Original Full Length ArticleMortality of combined serum phosphorus and parathyroid hormone concentrations and their changes over time in hemodialysis patients
Introduction
Abnormalities in serum calcium, phosphorus (P), and parathyroid hormone (PTH) levels are common in patients with chronic kidney disease (CKD). These biochemical changes together with elevation of fibroblast growth factor-23 (FGF-23) and abnormalities in vitamin D metabolism constitute a systemic syndrome known as chronic kidney disease–mineral and bone disorder (CKD-MBD). Observational studies have found associations of serum phosphorus (P) and parathyroid hormone (PTH) with mortality in patients with CKD [1], [2] and in patients on maintenance dialysis [3], [4], [5], [6], [7], [8], [9], [10], [11]. Although no conclusive clinical trials have been conducted yet, hyperphosphatemia and secondary hyperparathyroidism have been recommended as major targets to treat CKD-MBD [12], [13]. Since serum P and PTH levels are physiologically interrelated, [14], [15] it may be plausible that both parameters be considered simultaneously in risk stratification, planning and adjusting treatments for CKD-MBD. In this respect, a model combining serum P with PTH level as a “bivariate” predictor may fit a survival model better than a model that treats each parameter separately. In addition to static levels of serum P and PTH, dynamic change over time may be also important. However, effect of changes in serum P and PTH levels on mortality has been insufficiently evaluated, especially in discordant (i.e. increase in serum P level but decrease in PTH level or vice versa) changes [16].
We hypothesized that concurrent preferable levels of serum P and PTH are associated with better survival in hemodialysis (HD) patients, and that changes in serum P and PTH levels to a preferable level would also be associated with lower mortality. Evaluation for discordant changes may give insight about situations faced during treatment of CKD-MBD in clinical practice. We evaluated our hypothesis with a large and contemporary cohort of HD patients.
Section snippets
Patients
We retrospectively examined data from all patients receiving HD treatment from July 1, 2001, to June 30, 2006 in a large dialysis care organization in the United States (DaVita Inc.). As a dialysis population is a dynamic cohort with a high turnover rate, a non-concurrent cohort was formed. Prevalent patients as of July 1, 2001 and incident patients from July 1, 2001 to June 30, 2006 were included, which has been described in our previous studies [17], [18]. The first (baseline) quarter for
Baseline characteristics
The cohort included 107,299 HD patients, who were 64 ± 15 (mean ± SD) years old, 45% women, 42% Caucasian, 33% African-American, and 15% Hispanic. At the start of dialysis, 59% of HD patients had diabetes mellitus and 80% had hypertension. Mean baseline serum P level was 5.6 mg/dL (SD, 1.5) and median intact PTH level was 244 pg/dL (IQR, 144–417). Baseline characteristics stratified by each baseline serum P and intact PTH level are presented in Table 1. Patients with higher serum P level tended to be
Discussion
This study provides detailed information on mortality outcomes according to the combination of serum P and PTH levels in a large cohort of HD patients. Patients with a combination of preferable serum P (3.5– < 5.5 mg/dL) and preferable PTH (150– < 300 pg/mL) levels tended to have the lowest mortality risk. Change in serum P level to this preferable range was associated with low risk of mortality, whereas only increase in low serum PTH level to its preferable range was significantly associated with
Acknowledgments
We thank DaVita Clinical Research (DCR) for providing the clinical data for this research. The work is supported by Dr. KKZ's NIH (NIDDK) grants K24-DK091419, R01-DK078106, a philanthropic grant from Mr. Harold Simmons and research grants from DaVita Clinical Research. Dr. KKZ was the medical director of DaVita Harbor-UCLA/MFI in Long Beach, CA during 2007–2012. Dr. MZM work was supported by the National Institute on Aging of the National Institutes of Health under Award Number R21AG047036.
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These authors contributed equally.
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Reprint request: Kamyar Kalantar-Zadeh, MD, MPH, PhD. Harold Simmons Center for Kidney Disease Research & Epidemiology, Division of Nephrology & Hypertension, University of California Irvine, School of Medicine, 101 The City Drive South, City Tower, Suite 400, ZOT: 4088, Orange, CA 92868-3217, USA. Fax: + 1 714 456 6034.