International variations in serum PTH and calcium levels and their mortality associations in peritoneal dialysis patients: Results from PDOPPS

Kosaku Nitta; Brian Bieber; Angelo Karaboyas; David W Johnson; Talerngsak Kanjanabuch; Yong-Lim Kim; Mark Lambie; John Hartman; Jenny I Shen; Mihran Naljayan; Roberto Pecoits-Filho; Bruce M Robinson; Ronald L Pisoni; Jeffrey Perl; Hideki Kawanishi

doi:10.1177/08968608241235516

International variations in serum PTH and calcium levels and their mortality associations in peritoneal dialysis patients: Results from PDOPPS

Perit Dial Int. 2024 Mar 19:8968608241235516. doi: 10.1177/08968608241235516. Online ahead of print.

Authors

Kosaku Nitta¹, Brian Bieber², Angelo Karaboyas², David W Johnson^{3

4

5}, Talerngsak Kanjanabuch⁶, Yong-Lim Kim⁷, Mark Lambie⁸, John Hartman⁹, Jenny I Shen¹⁰, Mihran Naljayan¹¹, Roberto Pecoits-Filho², Bruce M Robinson¹², Ronald L Pisoni², Jeffrey Perl¹³, Hideki Kawanishi¹⁴

Affiliations

¹ Department of Nephrology, Tokyo Women's Medical University, Shinjuku, Japan.
² Arbor Research Collaborative for Health, Ann Arbor, MI, USA.
³ Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia.
⁴ Department of Kidney and Transplant Services, Princess Alexandra, Brisbane, Australia.
⁵ Translational Research Institute, Brisbane, Australia.
⁶ Division of Nephrology, Department of Medicine and Center of Excellence in Kidney Metabolic Disorders and Dialysis Policy & Practice Program (DiP3), School of Global Health, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁷ School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
⁸ Medicine and Health Sciences, Keele University, Keele, UK.
⁹ Visonex, Green Bay, WI, USA.
¹⁰ The Lundquist Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA, USA.
¹¹ Home Modalities, DaVita Kidney Care, Denver, CO, USA.
¹² Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
¹³ Division of Nephrology, St. Michael's Hospital and the Keenan Research Center in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹⁴ Akane Foundation, Tsuchiya General Hospital, Nakaku, Hiroshima, Japan.

PMID: 38501163
DOI: 10.1177/08968608241235516

Abstract

Background: Mineral bone disorder (MBD) in chronic kidney disease (CKD) is associated with high symptom burden, fractures, vascular calcification, cardiovascular disease and increased morbidity and mortality. CKD-MBD studies have been limited in peritoneal dialysis (PD) patients. Here, we describe calcium and parathyroid hormone (PTH) control, related treatments and mortality associations in PD patients.

Methods: We used data from eight countries (Australia and New Zealand (A/NZ), Canada, Japan, Thailand, South Korea, United Kingdom, United States (US)) participating in the prospective cohort Peritoneal Dialysis Outcomes and Practice Patterns Study (2014-2022) among patients receiving PD for >3 months. We analysed the association of baseline PTH and albumin-adjusted calcium (calcium^Alb) with all-cause mortality using Cox regression, adjusted for potential confounders, including serum phosphorus and alkaline phosphatase.

Results: Mean age ranged from 54.6 years in South Korea to 63.5 years in Japan. PTH and serum calcium^Alb were measured at baseline in 12,642 and 14,244 patients, respectively. Median PTH ranged from 161 (Japan) to 363 pg/mL (US); mean calcium^Alb ranged from 9.1 (South Korea, US) to 9.8 mg/dL (A/NZ). The PTH/mortality relationship was U-shaped, with the lowest risk at PTH 300-599 pg/mL. Mortality was nearly 20% higher at serum calcium^Alb 9.6+ mg/dL versus 8.4-<9.6 mg/dL. MBD therapy prescriptions varied substantially across countries.

Conclusions: A large proportion of PD patients in this multi-national study have calcium and/or PTH levels in ranges associated with substantially higher mortality. These observations point to the need to substantially improve MBD management in PD to optimise patient outcomes.

Lay summary: Chronic kidney disease-mineral bone disorder (MBD) is a systemic condition, common in dialysis patients, that results in abnormalities in parathyroid hormone (PTH), calcium, phosphorus and vitamin D metabolism. A large proportion of peritoneal dialysis (PD) patients in this current multi-national study had calcium and/or PTH levels in ranges associated with substantially higher risks of death. Our observational study design limits our ability to determine whether these abnormal calcium and PTH levels cause more death due to possible confounding that was not accounted for in our analysis. However, our findings, along with other recent work showing 48-75% higher risk of death for the one-third of PD patients having high phosphorus levels (>5.5 mg/dL), should raise strong concerns for a greater focus on improving MBD management in PD patients.

Keywords: Calcium; epidemiology; mortality; parathyroid hormone; peritoneal dialysis.