Nonoxidized, biologically active parathyroid hormone determines mortality in hemodialysis patients

J Clin Endocrinol Metab. 2013 Dec;98(12):4744-51. doi: 10.1210/jc.2013-2139. Epub 2013 Oct 30.

Abstract

Background: It was shown that nonoxidized PTH (n-oxPTH) is bioactive, whereas the oxidation of PTH results in a loss of biological activity.

Methods: In this study we analyzed the association of n-oxPTH on mortality in hemodialysis patients using a recently developed assay system.

Results: Hemodialysis patients (224 men, 116 women) had a median age of 66 years. One hundred seventy patients (50%) died during the follow-up period of 5 years. Median n-oxPTH levels were higher in survivors (7.2 ng/L) compared with deceased patients (5.0 ng/L; P = .002). Survival analysis showed an increased survival in the highest n-oxPTH tertile compared with the lowest n-oxPTH tertile (χ², 14.3; P = .0008). Median survival was 1702 days in the highest n-oxPTH tertile, whereas it was only 453 days in the lowest n-oxPTH tertile. Multivariable-adjusted Cox regression showed that higher age increased odds for death, whereas higher n-oxPTH reduced the odds for death. Another model analyzing a subgroup of patients with intact PTH (iPTH) concentrations at baseline above the upper normal range of the iPTH assay (70 ng/L) revealed that mortality in this subgroup was associated with oxidized PTH but not with n-oxPTH levels.

Conclusions: The predictive power of n-oxPTH and iPTH on the mortality of hemodialysis patients differs substantially. Measurements of n-oxPTH may reflect the hormone status more precisely. The iPTH-associated mortality is most likely describing oxidative stress-related mortality.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Biomarkers / chemistry
  • Biomarkers / metabolism
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Follow-Up Studies
  • Germany / epidemiology
  • Humans
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Mortality
  • Oxidation-Reduction
  • Oxidative Stress*
  • Parathyroid Hormone / blood*
  • Parathyroid Hormone / chemistry
  • Parathyroid Hormone / metabolism
  • Prognosis
  • Prospective Studies
  • Protein Stability
  • Renal Dialysis / adverse effects*
  • Survival Analysis

Substances

  • Biomarkers
  • PTH protein, human
  • Parathyroid Hormone