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)

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2010 Apr 13

PMID 20382692

Citations 31

Authors

Katherine Wesseling-Perry

G Chris Harkins

He-Jing Wang

Robert Elashoff

Barbara Gales

Mara J Horwitz

Andrew F Stewart

Harald Juppner

Isidro B Salusky

Affiliations

Soon will be listed here.

Abstract

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 x 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.

Citing Articles

Clinical Utility of Bone Turnover Markers in Chronic Kidney Disease.

Srisuwarn P, Eastell R, Salam S J Bone Metab. 2024; 31(4):264-278.

PMID: 39701107 PMC: 11658837. DOI: 10.11005/jbm.24.789.

Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS.

Yamamoto S, Jorgensen H, Zhao J, Karaboyas A, Komaba H, Vervloet M Kidney Int Rep. 2024; 9(4):863-876.

PMID: 38765600 PMC: 11101738. DOI: 10.1016/j.ekir.2024.01.002.

Parathyroid hormone-PTH1R signaling in cardiovascular disease and homeostasis.

Towler D Trends Endocrinol Metab. 2024; 35(7):648-660.

PMID: 38429163 PMC: 11233248. DOI: 10.1016/j.tem.2024.02.005.

Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy.

Laster M, Pereira R, Noche K, Gales B, Salusky I, Albrecht L Nutrients. 2023; 15(19).

PMID: 37836411 PMC: 10574198. DOI: 10.3390/nu15194127.

Response to Letter to the Editor From Sumi et al: "Lower Bone Turnover and Skeletal PTH Responsiveness in Japanese Compared to European Patients Receiving Hemodialysis".

Jorgensen H, Evenepoel P, Komaba H, Mazzaferro S, Vervloet M, Cavalier E J Clin Endocrinol Metab. 2022; 108(3):e42-e43.

PMID: 36469693 PMC: 9931179. DOI: 10.1210/clinem/dgac698.

References

Antoniucci D, Yamashita T, Portale A . Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab. 2006; 91(8):3144-9. DOI: 10.1210/jc.2006-0021. View

Horst R, Reinhardt T, Hollis B . Improved methodology for the analysis of plasma vitamin D metabolites. Kidney Int Suppl. 1990; 29:S28-35. View

Wesseling-Perry K, Pereira R, Wang H, Elashoff R, Sahney S, Gales B . Relationship between plasma fibroblast growth factor-23 concentration and bone mineralization in children with renal failure on peritoneal dialysis. J Clin Endocrinol Metab. 2008; 94(2):511-7. PMC: 2646517. DOI: 10.1210/jc.2008-0326. View

Salusky I, Goodman W, Kuizon B, Lavigne J, Zahranik R, Gales B . Similar predictive value of bone turnover using first- and second-generation immunometric PTH assays in pediatric patients treated with peritoneal dialysis. Kidney Int. 2003; 63(5):1801-8. DOI: 10.1046/j.1523-1755.2003.00915.x. View

Sitara D, Razzaque M, St-Arnaud R, Huang W, Taguchi T, Erben R . Genetic ablation of vitamin D activation pathway reverses biochemical and skeletal anomalies in Fgf-23-null animals. Am J Pathol. 2006; 169(6):2161-70. PMC: 1762489. DOI: 10.2353/ajpath.2006.060329. View

Salusky I, Kuizon B, Belin T, Ramirez J, Gales B, Segre G . Intermittent calcitriol therapy in secondary hyperparathyroidism: a comparison between oral and intraperitoneal administration. Kidney Int. 1998; 54(3):907-14. DOI: 10.1046/j.1523-1755.1998.00045.x. View

Parisien M, Cosman F, Mellish R, Schnitzer M, Nieves J, Silverberg S . Bone structure in postmenopausal hyperparathyroid, osteoporotic, and normal women. J Bone Miner Res. 1995; 10(9):1393-9. DOI: 10.1002/jbmr.5650100917. View

Nakanishi S, Kazama J, Nii-Kono T, Omori K, Yamashita T, Fukumoto S . Serum fibroblast growth factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients. Kidney Int. 2005; 67(3):1171-8. DOI: 10.1111/j.1523-1755.2005.00184.x. View

Slatopolsky E, Finch J, CLAY P, Martin D, Sicard G, Singer G . A novel mechanism for skeletal resistance in uremia. Kidney Int. 2000; 58(2):753-61. DOI: 10.1046/j.1523-1755.2000.00222.x. View

10.

Brown W, Juppner H, Langman C, Price H, Farrow E, White K . Hypophosphatemia with elevations in serum fibroblast growth factor 23 in a child with Jansen's metaphyseal chondrodysplasia. J Clin Endocrinol Metab. 2008; 94(1):17-20. PMC: 2630869. DOI: 10.1210/jcem.94.2.9988. View

11.

Rousseau L, Brossard J, LePage R, DAmour P . Synthetic carboxyl-terminal fragments of parathyroid hormone (PTH) decrease ionized calcium concentration in rats by acting on a receptor different from the PTH/PTH-related peptide receptor. Endocrinology. 2001; 142(4):1386-92. DOI: 10.1210/endo.142.4.8093. View

12.

Sitara D . Correlation among hyperphosphatemia, type II sodium phosphate transporter activity, and vitamin D metabolism in Fgf-23 null mice. Ann N Y Acad Sci. 2007; 1116:485-93. DOI: 10.1196/annals.1402.021. View

13.

Lorenz-Depiereux B, Bastepe M, Benet-Pages A, Amyere M, Wagenstaller J, Muller-Barth U . DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet. 2006; 38(11):1248-50. PMC: 5942547. DOI: 10.1038/ng1868. View

14.

Wesseling-Perry K, Harkins G, Wang H, Sahney S, Gales B, Elashoff R . Response of different PTH assays to therapy with sevelamer or CaCO3 and active vitamin D sterols. Pediatr Nephrol. 2009; 24(7):1355-61. PMC: 2688609. DOI: 10.1007/s00467-009-1143-8. View

15.

Krajisnik T, Bjorklund P, Marsell R, Ljunggren O, Akerstrom G, Jonsson K . Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol. 2007; 195(1):125-31. DOI: 10.1677/JOE-07-0267. View

16.

Sneddon W, Syme C, Bisello A, Magyar C, Rochdi M, Parent J . Activation-independent parathyroid hormone receptor internalization is regulated by NHERF1 (EBP50). J Biol Chem. 2003; 278(44):43787-96. DOI: 10.1074/jbc.M306019200. View

17.

Kuwahara M, Inoshita S, Nakano Y, Terada Y, Takano Y, Sasaki S . Expression of bone type 1 PTH receptor in rats with chronic renal failure. Clin Exp Nephrol. 2007; 11(1):34-40. DOI: 10.1007/s10157-006-0455-2. View

18.

Urena P, Ferreira A, Morieux C, Drueke T, De Vernejoul M . PTH/PTHrP receptor mRNA is down-regulated in epiphyseal cartilage growth plate of uraemic rats. Nephrol Dial Transplant. 1996; 11(10):2008-16. DOI: 10.1093/oxfordjournals.ndt.a027089. View

19.

Nagano N, Miyata S, Abe M, Kobayashi N, Wakita S, Yamashita T . Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats. Kidney Int. 2006; 69(3):531-7. DOI: 10.1038/sj.ki.5000020. View

20.

. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003; 42(4 Suppl 3):S1-201. View