Link Found between Cholesterol and Kidney Disease

Researchers at the Johns Hopkins School of Public Health have found that high levels of triglycerides and low levels of high-density (good) cholesterol in the blood predict the onset of chronic kidney disease. In contrast, total cholesterol and low-density lipoprotein (LDL) cholesterol which are important determinants of heart disease risk did not predict kidney disease risk. Individuals who went on to experience an onset of chronic kidney disease were also substantially more likely to be older, black, diabetic, and hypertensive at the start of the study. The study appeared in the June 2000 issue of Kidney International.

Five to ten million Americans are estimated to have early stages of chronic kidney disease, having lost at least half of their normal kidney function. Chronic kidney disease shares many common risk factors with heart disease, including hypertension and diabetes, but the role of cholesterol has been less certain. The current study was the first to assess the association between a large number of lipids in the blood and a subsequent decline in kidney function in a large sample of the general population. The findings, which could help identify modifiable risk factors that predict development and progression of kidney disease, suggest that cholesterol treatment for preventing heart disease may not be as effective at preventing kidney disease.

Senior author Josef Coresh, MD, PhD, associate professor, Epidemiology, Biostatistics, and Medicine, Johns Hopkins School of Public Health, noted, "Chronic kidney disease is only beginning to be recognized as a major public health problem. Our goal is to systematically understand why some individuals' kidney function declines more rapidly and why these individuals are at an increased risk of kidney failure and death. Heart and kidney disease share many common risk factors. Understanding the similarities and differences will help us understand why treated kidney disease incidence is increasing while heart disease is decreasing."

The report focused on the risk of declining kidney function over the three years following a baseline examination. A total of 15,792 men and women ages 45 to 64 were followed at three-year intervals since 1987 as participants in the Atherosclerosis Risk in Communities Study. At the baseline examination, participants answered questions about kidney disease risk factors and gave blood samples, which were tested for the following lipid levels: total cholesterol, HDL cholesterol, LDL cholesterol, apolipoproteins A and B, and triglycerides.

Creatinine, a breakdown product of muscle, was used to detect chronic kidney disease. Since a rising level in creatinine in the bloodstream indicates a decline in the kidney's capacity to filter blood, the investigators used an increase of 0.4 milligrams of creatinine per deciliter of blood to indicate a significant decline in kidney function.

The data revealed that higher triglyceride levels were consistently associated with a greater risk of increased creatinine levels, and thus a decrease in kidney function. Similarly, lower levels of high density lipoprotein (HDL or good) cholesterol and apolipoprotein-A (the major protein in HDL cholesterol) were associated with greater risk. In contrast, total cholesterol and low-density lipoprotein cholesterol showed no association with the risk of chronic kidney disease.

Individuals who went on to develop a rise in creatinine had a higher mean age and were substantially more likely to be black, have diabetes, and use anti-hypertensive medications at baseline. For each three-fold increase in triglyceride levels, the risk of a rise in creatinine was 2.39 times greater among African Americans and 1.31 times greater among whites. The associations remained when the study was limited to individuals with normal kidney function at baseline.

Lead author Paul Muntner, research assistant, Epidemiology, Johns Hopkins School of Public Health, said, "Among the lipids we investigated, triglycerides had the strongest and most statistically significant association with a future decline in renal function. Individuals with high triglycerides were 1.5 times more likely to experience a decline in kidney function compared to individuals with low triglycerides." These associations persisted even after taking into consideration such variables as sex, race, age, systolic blood pressure, diabetes status, and type of blood pressure medication used.

Support for this study was provided by the National Heart, Lung, and Blood Institute; by a training grant from the National Institutes of Health; and by grants from the National Institute of Diabetes, Digestive, and Kidney Disease and the National Center for Research Resources.