Pathogenesis of SHPT
SHPT results from a complex interplay of changes in vitamin metabolism as kidney function declines.2-5
Phosphorus retention increases. |
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Production of the active vitamin D hormone decreases. |
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Serum calcium decreases. |
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Fibroblast growth factor 23 (FGF23) increases. |
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Intact parathyroid hormone (iPTH) increases. |
In a healthy individual, iPTH maintains a balance in serum calcium and phosphorus. In a patient with CKD resulting in SHPT, the circulating levels of these minerals change, and along with the drop in active vitamin D, signal the parathyroid glands to increase iPTH secretion.3
Metabolism of vitamin D into its hormonal form, calcitriol, is important in the regulation of iPTH. Reduced kidney function leads to a reduction in renal 1α-hydroxylase activity, hindering the conversion of 25-hydroxyvitamin D (25D) to 1,25-dihydroxyvitamin D (1,25D), the active hormone.3,4
Consequences of SHPT
Ineffective treatment of SHPT is associated with earlier onset of dialysis and an increased risk of death.5,6 Potential complications without effective treatment include
- More rapid progression of CKD6,7
- Increased risk of cardiovascular disease8
- Decreased bone mineral density9
A growing body of research suggests that initiation of effective treatment earlier in the course of disease, before irreversible complications develop, could help to address a long-standing therapeutic gap in the management of SHPT.7,10
Learn more about the latest research on SHPT and its management
Explore resourcesREFERENCES: 1. Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007;71(1):31-38. doi:10.1038/sj.ki.5002009 2. Slatopolsky E, Brown A, Dusso A. Pathogenesis of secondary hyperparathyroidism. Kidney Int Suppl. 1999;73:S14-S19. doi:10.1046/j.1523-1755.1999.07304.x 3. Tomasello S. Secondary hyperparathyroidism and chronic kidney disease. Diabetes Spectr. 2008;21(1):19-25. https://doi.org/10.2337/diaspect.21.1.19 4. Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol. 2011;6(4):913-921. doi:10.2215/CJN.06040710 5. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD-MBD). Kidney Int Suppl (2011). 2017;7(1):1-59. doi:10.1016/j.kisu.2017.04.001 6. Schumock GT, Andress D, E Marx S, Sterz R, Joyce AT, Kalantar-Zadeh K. Impact of secondary hyperparathyroidism on disease progression, healthcare resource utilization and costs in pre-dialysis CKD patients. Curr Med Res Opin. 2008;24(11):3037-3048. doi:10.1185/03007990802437943 7. Bishop CW, Ashfaq A, Strugnell SA, et al. Sustained reduction of elevated intact parathyroid hormone concentrations with extended-release calcifediol slows chronic kidney disease progression in secondary hyperparathyroidism patients. Am J Nephrol. Published online August 27, 2024. doi:10.1159/000541138 8. Fisher A, Srikusalanukul W, Davis M, Smith P. Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links. Clin Interv Aging. 2013;8:239-256. doi:10.2147/CIA.S38856 9. Rix M, Andreassen H, Eskildsen P, Langdahl B, Olgaard K. Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int. 1999;56(3):1084-1093. doi:10.1046/j.1523-1755.1999.00617.x 10. Bishop CW, Ashfaq A, Choe J, et al. Extended-release calcifediol normalized 1,25-dihydroxyvitamin D and prevented progression of secondary hyperparathyroidism in hemodialysis patients in a pilot randomized clinical trial. Am J Nephrol. Published online June 4, 2025. doi:10.1159/000546615
