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Should all patients with chronic kidney disease take a statin?

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We think some patients with chronic kidney disease should take a statin, particularly those in stages 1 through 4 (ie, not yet on dialysis1)* who have low-density lipoprotein cholesterol (LDL-C) levels higher than 100 mg/dL. However, few studies have addressed this question.

*Stages of chronic kidney disease1:
Stage 1—kidney damage with normal or high glomerular filtration rate (GFR ≥ 90 mL/min/1.73 m2)
Stage 2—kidney damage with mildly decreased GFR (60–89 mL/min/1.73 m2)
Stage 3—moderately decreased GFR (30–59 mL/min/1.73 m2)
Stage 4—severely decreased GFR (15–29 mL/min/1.73 m2)
Stage 5—kidney failure (GFR < 15 mL/min/1.73 m2 or dialysis)

The answer is murkier in patients on dialysis. Only one study has been done in this population, and it found no benefit from statin therapy. However, we would prescribe a statin for a dialysis patient who had known coronary artery disease and an LDL-C level higher than 100 mg/dL.

RATIONALE FOR STATIN USE: KIDNEY PATIENTS ARE AT RISK

Cardiovascular disease is common among patients with chronic kidney disease. While the risks of cardiovascular disease and death are highest among those requiring dialysis, earlier stages of chronic kidney disease also are associated with cardiovascular disease.2–4

The prevalence of traditional risk factors, particularly diabetes and hypertension, is high in all stages of kidney disease, and dyslipidemia is extremely common. Patients with chronic kidney disease who are not on dialysis tend to have lower levels of high-density lipoprotein cholesterol and higher levels of triglycerides, lipoprotein remnants, lipoprotein(a), and LDL-C. The lipid profile of dialysis patients is more complex, as malnutrition and inflammation in this population may lead to low cholesterol levels.

Since statins are effective for primary and secondary prevention of cardiovascular events in those in the general population with high LDL-C,5 we could expect that the same holds true for patients with chronic kidney disease. Furthermore, if kidney disease were considered a coronary heart disease equivalent, more than 85% of those with stage 3, 4, or 5 disease would qualify for lipid-lowering therapy by LDL-C criteria.6

However, compared with the large body of evidence in those without kidney disease, we have few data on the effect of statins on cardiovascular outcomes in those with kidney disease. Five of seven major trials of statins excluded patients with chronic kidney disease by using a creatinine cutoff or by excluding patients with known kidney disease.7

Renoprotective effects

Besides their cardiovascular effects, statins may slow the progression of kidney disease.

A subgroup analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) trial8 showed a 12% increase in creatinine clearance in the group receiving atorvastatin (Lipitor) (P = .0001). In comparison, creatinine clearance decreased by 4% in the placebo group.

A subgroup analysis of the Cholesterol and Recurrent Events (CARE) trial, a secondary prevention trial of pravastatin (Pravachol) vs placebo, showed a similar effect for patients with a glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 at baseline.9

A meta-analysis of 27 randomized trials (39,704 participants) concluded that, compared with no treatment, statins slowed the loss of GFR by a mean of 1.22 mL/min/year (95% confidence interval 0.44–2.0).10

Statins may confer this benefit independently of lipid-lowering. These drugs seem to decrease proteinuria, possibly by improving endothelial function or decreasing inflammation.11 A meta-analysis (1,384 patients) noted that 13 of 15 published studies found an antiproteinuric effect, with a greater effect in those with greater baseline proteinuria.12

The Prospective Evaluation of Proteinuria and Renal Function in Diabetic Patients With Progressive Renal Disease Trial (PLANET) will enroll 345 diabetic patients with protein-uria and hypercholesterolemia and examine the effects of rosuvastatin (Crestor) and atorvastatin on proteinuria and GFR.13

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