Atorvastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease
Status:
Enrolling by invitation
Trial end date:
2026-12-01
Target enrollment:
Participant gender:
Summary
Polycystic Kidney Disease (PKD) is the most common genetic disease leading to End Stage
Kidney Disease (ESKD), 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 to be both 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. The investigators thus
hypothesize that correction of acidosis along with statin treatment will be a safe and
effective therapeutic regimen to slow CKD progression in the adult ADPKD population and
improve overall quality of life in these patients. To test this hypothesis, the investigators
will 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, atorvastatin (20 mg
po qd), and atorvastatin plus sodium bicarbonate tablets (upto 1800mg po total daily dose)
over one year. At the beginning of the study, the investigators will determine the genotype
of the trial participants. During the study period, through study visits along with serial
blood draws and urinary measurements, the investigators will evaluate safety and tolerability
of these treatment regimens, follow renal function and investigate the role of these
treatments on acidosis, inflammatory and metabolic biomarkers in patients enrolled at an
outpatient facility. Serial follow-up imaging study will also be done in selected patients.
This study will establish the framework for larger clinical trials in ADPKD. Moreover, if the
results of this study suggest safety/tolerability or potential benefits of statins and alkali
therapy in this ADPKD population, the investigators will seek extramural funding for a larger
clinical trial to test this therapeutic strategy in ADPKD.