles to follow have been solicited to outline what would appear to represent opposing points of view. Careful analysis of the information presented, however, should convince the reader that certain patients at risk are more likely to be encountered by nephrologists and as such account for the growing awareness of renal complications of nonsteroidal therapy. Extensive use of the compounds by rheumatologists in outpatient practice on otherwise healthy individuals, as well as a certain inevitable degree of underemphasis of adverse reactions by drug manufacturers, probably accounts for the different perceptions of risk. Dr. William L. Henrich of the University of Texas Health Science Center and Chief ot the Nephrology Section at the VA Medical Center in Dallas reviews renal prostaglandin physiology in experimental animals and man emphasizing the critical role these compounds play in situations where renal blood flow is threatened such as extracellular fluid volume depletion. cirrhosis, pre-existing renal disease, sodium restriction and congestive heart failure. Furthermore, he outlines evidence concerning the role of prostaglandins in protection from ischemic acute renal failure. He details the predisposing risk factors for development of renal dysfunction in patients receiving nonsteroidal anti-inflammatory drugs and gives his recommendation for monitoring patients during therapy. Dr. Andrei Calin of the Department of Medicine and Division of Immunology at Stanford University and Chief of the Rheumatology Section at the Palo Alto VA highlights the paucity of reports of renal dysfunction considering the large numbers of individuals actually taking nonsteroidal drugs. He challenges the role of prostaglandin inhibition as the sole explanation of nonsteroidal drug action. He then identifies the same patient risk groups as outlined by Dr. Henrich and concludes with practical recommendations for nephrologists. Thus, we can conclude that the pharmacologic properties of nonsteroidal drugs can produce renal functional and adverse renal reactions depending on the nature of the patient population and level of awareness of the prescribing physician. With the discovery of new uses of nonsteroidal agents due to the rapidly expanding body of knowledge in prostaglandin biology and a pharmaceutical industry intensively competing for profits, the clinical nephrologist should be on the alert for nephrotoxicity from this class of drugs. Anticipation of clinical circumstances during which the use of nonsteroidal drugs may be hazardous is the responsibility of all prescribers and an educational objective towards which industry and academic nephrologists could direct their attention.