The Calcemic Response to Continuous Parathyroid Hormone (PTH)(1-34) Infusion in End-Stage Kidney Disease Varies According to Bone Turnover: A Potential Role for PTH(7-84)

• Published in: The journal of clinical endocrinology and metabolism Vol. 95; no. 6; pp. 2772 - 2780
• Main Authors: Wesseling-Perry, Katherine, Harkins, G. Chris, Wang, He-jing, Elashoff, Robert, Gales, Barbara, Horwitz, Mara J., Stewart, Andrew F., Jüppner, Harald, Salusky, Isidro B.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.06.2010; Copyright by The Endocrine Society; Endocrine Society; The Endocrine Society
• Subjects: Adolescent; Biological and medical sciences; Biopsy; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone and Bones - pathology; Bone Development - drug effects; Bone turnover; Calcification, Physiologic - drug effects; Calcium - blood; Calcium - urine; Dialysis; Disease resistance; End-stage renal disease; Endocrinopathies; Feeding. Feeding behavior; Female; Fibroblast growth factor 23; Fibroblast Growth Factors - blood; Fundamental and applied biological sciences. Psychology; Hemodialysis; Humans; Kidney diseases; Kidney Failure, Chronic - drug therapy; Kidney Failure, Chronic - pathology; Male; Medical sciences; Original; Parathyroid hormone; Parathyroid Hormone - physiology; Parathyroid Hormone - therapeutic use; Peptide Fragments - physiology; Phosphorus; Phosphorus - blood; Renal Dialysis; Skeleton; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Vitamin D; Young Adult; Kidney disease; Obesity; Urinary system disease; Antiosteoporotic; Nutrition; Continuous; Peptide hormone; Nutrition disorder; Metabolic diseases; Osteoarticular system; Osteoforming; Parathyroid hormone; Perfusion; Renal failure; Turnover; Bone; Endocrinology; Nutritional status; Teriparatide
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2009-1909

Context: Factors contributing to PTH resistance in dialysis patients remain elusive. Objectives: The study assessed the skeletal and biochemical response to 46 h of PTH(1-34) infusion in dialysis patients. Design: The study was a prospective, controlled assessment of response to PTH(1-34). Setting: The study was performed at the University of California, Los Angeles, General Clinical Research Center. Participants: Nineteen dialysis patients and 17 healthy volunteers were studied. Intervention: PTH(1-34) was infused at a rate of 8 pmol/kg · h for 46 h. Bone biopsy was performed in all dialysis patients. Main Outcome Measures: Serum calcium, phosphorus, 1,25-dihydroxyvitamin D, PTH (four separate assays), and FGF-23 were determined at baseline and h 7, 23, 35, and 46 of the infusion. Results: Serum calcium levels rose in healthy volunteers (9.2 ± 0.1 to 11.9 ± 0.3 mg/dl; P < 0.01) and in dialysis patients with adynamic/normal bone turnover (9.0 ± 0.3 to 10.7 ± 0.7 mg/dl; P < 0.05) but did not change in dialysis patients with high bone turnover. Serum phosphorus levels declined in healthy volunteers (3.9 ± 0.1 to 3.5 ± 0.1 mg/dl; P < 0.05) but increased in all dialysis patients (6.7 ± 0.4 to 8.0 ± 0.3 mg/dl; P < 0.05). Full-length PTH(1-84) declined in all subjects; however, PTH(7-84) fragments declined only in healthy subjects and in dialysis patients with normal/adynamic bone but remained unchanged in dialysis patients with high bone turnover. Conclusions: The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH. PTH(7-84) may contribute to this phenomenon.The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH and PTH(7-84) may contribute to this phenomenon.