Glucocorticoids and body fat associated with renal uric acid and oxalate, but not calcium excretion, in healthy children Lijie Shi a, ⁎ , Shoma Berkemeyer a , Anette E. Buyken a , Christiane Maser-Gluth b , Thomas Remer a a Research Institute of Child Nutrition, Dortmund, Germany b Department of Pharmacology, University of Heidelberg, Heidelberg, Germany Received 29 August 2008; accepted 18 June 2009 Abstract In patients with hypercortisolism, who are frequently obese, the prevalence of elevated urinary excretion rates of the potential lithogenic factors (calcium, oxalate, and uric acid) is increased. We examined whether the 24-hour urinary excretion rates of calcium, oxalate, and uric acid are already associated with body fat and endogenous glucocorticoids in healthy free-living children, taking relevant nutritional and acid- base factors into account. Urinary analyte excretions were determined in 24-hour urine samples of 300 healthy children aged 4 to 14 years. Potentially bioactive free glucocorticoids were assessed as urinary free cortisol + urinary free cortisone. Associations of glucocorticoids and percentage body fat with the outcome variables were examined in regression models adjusted for sex, height, growth velocity, urinary volume, net acid excretion, and relevant nutritional factors. Percentage body fat and urinary free cortisol + urinary free cortisone explained most of the growth-independent variation of urinary uric acid and also a relevant part of oxalate, but none of calcium. Net acid excretion, an indicator of endogenous acid production, and dietary protein, salt, and fiber intakes were also variably associated with the outcomes urinary calcium, oxalate, and uric acid. In conclusion, body fatness and potentially bioactive free glucocorticoids (even in the physiologic range) appear to affect urinary excretion rates of oxalate and uric acid, whereas urinary calcium output is more strongly related to dietary factors in healthy children. Our data provide the first in vivo–based evidence that the obesity- or hypercortisolism-associated urolithiasis may be a pathophysiologic continuation of the corresponding endocrine metabolic variations in healthy children. © 2010 Elsevier Inc. All rights reserved. 1. Introduction Overweight and obesity are strongly associated with an elevated risk of kidney stone formation (urolithiasis) [1]. This may be due to an increased urinary excretion of potential lithogenic factors, such as calcium, oxalate, and/or uric acid, which has been observed in people with greater body mass index (BMI) [1,2]. However, the mechanisms for these changes in urinary output are still not clear. Obesity- associated particular dietary patterns (eg, high-protein, high- salt, or high–acid-forming diet) [3] or other related metabolic alterations (eg, insulin resistance [4,5]) may be relevant. In fact, increased body fatness and excessive excretion of urinary potential lithogenic factors were both observed in patients with Cushing syndrome [6], which is characterized by persistent, inappropriate glucocorticoid excess. Thus, it is worthy to generally examine the association of body fat, glucocorticoid, and urinary excretion of potential lithogenic factors. Although kidney stones are relatively uncommon in children, metabolic alterations or abnormalities in the growing years may portend relevant long-term consequences. Persis- tently increased urinary excretion of calcium and/or uric acid in children not only can increase the risk for stone forming, but may also be indicative of an impairment of calcium home- ostasis and/or uric acid metabolism. Disorders of uric acid metabolism often coexist with metabolic syndrome [7] and are considered to be a critical health problem. The examination of normal physiologic ranges of potentially lithogenic factors can help identify the initially underlying metabolic, hormonal, and nutritional causes, which may in the long run lead to urolithiasis. Based on this background, we examined to what extent 24-hour urinary excretion of calcium, oxalate, and uric acid is associated with body fat as well as endogenous glucocorticoids in free-living Available online at www.sciencedirect.com Metabolism Clinical and Experimental 59 (2010) 134 – 139 www.metabolismjournal.com ⁎ Corresponding author. Research Institute of Child Nutrition, Depart- ment of Nutrition and Health, 44225 Dortmund, Germany. Tel.: +49 231 792210 23; fax: +49 231 711581. E-mail address: shi@fke-do.de (L. Shi). 0026-0495/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2009.06.027