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Abnormal mineral metabolism and mortality in hemodialysis patients with secondary hyperparathyroidism: evidence from marginal structural models used to adjust for time-dependent confounding.
Am J Kidney Dis. 2014 Jun; 63(6):979-87.AJ

Abstract

BACKGROUND

Hemodialysis patients with mineral and bone disorders (MBDs) have an abnormally high relative risk of death, but their absolute risk of death is unknown. Further, previous studies have not accounted for possible time-dependent confounding of the association between MBD markers and death due to the effect of markers of MBD on treatments, which subsequently may affect MBD markers.

STUDY DESIGN

Multicenter, 3-year, prospective, case-cohort study.

SETTING & PARTICIPANTS

8,229 hemodialysis patients with secondary hyperparathyroidism (parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators) at 86 facilities in Japan.

PREDICTORS

Serum phosphorus, calcium, and parathyroid hormone levels.

OUTCOME

All-cause mortality.

MEASUREMENTS

Marginal structural models were used to compute absolute differences in all-cause mortality associated with different levels of predictors while accounting for time-dependent confounding.

RESULTS

The association between phosphorus level and mortality appeared U-shaped, although only higher phosphorus level categories reached statistical significance: compared to those with phosphorus levels of 5.0-5.9 mg/dL (1.61-1.93 mmol/L), patients with the highest (≥9.0 mg/dL [≥2.90 mmol/L]) phosphorus levels had 9.4 excess deaths/100 person-years (rate ratio, 2.79 [95% CI, 1.26-6.15]), whereas no association was found for the lowest phosphorus category (<3.0 mg/dL [<0.97 mmol/L]; rate ratio, 1.54 [95% CI, 0.87-2.71]). Similarly, hypercalcemia (≥10.0 mg/dL [≥2.50 mmol/L]) was associated with excess deaths, and the highest level of hypercalcemia (≥11.0 mg/dL [≥2.75 mmol/L]) was associated with 5.8 excess deaths/100 person-years (rate ratio, 2.38 [95% CI, 1.77-3.21]) compared to those with levels of 9.0-9.4 mg/dL (2.25-2.37 mmol/L). Abnormally high parathyroid hormone levels were not associated with excess deaths.

LIMITATIONS

Possible residual confounding.

CONCLUSIONS

These results reinforce the idea that serum calcium (in addition to phosphorus) level is an important predictor of the absolute risk of death in hemodialysis patients with secondary hyperparathyroidism.

Authors+Show Affiliations

Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto and Tokyo, Japan; Department of Healthcare Epidemiology, School of Public Health, Kyoto University Faculty of Medicine, Kyoto, Japan.Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto and Tokyo, Japan.Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto and Tokyo, Japan; Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan.Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto and Tokyo, Japan; Division of Nephrology, Showa University School of Medicine, Tokyo, Japan; Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Fukushima, Japan.Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto and Tokyo, Japan; Department of Healthcare Epidemiology, School of Public Health, Kyoto University Faculty of Medicine, Kyoto, Japan; Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Fukushima, Japan.Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto and Tokyo, Japan; Department of Healthcare Epidemiology, School of Public Health, Kyoto University Faculty of Medicine, Kyoto, Japan; Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Fukushima, Japan.Division of Nephrology, Showa University School of Medicine, Tokyo, Japan.Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto and Tokyo, Japan; Department of Healthcare Epidemiology, School of Public Health, Kyoto University Faculty of Medicine, Kyoto, Japan; Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Fukushima, Japan. Electronic address: fukuhara.shunichi.6m@kyoto-u.ac.jp.

Pub Type(s)

