Do Statins Protect the Kidney by Reducing Proteinuria?

The first time someone proposed that dyslipidemia caused progressive kidney disease was more than a century ago (1). The proposal has support from experimental and clinical evidence (2), and some have suggested that lipid-modifying medication may reduce proteinuria and prevent kidney function loss. This editorial focuses on statins, which have been the most extensively studied class of lipid-lowering drug.

A recent systematic review of 27 randomized trials (with a total of 39 704 participants) suggested that statins reduce the rate of kidney function loss by 1.2 mL/min per year (95% CI, 0.4 to 2.0 mL/min per year), which is equivalent to an approximately 76% reduction (3). In this issue, Douglas and colleagues (4) report the findings of a rigorously conducted systematic review of the effect of statins on urinary protein excretion, a powerful predictor of kidney function loss.

Douglas and colleagues identified 15 randomized studies that examined the change in proteinuria or albuminuria in a total of 1384 patients after taking a statin or placebo. Eligible trials measured urinary protein excretion at baseline and at follow-up with 24-hour urine collections or the ratio of protein to creatinine in the urine. Eight trials exclusively studied people with diabetes mellitus. Many of the remaining studies had a mixed population of participants, including some with glomerulonephritis. The median follow-up was 6 months, and the statin doses in the individual studies ranged from low to intermediate. None of the included trials examined the renal effects of high-dose statin therapy.

Because the effect of statins on proteinuria varied considerably among the studies, Douglas and colleagues did not pool the results of all 15 trials. Instead, based on an a priori hypothesis about what caused the between-study variability, they stratified analyses according to the level of baseline urinary protein excretion: overt proteinuria (≥300 mg/d), …