Analgesics nephropathy

Tubular and interstitial diseases (e.g., analgesic nephropathy, drug-induced nephritis, oxalate nephropathy, radiation nephritis, acute tubular necrosis, and sarcoidosis)... 

Type C (continuous) reactions are due to long-term use of the drug (e.g. analgesic nephropathy or peripheral neuropathy with reverse transcriptase inhibitors). 

Toxicity. The estimated minimum lethal dose is 5g. Prolonged use of phenacetin is associated with analgesic nephropathy it may also produce haemolytic anaemia and methaemoglobinae-mia. 

Kidney. Gold salts may cause nephropathy see also Analgesic nephropathy (p. 284). 

Analgesia NSAIDs are effective for pain of mild to moderate intensity including musculoskeletal and postoperative pain, and osteo- and inflammatory arthritis they have the advantage of not causing dependence, unlike opioids (but see analgesic nephropathy, below). 

Albuminuria, hematuria, and acute renal insufficiency have been observed, and aminophenazone causes direct renal damage even at therapeutic doses. It can also contribute to analgesic nephropathy (SED-8, 211) (8,9). 

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medications that contain fixed combinations of analgesics (paracetamol, aspirin, or propyphenazone plus caffeine) be withdrawn from the market, following the example of their US colleagues in the National Kidney Foundation (27). 

NSAID-induced renal toxicity, comprising interstitial nephritis and renal papillary necrosis. The condition, named analgesic nephropathy, was not uncommon and was serious. In a number of cases malignancies in the urinary tract also occurred. 

Clinical evidence suggestive of analgesic nephropathy includes nocturia, renal insufficiency with severe acidosis, persistent urinary tract infection with colic, hematuria, and hypertension (40,41). Nocturia resulting from failure to concentrate urine is usually the earliest functional defect, but like the other symptoms it is non-specific, rendering the diagnosis of analgesic nephropathy difficult. A CT scan showing bilateral small kidneys with bumpy contours, and papillary calcification is accepted to be of sufficient specificity (38,39). 

Analgesic nephropathy is mostly diagnosed between the ages of 30 and 70 years, with a peak in the fourth decade, and there is a familial predisposition (SEDA-6, 80). 

The prevalence of analgesic nephropathy is particularly high when there is intensive use of analgesics. There is evidence from animal and clinical work to suggest that hypovolemia plays a part, and that the risk of nephropathy is greatest in women and the elderly. Because of the long latent period of over 10 years, the condition has continued to appear despite the withdrawal of phenacetin. 

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. 

By the early 1980s, most countries had severely restricted or entirely prohibited the sale of phenacetin. Subsequent data from several of these countries suggested that the number of new patients with analgesic nephropathy fell as a result of the prohibition of phenacetin in analgesic mixtures. 

It soon became clear that the major causative agent in analgesic nephropathy was phenacetin, improperly used long-term and especially in combinations with other analgesics, and this identification led to its virtual disappearance in the mid-1970s, following regulatory action. 

The history of analgesic nephropathy must not be dismissed as involving only a drug now obsolete. 

Schwarz A, Preuschof L, ZeUner D. Incidence of analgesic nephropathy in Berlin since 1983. Nephrol Dial Transplant 1999 14(1) 109-12. 

Elseviers MM, Bosteels V, Cambier P, De Paepe M, Godon JP, Lins R, Lornoy W, Matthys E, Moeremans C, Roose R, et al. Diagnostic criteria of analgesic nephropathy in patients with end-stage renal failure results of the Belgian study. Nephrol Dial Transplant 1992 7(6) 479-86. 

Elseviers MM, Waller I, Nenoy D, Levora J, Matousovic K, Tanquerel T, Pommer W, Schwarz A, Keller E, Thieler H, et al. Evaluation of diagnostic criteria for analgesic nephropathy in patients with end-stage renal failure results of the ANNE study. Analgesic Nephropathy Network of Europe. Nephrol Dial Transplant 1995 10(6) 808-14. 

Prescott LF. Analgesic nephropathy a reassessment of the role of phenacetin and other analgesics. Drugs 1982 23 (l-2) 75-149. 

Cove-Smith JR, Knapp MS. Analgesic nephropathy an important cause of chronic renal failure. Q J Med 1978 47(185) 49-69. 

McCredie M, Stewart JH, Mahony JF. Is phenacetin responsible for analgesic nephropathy in New South Wales Clin Nephrol 1982 17(3) 134-40. 

Murray RM. Analgesic nephropathy removal of phenace-tin from proprietary analgesics. BMJ 1972 4(833) 131-2. 

McAnally JF, Winchester JF, Schreiner GE. Analgesic nephropathy. An uncommon cause of end-stage renal disease. Arch Intern Med 1983 143(10) 1897-9. 

Schreiner GE, McAnally JF, Winchester JF. Chnical analgesic nephropathy. Arch Intern Med 1981 141(3 Spec No) 349-57. 

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

MacDonald IM, Dumble U, Doran T, et al. Increased frequency of HLA-B12 in analgesic nephropathy. Aust NZ J Med I978 8 233. 

Phenazone nephrotoxicity is well-established, but information is limited. Experimental papillary necrosis can easily be provoked analgesic nephropathy is probably a real danger with antipyrine, especially when it is combined with a stronger inhibitor of prostaglandin sjmthesis. The effect is probably toxic, since inhibition of prostaglandins is not a marked characteristic of phenazone. Two reports have suggested a causal link between phenazone and renal carcinoma, as is well-known for phenacetin (3,4), but this has not been confirmed. 

Gregg NJ, Elseviers MM, De Broe ME, Bach PH. Epidemiology and mechanistic basis of analgesic nephropathy Toxicol Lett 1989 46 141-151. 

Mudge GH. Analgesic nephropathy renal drug distribution and metabolism. In Nephrotoxic mechanisms of drugs and environmental toxins. Porter GA (editor). Plenum Med Book Co, New York, Eondon 1982 p 209-225. 

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