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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

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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.

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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

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Author notes

    Authors and Affiliations

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

      Sul A Lee, Geun Woo Ryu, Jong Hyun Jhee, Hyung Woo Kim, Seohyun Park, Su-Young Jung, Hyung Jung Oh, Jung Tak Park, Seung Hyeok Han, Shin-Wook Kang & Tae-Hyun Yoo

    2. Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si, Korea

      Mi Jung Lee

    3. Department of Internal Medicine, College of Medicine; Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul, 120-752, Korea

      Tae-Hyun Yoo

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    1. Sul A Lee
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    Correspondence to Tae-Hyun Yoo.

    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.

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    None.

    Additional information

    Sul A Lee and Mi Jung Lee contributed equally to this work.

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    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

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