Elsevier

Bone

Volume 61, April 2014, Pages 201-207
Bone

Original Full Length Article
Mortality of combined serum phosphorus and parathyroid hormone concentrations and their changes over time in hemodialysis patients

https://doi.org/10.1016/j.bone.2014.01.016Get rights and content

Highlights

  • A large cohort of hemodialysis patients

  • We model mortality of combined serum phosphorus and parathyroid hormone levels.

  • Survival may be greatest with controlling both serum P and PTH levels in balance.

Abstract

Background

Mineral and bone disorder (MBD) is common and associated with mortality in patients with chronic kidney disease (CKD) Given that disarrays in serum phosphorus (P) and parathyroid hormone (PTH) levels and their changes over time are closely interrelated, modeling mortality–predictability of their combinations may help improve CKD patient management.

Methods

A historical cohort study was undertaken to evaluate the joint effect of serum P and PTH levels on mortality in 107,299 chronic hemodialysis (HD) patients. Changes in serum P and PTH levels over 6 months, in particular discordant changes, were also modeled with mortality.

Results

HD patients were 64 ± 15 (mean ± SD) years old and included 45% women, 33% African-American, and 59% diabetic. Compared with serum P level ≥ 7.0 mg/dL and PTH level ≥ 600 pg/mL, adjusted hazard ratio (HR) tended to be lowest in patients with serum P level of 3.5– < 5.5 mg/dL combined with PTH level of 150– < 300 pg/mL (HR 0.64, 95% confidence interval 0.61–0.67). A change over time in serum P level towards the 3.5– < 5.5 mg/dL range from higher or lower ranges was associated with a decreased mortality, whereas only change in PTH level from < 150 pg/mL to 150– < 300 pg/mL range was associated with a lower risk of mortality. Upon discordant changes of PTH and P, i.e., decrease in one of the two measures while the other increased, no change in mortality risk was observed.

Conclusion

In CKD-MBD management, patent survival is the greatest with controlling both serum P and PTH levels in balance. Tailoring an individualized treatment strategy in CKD-MBD may benefit patients. Further studies are needed.

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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    1

    These authors contributed equally.

    2

    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.

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