Abstract
Summary
Abnormal bone dynamics is a major risk factor for cardiovascular disease in patients with chronic kidney disease. The level of serum intact parathyroid hormone (iPTH) is widely used as a bone dynamic marker. We investigated the effect of the mean level of serum iPTH on overall mortality and cardiovascular outcomes in incident dialysis patients.
Purpose
Chronic kidney disease–mineral bone disorder (CKD–MBD) is a major risk factor for cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). CKD–MBD is classified as low- or high-turnover bone disease according to the bone dynamics; both are related to vascular calcification in ESRD. To evaluate the prognostic value of abnormal serum parathyroid hormone (PTH) levels on ESRD patients, we investigated the effects of time-averaged serum intact PTH (TA-iPTH) levels on overall mortality and major adverse cardiac and cerebrovascular events (MACCEs) in incident dialysis patients.
Methods
Four hundred thirteen patients who started dialysis between January 2009 and September 2013 at Yonsei University Health System were enrolled. The patients were divided into three groups according to TA-iPTH levels during the 12 months after the initiation of dialysis: group 1, <65 pg/ml; group 2, 65–300 pg/ml; and group 3, >300 pg/ml. Cox regression analyses were performed to determine the prognostic value of TA-iPTH for overall mortality and MACCEs.
Results
The mean age of the patients was 57 ± 15 years, and 222 patients (54 %) were men. During the median follow-up of 40.8 ± 29.3 months, 49 patients (12 %) died, and MACCEs occurred in 55 patients (13 %). The multivariate Cox regression analyses demonstrated that a low TA-iPTH level was an independent risk factor for both overall mortality (group 2 as reference; group 1: hazard ratio (HR) = 2.06, 95 % confidence interval (CI) = 1.11–3.83, P = 0.023) and MACCEs (HR = 1.82, 95 % CI = 1.04–3.20, P = 0.036) in incident dialysis patients after adjustment for confounding factors.
Conclusion
Low serum TA-iPTH is a useful clinical marker of both overall mortality and MACCEs in patients undergoing incident dialysis, mediated by vascular calcification.
This is a preview of subscription content, access via your institution.


Abbreviations
- CKD–MBD:
-
Chronic kidney disease–mineral bone disorder
- CVD:
-
Cardiovascular disease
- ESRD:
-
End-stage renal disease
- PTH:
-
Parathyroid hormone
- TA-iPTH:
-
Time-averaged serum intact PTH
- MACCEs:
-
Major adverse cardiac and cerebrovascular events
- HR:
-
Hazard ratio
- CI:
-
Confidence interval
- CKD:
-
Chronic kidney disease
- ABD:
-
Adynamic bone disease
- iPTH:
-
Intact parathyroid hormone
- AoACS:
-
Aortic arch calcification score
- YUHS:
-
Yonsei University Health System
- BMI:
-
Body mass index
- AUC:
-
Area under the curve
- CV:
-
Coefficient of variation
- AoAC:
-
Aortic arch calcification
- ACS:
-
Acute coronary syndrome
- SD:
-
Standard deviation
- CRP:
-
C-reactive protein
- hs-CRP:
-
High-sensitivity CRP
- OR:
-
Odds ratio
- K/DOQI:
-
Kidney Disease Outcomes Quality Initiative
- MESA:
-
Multi-Ethnic Study of Atherosclerosis
- MICS:
-
Malnutrition–inflammation–cachexia syndrome
- bALP:
-
Bone-specific alkaline phosphatase
- BMD:
-
Bone mineral density
- EBCT:
-
Electron beam computed tomography
- MSCT:
-
Multislice CT
References
Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15:2208–2218
Young EW, Akiba T, Albert JM, McCarthy JT, Kerr PG, Mendelssohn DC, Jadoul M (2004) Magnitude and impact of abnormal mineral metabolism in hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 44:34–38
Jeloka T, Mali M, Jhamnani A, Konde S, Jadhav V (2012) Are we overconcerned about secondary hyperparathyroidism and underestimating the more common secondary hypoparathyroidism in our dialysis patients? J Assoc Physicians India 60:102–105
Avram MM, Mittman N, Myint MM, Fein P (2001) Importance of low serum intact parathyroid hormone as a predictor of mortality in hemodialysis and peritoneal dialysis patients: 14 years of prospective observation. Am J Kidney Dis 38:1351–1357
Torres PU, Bover J, Mazzaferro S, de Vernejoul MC, Cohen-Solal M (2014) When, how, and why a bone biopsy should be performed in patients with chronic kidney disease. Semin Nephrol 34:612–625
Rao SD, Matkovic V, Duncan H (1980) Transiliac bone biopsy. Complications and diagnostic value. Henry Ford Hosp Med J 28:112–115
Ha SK, Park CH, Seo JK, Park SH, Kang SW, Choi KH, Lee HY, Han DS (1996) Studies on bone markers and bone mineral density in patients with chronic renal failure. Yonsei Med J 37:350–356
Cannata Andia JB (2000) Adynamic bone and chronic renal failure: an overview. Am J Med Sci 320:81–84
Kalantar-Zadeh K, Kuwae N, Regidor DL, Kovesdy CP, Kilpatrick RD, Shinaberger CS, McAllister CJ, Budoff MJ, Salusky IB, Kopple JD (2006) Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 70:771–780
National Kidney Foundation (2003) K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:S1–201
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int 76 (Suppl 113):S1–S130
Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, Komaba H, Ando R, Kakuta T, Fujii H (2013) Clinical practice guideline for the management of chronic kidney disease‐mineral and bone disorder. Ther Apher Dial 17:247–288
