Effects of the Peroxisomal Proliferator-Activated Receptor-γ Agonist Pioglitazone on Renal and Hormonal Responses to Salt in Healthy Men

• Published in: The journal of clinical endocrinology and metabolism Vol. 89; no. 3; pp. 1140 - 1145
• Main Authors: Zanchi, Anne, Chiolero, Arnaud, Maillard, Marc, Nussberger, Jürg, Brunner, Hans-Rudolf, Burnier, Michel
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.03.2004; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adult; Aldosterone; Aldosterone - blood; Atrial Natriuretic Factor - blood; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Body weight gain; Cross-Over Studies; Diabetes mellitus (non-insulin dependent); Diet; Diet, Sodium-Restricted; Edema; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Heart rate; Hemodynamics; Humans; Hypoglycemic Agents - administration & dosage; Kidneys; Lithium; Male; Medical sciences; Pioglitazone; Placebos; Reabsorption; Receptors, Cytoplasmic and Nuclear - agonists; Renal Circulation - drug effects; Renal function; Renin; Renin - blood; Sodium; Sodium Chloride - pharmacokinetics; Sodium Chloride - urine; Thiazolidinediones - administration & dosage; Transcription Factors - agonists; Vertebrates: endocrinology; Human; Salt; Agonist; Urinary system; Pioglitazone; Peroxisome proliferator activated receptor gamma; Male; Thiazolidinedione derivatives; Endocrinology; Kidney
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-031526

Glitazones are used in the treatment of type 2 diabetes as efficient insulin sensitizers. They can, however, induce peripheral edema through an unknown mechanism in up to 18% of cases. In this double-blind, randomized, placebo-controlled, four-way, cross-over study, we examined the effects of a 6-wk administration of pioglitazone (45 mg daily) or placebo on the blood pressure, hormonal, and renal hemodynamic and tubular responses to a low (LS) and a high (HS) sodium diet in healthy volunteers. Pioglitazone had no effect on the systemic and renal hemodynamic responses to salt, except for an increase in daytime heart rate. Urinary sodium excretion and lithium clearance were lower with pioglitazone, particularly with the LS diet (P < 0.05), suggesting increased sodium reabsorption at the proximal tubule. Pioglitazone significantly increased plasma renin activity with the LS (P = 0.02) and HS (P = 0.03) diets. Similar trends were observed with aldosterone. Atrial natriuretic levels did not change with pioglitazone. Body weight increased with pioglitazone in most subjects. Pioglitazone stimulates plasma renin activity and favors sodium retention and weight gain in healthy volunteers. These effects could contribute to the development of edema in some subjects treated with glitazones.