Higher diet-dependent renal acid load associates with higher glucocorticoid secretion and potentially bioactive free glucocorticoids in healthy children

Abstract

Metabolic acidosis induces elevated glucocorticoid (GC) levels. However, the influence of less strong daily acid loads on GCs is largely unexplored. To investigate this, we studied whether higher acid loads in children, fully within the normal range of habitual diets, associate with endogenous GCs. In a specific quasi-experimental design, we examined 200 6- to 10-year-old healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study equally divided to either high or low 24-hour renal net acid excretion. Major urinary GC metabolites were analyzed by gas chromatography-mass spectrometry to assess daily adrenal GC secretion and metabolites of tissue cortisol catabolism (6β-hydroxycortisol and 20α-dihydrocortisol). Liquid chromatography-mass spectrometry was used to quantify urinary free cortisol and cortisone. After confounder adjustment, significant positive associations were unmasked for urinary potential renal acid load and net acid excretion with adrenal GC secretion, free cortisone, free cortisone plus cortisol, 6β-hydroxycortisol, and 20α-dihydrocortisol. An inverse association emerged for an enzymatic marker (5β-reductase) of irreversible GC inactivation. Our data suggest that existing moderate elevations in diet-dependent acid loads suffice to raise GCs and affect cortisol metabolism. Thus, potential detrimental effects of high acid loading appear to be mediated, in part, by increased GC activity via increased GC secretion and/or reduced GC inactivation. Higher cortisone levels, directly available for intracrine activation to cortisol may play a special role.

Untangling the complex relationship between dietary acid load and glucocorticoid metabolism

“…One important issue is the causal relationship of NAE and glucocorticoid metabolism. Exogenous acid loads, typically of greater magnitude than the variations observed in the article by Esche et al , 3 increase NAE excretion and stimulate glucocorticoid metabolism. On the other hand, primary increases in glucocorticoid metabolism, as shown in studies using exogenous glucocorticoid administration, increase renal NAE.…”

“…3 A previous report from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study showed significant correlation between higher glucocorticoid hormone levels and impaired bone characteristics in children. 6 Thus, one possible extrapolation is that higher dietary acid loads lead to impaired bone formation in children.…”

“…The manuscript by Esche et al. 3 (2016) in the current issue of Kidney International is an important contribution to our understanding of this complex process.…”

“…3 This is a carefully performed study that examined normal community-living children and sought to correlate differences in dietary acid loads and renal NAE with glucocorticoid hormone metabolism. It used children 6 to 10 years of age enrolled in the prospective, observational Dortmund Nutritional and Anthropometric Longitudinally Designed Study that began in 1985.…”

Acid-Base and Electrolyte Managements in Chronic Kidney Disease and End-Stage Renal Disease: Case-Based Discussion

“…In children, even mild acidosis can elevate glucocorticoid activity [6, 7], contributing to muscle wasting and bone demineralization. Dietary intake of alkali precursors and alkali therapy have been shown to prevent or correct acidosis, attenuate acidosis-related adverse effects and retard CKD progression [7-11].…”