Bisphosphonate versus non-bisphosphonate treatment for hypercalcemia of malignancy in patients with renal dysfunction

Background: Bisphosphonates are the backbone of treatment for hypercalcemia of malignancy (HCM). However, concern regarding their safety in patients with renal dysfunction exists. The safety and effectiveness of bisphosphonates compared to other treatment options for HCM in the setting of renal dysfunction have not been evaluated. Methods: A retrospective cohort analysis of adult patients with HCM and renal dysfunction defined as a creatinine clearance (CrCl) <60 mL/min who received front-line bisphosphonate versus non-bisphosphonate therapy from 1/2015 to 4/2021 was conducted. The primary endpoint was the incidence of all-grade serum creatinine (SCr) elevation from baseline by day 30 from initial HCM-directed therapy. A multivariate logistic regression was conducted to examine predictors of worsening renal function. Results: Of 129 patients, 111 (86%) patients received bisphosphonates and 18 (14%) received non-bisphosphonate first-line HCM-directed therapy. All-grade SCr elevation occurred similarly between bisphosphonate and non-bisphosphonate groups, 27.9% versus 27.8% respectively ( p = 0.99). Receipt of bisphosphonates did not significantly impact the incidence of all-grade SCr elevation ( p = 0.195) while chronic kidney disease (CKD) at baseline did ( p = 0.003). Conclusions: Bisphosphonates appear to be as safe as non-bisphosphonate therapy in patients with baseline renal dysfunction for the treatment of HCM.