Analgesic use and chronic renal failure: A critical review of the epidemiologic literature
1998; Elsevier BV; Volume: 54; Issue: 3 Linguagem: Inglês
10.1046/j.1523-1755.1998.00043.x
ISSN1523-1755
AutoresJoseph K. McLaughlin, Loren Lipworth, Wong‐Ho Chow, William J. Blot,
Tópico(s)Pharmacological Effects and Toxicity Studies
ResumoAnalgesic use and chronic renal failure: A critical review of the epidemiologic literature. Heavy use of analgesics, particularly over-the-counter (OTC) products, has long been associated with chronic renal failure. Most of the earlier reports implicated phenacetin-containing analgesics as the risk factor. Since the early 1980s, several case-control studies have reported associations between chronic renal failure and use of other forms of analgesics, including acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs (NSAIDs). Findings from these studies, however, should be interpreted with caution because of a number of inherent limitations and potential biases in the study design and data collection procedures. These limitations include: failure to identify patients early enough in the natural history of their disease to collect reliable information on analgesic use at an etiologically relevant time period; selection bias due to incomplete identification of subjects or low response rates; selection of cases and controls from different population bases; failure to employ survey techniques to improve reliability of recall of analgesic use; failure to collect detailed information on analgesic use such as year started and ended and reasons for switching analgesics; lack of standardization in the definition of regular analgesic use; and failure to adjust for phenacetin use and other confounding factors when assessing associations with analgesics other than those containing phenacetin. It is our hope that this review of study design limitations will lead to improvements in future studies of chronic renal failure risk. Since use of analgesics is widespread and new OTC products are introduced frequently, the potential impact of these drugs on the development of chronic renal failure may be significant, thus warranting continued evaluation of these products for any renal toxicity. Analgesic use and chronic renal failure: A critical review of the epidemiologic literature. Heavy use of analgesics, particularly over-the-counter (OTC) products, has long been associated with chronic renal failure. Most of the earlier reports implicated phenacetin-containing analgesics as the risk factor. Since the early 1980s, several case-control studies have reported associations between chronic renal failure and use of other forms of analgesics, including acetaminophen, aspirin, and other non-steroidal anti-inflammatory drugs (NSAIDs). Findings from these studies, however, should be interpreted with caution because of a number of inherent limitations and potential biases in the study design and data collection procedures. These limitations include: failure to identify patients early enough in the natural history of their disease to collect reliable information on analgesic use at an etiologically relevant time period; selection bias due to incomplete identification of subjects or low response rates; selection of cases and controls from different population bases; failure to employ survey techniques to improve reliability of recall of analgesic use; failure to collect detailed information on analgesic use such as year started and ended and reasons for switching analgesics; lack of standardization in the definition of regular analgesic use; and failure to adjust for phenacetin use and other confounding factors when assessing associations with analgesics other than those containing phenacetin. It is our hope that this review of study design limitations will lead to improvements in future studies of chronic renal failure risk. Since use of analgesics is widespread and new OTC products are introduced frequently, the potential impact of these drugs on the development of chronic renal failure may be significant, thus warranting continued evaluation of these products for any renal toxicity. Abuse of analgesics has long been associated with the development of chronic renal failure. The clinically well-defined entity of classic analgesic nephropathy is a slowly progressing disease resulting from the daily consumption over several years of mixtures containing at least two antipyretic analgesics, usually combined with caffeine and/or codeine, both creating a psychological dependence. It is characterized by renal papillary necrosis and chronic interstitial nephritis1.Burry A.F. The evolution of analgesic nephropathy.Nephron. 