Effect of Pravastatin on Total Kidney Volume, Left Ventricular Mass Index, and Microalbuminuria in Pediatric Autosomal Dominant Polycystic Kidney Disease

Abstract

Background and objectives In autosomal dominant polycystic kidney disease (ADPKD), progressive kidney cyst formation commonly leads to ESRD. Because important manifestations of ADPKD may be evident in childhood, early intervention may have the largest effect on long-term outcome. Statins are known to slow progressive nephropathy in animal models of ADPKD. This randomized double-blind placebo-controlled phase III clinical trial was conducted from 2007 to 2012 to assess the effect of pravastatin on height-corrected total kidney volume (HtTKV) and left ventricular mass index (LVMI) by magnetic resonance imaging (MRI) and urine microalbumin excretion (UAE) in children and young adults with ADPKD.Designs, setting, participants, & measurements There were 110 pediatric participants with ADPKD and normal kidney function receiving lisinopril who were randomized to treatment with pravastatin or placebo for a 3-year period with evaluation at 0, 18, and 36 months. The primary outcome variable was a $20% change in HtTKV, LVMI, or UAE over the study period.Results Ninety-one participants completed the 3-year study (83%). Fewer participants receiving pravastatin achieved the primary endpoint compared with participants receiving placebo (69% versus 88%; P=0.03). This was due primarily to a lower proportion reaching the increase in HtTKV (46% versus 68%; P=0.03), with similar findings observed between study groups for LVMI (25% versus 38%; P=0.18) and UAE (47% versus 39%; P=0.50). The percent change in HtTKV adjusted for age, sex, and hypertension status over the 3-year period was significantly decreased with pravastatin (23%63% versus 31%63%; P=0.02).Conclusions Pravastatin is an effective agent to slow progression of structural kidney disease in children and young adults with ADPKD. These findings support a role for early intervention with pravastatin in this condition.

Recent important strategies in the management of chronic kidney disease

“…Likewise, somatostatin (octreotide) and the mammalian target of rapamycin (mTOR) inhibitor rapamycin have been used, but with limited or disappointing results, and are also excessively expensive. [20,23] Cadnapaphornchai et al [24] recently reported on the prevention of a reduction in kidney volume and cyst growth, which was accom panied by kidney functional stability, using pravastatin in children and adults, with striking results. The use of statins is not new and both experimental and clinical mechanisms of renal protection in ADPKD have previously been shown.…”

“…In addition, statins inhibit angiogenesis. [24] It would be interesting to investigate whether the production of glycogen synthase kinase-3β (GSK3β) is altered. GSK3β has recently been shown to play a role in ADPKD via induction of proliferation of cystic epithelial cells.…”

New options in the treatment of autosomal dominant polycystic kidney disease

“…26 The randomized double-blind placebo-controlled trial conducted with 110 children with ADPKD and normal kidney function studied the effect of pravastatin on the progression of disease. 27 All patients had lisinopril treatment. They were randomized to treatment with pravastatin or placebo.…”

“…The number of patients reaching end point for TKV was significantly lower in the pravastatin group. 27 …”

Novel Treatments of Autosomal Dominant Polycystic Kidney Disease

“…This issue of CJASN also includes the first published randomized placebo-controlled clinical trial of deliberate statin use to evaluate potential benefit on height-corrected TKV change of ADPKD in children and young adults (43). This trial evaluated either 20 or 40 mg pravastatin combined with an angiotensin-converting enzyme inhibitor in young patients aged 8-22 years with ADPKD.…”