Mineral metabolism in CKD: adaptation devolves into maladaptation. Mineral metabolism in CKD: adaptation devolves into maladaptation. (A) Adaptation: High dietary phosphate intake and reduced phosphate excretory capacity due to CKD stimulate bone production of fibroblast growth factor-23 (FGF-23). Increased FGF-23 levels stimulate phosphaturia and reduce circulating concentrations of 1,25-dihydroxyvitamin D, which decreases the efficiency of intestinal calcium and phosphate absorption. Secondary increases in parathyroid hormone levels in response to impaired calcium absorption further enhance phosphaturia and stimulate bone resorption. Collectively, these adaptations result in normal serum calcium and phosphate levels. (B) Maladaptation: Continuous activation of these initially adaptive pathways due to unrelenting CKD may lead ultimately to maladaptive adverse effects in several end organs, including cardiac hypertrophy that promotes heart failure, progression of CKD to ESRD, and renal osteodystrophy that increases risk of fracture. Myles Wolf CJASN 2015;10:1875-1885 ©2015 by American Society of Nephrology