1967; 5: 185-201Crossref Scopus (63) Google Scholar,2.Mihatsch M.F. Zollinger H.U. The pathology of analgesic nephropathy,.in: Stewart J.H. Analgesic and NSAID-Induced Kidney Disease. Oxford University Press, New York1993: 67-85Google Scholar, which once established tend to progress to end-stage renal disease (ESRD). Efforts to halt or even slow the progression have for the most part been unsuccessful3.Hunsicker L.G. Levey As Progression of chronic renal disease: Mechanisms, risk factors, and testing of interventions,.in: Jacobson H.R. Striker G.E. Klahr S. The Principles and Practice of Nephrology. Mosby, New York1995Google Scholar,4.Klahr S. Schreiner G. Ichikawa I. The progression of renal disease.N Engl J Med. 1988; 318: 1657-1666Crossref PubMed Scopus (735) Google Scholar. The incidence of ESRD and expenditures related to its treatment have been increasing consistently in the United States5.Peitzman S.J. From dropsy to Bright's disease to end-stage renal disease.Milbank Quart. 1989; 67: 16-32Crossref PubMed Scopus (16) Google Scholar; in 1989, an estimated 200,000 persons received treatment for ESRD and the direct costs of such therapy amounted to $6 billion5.Peitzman S.J. From dropsy to Bright's disease to end-stage renal disease.Milbank Quart. 1989; 67: 16-32Crossref PubMed Scopus (16) Google Scholar. The progressive nature of chronic renal disease and the high costs of its treatment underscore the importance of identifying preventable causes of this disease. In particular, given the extensive worldwide market for analgesics and the general acceptance of their safety, detailed evaluation of the potential renal toxicity of these drugs is warranted. Since the association between abuse or long-term heavy use of analgesics and chronic interstitial nephritis was first recognized more than four decades ago6.Spuhler O. Zollinger H.U. Die chronische interstitielle nephritis.Zeitschrift fur Klinische Medizin. 1953; 151: 1-50PubMed Google Scholar, numerous cases of analgesic-associated nephropathy have been documented7.Prescott L.F. Analgesic nephropathy: A reassessment of the role of phenacetin and other analgesics.Drugs. 1982; 23: 75-149Crossref PubMed Scopus (123) Google Scholar, but a causal association has not been conclusively established. The majority of reports have implicated heavy consumption of analgesic mixtures containing phenacetin as the responsible agent7.Prescott L.F. Analgesic nephropathy: A reassessment of the role of phenacetin and other analgesics.Drugs. 1982; 23: 75-149Crossref PubMed Scopus (123) Google Scholar, 8.McCredie M. Stewart J.H. Mahoney J.F. Is phenacetin responsible for analgesic nephropathy in New South Wales?.Clinic Nephrol. 1982; 17: 134-140PubMed Google Scholar, 9.McCredie M. Stewart J.H. Does paracetamol cause urothelial cancer or renal papillary necrosis?.Nephron. 1988; 49: 296-300Crossref PubMed Scopus (50) Google Scholar, 10.Elseviers M.M. De Broe M.E. The implication of analgesics in human kidney disease,.in: Stewart J.H. Analgesic and NSAID-Induced Kidney Disease. Oxford University Press, New York1993: 32-47Google Scholar. By the late 1960s phenacetin was removed from the market in Scandinavia and by the 1970s was subsequently removed in many industrialized countries7.Prescott L.F. Analgesic nephropathy: A reassessment of the role of phenacetin and other analgesics.Drugs. 1982; 23: 75-149Crossref PubMed Scopus (123) Google Scholar,11.Gloor F.F. Historical introduction.in: Stewart J.H. Analgesic and NSAID-Induced Kidney Disease. Oxford University Press, New York1993: 1-4Google Scholar. In the United States, all phenacetin preparations were required after 1964 to bear a warning about possible kidney damage12.Us FOOD Drug Administration: Food and drugs.US Code Fed Regul, Title. 