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The rationale for intermittent administration of PTH in the management of mineral and bone disorder of chronic kidney disease

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Abstract

A major complication of chronic kidney disease is the derangement of mineral metabolism, leading to increased risk of fractures and cardiovascular mortality. Current therapeutic regimens are focused on reducing parathyroid hormone levels caused by secondary hyperparathyroidism, and the active vitamin D metabolite l,25(OH)2D, with limited success. It may be a more effective approach, however, if we could target the delayed response of parathyroid hormone in the early retention of phosphate following loss of renal function.

We propose intermittent administration (even in stage 2 chronic kidney disease) of parathyroid hormone, known for its bone anabolic effects compared to the catabolic effects of the continuously elevated parathyroid hormone associated with the hyperparathyroid state, to mitigate the retention of phosphate. This approach may prevent the compensatory responses of the other two major calcium- and phosphate-regulating hormones (FGF-23 and l,25(OH)2D) that lead to further worsening of the derangement of mineral metabolism.

In addition to its strong theoretical basis, there are data supporting the need for further research focused on the use of intermittent parathyroid hormone in the management of chronic kidney disease-mineral bone disorder.

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References

  1. GBD Chronic Kidney Disease Collaboration (2020) Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 395(10225):709–733

    Article  Google Scholar 

  2. Center for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2021, Atlanta, GA, 2021.

  3. Pazianas M, Miller PD (2020) Current understanding of mineral and bone disorders of chronic kidney disease and the scientific grounds on the use of exogenous parathyroid hormone in its management. J Bone Metab 27(1):1–13

    Article  PubMed  PubMed Central  Google Scholar 

  4. Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G, Kidney Disease: Improving Global Outcomes (KDIGO) (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69(11):1945–1953

    Article  CAS  PubMed  Google Scholar 

  5. Malluche HH, Ritz E, Lange HP et al (1976) Bone histology in incipient and advanced renal failure. Kidney Int 9:355–362

    Article  CAS  PubMed  Google Scholar 

  6. Wolf M (2010) Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol 21:1427–1435

    Article  CAS  PubMed  Google Scholar 

  7. Isakova T, Ix JH, Sprague SM et al (2015) Rationale and approaches to phosphate and fibroblast growth factor 23 reduction in CKD. J Am Soc Nephrol 26:2328–2339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ketteler M, Block GA, Evenepoel P et al (2017) Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. Kidney Int 92:26–36

    Article  PubMed  Google Scholar 

  9. Ruospo M, Palmer SC, Natale P et al (2018) Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev 8:Cd006023

    PubMed  Google Scholar 

  10. Memmos DE, Eastwood JB, Talner LB et al (1981) Double-blind trial of oral 1,25-dihydroxy vitamin D3 versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis. Br Med J (Clin Res Ed) 282:1919–1924

    Article  CAS  PubMed  Google Scholar 

  11. Toussaint ND, Damasiewicz MJ (2017) Do the benefits of using calcitriol and other vitamin D receptor activators in patients with chronic kidney disease outweigh the harms? Nephrology (Carlton) 22(Suppl 2):51–56

    Article  CAS  PubMed  Google Scholar 

  12. Nemeth EF, Goodman WG (2016) Calcimimetic and calcilytic drugs: Feats, flops, and futures. Calcif Tissue Int 98:341–358

    Article  CAS  PubMed  Google Scholar 

  13. Vervloet M (2019) Renal and extrarenal effects of fibroblast growth factor 23. Nat Rev Nephrol 15:109–120

    Article  CAS  PubMed  Google Scholar 

  14. Musgrove J, Wolf M (2020) Regulation and effects of FGF23 in chronic kidney disease. Annu Rev Physiol 10(82):365–390

    Article  Google Scholar 

  15. Isakova T, Wolf MS (2010) FGF23 or PTH: which comes first in CKD ? Kidney Int 78(10):947–949

    Article  CAS  PubMed  Google Scholar 

  16. Pazianas M, Miller PD (2020) The CKD-MBD syndrome: hysteresis in PTH involvement and PTH administration for its management. J Bone Miner Res 35(12):2313–2317

    Article  CAS  PubMed  Google Scholar 

  17. Drüeke TB, Massy ZA (2016) Changing bone patterns with progression of chronic kidney disease. Kidney Int 89:289–302

    Article  PubMed  Google Scholar 

  18. Dobnig H, Turner RT (1997) The effects of programmed administration of human parathyroid hormone fragment (1–34) on bone histomorphometry and serum chemistry in rats. Endocrinology 138(11):4607–4612

