Analgesic Use and Chronic Renal Disease

Sandler, Dale P.; Smith, Jennifer A.; Weinberg, Clarice R.; Vm, Buckalew; Vw, Dennis; Wb, Blythe; Wp, Burgess

doi:10.1056/nejm198905113201903

Cited by 234 publications

(98 citation statements)

References 34 publications

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“…One such possible pathway is the shared ability of these drugs to induce renal damage leading to increased cell proliferation at the target site, a recognized mechanism of increased cancer risk in humans (Henderson et al, 1991). Aspirin, non-aspirin NSAID, phenacetin and acetaminophen used alone or in combination have been reported to be associated with chronic nephropathy, chronic renal failure or endstage renal disease in several case-control studies (Pommer et al, 1989;Sandler et al, 1989;Perneger et al, 1994). In vivo and in vitro rodent models have shown that aspirin, non-aspirin NSAID and acetaminophen undergo in situ metabolic activation in the kidney with subsequent covalent binding of the highly reactive metabolites to tissue/microsomal proteins, leading to tubular necrosis (Mitchell et al, 1977;McMurtry et al, 1978;Kyle and Kocsis, 1985;Emeigh Hart et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Regular use of analgesics is a risk factor for renal cell carcinoma

et al. 1999

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Summary Phenacetin-based analgesics have been linked to the development of renal pelvis cancer and renal cell carcinoma (RCC). The relationship between non-phenacetin types of analgesics and kidney cancer is less clear, although laboratory evidence suggests that these drugs possess carcinogenic potential. A population-based case-control study involving 1204 non-Asian RCC patients aged 25-74 and an equal number of sex-, age-and race-matched neighbourhood controls was conducted in Los Angeles, California, to investigate the relationship between sustained use of analgesics and risk of RCC according to major formulation categories. Detailed information on medical and medication histories, and other lifestyle factors was collected through in-person interviews. Regular use of analgesics was a significant risk factor for RCC in both men and women (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.4-1.9 for both sexes combined). Risks were elevated across all four major classes of analgesics (aspirin, non-steroidal anti-inflammatory agents other than aspirin, acetaminophen and phenacetin). Within each class of analgesics, there was statistically significant increasing risk with increasing level of exposure. Although there was some minor variability by major class of formulation, in general individuals in the highest exposure categories exhibited approximately 2.5-fold increase in risk relative to non-or irregular users of analgesics. Subjects who took one regular-strength (i.e. 325 mg) aspirin a day or less for cardiovascular disease prevention were not at an increased risk of RCC (OR = 0.9, 95% CI = 0.6-1.4).

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Section: Discussionmentioning

confidence: 99%

Regular use of analgesics is a risk factor for renal cell carcinoma

et al. 1999

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“…The results of recent epidemiological studies have been conflicting. Murray et al (1983) could find no association between paracetamol consumption and end-stage renal disease but Sandler et al (1989) have claimed that the daily use of paracetamol significantly increases the risk of chronic renal disease. However, in the latter study proper information about paracetamol use was not provided, drug histories in most cases were obtained retrospectively by proxy and there was no confirmation of the renal diagnosis.…”

Section: Urine Volume and Osmolalitymentioning

confidence: 99%

The comparative effects of paracetamol and indomethacin on renal function in healthy female volunteers.