1978; 21: 38-39Google Scholar, and the drug was banned from the market in 198313.US Congress Federal Register. DC, WashingtonOctober 5, 1983Google Scholar. Several large analytic epidemiologic studies have more recently raised concern that chronic renal failure may be linked to heavy use of not only phenacetin, but also of a number of commonly used analgesics such as aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), and acetaminophen14.Sandler D.P. Burr R. Weinberg C.R. Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease.Ann Int Med. 1991; 115: 165-172Crossref PubMed Scopus (185) Google Scholar, 15.Sandler D.P. Smith J.C. Weinberg C.R. Buckalew V.M. Blythe V.W. Burgess W.P. Analgesic use and chronic renal disease.N Engl J Med. 1989; 320: 1238-1243Crossref PubMed Scopus (223) Google Scholar, 16.Perneger T.V. Whelton P.K. Klag M.J. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs.N Engl J Med. 1994; 331: 1675-1679Crossref PubMed Scopus (430) Google Scholar. In the United States, NSAID prescriptions increased rapidly from 27.5 million in 1973 to 66.7 million in 1983, although use of prescribed NSAIDs has stabilized since then. This phenomenon may be explained in part by the increased awareness among physicians of the gastrointestinal side effects of excessive NSAID use, as well as by approval of various NSAIDs for over-the-counter (OTC) sales17.Gabriel S.E. Jaakkimainen L. Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs: A meta-analysis.Ann Int Med. 1991; 115: 787-796Crossref PubMed Scopus (1233) Google Scholar,18.Allison M.C. Howatson A.G. Torrance C.J. Lee F.D. Russell R.I. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs.N Engl J Med. 1992; 327: 749-754Crossref PubMed Scopus (975) Google Scholar. Since the 1980s, the stagnant market share of prescription NSAIDs has been replaced by increasing sales of acetaminophen and of former prescription-only NSAIDs such as ibuprofen, which now account for about one third of the OTC analgesic market share. As early as 1980, aspirin substitutes (primarily acetaminophen) accounted for $300 million of the then $1.2 billion spent on analgesic medication in the United States19.Consumer Expenditure Study Internal analgesics.Product Marketing and Cosmetic and Fragrance Retailing. 1981; 10: 38Google Scholar. Of the OTC analgesics, acetaminophen has generated the greatest concern with respect to renal disease because it is the major metabolite of phenacetin20.Hinson J.A. Reactive metabolites of phenacetin and acetaminophen: A review.Environ Health Perspect. 1983; 50: 37-49Crossref PubMed Scopus (17) Google Scholar,21.Segasothy M. Suleiman A.B. Puvanesqary M. Rohana A. Paracetamol; a cause for analgesic nephropathy and end-stage renal disease.Nephron. 1988; 50: 50-54Crossref PubMed Scopus (34) Google Scholar, although not the only metabolite22.Insel P.A. Analgesic-antipyretics and antiinflammatory agents,.in: Gilman A.G. Nies A.S. Taylor P. Goodman and Gilman's The Pharmacological Basis of Therapeutics. Pergamon Press, New York1990: 656-658Google Scholar,23.Prescott L.F. Kinetics and metabolism of paracetamol and phenacetin.Br J Clin Pharm. 1980; 10: 2915-2985Google Scholar, and because acetaminophen-induced renal necrosis has been observed in susceptible laboratory animals24.Newton J.F. Kuo C.H. Gemborys M.W. Mudge G.H. Hook J.B. Nephrotoxicity of p-aminophenol, a metabolite of acetaminophen, in the Fischer 344 rat.Toxicol Appl Pharmacol. 1982; 65: 336-344Crossref PubMed Scopus (111) Google Scholar, 25.McMurty R.J. Snodgrass W.R. Mitchell J.R. Renal necrosis, glutathione depletion and covalent binding after acetaminophen.Toxicol Appl Pharmacol. 1978; 46: 87-100Crossref PubMed Scopus (208) Google Scholar, 26.Placke M.E. Wyand D.S. Cohen S.D. Extrahepatic lesions induced by acetaminophen in the mouse.Toxicol Pathol. 1987; 15: 381-383Crossref PubMed Scopus (64) Google Scholar, 27.Burrell J.H. Yong J.L. Macdonald G.J. Irreversible damage to the medullary intersttium in experimental analgesic nephropathy in F344 rats.J Pathol. 