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Clin Kidney J
Clin Kidney J
ckj
Clinical Kidney Journal
2048-8505
2048-8513
Oxford University Press

10.1093/ckj/sfae252
sfae252
Letter to the Editor
AcademicSubjects/MED00340
Immobilization-associated hypercalcaemia in patients with malignancy in the hospital setting
https://orcid.org/0000-0002-7190-6665
Kanduri Swetha R Department of Nephrology, Ochsner Health System, New Orleans, LA, USA
Ochsner Clinical School, University of Queensland, Brisbane, Queensland, Australia

Stark Anabella Department of Nephrology, Ochsner Health System, New Orleans, LA, USA

https://orcid.org/0000-0001-9670-1095
Velez Juan Carlos Q Department of Nephrology, Ochsner Health System, New Orleans, LA, USA
Ochsner Clinical School, University of Queensland, Brisbane, Queensland, Australia

Correspondence to: Swetha R. Kanduri; E-mail: Svetarani@gmail.com
9 2024
22 8 2024
22 8 2024
17 9 sfae25203 8 2024
18 9 2024
© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
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pmcTo the Editor,

Malignancy-associated hypercalcaemia (MAH) is encountered in 10–30% of patients with cancer and is associated with poor prognosis [1]. Direct bone invasion (primary bone cancer, bone metastasis or multiple myeloma) and humoral hypercalcaemia, i.e. mediated by elevated parathyroid hormone (PTH), PTH-related peptide (PTHrP) and calcitriol, are the main aetiologies [2]. Although a significant proportion of patients with malignancy have poor functional status, immobilization-associated hypercalcaemia (Immob-HCa) is not well recognized in this population. Thus we examined the relative contribution of Immob-HCa to all causes of MAH in the hospital setting.

A retrospective review of medical records was conducted searching for cases of MAH over a 3-year period. All patients with active malignancy and presenting to the hospital with serum calcium (sCa) levels >11.0 mg/dl were included. Patients with end-stage kidney disease and kidney transplantation were excluded. Cases of hypercalcaemia due to bone metastasis, multiple myeloma, elevated PTH, PTHrP or calcitriol were captured. Cases were classified as undetermined if the cause of hypercalcaemia was not ascertainable due to incomplete laboratory workup. Definite Immob-HCa was defined as the presence of immobility >4 weeks prior to admission or an Eastern Cooperative Oncology Group performance score >4, needing complete assistance and with the absence of disqualifying laboratory/clinical data (PTH >60 ng/dl, 1,25-dihydroxyvitamin D >70 pg/ml, 25-hydroxy vitamin D >80 ng/ml, PTHrP >2.5 pmol/l, lytic lesion by imaging or alternative aetiology like exposure to thiazide or calcium or vitamin D supplementation). Probable Immob-HCa was defined as documented immobility and the absence of an alternative aetiology, but incomplete laboratory data.

A total of 145 patients with in-hospital MAH were identified. The median age was 68 years [interquartile range (IQR) 33–92], 45% women, 64% white, 31% self-identified black and the median peak sCa was 12.1 mg/dl (IQR 11.2–17.8). High ionized calcium was verified in 41 patients (28%). A total of 74 patients (51%) had evidence of bone metastasis (including primary bone cancer), multiple myeloma accounted for 7 patients (5%), elevated PTH consistent with hyperparathyroidism in 10 patients (7%), PTHrP in 11 patients (8%) and elevated calcitriol in 3 patients (2%). One patient was categorized as definite Immob-HCa and four as probable Immob-HCa. The aetiology of MAH was undetermined in 35 patients (24%). Thus Immob-HCa accounted for up to 4% (5/145) of in-hospital MAH. Concomitant acute kidney injury was present in 3 of 5 (60%) cases of Immob-HCa.

Our results are consistent with previously published literature that MAH is predominantly encountered secondary to bone lesions [3, 4]. Undetermined cause due to incomplete laboratory workup was encountered in a quarter of patients with MAH. Our novel contribution is that Immob-HCa accounted for ≈1 in 25 cases of MAH.

The symptoms of hypercalcaemia typically manifest within 10 days–>6 months of immobilization. The exact mechanism is unknown; however, it is postulated as an imbalance between osteoclastic bone resorption and osteoblast mediated bone formation triggered by a lack of mechanosensory activity. Decreased mechanical forces from prolonged bedrest potentially increases osteoclastic bone activity promoting bone resorption, while an increase in sclerostin levels further reduces osteoblastic bone formation [5]. In addition to intravenous hydration and anti-resorptive agents, early mobilization is recommended in the management of Immob-HCa.

Our study has limitations. It is a retrospective study with a small sample size. Incomplete laboratory data, including unavailability of bone resorption markers, might have underestimated the incidence of Immob-HCa. Nevertheless, it constitutes the first report of the relative contribution of Immob-HCa to all causes of MAH in the hospital setting.

In conclusion, Immob-HCa should be included in the differential diagnosis of MAH. Early mobilization of the patients should be encouraged to reduce the probability of Immob-HCa (Fig. 1).

Figure 1: Various causes of MAH in hospitalized patients and the relative contribution of Immob-HCa.

ETHICS

The study was conducted with approval of the institutional review board and waiver of informed consent. The study was conducted in accordance with the Declaration of Helsinki.

FUNDING

None declared.

AUTHORS’ CONTRIBUTIONS

A.S. was responsible for data collections. S.K. wrote the manuscript and drafted the figure. J.C.Q.V. was responsible for formatting and overall supervision.

CONFLICT OF INTEREST STATEMENT

J.C.Q.V. has served as advisor and consultant for Mallinckrodt Pharmaceuticals. He has also provided consultative work for Travere Therapeutics and Calliditas. The remaining authors report no conflicts of interest.
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