Skip to main content
Erschienen in: Osteoporosis International 10/2019

31.05.2019 | Original Article

Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease

verfasst von: S. Geng, Z. Kuang, P.L. Peissig, D. Page, L. Maursetter, K.E. Hansen

Erschienen in: Osteoporosis International | Ausgabe 10/2019

Einloggen, um Zugang zu erhalten

Abstract

Summary

Doctors do not know whether treatment of high parathyroid hormone levels is linked to better outcomes in their patients with kidney disease. In this study, lower parathyroid hormone levels at baseline were linked to lower risk of fracture, vascular events, and death in people with kidney disease.

Purpose

Chronic kidney disease (CKD) affects ~ 20% of older adults, and secondary hyperparathyroidism (HPT) is a common condition in these patients. To what degree HPT predicts fractures, vascular events, and mortality in pre-dialysis CKD patients is debated. In stage 3 and 4 CKD patients, we assessed relationships between baseline serum PTH levels and subsequent 10-year probabilities of clinical fractures, vascular events, and death.

Methods

We used Marshfield Clinic Health System electronic health records to analyze data from adult CKD patients receiving care between 1985 and 2013, and whose PTH was measured using a second-generation assay. Covariates included PTH, age, gender, tobacco use, vascular disease, diabetes, hypertension, hyperlipidemia, obesity, GFR, and use of osteoporosis medications.

Results

Five thousand one hundred eight subjects had a mean age of 68 ± 17 years, 48% were men, and mean follow-up was 23 ± 10 years. Fractures, vascular events, and death occurred in 18%, 71%, and 56% of the cohort, respectively. In univariate and multivariate models, PTH was an independent predictor of fracture, vascular events, and death. The hazards of fracture, vascular events and death were minimized at a baseline PTH of 0, 69, and 58 pg/mL, respectively.

