Analgesic nephropathy prevention

Analgesic nephropathy is one of the few renal diseases currently suitable for primary prevention. 

Bennett WM, De Broe ME. Analgesic nephropathy-a preventable renal disease. N Engl J Med 1989 320 1269-1271. 

NSAIDs block the synthesis of COX products of arachidonic acid, which have a critical role in renal hemodynamics, control of tubular function, and renin release. It is now apparent that two isoforms of COX synthesize prostaglandins. COX-1 is a resident or constitutive form and COX-2 is an inducible form that increases with disorders of inflammation. NSAIDs are nonspecific inhibitors of both COX isoforms. Analgesic nephropathy is a common cause of ESRD in a number of countries, reaching 10% in Switzerland and Australia, but is essentially a preventable condition for which biochemical monitoring has proved useful. The incidence of this disease has decreased over the last decade as awareness has improved and phenacetin was withdrawn from over-the-counter analgesic mixtures. In the United States, 1 in 5 citizens (50 miflion) report that they use an... 

Prevention has depended primarily on pnblic health efforts to restrict the sale of phenacetin and combination analgesics. This has effectively rednced analgesic nephropathy in Anstralia and Europe. However, risk continues with continued availability of OTC combination analgesics containing aspirin, acetaminophen, and caffeine in the United States and thronghont the world. 

Treatment of established nephrotoxicity reqnires cessation of analgesic consumption. This can prevent progression and may improve renal fnnction. Persistent surreptitions analgesic abuse should be considered if renal fnnction continnes to decline. Patients shonld also be monitored for associated transitional cell carcinoma of the renal pelvis, calyces, nreters, and bladder, which may present years after analgesic nephropathy is diagnosed. 

Bennett WM, De Broe ME. Analgesic nephropathy - a preventable renal disease. N Engl J Med 1989 320 1269-1271. Mihatsch MJ, Staehelin HB, Musfeld D, Perret E, Oberholzer M. Phenacetin-Abusus Kardiovaskulare Risikofactoren. Nieren Hochdruck 1983 3 83-92. 

Mechanisms of analgesic nephropathy remain unclear. The renal lesion begins in the papillary tip as a result of accumulated toxic metabolites, decreased blood flow, and impaired cellular energy production. The metabolism of phenacetin to acetaminophen, which is then oxidized to toxic free radicals that are concentrated in the papilla, appears to be the initiating factor that causes toxicity by mechanisms analogous to acetaminophen hepatotoxicity. Toxicity is prevented by availability of reduced glutathione. However, salicylates deplete renal glutathione and thereby facilitate phenacetin and acetaminophen toxicity (Silva 2004 Braden et al. 2005). 

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