HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis

Abstract

Dyslipidaemia occurs frequently in chronic kidney disease (CKD) patients and contributes both to cardiovascular disease and worsening renal function. Statins are widely used in non-dialysis dependent CKD patients (pre-dialysis) even though evidence favouring their use is lacking. To evaluate the benefits and harms of statins in CKD patients who were not receiving renal replacement therapy. We searched MEDLINE, EMBASE, CENTRAL (in The Cochrane Library), and hand-searched reference lists of textbooks, articles and scientific proceedings. Randomised controlled trials (RCTs) and quasi-RCTs comparing statins with placebo, no treatment or other statins in adult pre-dialysis CKD patients. Two authors independently assessed study quality and extracted data. Results were expressed as mean difference (MD) for continuous outcomes (lipids, creatinine clearance and proteinuria) and risk ratio (RR) for dichotomous outcomes (all-cause mortality, cardiovascular mortality, fatal and non-fatal cardiovascular events, elevated liver enzymes, rhabdomyolysis and withdrawal rates) with 95% confidence intervals (CI). Twenty six studies (25,017 participants) comparing statins with placebo were identified. Total cholesterol decreased significantly with statins (18 studies, 1677 patients: MD -41.48 mg/dL, 95% CI -49.97 to -33.99). Similarly, LDL cholesterol decreased significantly with statins (16 studies, 1605 patients: MD -42.38 mg/dL, 95% CI -50.71 to -34.05). Statins decreased both the risk of all-cause (21 RCTs, 18,781 patients, RR 0.81, 95% CI 0.74, 0.89) and cardiovascular deaths (20 studies, 18,746 patients: RR 0.80, 95% CI 0.70 to 0.90). Statins decreased 24-hour urinary protein excretion (6 studies, 311 patients: MD -0.73 g/24 h, 95% CI -0.95 to -0.52), but there was no significant improvement in creatinine clearance - a surrogate marker of renal function (11 studies, 548 patients: MD 1.48 mL/min, 95% CI -2.32 to 5.28).The incidence of rhabdomyolysis, elevated liver enzymes and withdrawal rates due to adverse events (well known complications of statins use), were not significantly different between patients receiving statins and placebo. Statins significantly reduced the risk of all-cause and cardiovascular mortality in CKD patients who are not receiving renal replacement therapy. They do not impact on the decline in renal function as measured by creatinine clearance, but may reduce protein excretion in urine. Statins appear to be safe in this population. Guidelines recommendations on hyperlipidaemia management in CKD patients could therefore be followed targeting higher proportions of patients receiving a statin, with appropriate monitoring of adverse events.