Conclusions

We found that among individuals with stage 3 and 4 CKD, PTH was an independent predictor of fractures, vascular events, and death. Additional epidemiologic studies are needed to confirm these findings. If a target PTH range can be confirmed, then randomized placebo-controlled trials will be needed to confirm that treating HPT reduces the risk of fracture, vascular events, and death.
Literatur
1.
Zurück zum Zitat Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS (2007) Prevalence of chronic kidney disease in the United States. Jama 298:2038–2047CrossRef Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, Van Lente F, Levey AS (2007) Prevalence of chronic kidney disease in the United States. Jama 298:2038–2047CrossRef
2.
Zurück zum Zitat National Institute of Diabetes and Digestive and Kidney Diseases (2016) kidney disease statistics for the United States. Accessed November 27, 2018 National Institute of Diabetes and Digestive and Kidney Diseases (2016) kidney disease statistics for the United States. Accessed November 27, 2018
3.
Zurück zum Zitat Saran R, Li Y, Robinson B et al (2015) US renal data system 2014 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis 66(Svii):S1–S305 Saran R, Li Y, Robinson B et al (2015) US renal data system 2014 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis 66(Svii):S1–S305
4.
Zurück zum Zitat Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL (2007) 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 71:31–38CrossRef Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL (2007) 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 71:31–38CrossRef
5.
Zurück zum Zitat Stavroulopoulos A, Porter CJ, Roe SD, Hosking DJ, Cassidy MJ (2008) Relationship between vitamin D status, parathyroid hormone levels and bone mineral density in patients with chronic kidney disease stages 3 and 4. Nephrology (Carlton) 13:63–67 Stavroulopoulos A, Porter CJ, Roe SD, Hosking DJ, Cassidy MJ (2008) Relationship between vitamin D status, parathyroid hormone levels and bone mineral density in patients with chronic kidney disease stages 3 and 4. Nephrology (Carlton) 13:63–67
6.
Zurück zum Zitat Ramos AM, Albalate M, Vazquez S, Caramelo C, Egido J, Ortiz A (2008) Hyperphosphatemia and hyperparathyroidism in incident chronic kidney disease patients. Kidney Int Suppl 74:S88–S93CrossRef Ramos AM, Albalate M, Vazquez S, Caramelo C, Egido J, Ortiz A (2008) Hyperphosphatemia and hyperparathyroidism in incident chronic kidney disease patients. Kidney Int Suppl 74:S88–S93CrossRef
8.
Zurück zum Zitat Bianchi ML, Colantonio G, Montesano A, Trevisan C, Ortolani S, Rossi R, Buccianti G (1992) Bone mass status in different degrees of chronic renal failure. Bone 13:225–228CrossRef Bianchi ML, Colantonio G, Montesano A, Trevisan C, Ortolani S, Rossi R, Buccianti G (1992) Bone mass status in different degrees of chronic renal failure. Bone 13:225–228CrossRef
9.
Zurück zum Zitat Rix M, Andreassen H, Eskildsen P, Langdahl B, Olgaard K (1999) Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int 56:1084–1093CrossRef Rix M, Andreassen H, Eskildsen P, Langdahl B, Olgaard K (1999) Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int 56:1084–1093CrossRef
10.
Zurück zum Zitat Tsuchida T, Ishimura E, Miki T, Matsumoto N, Naka H, Jono S, Inaba M, Nishizawa Y (2005) The clinical significance of serum osteocalcin and N-terminal propeptide of type I collagen in predialysis patients with chronic renal failure. Osteoporos Int 16:172–179CrossRef Tsuchida T, Ishimura E, Miki T, Matsumoto N, Naka H, Jono S, Inaba M, Nishizawa Y (2005) The clinical significance of serum osteocalcin and N-terminal propeptide of type I collagen in predialysis patients with chronic renal failure. Osteoporos Int 16:172–179CrossRef
11.
Zurück zum Zitat Przedlacki J, Manelius J, Huttunen K (1995) Bone mineral density evaluated by dual-energy X-ray absorptiometry after one-year treatment with calcitriol started in the predialysis phase of chronic renal failure. Nephron 69:433–437CrossRef Przedlacki J, Manelius J, Huttunen K (1995) Bone mineral density evaluated by dual-energy X-ray absorptiometry after one-year treatment with calcitriol started in the predialysis phase of chronic renal failure. Nephron 69:433–437CrossRef
12.
Zurück zum Zitat Rix M, Eskildsen P, Olgaard K (2004) Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure. Nephrol Dial Transplant 19:870–876CrossRef Rix M, Eskildsen P, Olgaard K (2004) Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure. Nephrol Dial Transplant 19:870–876CrossRef
13.
Zurück zum Zitat (2003) K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:S1–S201 (2003) K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:S1–S201
14.
Zurück zum Zitat 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 7:1–59CrossRef 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 7:1–59CrossRef
