Sodium-Glucose Co-Transporter Protein 2 Inhibitors Induced Hypercalcemia: A Case Series and Literature Review

Masri, Dana El; Fares, Jocelyne; Jamil, Yasser

doi:10.1016/j.aace.2021.07.002

Cited by 3 publications

(2 citation statements)

References 17 publications

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“…Case reports have documented reversible hypercalcemia with sodium-glucose cotransporter protein 2 inhibitors, likely due to osmotic diuresis and volume contraction. Underlying risk factors (dehydration, high calcium intake, thiazides, acidosis, undiagnosed PHPT) were typically present . Estimates of the frequency are not available, but a meta-analysis of 25 RCTs indicated that the increase in serum calcium was not consistent with a meaningful change .…”

Section: Observations and Discussionmentioning

confidence: 99%

Hypercalcemia

Walker

Shane

2022

JAMA

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ImportanceHypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (&lt;3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (&gt;3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma.ObservationsApproximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (&lt;20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival.Conclusions and RelevanceMild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.

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Section: Observations and Discussionmentioning

confidence: 99%

Hypercalcemia

Walker

Shane

2022

JAMA

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“…To our knowledge, only three papers reviewed this subject in the available literature written in the English language. All of them are case reports and case series, with a total of five patients [ 2 ]. We present herein a case of primary hyperparathyroidism masked by the use of empagliflozin.…”

Section: Introductionmentioning

confidence: 99%

Masked Primary Hyperparathyroidism by Empagliflozin Use

Awada¹,

Melhem²,

Khalaf³

et al. 2022

Cureus

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Sodium-glucose cotransporter-2 inhibitors are drugs that regulate blood sugar by decreasing glucose reabsorption from the proximal renal tubules. Primary hyperparathyroidism masked by empagliflozin is very rare and only a few cases are reported in the literature. We report a case of a 57-year-old man with a known history of diabetes on empagliflozin for two years who presented with hypercalcemia and equivocal parathyroid hormone level. Upon cessation of this medication, he had persistent hypercalcemia with a raised parathyroid level, which confirmed the diagnosis of primary hyperparathyroidism. We believe this case is one of the first cases reported in the literature.

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SGLT2 inhibitors in peritoneal dialysis: a promising frontier toward improved patient outcomes

Stepanova

2024

Ren Replace Ther

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Peritoneal dialysis (PD) stands as an important modality among kidney replacement therapies for end-stage kidney disease, offering patients remarkable flexibility and autonomy. Despite its widespread use, challenges such as glucose-related complications, peritoneal membrane fibrosis, declining renal function, and cardiovascular risks persist, necessitating innovative therapeutic approaches. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, originally developed for treating type 2 diabetes mellitus, have recently shown promise as add-on therapy for patients with diabetic and non-diabetic chronic kidney disease (CKD), even in advanced stages. This review describes the potential role of SGLT2 inhibitors as a breakthrough therapeutic option in PD, emphasizing their ability to address unmet clinical needs and improve patient outcomes. The multiple effects of SGLT2 inhibitors in CKD, including metabolic modulation, antihypertensive, diuretic, anemia-reducing, antioxidant, and antiinflammatory properties, are reviewed in the context of PD challenges. Additionally, the potentially protective influence of SGLT2 inhibitors on the integrity of the peritoneal membrane and the transport of solutes and water in the peritoneum are emphasized. Despite these encouraging results, the paper highlights the potential risks associated with SGLT2 inhibitors in PD and emphasizes the need for cautious and thorough investigation of dosing, long-term safety considerations, and patient-specific factors through comprehensive clinical trials. Looking forward, the review argues for well-designed studies to evaluate the expanded safety profile of SGLT2 inhibitors in PD, with particular attention paid to peritoneal membrane integrity and overall patient outcomes.

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Sodium-Glucose Co-Transporter Protein 2 Inhibitors Induced Hypercalcemia: A Case Series and Literature Review

Cited by 3 publications

References 17 publications

Hypercalcemia

Hypercalcemia

Masked Primary Hyperparathyroidism by Empagliflozin Use

SGLT2 inhibitors in peritoneal dialysis: a promising frontier toward improved patient outcomes

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