    Article  CAS  PubMed  Google Scholar 

  19. Knab VM, Corbin B, Andrukhova O, Hum JM, Ni P, Rabadi S, Maeda A, White KE, Erben RG, Jüppner H, Christov M (2017) Acute parathyroid hormone injection increases C-terminal but not intact fibroblast growth factor 23 levels. Endocrinology 158(5):1130–1139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Smith ER, Cai MM, McMahon LP, Holt SG (2012) Biological variability of plasma intact and C-terminal FGF23 measurements. J Clin Endocrinol Metab 97(9):3357–3365

    Article  CAS  PubMed  Google Scholar 

  21. Shimada T, Urakawa I, Isakova T, Yamazaki Y, Epstein M, Wesseling-Perry K, Wolf M, Salusky IB, Juppner H (2010) Circulating fibroblast growth factor 23 in patients with end-stage renal disease treated by peritoneal dialysis is intact and biologically active. J Clin Endocrinol Metab 95(2):578–585

    Article  CAS  PubMed  Google Scholar 

  22. Gutierrez OM, Smith KT, Barchi-Chung A, Patel NM, Isakova T, Wolf M (2012) (1–34) Parathyroid hormone infusion acutely lowers fibroblast growth factor 23 concentrations in adult volunteers. Clin J Am Soc Nephrol 7(1):139–145

    Article  CAS  PubMed  Google Scholar 

  23. Burnett-Bowie SM, Henao MP, Dere ME, Lee H, Leder BZ (2009) Effects of hPTH(1–34) infusion on circulating serum phosphate, 1,25-dihydroxyvitamin D, and FGF23 levels in healthy men. J Bone Miner Res 24:1681–1685

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lavi-Moshayoff V, Wasserman G, Meir T, Silver J, Naveh-Many T (2010) PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol 299:F882-889

    Article  CAS  PubMed  Google Scholar 

  25. Miller PD, Schwartz EN, Chen P, Misurski DA, Krege JH (2007) Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment. Osteoporos Int 18(1):59–68

    Article  CAS  PubMed  Google Scholar 

  26. Sebastian EM, Suva LJ, Friedman PA (2008) Differential effects of intermittent PTH(1–34) and PTH(7–34) on bone microarchitecture and aortic calcification in experimental renal failure. Bone 43:1022–1030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ota M, Takahata M, Shimizu T et al (2017) Efficacy and safety of osteoporosis medications in a rat model of late-stage chronic kidney disease accompanied by secondary hyperparathyroidism and hyperphosphatemia. Osteoporos Int 28:1481–1490

    Article  CAS  PubMed  Google Scholar 

  28. Yuan Q, Sato T, Densmore M, Saito H, Schüler C, Erben RG, Lanske B (2011) FGF-23/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH. J Bone Miner Res 26(9):2026–2035

    Article  CAS  PubMed  Google Scholar 

  29. Sridharan M, Cheung J, Moore AE, Frost ML, Fraser WD, Fogelman I, Hampson G (2010) Circulating fibroblast growth factor-23 increases following intermittent parathyroid hormone (1–34) in postmenopausal osteoporosis: Association with biomarker of bone formation. Calcif Tissue Int 87:398–405

    Article  CAS  PubMed  Google Scholar 

  30. Karpf DB, Pihl S, Mourya S, Mortensen E, Kovoor E, Markova D, Leff JA (2020) A randomized double-blind placebo-controlled first-in-human phase 1 trial of TransCon PTH in healthy adults. J Bone Miner Res 35(8):1430–1440

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Musculoskeletal Sciences, Oxford University, Oxford, OX3 7LD, UK

    Michael Pazianas

  2. University of Colorado Health Sciences Center, Denver, CO, 80262, USA

    Paul D. Miller

  3. Colorado Center for Bone Health, Lakewood, CO, USA

    Paul D. Miller

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  1. Michael Pazianas
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Correspondence to Michael Pazianas.

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Pazianas, M., Miller, P.D. The rationale for intermittent administration of PTH in the management of mineral and bone disorder of chronic kidney disease. J Nephrol 37, 337–342 (2024). https://doi.org/10.1007/s40620-023-01642-8

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