15.
Zurück zum Zitat Gao P, D'Amour P (2005) Evolution of the parathyroid hormone (PTH) assay--importance of circulating PTH immunoheterogeneity and of its regulation. Clin Lab 51:21–29PubMed Gao P, D'Amour P (2005) Evolution of the parathyroid hormone (PTH) assay--importance of circulating PTH immunoheterogeneity and of its regulation. Clin Lab 51:21–29PubMed
16.
Zurück zum Zitat Herberth J, Monier-Faugere MC, Mawad HW, Branscum AJ, Herberth Z, Wang G, Cantor T, Malluche HH (2009) The five most commonly used intact parathyroid hormone assays are useful for screening but not for diagnosing bone turnover abnormalities in CKD-5 patients. Clin Nephrol 72:5–14CrossRef Herberth J, Monier-Faugere MC, Mawad HW, Branscum AJ, Herberth Z, Wang G, Cantor T, Malluche HH (2009) The five most commonly used intact parathyroid hormone assays are useful for screening but not for diagnosing bone turnover abnormalities in CKD-5 patients. Clin Nephrol 72:5–14CrossRef
17.
Zurück zum Zitat Magnan EM, Palta M, Johnson HM, Bartels CM, Schumacher JR, Smith MA (2015) The impact of a patient's concordant and discordant chronic conditions on diabetes care quality measures. J Diabetes Complicat 29:288–294CrossRef Magnan EM, Palta M, Johnson HM, Bartels CM, Schumacher JR, Smith MA (2015) The impact of a patient's concordant and discordant chronic conditions on diabetes care quality measures. J Diabetes Complicat 29:288–294CrossRef
18.
Zurück zum Zitat Johnson HM, Bartels CM, Thorpe CT, Schumacher JR, Pandhi N, Smith MA (2015) Differential diagnosis and treatment rates between systolic and diastolic hypertension in young adults: a multidisciplinary observational study. J Clin Hypertens (Greenwich) 17:885–894CrossRef Johnson HM, Bartels CM, Thorpe CT, Schumacher JR, Pandhi N, Smith MA (2015) Differential diagnosis and treatment rates between systolic and diastolic hypertension in young adults: a multidisciplinary observational study. J Clin Hypertens (Greenwich) 17:885–894CrossRef
19.
Zurück zum Zitat Therneau TM, Grambsch PM (2000) Modeling survival data: extending the cox model. Springer-Verlag, New YorkCrossRef Therneau TM, Grambsch PM (2000) Modeling survival data: extending the cox model. Springer-Verlag, New YorkCrossRef
20.
Zurück zum Zitat Hastie T, Tibshirani R, Friedman JH (2009) The elements of statistical learning : data mining, inference, and prediction. Springer, New York, NYCrossRef Hastie T, Tibshirani R, Friedman JH (2009) The elements of statistical learning : data mining, inference, and prediction. Springer, New York, NYCrossRef
21.
Zurück zum Zitat Iki M, Fujita Y, Tamaki J, Kouda K, Yura A, Sato Y, Moon JS, Harano A, Hazaki K, Kajita E, Hamada M, Arai K, Tomioka K, Okamoto N, Kurumatani N (2017) Incident fracture associated with increased risk of mortality even after adjusting for frailty status in elderly Japanese men: the Fujiwara-kyo osteoporosis risk in men (FORMEN) cohort study. Osteoporos Int 28:871–880CrossRef Iki M, Fujita Y, Tamaki J, Kouda K, Yura A, Sato Y, Moon JS, Harano A, Hazaki K, Kajita E, Hamada M, Arai K, Tomioka K, Okamoto N, Kurumatani N (2017) Incident fracture associated with increased risk of mortality even after adjusting for frailty status in elderly Japanese men: the Fujiwara-kyo osteoporosis risk in men (FORMEN) cohort study. Osteoporos Int 28:871–880CrossRef
22.
Zurück zum Zitat Cauley JA, Lui LY, Ensrud KE, Zmuda JM, Stone KL, Hochberg MC, Cummings SR (2005) Bone mineral density and the risk of incident nonspinal fractures in black and white women. Jama 293:2102–2108CrossRef Cauley JA, Lui LY, Ensrud KE, Zmuda JM, Stone KL, Hochberg MC, Cummings SR (2005) Bone mineral density and the risk of incident nonspinal fractures in black and white women. Jama 293:2102–2108CrossRef
23.
Zurück zum Zitat Stehman-Breen C (2004) Osteoporosis and chronic kidney disease. Semin Nephrol 24:78–81CrossRef Stehman-Breen C (2004) Osteoporosis and chronic kidney disease. Semin Nephrol 24:78–81CrossRef
24.
Zurück zum Zitat (July 2016) QickFacts; Marshfield, Wisconsin. United States Census Bureau, (July 2016) QickFacts; Marshfield, Wisconsin. United States Census Bureau,
25.
Zurück zum Zitat Komaba H, Taniguchi M, Wada A, Iseki K, Tsubakihara Y, Fukagawa M (2015) Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int 88:350–359CrossRef Komaba H, Taniguchi M, Wada A, Iseki K, Tsubakihara Y, Fukagawa M (2015) Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int 88:350–359CrossRef
26.
Zurück zum Zitat Tentori F, Wang M, Bieber BA, Karaboyas A, Li Y, Jacobson SH, Andreucci VE, Fukagawa M, Frimat L, Mendelssohn DC, Port FK, Pisoni RL, Robinson BM (2015) Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study. Clin J Am Soc Nephrol 10:98–109CrossRef Tentori F, Wang M, Bieber BA, Karaboyas A, Li Y, Jacobson SH, Andreucci VE, Fukagawa M, Frimat L, Mendelssohn DC, Port FK, Pisoni RL, Robinson BM (2015) Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study. Clin J Am Soc Nephrol 10:98–109CrossRef
