DRUG SIDE EFFECTS

SIDE EFFECTS OF DRUGS

Letter to the Editor

Kidney International (2001) 59, 2370–2371; doi:10.1046/j.1523-1755.2001.07572.x

Letter from Ranjit S Nanra

Ranjit S Nanra

Newcastle, New South Wales, Australia

Correspondence: , Prof R.S. Nanra, F.R.A.C.P. Department of Nephrology, John Hunter Hospital, New Lambton Heights, Newcastle NSW 2305, Australia. E-mail: mdrsn@mail.newcastle.edu.au

To the Editor: I was fascinated by the paper by Feinstein et al in the December issue of Kidney International⁵. In animal studies, the incidence and severity of experimental renal papillary necrosis (RPN) induced by nonphenacetin-containing analgesics ["aspirin plus (paracetamol or salicylamide) plus caffeine," 38 to 75% RPN] and that by phenacetin-containing analgesics (17 to 70% RPN) are similar⁶. In Australia, clinical and pathologic studies showed that the addictive abuse of nonphenacetin containing combined analgesics over a period of more than 8 years was associated with ongoing analgesic nephropathy (AN) and renal failure⁷. These data do not support the conclusion that "sufficient evidence is absent to associate nonphenacetin combined analgesics with nephropathy."

The Committee has questioned the specificity of the diagnosis of AN. The clinical diagnosis of this condition is firm and includes a reliable history of analgesic abuse and radiologic demonstration of RPN (criteria and references in⁸). RPN is usually not a histologic diagnosis.

This review article asserts that "the association [of AN] with phenacetin is established." All experimental and clinical data suggest that the association of AN is with "(aspirin or antipyrine) plus phenacetin plus caffeine," and not phenacetin alone. Alone, the nephrotoxicity of the combined analgesic mixtures is greater than aspirin, which is greater than phenacetin. The medullary toxicity of phenacetin is likely due to paracetamol, the major immediate metabolite of phenacetin, because paracetamol and not phenacetin concentrates in the medulla [reviewed in 2–4].

The restriction of all combined analgesics in Australia in 1979 has led to a decrease in new patients with AN commencing dialysis, from 21% in 1979 to 5% in 1999, and in patients 45 to 64 years of age, from 30 to 9 patients per million population per year.

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References

References

5.	Feinstein AR, Heinemann LAJ & Curhan GC et al. Relationship between nonphenacetin combined analgesics and nephropathy: A review. Kidney Int 2000; 58: 2259–2264 10.1046/j.1523-1755.2000.00410.x. | Article | PubMed | ISI | ChemPort |
6.	Nanra RS. Experimental renal effects of analgesics, rat,. inMonographs on Pathology of Laboratory Animals, Urinary System 1997; 2nd ed. edited by Jones TC, Hard GC, Mohr U New York, Springer-Verlag pp 289–299.
7.	Nanra RS, Stuart-Taylor J, De Leon AH & White KH. Analgesic nephropathy: Etiology, clinical syndrome, and clinicopathologic correlations in Australia. Kidney Int 1978; 13: 79–92. | PubMed | ISI | ChemPort |
8.	Kincaid-Smith P & Nanra RS. Lithium-induced and analgesic-induced renal diseases,. inDiseases of the Kidney 1993; 5th ed. edited by Schrier RW, Gottschalk CW Boston, Little, Brown and Company pp 1099–1130