Risk Of Chronic Renal Disease Research Articles

A review of epidemiologic studies of nonnarcotic analgesics and chronic renal disease.

The relationship of long-term and heavy exposure of nonnarcotic analgesics to the risk of chronic renal disease (CRD) has been the object of intensive clinical, pharmacologic, toxicologic, and epidemiologic research for 4 decades. The clinical evidence of an increased risk has been suggestive but inconclusive. The experimental evidence in animal models has been inconsistent, and in any case it cannot be generalized to humans. The epidemiologic evidence has been unsatisfactory for the most part: most of the early studies had severe methodologic limitations; moreover, they related mainly to phenacetin-containing drugs and did not have useful information on other analgesics. Since 1980, 9 analytical epidemiologic studies have attempted to confirm that a causal relationship exists between phenacetin or other analgesics and CRD. In the aggregate, despite methodologic flaws, this work suggests that excessive use of phenacetin-containing analgesics probably causes renal papillary necrosis and interstitial nephritis. In contrast, there is no convincing epidemiologic evidence that nonphenacetin-containing analgesics (including acetaminophen, aspirin, and mixtures of these two compounds) or that nonsteroidal antiinflammatory drugs cause CRD. Moreover, the nature of dose-response relationships, the types of renal disease possibly caused by analgesics, and the cofactors that might be related both to analgesic use and to the development of CRD in humans are still uncertain, and the pathologic mechanisms of analgesic-induced CRD in humans remain unclear. It may take many years before all the outstanding issues are settled. Until they are, as a matter of good clinical judgment it would be prudent to consider all analgesics as potentially nephrotoxic and, as much as possible, to avoid excessive, protracted use.

Acetaminophen and adverse chronic renal outcomes: An appraisal of the epidemiologic evidence

This article critically reviews existing epidemiologic studies of the association between habitual acetaminophen use and chronic renal disease exclusive of neoplasia. Relevant primary studies were identified by searching the Medline database from 1966 to March 1995. There are several case reports of analgesic nephropathy following exposure to acetaminophen alone, but the accuracy with which other causes of this lesion were excluded is unclear. Three case control studies have found an increased risk (odds ratio range, 2 to 4) with habitual acetaminophen exposure for papillary necrosis, chronic renal failure, or end-stage renal disease. These studies have been open to confounding by indication. It is also difficult to determine the risk with acetaminophen alone given the prevalent use of analgesic mixtures in the populations studied. Two prospective cohort studies have suggested an increased risk of renal impairment or papillary calcification following regular analgesic exposure. One of these studies was of subjects taking phenacetin-containing analgesic mixtures and the study population of the other was too small to reach statistically significant conclusions. Recent study results have raised the possibility that habitual acetaminophen use could increase the likelihood or rate of progression of chronic renal disease in general. This review suggests that there is currently insufficient evidence to conclude that habitual use of acetaminophen as a sole analgesic is associated with an increased risk of chronic renal disease. Further research is required to examine this question. Prudence suggests that habitual use of acetaminophen should be discouraged in the absence of strong medical indications.

Nonsteroidal Anti-inflammatory Drugs and the Risk for Chronic Renal Disease

To evaluate the risk for chronic renal disease associated with regular use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs). Multicenter case-control study. Patients were 554 North Carolina residents (age range, 30 to 79 years) hospitalized between 1980 and 1982 with a discharge diagnosis indicating newly diagnosed chronic renal dysfunction and a serum creatinine level consistently at or above 130 mumol/L (1.5 mg/dL). Controls were 516 persons chosen randomly by telephone screening (if younger than 65 years of age) and from listings of Medicare recipients (if 65 years of age or older), frequency-matched to patients by age, race, sex, and proximity to study hospitals. Data on use of prescription NSAIDs and other analgesics before 1980, other risk factors, and potential confounders were obtained by telephone interviews. Patients were classified by frequency and duration of use; daily users were those who took an NSAID for at least 360 consecutive days. A twofold risk for chronic renal disease was associated with previous daily use of NSAIDs (adjusted odds ratio, 2.1; 95% Cl, 1.1 to 4.1). Increased risk was predominantly limited to men older than 65 years, for whom the odds ratio for daily use was 10.0 (Cl, 1.2 to 82.7) after adjusting for use of other analgesics. In other age-sex groups, the risk associated with NSAID use tended to be increased among those with heart disease or other factors that might indicate compromised renal circulation. These findings did not result from confounding by known renal disease risk factors and were not readily explained by potential biases. Regular use of NSAIDs may increase the risk for chronic kidney disease in some high-risk groups. With the recent over-the-counter availability and increasing popularity of NSAIDs, the possibility of an increased risk for chronic renal disease associated with their use may warrant further scrutiny.