Polycystic Kidney Disease (PKD) is the most common genetic disease leading to End Stage Kidney Disease, affecting between 1 in 500-1000 individuals from every ethnic group. The autosomal dominant (ADPKD) form arises from a two-hit downregulation of proteins encoded by either PKD1 or PKD2. Although many potential therapies have been studied to slow progression of ADPKD, none to date have been proven safe and effective in slowing disease progression. Cholesterol-lowering agents called statins have shown promise in the treatment of younger ADPKD patients, reducing inflammation and progression as assessed by kidney growth, but their utility appears to be limited in older populations and those with more advanced chronic kidney disease (CKD). Recent evidence suggests that acidosis, as often seen in patients with worsening CKD and which may enhance CKD progression, limits the effectiveness of statins and enhances their potential toxicity. We thus hypothesize that correction of acidosis along with statin treatment will be a safe and effective therapy to slow CKD progression in adult ADPKD patients and improve their overall quality of life.

We will therefore conduct a pilot open-label randomized clinical trial in ADPKD patients with estimated GFR >45 min (Stage 1-3a CKD) comparing three treatment groups: control, pravastatin (40 mg po qd), and pravastatin plus sodium citrate solution (30 mL po qd) over one year. Through study visits we will evaluate safety/tolerability of these treatments, follow renal function and investigate the role of these treatments on acidosis, inflammatory, injury, and metabolic biomarkers in patients enrolled at our facility. We will establish the framework for larger clinical trials in ADPKD at KSOM. Moreover, if the results of this study suggest safety/tolerability or benefits of statins and alkali therapy in this population, we will seek extramural funding for a larger clinical trial to test this therapeutic strategy in ADPKD. 

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