Simvastatin dose and acute kidney injury without concurrent serious muscle injury: A nationwide nested case-control study

BACKGROUND: Inconsistent findings from four observational studies suggest that the risk of acute kidney injury (AKI) may increase with increasing statin dose or potency, but none of the studies took statin-related severe muscle injury, including rhabdomyolysis, into account. We undertook a nationwide nested case-control study in New Zealand to examine the risk of AKI without concurrent serious muscle injury according to simvastatin dose in two cohorts: people without a history of renal disease and people with non-dialysis dependent chronic kidney disease. MATERIALS AND METHODS: A total of 334,710 people aged ≥ 18 years without a history of renal disease (cohort 1) and 5,437 with non-dialysis dependent chronic kidney disease (cohort 2) who initiated simvastatin therapy between 1 January 2006 and 31 December 2013 were identified using national pharmaceutical dispensing and hospital discharge data. Patients who developed AKI without concurrent serious muscle injury during follow-up (cases) were ascertained using hospital discharge and mortality data (n = 931 from cohort 1, n = 160 from cohort 2). Up to 10 controls per case, matched by date of birth, sex, and cohort entry date were randomly selected from the relevant cohort using risk set sampling. RESULTS: Relative to current use of 20mg simvastatin daily, the adjusted odds ratios and 95% confidence intervals (95% CI) in cohort 1 for current use of 40mg and 80mg were 0.9 (95% CI 0.7–1.2) and 1.3 (95% CI 0.7–2.3), respectively. The adjusted odds ratio for 40mg in cohort 2 was 1.1 (95% CI 0.7–1.9); the numbers taking 80mg were very small and the confidence interval was correspondingly wide. CONCLUSION: The findings of this study suggest that a relationship between statin dose and AKI may not exist independent of serious muscle injury.