1991; 164: 329-338Crossref PubMed Scopus (20) Google Scholar. However, the collective epidemiologic evidence with respect to acetaminophen as a single product is inconclusive. The majority of reports of chronic renal disease associated with acetaminophen use have been case series7.Prescott L.F. Analgesic nephropathy: A reassessment of the role of phenacetin and other analgesics.Drugs. 1982; 23: 75-149Crossref PubMed Scopus (123) Google Scholar, 28.Krikler D.M. Paracetamol and the kidney.Br Med J. 1967; iiGoogle Scholar, 29.Segasothy M. Kong B.C.T. Kamal A. Morad Z. Suleiman A.B. Analgesic nephropathy associated with paracetamol.Aust N Z J Med. 1984; 14: 23-26Crossref PubMed Scopus (16) Google Scholar. Most of the analytic epidemiologic data on analgesic use and chronic renal failure are derived from case-control studies9.McCredie M. Stewart J.H. Does paracetamol cause urothelial cancer or renal papillary necrosis?.Nephron. 1988; 49: 296-300Crossref PubMed Scopus (50) Google Scholar, 14.Sandler D.P. Burr R. Weinberg C.R. Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease.Ann Int Med. 1991; 115: 165-172Crossref PubMed Scopus (185) Google Scholar, 15.Sandler D.P. Smith J.C. Weinberg C.R. Buckalew V.M. Blythe V.W. Burgess W.P. Analgesic use and chronic renal disease.N Engl J Med. 1989; 320: 1238-1243Crossref PubMed Scopus (223) Google Scholar, 16.Perneger T.V. Whelton P.K. Klag M.J. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs.N Engl J Med. 1994; 331: 1675-1679Crossref PubMed Scopus (430) Google Scholar, 30.Murray T.G. Stolley P.D. Anthony J.C. Schinnar R. Hepler-Smith E. Jeffreys J.L. Epidemiologic study of regular analgesic use and end-stage renal disease.Arch Intern Med. 1983; 143: 1687-1693Crossref PubMed Scopus (88) Google Scholar, 31.Pommer W. Bronder E. Greiser E. Helmert U. Jesdinsky H.J. Klimpel A. Borner K. Molzahn M. Regular analgesic use and the risk of end-stage renal failure.Am J Nephrol. 1989; 9: 403-412Crossref PubMed Scopus (109) Google Scholar, 32.Morlans M. Laporte J.-R. Vidal X. Cabeza D. Stolley P.D. End-stage renal disease and non-narcotic analgesics: A case-control study.Br J Clin Pharmac. 1990; 30: 717-723Crossref PubMed Scopus (80) Google Scholar, 33.Steenland N.K. Thun M.J. Ferguson C.W. Port F.K. Occupational and other exposures associated with male end-stage renal disease: A case-control study.Am J Public Health. 1990; 80: 153-159Crossref PubMed Scopus (124) Google Scholar. To our knowledge, only two cohort studies34.Dubach U.C. Rosner B. Pfister E. Epidemiologic study of abuse of analgesics containing phenacetin: Renal morbidity and mortality (1968–1979).N Engl J Med. 1983; 308: 357-362Crossref PubMed Scopus (101) Google Scholar,35.Elseviers M.M. De Broe M. A long-term prospective controlled study of analgesic abuse in Belgium.Kidney Int. 1995; 48: 1912-1919Abstract Full Text PDF PubMed Scopus (56) Google Scholar have linked analgesic use to elevated risk of chronic renal failure, with similar risk estimates. Elseviers and De Broe35.Elseviers M.M. De Broe M. A long-term prospective controlled study of analgesic abuse in Belgium.Kidney Int. 1995; 48: 1912-1919Abstract Full Text PDF PubMed Scopus (56) Google Scholar reported a significant sixfold increase in risk of decreased renal function among abusers of any type of analgesic compared to controls; their estimate, however, was based on only 12 exposed cases. In the 10-year follow-up study by Dubach, Rosner and Pfister34.Dubach U.C. Rosner B. Pfister E. Epidemiologic study of abuse of analgesics containing phenacetin: Renal morbidity and mortality (1968–1979).N Engl J Med. 1983; 308: 357-362Crossref PubMed Scopus (101) Google Scholar, heavy use by young women of phenacetin-containing products was associated with an eightfold increased risk of developing renal failure, as measured by serum creatinine levels, but the absolute incidence of abnormal kidney function remained relatively small even among heavy users. Increased risk of mortality from urologic or renal disease was also reported in this study among heavy users of phenacetin36.Dubach U.C. Rosner B. Sturmer T. An epidemiologic study of abuse of analgesic drugs: Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987).N Engl J Med. 1991; 324: 155-160Crossref PubMed Scopus (97) Google Scholar. Another small cohort study demonstrated a nonsignificant positive association between high analgesic use and papillary calcification21.Segasothy M. Suleiman A.B. Puvanesqary M. Rohana A. Paracetamol; a cause for analgesic nephropathy and end-stage renal disease.Nephron. 