Ogawa T, Ishida H, Matsuda N, Fujiu A, Matsuda A, Ito K, Ando Y, Nitta K (2009) Simple evaluation of aortic arch calcification by chest radiography in hemodialysis patients. Hemodial Int 13:301–306
Cannata-Andia JB, Rodriguez-Garcia M, Carrillo-Lopez N, Naves-Diaz M, Diaz-Lopez B (2006) Vascular calcifications: pathogenesis, management, and impact on clinical outcomes. J Am Soc Nephrol 17:S267–S273
Komatsu M, Okazaki M, Tsuchiya K, Kawaguchi H, Nitta K (2014) Aortic arch calcification predicts cardiovascular and all-cause mortality in maintenance hemodialysis patients. Kidney Blood Press Res 39:658–667
Lee MJ, Shin DH, Kim SJ et al (2012) Progression of aortic arch calcification over 1 year is an independent predictor of mortality in incident peritoneal dialysis patients. PLoS One 7, e48793
Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM (2011) Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 109:697–711
Noordzij M, Cranenburg EM, Engelsman LF et al (2011) Progression of aortic calcification is associated with disorders of mineral metabolism and mortality in chronic dialysis patients. Nephrol Dial Transplant 26:1662–1669
Tsuchihashi K, Takizawa H, Torii T, Ikeda R, Nakahara N, Yuda S, Kobayashi N, Nakata T, Ura N, Shimamoto K (2000) Hypoparathyroidism potentiates cardiovascular complications through disturbed calcium metabolism: possible risk of vitamin D(3) analog administration in dialysis patients with end-stage renal disease. Nephron 84:13–20
Allison MA, Budoff MJ, Nasir K, Wong ND, Detrano R, Kronmal R, Takasu J, Criqui MH (2009) Ethnic-specific risks for atherosclerotic calcification of the thoracic and abdominal aorta (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol 104:812–817
Kalantar-Zadeh K, Shah A, Duong U, Hechter RC, Dukkipati R, Kovesdy CP (2010) Kidney bone disease and mortality in CKD: revisiting the role of vitamin D, calcimimetics, alkaline phosphatase, and minerals. Kidney Int Suppl 78:S10–S21
Dukkipati R, Kovesdy CP, Colman S, Budoff MJ, Nissenson AR, Sprague SM, Kopple JD, Kalantar-Zadeh K (2010) Association of relatively low serum parathyroid hormone with malnutrition-inflammation complex and survival in maintenance hemodialysis patients. J Ren Nutr 20:243–254
Shoben AB, Rudser KD, de Boer IH, Young B, Kestenbaum B (2008) Association of oral calcitriol with improved survival in nondialyzed CKD. J Am Soc Nephrol 19:1613–1619
Palmer SC, McGregor DO, Craig JC, Elder G, Macaskill P, Strippoli GF (2009) Vitamin D compounds for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev 4:cd008175
Zittermann A, Schleithoff SS, Koerfer R (2007) Vitamin D and vascular calcification. Curr Opin Lipidol 18:41–46
Haarhaus M, Monier-Faugere MC, Magnusson P, Malluche HH (2015) Bone alkaline phosphatase isoforms in hemodialysis patients with low versus non-low bone turnover: a diagnostic test study. Am J Kidney Dis 66:99–105
Malluche HH, Davenport DL, Cantor T, Monier-Faugere M-C (2014) Bone mineral density and serum biochemical predictors of bone loss in patients with CKD on dialysis. Clin J Am Soc Nephrol 9:1254–1262
Bover J, Urena P, Brandenburg V, Goldsmith D, Ruiz C, DaSilva I, Bosch RJ (2014) Adynamic bone disease: from bone to vessels in chronic kidney disease. Semin Nephrol 34:626–640
London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H (2003) Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18:1731–1740
Okuno S, Ishimura E, Kitatani K et al (2007) Presence of abdominal aortic calcification is significantly associated with all-cause and cardiovascular mortality in maintenance hemodialysis patients. Am J Kidney Dis 49:417–425
Chertow GM, Burke SK, Raggi P (2002) Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 62:245–252
Sigrist MK, Taal MW, Bungay P, McIntyre CW (2007) Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease. Clin J Am Soc Nephrol 2:1241–1248
Karohl C, D’Marco Gascon L, Raggi P (2011) Noninvasive imaging for assessment of calcification in chronic kidney disease. Nat Rev Nephrol 7:567–577
Hashimoto H, Iijima K, Hashimoto M, Son BK, Ota H, Ogawa S, Eto M, Akishita M, Ouchi Y (2009) Validity and usefulness of aortic arch calcification in chest X-ray. J Atheroscler Thromb 16:256–264
Ogawa T, Ishida H, Akamatsu M, Matsuda N, Fujiu A, Ito K, Ando Y, Nitta K (2010) Progression of aortic arch calcification and all-cause and cardiovascular mortality in chronic hemodialysis patients. Int Urol Nephrol 42:187–194
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The present study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Yonsei University Health System (YUHS) Clinical Trial Center. We obtained written informed consent from all of the participants.
Conflicts of interest
None.
Additional information
Sul A Lee and Mi Jung Lee contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary Table 1
(DOCX 18 kb)
Rights and permissions
About this article
Cite this article
Lee, S.A., Lee, M.J., Ryu, G.W. et al. Low serum intact parathyroid hormone level is an independent risk factor for overall mortality and major adverse cardiac and cerebrovascular events in incident dialysis patients. Osteoporos Int 27, 2717–2726 (2016). https://doi.org/10.1007/s00198-016-3636-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-016-3636-1