Statins Slow Kidney Disease Progression

The statin pravastatin slows the progression of kidney cysts in pediatric patients with autosomal dominant polycystic kidney disease (ADPKD), according to a new study, the first to show that early therapy with a pharmacologic agent can result in optimal long-term treatment of the disease.

ADPKD, the most common inherited renal disease, enlarges the kidneys due to the growth of tubular cysts and is often assumed to affect only adults. Because the disease is genetic, noted the researchers, early intervention is the best treatment strategy.

Pravastatin was tested because it has minimal drug interactions and is cleared for treating increased levels of lipids in the bloodstream in children older than 8 years, noted the study. Statins also improve endothelial dysfunction, an early indicator of ADPKD that manifests before hypertension. Additionally, children with ADPKD are hypertensive and have increased left ventricular mass index (LVMI), a condition statins improve in heart disease patients. The study also noted a 4-week therapy of simvastatin was shown to improve renal blood flow and kidney function in adult patients suffering from the disease.

The researchers tested pravastatin in pediatrics patients with bilateral cysts consistent with a family history of ADPKD or several cysts that indicated a new diagnosis of the disease. Over the 3-year trial period, 56 of the study’s patients aged 8 to 12 years and 13 to 22 years received daily doses of pravastatin 20 mg and 40 mg, respectively, while 54 patients received placebo. According to the findings, 69% of the patients on pravastatin and 88% of patients on placebo showed a greater than 20% increase in LVMI, urinary microalbumin excretion (UME) and, most significantly, total kidney volume.

There were no significant side effects that necessitated the discontinuation of either therapy although the researchers noted 3 patients became pregnant during the trial, which they said highlighted the importance of follow-up care when prescribing statins to female patients of childbearing age, even though the risks to children in utero appear to be minimal.

“Based on our findings, we strongly recommend consideration of pravastatin use in ADPKD children and young adults unless there is a medical reason against taking a statin,” says study lead author Dr. Melissa Cadnapaphornchai, associate professor of pediatrics and medicine at the University of Colorado Anschutz Medical Campus. “This is very exciting news as this is the first medication shown to help control kidney disease in ADPKD children.”

Pravastatin therapy in pediatrics would demand off-label use of the drug, noted the researchers, who called for frank discussions with patients and their families about the treatment’s potential risks and rewards.

The study was published online in the Clinical Journal of the American Society of Nephrology.

—Dan Cook

Reference:

1. Cadnapaphornchai MA, George DM, McFann K, et al. Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2014;9(5):886-896.