1988; 50: 50-54Crossref PubMed Scopus (34) Google Scholar. By contrast, increased risks associated with acetaminophen use have been reported in several15.Sandler D.P. Smith J.C. Weinberg C.R. Buckalew V.M. Blythe V.W. Burgess W.P. Analgesic use and chronic renal disease.N Engl J Med. 1989; 320: 1238-1243Crossref PubMed Scopus (223) Google Scholar, 16.Perneger T.V. Whelton P.K. Klag M.J. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs.N Engl J Med. 1994; 331: 1675-1679Crossref PubMed Scopus (430) Google Scholar, 30.Murray T.G. Stolley P.D. Anthony J.C. Schinnar R. Hepler-Smith E. Jeffreys J.L. Epidemiologic study of regular analgesic use and end-stage renal disease.Arch Intern Med. 1983; 143: 1687-1693Crossref PubMed Scopus (88) Google Scholar, 31.Pommer W. Bronder E. Greiser E. Helmert U. Jesdinsky H.J. Klimpel A. Borner K. Molzahn M. Regular analgesic use and the risk of end-stage renal failure.Am J Nephrol. 1989; 9: 403-412Crossref PubMed Scopus (109) Google Scholar, but not all9.McCredie M. Stewart J.H. Does paracetamol cause urothelial cancer or renal papillary necrosis?.Nephron. 1988; 49: 296-300Crossref PubMed Scopus (50) Google Scholar, case-control studies of chronic renal disease, with aspirin and other NSAIDs often implicated as well14.Sandler D.P. Burr R. Weinberg C.R. Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease.Ann Int Med. 1991; 115: 165-172Crossref PubMed Scopus (185) Google Scholar, 15.Sandler D.P. Smith J.C. Weinberg C.R. Buckalew V.M. Blythe V.W. Burgess W.P. Analgesic use and chronic renal disease.N Engl J Med. 1989; 320: 1238-1243Crossref PubMed Scopus (223) Google Scholar, 16.Perneger T.V. Whelton P.K. Klag M.J. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs.N Engl J Med. 1994; 331: 1675-1679Crossref PubMed Scopus (430) Google Scholar, 31.Pommer W. Bronder E. Greiser E. Helmert U. Jesdinsky H.J. Klimpel A. Borner K. Molzahn M. Regular analgesic use and the risk of end-stage renal failure.Am J Nephrol. 1989; 9: 403-412Crossref PubMed Scopus (109) Google Scholar, 32.Morlans M. Laporte J.-R. Vidal X. Cabeza D. Stolley P.D. End-stage renal disease and non-narcotic analgesics: A case-control study.Br J Clin Pharmac. 1990; 30: 717-723Crossref PubMed Scopus (80) Google Scholar. Inherent methodologic limitations and potential biases in study design and data collection, however, hamper the interpretation of associations between analgesic use and chronic renal failure or ESRD observed in case-control studies. The purpose of this review is to critically evaluate the existing epidemiologic evidence that use of analgesics may increase the risk of chronic renal failure, and to suggest methods for improving the design of future studies of this issue. To date, the results of at least seven case-control studies of chronic renal failure have been reported in the United States and Europe (Table 1). All but one33.Steenland N.K. Thun M.J. Ferguson C.W. Port F.K. Occupational and other exposures associated with male end-stage renal disease: A case-control study.Am J Public Health. 1990; 80: 153-159Crossref PubMed Scopus (124) Google Scholar were designed specifically to evaluate the role of analgesic use, but the studies varied according to case and control selection criteria, definition of analgesic use, and method of data collection. Many were based on relatively small numbers of users of large amounts of analgesics, making it difficult to meaningfully evaluate the role of these drugs in the etiology of renal failure. In one study, for instance, only 1.2% of controls and 0.6% of patients ever used acetaminophen in a single ingredient product30.Murray T.G. Stolley P.D. Anthony J.C. Schinnar R. Hepler-Smith E. Jeffreys J.L. Epidemiologic study of regular analgesic use and end-stage renal disease.Arch Intern Med. 1983; 143: 1687-1693Crossref PubMed Scopus (88) Google Scholar. The characteristics of these studies, as summarized in Table 1, will be reviewed below, with particular attention to methodologic strengths and weaknesses that could influence the interpretation of results.Table 1Case-control studies of analgesic use and chronic renal failure Open table in a new tab The diagnostic criteria for defining cases of chronic renal disease varied across studies. In fact, only two studies9.McCredie M. Stewart J.H. Does paracetamol cause urothelial cancer or renal papillary necrosis?.Nephron. 