27.
Zurück zum Zitat Lishmanov A, Dorairajan S, Pak Y, Chaudhary K, Chockalingam A (2012) Elevated serum parathyroid hormone is a cardiovascular risk factor in moderate chronic kidney disease. Int Urol Nephrol 44:541–547CrossRef Lishmanov A, Dorairajan S, Pak Y, Chaudhary K, Chockalingam A (2012) Elevated serum parathyroid hormone is a cardiovascular risk factor in moderate chronic kidney disease. Int Urol Nephrol 44:541–547CrossRef
28.
Zurück zum Zitat Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutiérrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M, Chronic Renal Insufficiency Cohort (CRIC) Study Group (2011) Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. Jama 305:2432–2439CrossRef Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutiérrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M, Chronic Renal Insufficiency Cohort (CRIC) Study Group (2011) Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. Jama 305:2432–2439CrossRef
29.
Zurück zum Zitat Scialla JJ, Xie H, Rahman M, Anderson AH, Isakova T, Ojo A, Zhang X, Nessel L, Hamano T, Grunwald JE, Raj DS, Yang W, He J, Lash JP, Go AS, Kusek JW, Feldman H, Wolf M, the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators (2014) Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 25:349–360CrossRef Scialla JJ, Xie H, Rahman M, Anderson AH, Isakova T, Ojo A, Zhang X, Nessel L, Hamano T, Grunwald JE, Raj DS, Yang W, He J, Lash JP, Go AS, Kusek JW, Feldman H, Wolf M, the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators (2014) Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 25:349–360CrossRef
30.
Zurück zum Zitat Yu N, Donnan PT, Flynn RWV, Murphy MJ, Smith D, Rudman A, Leese GP (2010) Increased mortality and morbidity in mild primary hyperparathyroid patients the parathyroid epidemiology and audit research study (PEARS). Clin Endocrinol 73:30–34 Yu N, Donnan PT, Flynn RWV, Murphy MJ, Smith D, Rudman A, Leese GP (2010) Increased mortality and morbidity in mild primary hyperparathyroid patients the parathyroid epidemiology and audit research study (PEARS). Clin Endocrinol 73:30–34
31.
Zurück zum Zitat Yu N, Leese GP, Donnan PT (2013) What predicts adverse outcomes in untreated primary hyperparathyroidism? The parathyroid epidemiology and audit research study (PEARS). Clin Endocrinol 79:27–34CrossRef Yu N, Leese GP, Donnan PT (2013) What predicts adverse outcomes in untreated primary hyperparathyroidism? The parathyroid epidemiology and audit research study (PEARS). Clin Endocrinol 79:27–34CrossRef
32.
Zurück zum Zitat Wetzel J, Pilz S, Grubler MR et al (2017) Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: the EPATH trial. J Clin Hypertens (Greenwich) 19:1173–1180CrossRef Wetzel J, Pilz S, Grubler MR et al (2017) Plasma parathyroid hormone and cardiovascular disease in treatment-naive patients with primary hyperparathyroidism: the EPATH trial. J Clin Hypertens (Greenwich) 19:1173–1180CrossRef
33.
Zurück zum Zitat Shekarkhar S, Foroughi M, Moatamedi M, Gachkar L (2014) The association of serum parathyroid hormone and severity of coronary artery diseases. Coron Artery Dis 25:339–342CrossRef Shekarkhar S, Foroughi M, Moatamedi M, Gachkar L (2014) The association of serum parathyroid hormone and severity of coronary artery diseases. Coron Artery Dis 25:339–342CrossRef
34.
Zurück zum Zitat Maeda S, Wu S, Juppner H, Green J, Aragay AM, Fagin JA, Clemens TL (1996) Cell-specific signal transduction of parathyroid hormone (PTH)-related protein through stably expressed recombinant PTH/PTHrP receptors in vascular smooth muscle cells. Endocrinology 137:3154–3162CrossRef Maeda S, Wu S, Juppner H, Green J, Aragay AM, Fagin JA, Clemens TL (1996) Cell-specific signal transduction of parathyroid hormone (PTH)-related protein through stably expressed recombinant PTH/PTHrP receptors in vascular smooth muscle cells. Endocrinology 137:3154–3162CrossRef
35.
Zurück zum Zitat Benson T, Menezes T, Campbell J, Bice A, Hood B, Prisby R (2016) Mechanisms of vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34 in rat bone resistance arteries. Osteoporos Int 27:1817–1826CrossRef Benson T, Menezes T, Campbell J, Bice A, Hood B, Prisby R (2016) Mechanisms of vasodilation to PTH 1-84, PTH 1-34, and PTHrP 1-34 in rat bone resistance arteries. Osteoporos Int 27:1817–1826CrossRef
Metadaten
Titel
Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease
verfasst von
S. Geng
Z. Kuang
P.L. Peissig
D. Page
L. Maursetter
K.E. Hansen
Publikationsdatum
31.05.2019
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 10/2019
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-019-05033-3

Weitere Artikel der Ausgabe 10/2019

Osteoporosis International 10/2019 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.