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Cholesterol and the risk of renal dysfunction in apparently healthy men
Elke S Schaeffner1,1,1, Tobias Kurth1,1,1, Gary C Curhan1,1
1Divisions of *Preventive Medicine, and Aging, and Cardiovascular Disease, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston; **Department of Ambulatory Care and Prevention, Harvard Medical School, Boston; Massachusetts Veterans Epidemiology Research and Information Center, VA Healthcare System, Boston, Massachusetts; Department of Nephrology, University of Freiburg, Germany; and Clinical Trial Service Unit, Oxford University, Oxford, United Kingdom.
Insights
High cholesterol, particularly low HDL and high non-HDL levels, significantly increases the risk of developing kidney dysfunction in men. These lipid abnormalities are linked to elevated creatinine and reduced creatinine clearance over time.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Epidemiology
Background:
- Abnormal lipid patterns are known in end-stage renal disease, but the link to early renal dysfunction is unclear.
- Understanding cholesterol's role in kidney function decline is crucial for preventative strategies.
Purpose of the Study:
- To investigate the association between cholesterol parameters and the development of renal dysfunction in initially healthy men.
- To quantify the risk of elevated creatinine and reduced creatinine clearance associated with various lipid profiles.
Main Methods:
- Prospective cohort study of 4,483 initially healthy men from the Physicians' Health Study.
- Blood samples collected in 1982 and 1996, with outcomes measured after 14 years.
- Logistic regression used to calculate multivariable-adjusted odds ratios for renal dysfunction markers (elevated creatinine, reduced creatinine clearance) based on cholesterol levels (total, HDL, non-HDL, cholesterol/HDL ratio).
Main Results:
- Elevated total cholesterol (≥240 mg/dl), low HDL (<40 mg/dl), high total cholesterol/HDL ratio (≥6.8), and high non-HDL cholesterol (≥196.1) were significantly associated with increased risk of elevated creatinine.
- Relative risks ranged from 1.77 to 2.34 for elevated creatinine.
- Similar, though less pronounced, associations were observed for reduced creatinine clearance.
Conclusions:
- Elevated total cholesterol, high non-HDL cholesterol, a high total cholesterol/HDL ratio, and low HDL are significant risk factors for developing renal dysfunction in men.
- These findings highlight the importance of lipid management in kidney disease prevention.
Abstract:
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 /= 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.