Dataset Information

A randomized phase 1b cross-over study of the safety of low-dose pioglitazone for treatment of autosomal dominant polycystic kidney disease.

ABSTRACT:

Background

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenetic disorders in humans and is characterized by numerous fluid-filled cysts that grow slowly, resulting in end-stage renal disease in the majority of patients. Preclinical studies have indicated that treatment with low-dose thiazolidinediones, such as pioglitazone, decrease cyst growth in rodent models of PKD.

Methods

This Phase 1b cross-over study compared the safety of treatment with a low dose (15 mg) of the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone or placebo in PKD patients, with each treatment given for 1 year. The study monitored known side effects of PPAR-γ agonist treatment, including fluid retention and edema. Liver enzymes and risk of hypoglycemia were assessed throughout the study. As a secondary objective, the efficacy of low-dose pioglitazone was followed using a primary assessment of total kidney volume (TKV), blood pressure (BP) and kidney function.

Results

Eighteen patients were randomized and 15 completed both arms. Compared with placebo, allocation to pioglitazone resulted in a significant decrease in total body water as assessed by bioimpedance analysis {mean difference 0.16 Ω [95% confidence interval (CI) 0.24-2.96], P = 0.024} and no differences in episodes of heart failure, clinical edema or change in echocardiography. Allocation to pioglitazone led to no difference in the percent change in TKV of -3.5% (95% CI -8.4-1.4, P = 0.14), diastolic BP and microalbumin:creatinine ratio.

Conclusions

In this small pilot trial in people with ADPKD but without diabetes, pioglitazone 15 mg was found to be as safe as placebo. Larger and longer-term randomized trials powered to assess effects on TKV are needed.

SUBMITTER: Blazer-Yost BL

PROVIDER: S-EPMC8243264 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundReduced kidney function and distorted kidney anatomy in patients with autosomal dominant polycystic kidney disease (ADPKD) may complicate stone interventions more compared with the general population.ObjectivesTo review studies describing the safety and efficacy of the 3 main stone interventions in adults with ADPKD: shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotomy (PCNL).DesignSystematic review.SettingAny country of origin.PatientsAdults with ADPKD who underwent SWL, ureteroscopy, or PCNL.MeasurementsBeing stone free after the intervention and postoperative complications as reported by each study, which included pain, bleeding, and fever.MethodsRelevant studies published until February 2019 were identified through a comprehensive search of MEDLINE, EMBASE, Web of Science, BIOSIS PREVIEW, and CINAHL. Studies were eligible for review if they reported at least one outcome following SWL, ureteroscopy, and/or PCNL in adults with ADPKD. We then abstracted information on study characteristics, patient characteristics, intervention details, and postintervention outcomes and assessed the methodological quality of each study using a modified Downs and Black checklist.ResultsWe screened 221 citations from which we identified 24 studies that met our review criteria. We identified an additional article when manually reviewing the reference list of an included article, yielding a total of 25 studies describing 311 patients (32 SWL, 42 ureteroscopy, and 237 PCNL). The percentage of patients who were stone free after 1 session ranged from 0% to 69% after SWL, 73% to 100% after ureteroscopy, and 45% to 100% after PCNL. The percentage of patients with ADPKD that experienced at least one postoperative complication ranged from 0% to 33% for SWL, 0% to 27% for ureteroscopy, and 0% to 100% for PCNL.LimitationsThe number and quality of studies published to date are limited.ConclusionsThe efficacy and safety of stone interventions in patients with ADPKD remains uncertain, with wide-ranging estimates reported in the literature.Trial registrationWe did not register the protocol of this systematic review.

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