Hypo-, hypercalcaemia prevalent among predialysis CKD patients with MBD

Episodes of hypocalcaemia and hypercalcaemia are relatively high among predialysis patients with chronic kidney disease (CKD), but the prevalence of these conditions does not seem to contribute to a higher risk of mortality and cardiovascular events, according to a Singapore study. 

"While hypocalcaemia and hypercalcaemia were not associated with [an] increased risk of short-term mortality and cardiovascular events among predialysis CKD patients, more studies are required to analyse the impact of hypercalcaemia and hypocalcaemia on these patients’ long-term clinical outcomes,” said the investigators. 

This retrospective cohort study included 400 adult CKD stage 4/5 patients who received treatment for CKD-mineral bone disease (MBD) between 2016 and 2017. Patients were followed up for 3 years. 

Hypocalcaemia and hypercalcaemia were characterized as serum corrected calcium (Ca2+) <2.10 and >2.46 mmol/L, respectively. Hypocalcaemia severity was classified as mild (Ca2+: between 1.90 and 2.10 mmol/L) or severe (Ca2+: <1.90 mmol/L), while hypercalcaemia severity was classified as mild (Ca2+: between 2.47 and 3.00 mmol/L), moderate (Ca2+: between 3.01 and 3.50 mmol/L), or severe (Ca2+: >3.50 mmol/L). 

The investigators performed a multivariate Cox regression analysis to examine the relationship of hypocalcaemia and/or hypercalcaemia with the clinical outcomes, namely all-cause mortality and cardiovascular events. 

Of the patients, 169 (42.2 percent) had hypocalcaemia and 94 (23.5 percent) had hypercalcaemia. Patients with CKD stage 5 showed a higher prevalence of severe hypercalcaemia than those with CKD stage 4 (40.5 percent vs 25.9 percent; p=0.004). [Singapore J Med 2024;65:421-429] 

Multivariate analysis, after adjustments, revealed no significant association between hypocalcaemia or hypercalcaemia and all-cause mortality (p>0.05) or the occurrence of cardiovascular events (p>0.05). 

Vitamin D deficiency 

“Pertaining to hypocalcaemia, the prevalence among our study population was significantly higher than that reported in other studies,” the investigators said. 

In the literature, the reported prevalence of hypocalcaemia among dialysis patients was 15 percent to 25 percent, while another study in India reported hypocalcaemia episodes in 23.8 percent of CKD nondialysis patients. [Indian J Endocrinol Metab 2016;20:460-467; BMC Nephrol 2012;13:116; Am J Kidney Dis 2008;52:519-530] 

“Potential reasons for this differing finding may be due to higher rates of vitamin D insufficiency in our study population (median 25-hydroxyl vitamin D level: 17.6 ng/mL),” the investigators said. “Vitamin D plays an important role in the regulation of CKD-MBD parameters, as vitamin D deficiency may worsen hypocalcaemia and lead to a compensatory increase in intact parathyroid hormone.” 

On the other hand, hypercalcaemia prevalence in the current study was lower than that seen among Chinese dialysis patients, but similar to that of CKD nondialysis patients in India and the US. 

In previous studies, hypercalcaemia prevalence ranged from 30 percent to 40 percent among dialysis patients and from 5 percent to 27 percent among CKD nondialysis patients. [Indian J Endocrinol Metab 2016;20:460-467; BMC Nephrol 2012;13:116; Clin J Am Soc Nephrol 2010;5:468-476] 

“Hypercalcaemia among CKD patients may be attributed to the use of vitamin D supplementation,” the investigators said. “Recent meta-analyses have supported the positive association between vitamin D usage and the risk of development of hypercalcaemia.” [Nephrology (Carlton) 2015;20:706-714; PLoS One 2013;8:e61387]   

“CKD-MBD is a complication of CKD involving derangements in serum calcium and phosphate,” according to the investigators.