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

Language

eng

PubMed ID

24119541

Citation

Fukagawa, Masafumi, et al. "Abnormal Mineral Metabolism and Mortality in Hemodialysis Patients With Secondary Hyperparathyroidism: Evidence From Marginal Structural Models Used to Adjust for Time-dependent Confounding." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 63, no. 6, 2014, pp. 979-87.
Fukagawa M, Kido R, Komaba H, et al. Abnormal mineral metabolism and mortality in hemodialysis patients with secondary hyperparathyroidism: evidence from marginal structural models used to adjust for time-dependent confounding. Am J Kidney Dis. 2014;63(6):979-87.
Fukagawa, M., Kido, R., Komaba, H., Onishi, Y., Yamaguchi, T., Hasegawa, T., Kurita, N., Fukuma, S., Akizawa, T., & Fukuhara, S. (2014). Abnormal mineral metabolism and mortality in hemodialysis patients with secondary hyperparathyroidism: evidence from marginal structural models used to adjust for time-dependent confounding. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 63(6), 979-87. https://doi.org/10.1053/j.ajkd.2013.08.011
Fukagawa M, et al. Abnormal Mineral Metabolism and Mortality in Hemodialysis Patients With Secondary Hyperparathyroidism: Evidence From Marginal Structural Models Used to Adjust for Time-dependent Confounding. Am J Kidney Dis. 2014;63(6):979-87. PubMed PMID: 24119541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Abnormal mineral metabolism and mortality in hemodialysis patients with secondary hyperparathyroidism: evidence from marginal structural models used to adjust for time-dependent confounding. AU - Fukagawa,Masafumi, AU - Kido,Ryo, AU - Komaba,Hirotaka, AU - Onishi,Yoshihiro, AU - Yamaguchi,Takuhiro, AU - Hasegawa,Takeshi, AU - Kurita,Noriaki, AU - Fukuma,Shingo, AU - Akizawa,Tadao, AU - Fukuhara,Shunichi, Y1 - 2013/10/08/ PY - 2013/02/03/received PY - 2013/08/22/accepted PY - 2013/10/15/entrez PY - 2013/10/15/pubmed PY - 2014/7/16/medline KW - Calcium KW - clinical epidemiology KW - death KW - end-stage renal disease KW - hemodialysis KW - hyperparathyroidism KW - hyperphosphatemia KW - mineral metabolism KW - parathyroid hormone (PTH) SP - 979 EP - 87 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 63 IS - 6 N2 - BACKGROUND: Hemodialysis patients with mineral and bone disorders (MBDs) have an abnormally high relative risk of death, but their absolute risk of death is unknown. Further, previous studies have not accounted for possible time-dependent confounding of the association between MBD markers and death due to the effect of markers of MBD on treatments, which subsequently may affect MBD markers. STUDY DESIGN: Multicenter, 3-year, prospective, case-cohort study. SETTING & PARTICIPANTS: 8,229 hemodialysis patients with secondary hyperparathyroidism (parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators) at 86 facilities in Japan. PREDICTORS: Serum phosphorus, calcium, and parathyroid hormone levels. OUTCOME: All-cause mortality. MEASUREMENTS: Marginal structural models were used to compute absolute differences in all-cause mortality associated with different levels of predictors while accounting for time-dependent confounding. RESULTS: The association between phosphorus level and mortality appeared U-shaped, although only higher phosphorus level categories reached statistical significance: compared to those with phosphorus levels of 5.0-5.9 mg/dL (1.61-1.93 mmol/L), patients with the highest (≥9.0 mg/dL [≥2.90 mmol/L]) phosphorus levels had 9.4 excess deaths/100 person-years (rate ratio, 2.79 [95% CI, 1.26-6.15]), whereas no association was found for the lowest phosphorus category (<3.0 mg/dL [<0.97 mmol/L]; rate ratio, 1.54 [95% CI, 0.87-2.71]). Similarly, hypercalcemia (≥10.0 mg/dL [≥2.50 mmol/L]) was associated with excess deaths, and the highest level of hypercalcemia (≥11.0 mg/dL [≥2.75 mmol/L]) was associated with 5.8 excess deaths/100 person-years (rate ratio, 2.38 [95% CI, 1.77-3.21]) compared to those with levels of 9.0-9.4 mg/dL (2.25-2.37 mmol/L). Abnormally high parathyroid hormone levels were not associated with excess deaths. LIMITATIONS: Possible residual confounding. CONCLUSIONS: These results reinforce the idea that serum calcium (in addition to phosphorus) level is an important predictor of the absolute risk of death in hemodialysis patients with secondary hyperparathyroidism. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/24119541/Abnormal_mineral_metabolism_and_mortality_in_hemodialysis_patients_with_secondary_hyperparathyroidism:_evidence_from_marginal_structural_models_used_to_adjust_for_time_dependent_confounding_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(13)01182-7 DB - PRIME DP - Unbound Medicine ER -