Hypercalcemia of Malignancy and Malignancy-Associated Kidney Damage: A Comprehensive Narrative Review with Clinical Relevance

Abstract

Hypercalcemia of malignancy (HCM) is a common paraneoplastic syndrome occurring in 10–30% of patients with advanced cancer. It is associated with significant morbidity and poor prognosis. This narrative review examines the mechanisms of HCM, its clinical presentation, diagnostic approach, and current management strategies, with particular emphasis on the interplay with kidney damage. Renal impairment both results from and exacerbates hypercalcemia, creating a vicious cycle that complicates therapy. Evidence-based recommendations, including those from the 2023 Endocrine Society Clinical Practice Guideline, highlight the role of hydration, antiresorptive agents (bisphosphonates and denosumab), and treatment of the underlying malignancy. Multidisciplinary collaboration between oncologists and nephrologists is essential for optimizing outcomes in patients with concurrent acute kidney injury or chronic kidney disease. Early recognition and mechanism-specific therapy can reverse renal dysfunction in many cases and improve quality of life.