Nonoxidized, Biologically Active Parathyroid Hormone Determines Mortality in Hemodialysis Patients

• Published in: The journal of clinical endocrinology and metabolism 2013-12, Vol.98 (12), p.4744-4751
• Main Authors: Tepel, Martin, Armbruster, Franz Paul, Grön, Hans Jürgen, Scholze, Alexandra, Reichetzeder, Christoph, Roth, Heinz Jürgen, Hocher, Berthold
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biomarkers - blood; Biomarkers - chemistry; Biomarkers - metabolism; Cohort Studies; Denmark - epidemiology; Endocrinopathies; Feeding. Feeding behavior; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Germany - epidemiology; Humans; Kidney Failure, Chronic - diagnosis; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - mortality; Kidney Failure, Chronic - therapy; Male; Medical sciences; 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; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2013-2139

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.