1988; 49: 296-300Crossref PubMed Scopus (50) Google Scholar,15.Sandler D.P. Smith J.C. Weinberg C.R. Buckalew V.M. Blythe V.W. Burgess W.P. Analgesic use and chronic renal disease.N Engl J Med. 1989; 320: 1238-1243Crossref PubMed Scopus (223) Google Scholar have specified objective diagnostic criteria, and in the remaining studies it is difficult to rule out subjective diagnosis by physicians who were aware of the patients’ analgesic use history. Moreover, most studies enrolled patients undergoing dialysis for ESRD, most likely as a result of the difficulty of diagnosing renal disease during the early stages. Thus, a critical limitation is the failure to identify and recruit chronic renal failure patients early enough in the natural course of their disease to insure that analgesic exposure information pertains to an etiologically relevant period prior to the development of the disease. Only in the study by Sandler et al14.Sandler D.P. Burr R. Weinberg C.R. Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease.Ann Int Med. 1991; 115: 165-172Crossref PubMed Scopus (185) Google Scholar,15.Sandler D.P. Smith J.C. Weinberg C.R. Buckalew V.M. Blythe V.W. Burgess W.P. Analgesic use and chronic renal disease.N Engl J Med. 1989; 320: 1238-1243Crossref PubMed Scopus (223) Google Scholar were cases patients with kidney disease newly diagnosed based on serum creatinine levels. In the other six studies, cases were patients drawn from hemodialysis or renal transplant centers30.Murray T.G. Stolley P.D. Anthony J.C. Schinnar R. Hepler-Smith E. Jeffreys J.L. Epidemiologic study of regular analgesic use and end-stage renal disease.Arch Intern Med. 1983; 143: 1687-1693Crossref PubMed Scopus (88) Google Scholar, 31.Pommer W. Bronder E. Greiser E. Helmert U. Jesdinsky H.J. Klimpel A. Borner K. Molzahn M. Regular analgesic use and the risk of end-stage renal failure.Am J Nephrol. 1989; 9: 403-412Crossref PubMed Scopus (109) Google Scholar, 32.Morlans M. Laporte J.-R. Vidal X. Cabeza D. Stolley P.D. End-stage renal disease and non-narcotic analgesics: A case-control study.Br J Clin Pharmac. 1990; 30: 717-723Crossref PubMed Scopus (80) Google Scholar, registries of patients with ESRD16.Perneger T.V. Whelton P.K. Klag M.J. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs.N Engl J Med. 1994; 331: 1675-1679Crossref PubMed Scopus (430) Google Scholar,33.Steenland N.K. Thun M.J. Ferguson C.W. Port F.K. Occupational and other exposures associated with male end-stage renal disease: A case-control study.Am J Public Health. 1990; 80: 153-159Crossref PubMed Scopus (124) Google Scholar, or outpatient clinics9.McCredie M. Stewart J.H. Does paracetamol cause urothelial cancer or renal papillary necrosis?.Nephron. 1988; 49: 296-300Crossref PubMed Scopus (50) Google Scholar. Once diagnosed with chronic renal insufficiency, patients are often advised to discontinue use of aspirin and other NSAIDs as these drugs increase the risk of bleeding, interfere with renal potassium excretion and may further compromise their glomerular filtration rate37.Morrison G. Kidney,.in: Tierney Jr, L.M. McPhee S.J. Papadakis M.A. Current Medical Diagnosis and Treatment. Appleton & Lange, Norwalk1995: 775Google Scholar, 38.Lakkis F.G. Martinez-Maldonado M. Conservative management of chronic renal failure and the uremic syndrome,.in: Jacobson H.R. Striker G.E. Klahr S. The Principles and Practice of Nephrology. Mosby, New York1995: 616Google Scholar, 39.Murray M.D. Brater D.C. Renal toxicity of the nonsteroidal anti-inflammatory drugs.Ann Rev Pharmacol Toxicol. 