What is the relationship between hypercalcemia and Acute Kidney Injury (AKI)?

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Last updated: April 16, 2025View editorial policy

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From the Guidelines

Hypercalcemia can cause acute kidney injury (AKI) and should be promptly treated with aggressive intravenous fluid resuscitation and loop diuretics to enhance calcium excretion, as recommended by recent clinical guidelines 1. The initial management of hypercalcemia-induced AKI should focus on restoring intravascular volume and promoting calcium excretion. This can be achieved through:

  • Aggressive intravenous fluid resuscitation with normal saline at 200-300 mL/hour to restore intravascular volume and enhance calcium excretion
  • Administration of loop diuretics like furosemide 20-40 mg IV to promote calcium excretion, but only after volume status is restored For moderate to severe hypercalcemia (calcium >12 mg/dL), bisphosphonates such as zoledronic acid 4 mg IV or pamidronate 60-90 mg IV should be given, with effects beginning within 24-48 hours and lasting for weeks 1. In life-threatening cases, calcitonin 4 IU/kg SC every 12 hours can provide rapid but temporary calcium reduction. Simultaneously, the underlying cause of hypercalcemia must be identified and treated, whether it's primary hyperparathyroidism, malignancy, or medication effects, as highlighted in the K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease 1. Hypercalcemia causes AKI through renal vasoconstriction, decreased glomerular filtration rate, and tubular dysfunction from calcium deposition, as well as impairing the kidney's concentrating ability, leading to polyuria and volume depletion, which further worsens kidney function. Monitoring serum calcium, renal function, and electrolytes is crucial during treatment, and nephrology consultation should be considered for severe or refractory cases, with close attention to electrolyte abnormalities, such as hypophosphatemia, hypokalemia, and hypomagnesemia, which are common in patients with AKI or CKD 1.

From the Research

Hypercalcemia and AKI

  • Hypercalcemia can result in acute kidney injury (AKI) due to various mechanisms, including excessive bone resorption, renal calcium retention, and excessive intestinal calcium absorption 2.
  • The association of AKI and hypercalcemia is often related to comorbidities such as cancer, multiple myeloma, hyperparathyroidism, sarcoidosis, vitamin D intoxication, and leprosy 2.
  • Treatment of hypercalcemia-induced AKI typically involves hydration, loop diuretics, and calcitonin, with the goal of reducing serum calcium levels and improving renal function 3, 2.

Treatment Options

  • Intravenous bisphosphonates, such as pamidronate or zoledronic acid, are effective in treating hypercalcemia and may be considered as a first-line treatment for hypercalcemic AKI 4.
  • Loop diuretics may be used to enhance renal excretion of calcium and prevent fluid overload, but their use should be carefully monitored to avoid volume depletion and worsening of AKI 3, 5.
  • Dialysis may be reserved for severe cases of hypercalcemia complicated by kidney failure 3.

Clinical Considerations

  • The severity of hypercalcemia and AKI should be assessed using criteria such as dehydration, mental status alteration, renal impairment, cardiac arrhythmias, and ionized calcium level 6.
  • Monitoring of neurological status, arterial blood pressure, cardiac pulses, oxygen saturation, and temperature is crucial in patients with hypercalcemic AKI 6.
  • Recognition and treatment of the underlying disease are essential in managing hypercalcemia and AKI, and a short diagnostic program should be initiated to guide appropriate treatment 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Acute renal failure and hypercalcemia.

Renal failure, 2006

Research

Hypercalcemia: an evidence-based approach to clinical cases.

Iranian journal of kidney diseases, 2009

Research

Treatment of acute hypercalcemia.

Medicinal chemistry (Shariqah (United Arab Emirates)), 2012

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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