Cholesterol and Your Kidneys: A Fatal Connection
Chronic kidney disease in itself has been found to be an independent predictor for the development of heart disease and is associated with an overall poorer prognosis. This effect occurs throughout the entire spectrum of kidney failure ranging from those with mild kidney disease to even those who have had successful kidney transplants. In one study of a million people with kidney failure who were not yet on dialysis, the risk of developing atherosclerosis was almost 35 times more likely than the risk of needing some type of kidney replacement therapy. In fact, the American National Kidney Foundation, the American College of Cardiology, and the American Heart Association consider people with chronic kidney disease to be at equal risk of a future cardiovascular event when compared to those who have already had a heart attack.
Many conditions that confer increased heart disease risk can also lead to chronic kidney damage. Some common examples are high blood pressure and diabetes. However, kidney failure can also adversely affect your cholesterol levels leading to further increased risk of heart disease. The main abnormality is high triglyceride levels. Almost half of people with chronic kidney failure have triglyceride levels above 200mg/dl (normal <150mg/dl), and a third have levels greater than 240mg/dl. About a third also have LDL levels greater than 130mg/dl and HDL levels tend to be somewhat lower as kidney function decreases.
The reason for the increase levels of triglycerides is due to reduced clearance. Triglycerides are not cleared by the kidney, but rather by enzymes in the liver and other body tissues that breakdown triglycerides. For reasons that are not clear, these clearing enzymes are not as active as the kidney fails. One possible explanation may be that an enzyme inhibitor normally cleared by the kidney accumulates as kidney function decreases. The triglycerides themselves are also somewhat chemically altered and may be more resistant to clearance. In any event, triglyceride levels increase. This degree of increased triglycerides may not be enough to significantly increase overall heart disease risk; however, if you combine it with lower HDL and higher LDL levels, then the overall heart disease risk can be significantly increased.
To complicate matters, a paradoxical phenomenon between total cholesterol and heart disease risk has been noted. In people with normal kidney function, higher levels of total cholesterol lead to an increased risk of heart disease and death. Conversely, several studies have noted that in people with chronic kidney failure, a lower total cholesterol level is associated with an increased risk of death. Some believe that the lower cholesterol level is more of a sign of chronic malnutrition and increased inflammation and not necessarily a cause of increase heart disease or death. However, this relationship is still not fully understood.
Because chronic kidney disease is markedly associated with heart disease, the recommended management of cholesterol in the setting of chronic kidney failure is similar to those who are known to have significant heart disease. Therapeutic lifestyle changes with diet and exercise and drug therapy such as statins are recommended to lower LDL to below 100mg/dl (even <70mg/dl) and to increase HDL to greater than 40mg/dl.
Medication for persistently high triglycerides can be considered for high risk people or if the triglyceride level is very high (>500mg/dl), but caution must be used since some medicines such as fibric acid derivatives are associated with more side effects in the setting of kidney failure.
The problem with the above recommendations is that there is very little data specifically looking at the effects of cholesterol lowering therapy in people with chronic kidney disease. The first study published in 2005 did not show any benefit with statin therapy in people with chronic kidney disease but it did not show any harm either. There are 2 more large scale studies currently in progress designed to answer this question. Until then, cholesterol management in chronic kidney disease remains similar to that in heart disease.