Cholesterol and the risk of renal dysfunction in apparently healthy men.

Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease, the association between cholesterol and the development of renal dysfunction is unclear. We evaluated this association in a prospective cohort study among 4,483 initially healthy men participating in the Physicians' Health Study who provided blood samples in 1982 and 1996. Main outcome measures were elevated creatinine, defined as >/= 1.5 mg/dl (133 micromol/L), and reduced estimated creatinine clearance, defined as </=55 ml/min. Cholesterol parameters included total cholesterol (<200, 200 to 239, and >/= 240 mg/dl), HDL (<40 or >/= 40 mg/dl), total non-HDL cholesterol, and the ratio of total cholesterol to HDL. We used logistic regression to calculate age- and multivariable adjusted odds ratios as a measure for the relative risk. After 14 yr, 134 men (3.0%) had elevated creatinine and 244 (5.4%) had reduced creatinine clearance. The multivariable relative risk for elevated creatinine was 1.77 (95% confidence interval [CI], 1.10 to 2.86) for total cholesterol >/= 240 mg/dl, 2.16 (95% CI, 1.42 to 3.27) for HDL <40 mg/dl, 2.34 (95% CI, 1.34 to 4.07) for the highest quartile of total cholesterol/HDL ratio (>/= >6.8), and 2.16 (95% CI, 1.22 to 3.80) for the highest quartile of non-HDL cholesterol (>/= 196.1). Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance. Elevated total cholesterol, high non-HDL cholesterol, a high ratio of total cholesterol/HDL, and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine <1.5 mg/dl.

[1]  Avram Mm Similarities between glomerular sclerosis and atherosclerosis in human renal biopsy specimens: a role for lipoprotein glomerulopathy. , 1989 .

[2]  J. Mustonen,et al.  Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy. , 2000, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[3]  D. Ford,et al.  Validity of physicians' self-reports of cardiovascular disease risk factors. , 1993, Annals of epidemiology.

[4]  Z. Varghese,et al.  LIPID NEPHROTOXICITY IN CHRONIC PROGRESSIVE GLOMERULAR AND TUBULO-INTERSTITIAL DISEASE , 1982, The Lancet.

[5]  R. Collins,et al.  PROBLEMS WITH MAILED BLOOD IN LARGE-SCALE EPIDEMIOLOGIC STUDIES AND METHODS OF CORRECTION , 1993 .

[6]  B. Kasiske,et al.  Lipids and progressive glomerulosclerosis. A model analogous to atherosclerosis. , 1988, American journal of nephrology.

[7]  V. Manninen,et al.  Effects of hypertension and dyslipidemia on the decline in renal function. , 1995, Hypertension.

[8]  O. Wiklund,et al.  Cholesterol: a renal risk factor in diabetic nephropathy? , 1993, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[9]  B. Kasiske,et al.  Pharmacologic Treatment of Hyperlipidemia Reduces Glomerular Injury in Rat 5/6 Nephrectomy Model of Chronic Renal Failure , 1988, Circulation research.

[10]  N. Madias,et al.  Serum creatinine as an index of renal function: new insights into old concepts. , 1992, Clinical chemistry.

[11]  A. Kliger,et al.  Chronic renal insufficiency: current understandings and their implications. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[12]  M. H. Gault,et al.  Prediction of creatinine clearance from serum creatinine. , 1975, Nephron.

[13]  F. Schena,et al.  Treatment of glomerulonephritides associated with hepatitis C virus infection. , 2000, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[14]  H. Mulec,et al.  Complex apolipoprotein B-containing lipoprotein particles are associated with a higher rate of progression of human chronic renal insufficiency. , 1998, Journal of the American Society of Nephrology : JASN.

[15]  A. Levey,et al.  Cardiovascular disease and chronic renal disease: a new paradigm. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[16]  J. Manson,et al.  Baseline characteristics of participants in the Physicians' Health Study: a randomized trial of aspirin and beta-carotene in U.S. physicians. , 1991, American journal of preventive medicine.

[17]  R. Wolfe,et al.  I. The USRDS and its products. , 1999, American Journal of Kidney Diseases.

[18]  W. Keane,et al.  The role of lipids in renal disease: future challenges. , 2000, Kidney international. Supplement.

[19]  C. Baigent,et al.  Study of Heart and Renal Protection (SHARP). , 2003, Kidney international. Supplement.

[20]  J. Coresh,et al.  Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. , 2000, Kidney international.

[21]  David Roth,et al.  A simplified equation to predict glomerular filtration rate from serum creatinine , 2000 .

[22]  M. Avram Similarities between glomerular sclerosis and atherosclerosis in human renal biopsy specimens: a role for lipoprotein glomerulopathy. , 1989, The American journal of medicine.

[23]  B. Kasiske,et al.  Renal injury of diet-induced hypercholesterolemia in rats. , 1990, Kidney international.

[24]  G. Remuzzi,et al.  Progression, remission, regression of chronic renal diseases , 2001, The Lancet.

[25]  B. Kasiske,et al.  Effect of lipid reduction on the progression of renal disease: a meta-analysis. , 2001, Kidney international.

[26]  A. Garg,et al.  Albuminuria and renal insufficiency prevalence guides population screening: results from the NHANES III. , 2003, Kidney international.

[27]  H. Oda,et al.  Recent advances in statins and the kidney. , 1999, Kidney international. Supplement.

[28]  W. Keane Lipids and the kidney. , 1994, Kidney international.

[29]  E. Rimm,et al.  Validity of Self‐Reported Waist and Hip Circumferences in Men and Women , 1990, Epidemiology.

[30]  Cockcroft Dw,et al.  Prediction of Creatinine Clearance from Serum Creatinine , 1976 .

[31]  J. Coresh,et al.  Microalbuminuria in the US population: third National Health and Nutrition Examination Survey. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[32]  H. Wedel,et al.  Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[33]  Final report on the aspirin component of the ongoing Physicians' Health Study. , 1989, The New England journal of medicine.

[34]  J. Manson,et al.  Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. , 1996, The New England journal of medicine.

[35]  W. Willett,et al.  Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. , 1986, American journal of epidemiology.

[36]  S. Silbiger,et al.  The impact of gender on the progression of chronic renal disease. , 1995, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[37]  A. Albertazzi,et al.  Lipids in the progression of chronic renal failure. , 1992, Nephron.

[38]  T. Louis,et al.  Long-term effects of antihypertensive agents on proteinuria and renal function. , 1995, Archives of internal medicine.

[39]  J. Mckenney,et al.  Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). , 2001, JAMA.

[40]  D. Bates,et al.  Diabetes, hemoglobin A(1c), cholesterol, and the risk of moderate chronic renal insufficiency in an ambulatory population. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.