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Abstract

We thank Sheng-Wen Niu and colleagues 1 Niu S.-W. He J.S. Lin H.Y.-H. Pioglitazone and nephrolithiasis. Kidney Int. 2019; 96: 518-519 Scopus (2) Google Scholar for highlighting their intriguing data on the association between pioglitazone use and incident nephrolithiasis in patients with type 2 diabetes in the Taiwanese National Health Insurance Research Database. In their population-based retrospective analysis, pioglitazone users experienced a 26% reduction in kidney stone incidence compared with matched diabetic nonpioglitazone users, and greater risk reduction was observed with higher cumulative pioglitazone exposure. 1 Niu S.-W. He J.S. Lin H.Y.-H. Pioglitazone and nephrolithiasis. Kidney Int. 2019; 96: 518-519 Scopus (2) Google Scholar These findings are in line with the results of our placebo-controlled metabolic study in uric acid stone formers showing that pioglitazone increases urinary pH and reduces net acid excretion (which would be expected to reduce uric acid stone risk) and urinary oxalate excretion (which would be expected to reduce calcium oxalate stone risk). 2 Maalouf N.M. Poindexter J.R. Adams-Huet B. et al. Increased production and reduced urinary buffering of acid in uric acid stone formers is ameliorated by pioglitazone. Kidney Int. 2019; 95: 1262-1268 Abstract Full Text Full Text PDF Scopus (7) Google Scholar Pioglitazone is a selective ligand of the nuclear transcription factor peroxisome-proliferator–activated receptor-γ that exerts multiple renal and extrarenal metabolic effects in humans, including altered release of adipokines such as adiponectin, promotion of fatty acid uptake and storage in adipose tissue, and modulation of insulin sensitivity by relieving the ectopic fat load in organs such as the liver and skeletal muscle. 3 Sarafidis P.A. Bakris G.L. Protection of the kidney by thiazolidinediones: an assessment from bench to bedside. Kidney Int. 2006; 70: 1223-1233 Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar We agree that in addition to the retrospective analysis and metabolic studies, we need to now move to 2 additional levels: (i) bench studies to better understand the mechanisms by which pioglitazone alters uric acid and calcium oxalate biochemical nephrolithiasis risk, and (ii) larger randomized clinical trials using stone burden and events to definitively prove or disprove a protective role of thiazolidinediones on stone disease recurrence and quality of life of the growing population of diabetic kidney stone formers. 4 Aune D. Mahamat-Saleh Y. Norat T. Riboli E. Body fatness, diabetes, physical activity and risk of kidney stones: a systematic review and meta-analysis of cohort studies. Eur J Epidemiol. 2018; 33: 1033-1047 Crossref Scopus (50) Google Scholar Increased production and reduced urinary buffering of acid in uric acid stone formers is ameliorated by pioglitazoneKidney InternationalVol. 95Issue 5PreviewIdiopathic uric acid nephrolithiasis is characterized by an overly acidic urine pH caused by the combination of increased acid production and inadequate buffering of urinary protons by ammonia. A large proportion of uric acid stone formers exhibit features of the metabolic syndrome. We previously demonstrated that thiazolidinediones improved the urinary biochemical profile in an animal model of the metabolic syndrome. In this proof-of-concept study, we examined whether the thiazolidinedione pioglitazone can also ameliorate the overly acidic urine in uric acid stone formers. Full-Text PDF Pioglitazone and nephrolithiasisKidney InternationalVol. 96Issue 2PreviewMaalouf et al.1 investigated the urinary biochemical effect of pioglitazone in patients with idiopathic uric acid nephrolithiasis. They showed that pioglitazone not only improved the metabolic syndrome, but also increased urine pH by reducing the acid load to the kidney, raising ammoniagenesis and ammonium excretion. However, the study size was small and whether pioglitazone will affect the incidence of nephrolithiasis in patients with the metabolic syndrome or diabetes or both is unknown. The interesting observation by Maalouf et al. Full-Text PDF