Aspirin analgesic nephropathy

As up to 10% of about 42 000 dialysis patients have suffered from renal insufficiency due to analgesic nephropathy (in the postphenacetin era), German nephrologists have demanded that medications that contain fixed combinations of analgesics (paracetamol, aspirin, or propyphenazone plus caffeine) be withdrawn from the market, following the example of their US colleagues in the National Kidney Foundation (27). 

In Belgium, the distribution of analgesic nephropathy in patients with terminal renal insufficiency was well correlated with the sale of drugs containing either aspirin -I- phenacetin or paracetamol + caffeine (SEDA-7,75), and it is estimated that Belgium, after Australia, had the second highest incidence of analgesic nephropathy in the world. 

Emkey RD, Mills JA. Aspirin and analgesic nephropathy. JAMA 1982 247(l) 55-7. 

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. 

Figure 2, Analgesic nephropathy is caused by abuse of analgesic mixtures plus caffeine/codeine. Left the potentiating effect of aspirin with both phenacetin and acetaminophen (see text). Adapted from [5, 9], with permission.

Macklon AF, Craft AW, Thompson M, Kerr DNS (1974) Aspirin and analgesic nephropathy. Br Med J 1 597-600... 

The mechanisms of salicylate-induced renal lesions are uncertain, but inhibition of medullary prostaglandin synthesis with resultant ischaemia has been proposed (137, 139 ). Further studies have confirmed that aspirin causes acute tubular damage (160, 161). It also inhibits renal tubular gluconeo-genesis (162). Aspirin readily produces typical renal papillary necrosis in rats in doses as low as 200 mg/kg/day and dehydration predisposes to nephrotoxicity (139 , 140 ). In another study, no comparable lesions were produced in rats in a short-term study using daily doses of 24-125 mg/kg. It was claimed that these doses were equivalent to consumption of 8—40 aspirin tablets daily in man (163). However, these calculations were based on comparisons of estimated total salicylate in the body derived from urinary excretion data. Such an approach is quite inappropriate since it does not take into account species differences in the extent or rate of absorption, distribution, protein binding, metabolism and renal medullary concentrations of salicylate. Experimental analgesic nephropathy has been critically reviewed (164 ). 

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