Prescott

Mattison

Menzies

et al. 1990

Brit J Clinical Pharma

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1 Renal function was assessed in 10 healthy female volunteers during administration of placebo, paracetamol (acetaminophen) (4.0 g daily) and indomethacin (150 mg daily) for 3 days under conditions of controlled sodium and fluid intake. 2 Paracetamol and indomethacin had no significant effect on the glomerular filtration rate and effective renal plasma flow as measured by the renal clearances of inulin, creatinine and p-aminohippurate (PAH). 3 Compared with placebo, paracetamol reduced the mean urinary excretion of prostaglandin E2 by 43% on the second day and 58% on the third treatment day (P < 0.01). With indomethacin the corresponding reductions were 73 and 80%. Paracetamol and indomethacin had much less effect on the excretion of prostaglandin 6-keto Fia, and a significant decrease was observed only on the third day. 4 The decreased urinary excretion of prostaglandin E2, produced by paracetamol was associated with a reduction in sodium excretion of more than 50% (P < 0.01) and delay in the onset of diuresis following an acute water load. 5 The renal effects of paracetamol and indomethacin appear to differ. Although indomethacin reduced prostaglandin excretion more than paracetamol it had a similar effect on sodium excretion and less initial antidiuretic action. Unlike paracetamol, indomethacin also reduced basal plasma renin activity. 6 Paracetamol reduced the total body clearance of PAH and increased its plasma halflife. This effect could be attributed to inhibition of the acetylation of PAH by paracetamol. 7 In normal use paracetamol does not appear to have the adverse renal effects associated with the non-steroidal anti-inflammatory analgesics and further studies are required to establish the clinical significance of these findings.

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“…Initially phenacetin was assumed to be the nephrotoxic common denominator (50,51,150,151), and this compound was progressively banned from over-the-counter (OTC) products, but it is now appreciated that many analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) have papillotoxic potential if used in excessive quantities. It is also apparent that the problem of excessive use of analgesics continues today (13,46,56,87,96,171,185,200,201) and this healthcare cost is probably preventable (46,47,59). Analgesic abuse is a frequent cause of analgesic nephropathy that leads to end-stage renal disease and upper urothelial carcinoma throughout Europe (46, 47, 58-64, 179,180,203,204), Australia (149-150, 171, 216), and other parts of the world (206)(207)(208)(209)(210).…”

Section: Introduchonmentioning

confidence: 99%

Renal Papillary Necrosis—40 Years On

Bach

Thanh

1998

Toxicol Pathol

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Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are well recognized as a major class of therapeutic agent that causes renal papillary necrosis (RPN). Over the last decade a broad spectrum of other therapeutic agents and many chemicals have also been rcportcd that have the potential to cause this lesion in animals and man. There is consensus that RPN is the primary lesion that can progress to cortical degeneration; and it is only at this stage that the lesion is easily diagnoscd. In the absence of sensitive and selective noninvasive biomarkers of RPN there is still no clear indication of which compound, under what circumstances, has the greatest potential to cause this lesion in man. Attempts to mimic RPN in rodents using analgesics and NSAIDs have not provided robust models of the lesion. Thus, much of the research has concentrated on those compounds that cause an acute or subacute RPN as the basis by which to study the pathogenesis of the lesion. Based on the mechanistic understanding gleaned from these model compounds it has been possible to transpose an understanding of the underlying processes to the analgesics and NSAIDs. The mechanism of RPN is still controversial. There are data that support microvascular changes and local ischemic injury as the underlying cause. Alternatively, several model papillotoxins, some analgesics, and NSAIDs target selectively for the medullary interstitial cells, which is the earliest reported aberration, after which there are a series of degenerative processes affecting other renal cell types. Many papillotoxins have the potential to undergo prostaglandin hydroperoxidase-mediated metabolic activation, specifically in the renal medullary interstitial cells. These reactive intermediates, in the presence of large quantities of polyunsaturated lipid droplets, result in localized and selective injury of the medullary interstitial cells. These highly differentiated cells do not repair, and it is generally accepted that continuing insult to these cells will result in their progressive erosion. The loss of these cells is thought to be central to the degenerative cascade that affects the cortex. There is still a need to understand better the primary mechanism and the secondary consequences of RPN so that the risk of chemical agents in use and novel molecules can be fully assessed.

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Analgesic Use and Chronic Renal Disease

Cited by 234 publications

References 34 publications

Regular use of analgesics is a risk factor for renal cell carcinoma

Regular use of analgesics is a risk factor for renal cell carcinoma

The comparative effects of paracetamol and indomethacin on renal function in healthy female volunteers.

Renal Papillary Necrosis—40 Years On

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