Association of Nonoxidized Parathyroid Hormone with Cardiovascular and Kidney Disease Outcomes in Chronic Kidney Disease

Abstract

Background and objectivesIn patients with CKD, elevated plasma parathyroid hormone (PTH) levels are associated with greater cardiovascular morbidity and mortality. However, the reference method for PTH measurement is disputed. It has been argued that measurement of nonoxidized PTH better reflects biologically active PTH than measurements with conventional assays.Design, setting, participants, & measurementsPTH and nonoxidized PTH levels were measured at study baseline in 535 patients with CKD with an eGFR range between 89 and 15 ml/min per 1.73 m2. Patients were followed over 5.1 years for the occurrence of acute heart failure, atherosclerotic events, CKD progression (doubling of serum creatinine or initiation of RRT), or all-cause death.ResultsAtherosclerotic events, acute heart failure, CKD progression, and deaths from any cause occurred in 116, 58, 73, and 85 patients, respectively. In Kaplan–Meier analyses, patients at the highest PTH and nonoxidized-PTH tertile (79–543 and 12–172 pg/ml, respectively) showed a higher rate of atherosclerotic events, acute heart failure, CKD progression, and death from any cause. After adjustment for eGFR and albuminuria, nonoxidized PTH was no longer associated with atherosclerotic events (hazard ratio third versus first tertile, 1.04 [95% confidence intervals, 0.62–1.75]), acute heart failure (hazard ratio third versus first tertile, 1.24 [95% confidence intervals, 0.59–2.62]), CKD progression (hazard ratio third versus first tertile, 0.93 [95% confidence intervals, 0.46–1.90]), and death from any cause (hazard ratio third versus first tertile, 1.23 [95% confidence intervals, 0.66–2.31]), and PTH lost its association with atherosclerotic events (hazard ratio third versus first tertile, 0.80 [95% confidence intervals, 0.46–1.38]) and CKD progression (hazard ratio third versus first tertile, 0.99 [95% confidence intervals, 0.46–2.10]), although it remained associated with acute heart failure (hazard ratio third versus first tertile, 2.76 [95% confidence intervals, 1.11–6.89]) and all-cause death (hazard ratio third versus first tertile, 2.35 [95% confidence intervals, 1.13–4.89]). After further adjustment for cardiovascular and kidney risk factors, PTH remained associated with all-cause death (hazard ratio third versus first tertile, 2.79 [95% confidence intervals, 1.32–5.89]), but with no other end point.ConclusionsIn a cohort of patients with CKD, PTH was associated with all-cause mortality; there was no association of nonoxidized PTH with any of the clinical outcomes examined.