A Target Trial Emulation to Investigate Kidney Protection from Statin Initiation in Adults with Normal Kidney Function

BACKGROUND: Evidence on the kidney-protective effects of statins in individuals with normal kidney function is mixed, with some trials suggesting benefits and others raising concerns about acute kidney injury. This study evaluates the impact of statin initiation on kidney function in adults with normal kidney function. METHODS: Sequential target trial emulation based on electronic health records in the Hong Kong Hospital Authority were conducted. Patients aged ≥ 18 years old with normal kidney function (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m 2 ) who met the indication for statin therapy (i.e. low-density lipoprotein cholesterol ≥ 100 mg/dL without cardiovascular disease or ≥ 70 mg/dL with cardiovascular diseases) in Hong Kong between January 2008 and December 2017 were included. Statin initiators and non-initiators were matched using 1:1 propensity score matching. Hazard ratio (HR) and 10-years absolute risk reduction (ARR) of outcomes, including impaired kidney function (eGFR <15 and <60 mL/min/1.73 m 2 ), kidney function deterioration (≥30% and ≥50% eGFR decline) and all-cause mortality, were estimated using weighted pooled logistic regression based on intention-to-treat approach. RESULTS: Among 449,595 statin initiators and 449,595 matched non-initiators, statin use was associated with a lower risk of eGFR <15 mL/min/1.73m 2 (HR: 0.92 [0.90, 0.95]; ARR: -0.33% [-0.42%, -0.24%]), eGFR <60 mL/min/1.73m 2 (HR: 0.97 [0.96, 0.98]; ARR: -0.98% [-1.12%, -0.84%]), ≥30% eGFR decline (HR: 0.94 [0.93, 0.95]; ARR: -1.81% [-2.00%, -1.60%]), ≥50% eGFR decline (HR: 0.90 [0.88, 0.91]; ARR: -0.98% [-1.11%, -0.85%]), and all-cause mortality (HR [95% CI]: 0.90 [0.89, 0.91]; ARR [95% CI]: -1.63% [-1.76%, -1.49%]). CONCLUSIONS: Statin initiation in adults with normal kidney function was associated with modestly lower all-cause mortality and kidney function impairment, supporting a potential kidney protective benefit of statins without increasing the risks of adverse kidney outcomes.