1993; 33: 435-465Crossref PubMed Scopus (280) Google Scholar. As an alternative, these patients are often advised to use acetaminophen for pain relief following their diagnosis. Patients with ESRD or those identified from hemodialysis units are likely to be prevalent cases in the final stages of their illness; they do not necessarily represent the population with non-terminal kidney disease in terms of patterns of analgesic use. It is the incidence of chronic renal failure, rather than the prevalence of ESRD, that is the more etiologically relevant outcome, since studies based on prevalent cases yield associations that may reflect determinants of duration and course of disease as much as the causes of disease. Thus, whether cases come from selected facilities or from a defined population, they should be limited to those newly diagnosed within a specified time period. Additional selection biases may be introduced when registries of patients with ESRD are used as a source for case identification, if case registration is incomplete or reporting of cases to the registry is selective16.Perneger T.V. Whelton P.K. Klag M.J. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs.N Engl J Med. 1994; 331: 1675-1679Crossref PubMed Scopus (430) Google Scholar,33.Steenland N.K. Thun M.J. Ferguson C.W. Port F.K. Occupational and other exposures associated with male end-stage renal disease: A case-control study.Am J Public Health. 1990; 80: 153-159Crossref PubMed Scopus (124) Google Scholar. For instance, among cases identified from the Mid-Atlantic Renal Coalition in the study by Perneger, Whelton and Klag16.Perneger T.V. Whelton P.K. Klag M.J. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs.N Engl J Med. 1994; 331: 1675-1679Crossref PubMed Scopus (430) Google Scholar, 54% were blacks. Analyses of the data as presented would indicate that blacks have a sevenfold increased risk for ESRD compared with whites, a relative risk that is clearly overestimated based on the descriptive epidemiology of the disease. The substantially higher percentage of blacks suggests differential referral and registration by race. When cases are recruited only from selected area clinics and dialysis units or, alternatively, when patients referred from outside the study area are not excluded from the study, the primary study base that gave rise to the cases, and therefore the comparability of controls, is difficult to define. Finally, the representativeness of the case population may be limited by a low response rate or selective non-response among patients. In one study33.Steenland N.K. Thun M.J. Ferguson C.W. Port F.K. Occupational and other exposures associated with male end-stage renal disease: A case-control study.Am J Public Health. 1990; 80: 153-159Crossref PubMed Scopus (124) Google Scholar, for instance, only 53% of the eligible cases identified from a registry were eventually interviewed, and the non-respondents were more likely to be black and living in inner cities than study participants. In another study15.Sandler D.P. Smith J.C. Weinberg C.R. Buckalew V.M. Blythe V.W. Burgess W.P. Analgesic use and chronic renal disease.N Engl J Med. 1989; 320: 1238-1243Crossref PubMed Scopus (223) Google Scholar, white patients again were more likely than black patients to participate. The true relationship between analgesic use and chronic renal failure could be distorted in these studies if non-response is selective with respect to exposure, that is, if black patients or those living in inner cities have unusually high or low use of analgesics. In order to have valid comparisons between groups in case-control studies, controls must be drawn from the same source population that gave rise to the cases40.Wacholder S. McLaughlin J.K. Silverman D.T. Mandel J.S. Selection of controls in case-control studies. I. Principles.Am J Epidemiol. 1992; 135: 1019-1028PubMed Google Scholar. Patients identified from population-based registries or from all clinics serving a well-defined geographic area14.Sandler D.P. Burr R. Weinberg C.R. Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease.Ann Int Med. 1991; 115: 165-172Crossref PubMed Scopus (185) Google Scholar, 15.Sandler D.P. Smith J.C. Weinberg C.R. Buckalew V.M. Blythe V.W. Burgess W.P. Analgesic use and chronic renal disease.N Engl J Med. 1989; 320: 1238-1243Crossref PubMed Scopus (223) Google Scholar, 16.Perneger T.V. Whelton
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