What is the effect of cholesterol lowering interventions in CKD patients?
Blood lipid (cholesterol) level is one of the biochemical markers linked to nutritional status and used to define PEW in CKD.
However, in the general population, lowering blood cholesterol is the cornerstone of primary and secondary cardiovascular disease (CVD) prevention.
Given the extremely high CVD morbidity and mortality observed in the CKD population, it appeared seemingly reasonable to use cholesterol-lowering therapies in patients on dialysis, especially because such pharmacologic interventions are not only antiinflammatory, but they are not burdened by worsening PEW.
One issue that appeared to contradict the cholesterol-CVD paradigm in the CKD population was that high cholesterol was not associated with higher mortality in CKD. In fact, epidemiologic data showed that high lipids may in fact be protective. This is referred to as the “lipid paradox” and is another component of the “reverse epidemiology” phenomenon.
• Due to the uncertainty, two randomized controlled trials (Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events [AURORA] and Die Deutsche Diabetes Dialyse Studie [4D Study]) were designed to test the hypothesis that lowering blood cholesterol by statin therapy can decrease CVD event rates and mortality in patients in dialysis. Both of these studies yielded negative results, corroborating the findings of epidemiologic studies, and again suggesting that the classical Framingham risk factor patterns cannot be automatically translated to patients with kidney disease.
• A third study (Study of Heart and Renal Protection, SHARP) enrolled patients with non–dialysis-dependent CKD (besides dialysis patients) found that cholesterol lowering resulted in lower risk of a composite CVD event rate. SHARP did not find improvement in all-cause mortality. The CVD benefit of cholesterol lowering was significant only in patients with CKD not on renal replacement therapy, but there was no statistically significant interaction with dialysis status, suggesting that the lack of statistically significant effect in patients on hemodialysis may have been the result of the lower number of patients on hemodialysis enrolled. The results of SHARP suggest that therapeutic cholesterol lowering has a modest CVD benefit in patients with kidney diseases, especially those with non–dialysis-dependent CKD.
