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.
ABSTRACT
BACKGROUND: Chronic Kidney Disease (CKD) is associated with alterations in phosphorus excretion, and increases in fibroblast growth factor (FGF23) and parathyroid hormone (PTH). Plant protein-based phytate-bound phosphorus, is less bioavailable than that from animal sources. Our one-week study that was conducted previously showed that a nearly 100% plant protein-based diet benefits mineral metabolism in CKD; however, this diet may not be acceptable to patients. Here we hypothesize that a diet containing 70% protein from plants has similar efficacy and is tolerated by CKD patients. METHODS: Thirteen subjects with CKD 3-4 received an omnivorous diet containing 70% protein from plants for 4 weeks. The primary outcome was change in 24 h urine phosphorus. Secondary outcomes were changes in serum phosphorus, FGF23, PTH, urine sodium excretion, grip strength and fat free mass. Repeated measures analysis of variance (ANOVA) was used to test differences in parameters over the 4 weeks. RESULTS: Mean age of subjects was 54.8 years. Median eGFR was 26 (IQR 14.7) ml/min/1.73 m(2). Over the 4-week period, urine phosphorus significantly decreased by 215 ± 232 mg/day (p < 0.001). No significant changes in serum FGF23, phosphorus or PTH were noted. Urine sodium and titratable acid decreased significantly on the diet. Hand grip strength and fat-free mass did not change. There were two hyperkalemia events both 5.8 mEq/l, corrected by food substitutions. No other adverse events were observed. CONCLUSIONS: A 70% plant protein diet is safe, tolerated, and efficacious in lowering urine phosphorus excretion and may be an alternative to phosphate binders.
