Potential link found between vitamin D therapy and higher risk of hypercalcemia in CRF


Patients with chronic kidney disease (CRF) and high parathyroid hormone levels treated with active vitamin D therapy had significantly higher risks of hypercalcemia, the researchers concluded in a meta-analysis.

According to a recent meta-analysis, active vitamin D treatment significantly increases the risk of hypercalcemia in patients with chronic kidney disease without dialysis (ND-CKD) and secondary hyperparathyroidism (SHPT) compared to placebo.

The systematic review of the literature and the meta-analysis, published in Kidney Clinical Journal, used published randomized, placebo-controlled clinical trials of active vitamin D to clarify the relationship between active vitamin D and SHPT in patients with ND-CKD. SHPT is a common complication in patients with CRF and is characterized by excessive secretion of parathyroid hormone (PTH), which can lead to worsening kidney function. The condition affects 40% to 82% of patients with stage 3 and stage 4 CKD.

“These observations highlight the urgent need for new treatments for SHPT in patients with ND-CKD that effectively reduce PTH levels while avoiding unwanted elevations in serum calcium,” the investigators wrote.

SHPT is also strongly associated with CKD-mineral bone disorders and if elevations in serum PTH are left untreated, patients may present with bone disease and vascular and valve calcification, which may lead to increased risk of bone fractures. cardiovascular disease and mortality.

The pathogenesis of SHPT involves several factors, including the presence of hypocalcemia, phosphate retention and associated increases in fibroblast growth factor 23 and insufficient levels of vitamin D. Patients with CRF frequently have low vitamin D levels, which strongly contributes to the development of SHPT.

Investigators searched 3 literature databases and their data cut-off date was May 14, 2020. For inclusion, studies had to be randomized, double-blind, placebo-controlled trials of adults. patients with ND-CKD and SHPT, evaluating the active vitamin as monotherapy. D. Studies should also involve at least 30 participants per treatment arm and have a study period of at least 6 weeks.

A total of 1704 articles were identified, of which 6 studies covering 799 patients were eligible for analysis. The duration of the studies varied between 16 weeks and 2 years. Five of the studies evaluated the use of paricalcitol and 1 evaluated alfacalcidol. Across all studies, hypercalcaemia was reported in 1.1% to 43.3% of patients treated with active vitamin D treatment, which was significantly higher than in patients treated with placebo (range from 0.0% to 3.4%).

In the main meta-analysis of the 6 studies, the investigators observed that patients with ND-CKD and SHPT treated with active vitamin D treatment had a 6.6 times greater risk of hypercalcemia than those placebo-treated (odds ratio [OR], 6.63; 95% CI, 2.37-18.55; P <.001>

Two sensitivity analyzes were performed to assess the robustness of the results of the primary analysis. A sensitivity analysis involved the exclusion of a study identified as having a high risk of bias and found that active vitamin D treatment was associated with a 6.2 times greater likelihood of hypercalcemia compared to placebo ( OR, 7.22; 95% CI: 2.21-23.60; P = .001). The other analysis excluded 2 studies which represented a large proportion of observed hypercalcaemia episodes, concluding that active vitamin D treatment was associated with a 2.0-fold higher risk of hypercalcemia compared to placebo (OR, 3.03; 95% CI, 1.06-8.71; P = .039).

The meta-analysis and review had several limitations, including the small number of studies, heterogeneity of study designs, and lack of control for confounding factors.

“Future analyzes of real-world data could help overcome a number of these limitations, as it could allow an increasingly large population to be assessed,” the investigators noted.


Cozzolino M, Bernard L, Csomor PA. Active vitamin D increases the risk of hypercalcemia in non-dialysis chronic renal failure patients with secondary hyperparathyroidism: a systematic review and meta-analysis. Clin Kidney J. Nov 29, 2021; 14 (10): 2437-2443. doi: 10.1093 / ckj / sfab091


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