IND 117464 Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney Disease

Project: Research project

Project Details


There is a critical need for safe, inexpensive treatments that can delay the progression of cyst enlargement
and the accompanying destruction of the renal parenchyma that leads to renal failure in the majority of
autosomal polycystic kidney disease (ADPKD) patients. In ADPKD, the earlier the onset of treatment, the
greater the potential benefit to the patient, therefore, drugs for this disease should be considered life-long
therapy. Our overall goal is to develop efficacious drugs that can be safely used from the time of diagnosis
in ADPKD patients. The objective in the proposed studies is to conduct a preliminary evaluation of drug
therapy using a low dose of an insulin sensitizing agent, the PPAR? agonist, pioglitazone, in the treatment of
ADPKD. Our previous cell culture studies showed that low doses of PPAR? agonists, including pioglitazone,
inhibit the synthesis of the CFTR (cystic fibrosis transmembrane conductance regulator) Cl- channel in the
cell type that lines the renal cysts. CFTR is the major ion channel postulated to be involved in transepithelial
Cl- and, secondarily, water flux into the cyst lumen resulting in cyst expansion. Our in vivo animal studies
have shown that the two FDA approved PPAR? agonists, pioglitazone or rosiglitazone, inhibited cyst growth
in the PCK rat model of PKD. In addition to inhibiting cyst growth, PPAR? agonist therapy is expected to
have beneficial effects on other parameters of PKD such as dyslipidemia, hypertension and endothelial
function. Based on these data, we hypothesize that treatment with low dose pioglitazone will slow
cyst expansion in human ADPKD patients and delay the progression of disease. The proposed study
is a double-blind, placebo controlled, cross-over trial of pioglitazone (15 mg/day) versus placebo therapy for
the treatment of ADPKD. The study is a pilot study to test the safety and efficacy of pioglitazone to slow
progression of PKD assessed by percent change in kidney volume by MRI compared to one year of
placebo. 28 subjects will be enrolled. A one year cross-over design provides the best opportunity to obtain
meaningful safety and efficacy data in a short term protocol by allowing each patient to serve as his/her own
control. This will facilitate the design of a future multi center randomized trial. Based on data from large
scale studies in normal volunteers and diabetic patients, low dose pioglitazone is relatively safe for long
term treatment. Thus, this drug may provide a safe option for treatment of ADPKD patients and an increase
in length and quality of life.
Effective start/end date7/1/156/30/18


  • National Institutes of Health: $199,592.00
  • National Institutes of Health: $198,120.00


  • Medicine(all)

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