#NKFClinicals 2018: Hypercalcemia of Malignancy

Renal Emergencies in the Cancer Patient: A Case-Based Session (April 13, 2018)

Presenter: Rimda Wanchoo (@renalmyeloma)

This complication occurs in up to 30% of patients with cancer.

There are four main mechanisms of hypercalcemia of malignancy (HOM):

  1. Humoral hypercalcemia of malignancy: This is the most common cause of HOM, accounting for 80% of the cases. PTHrP stimulates bone resorption and stimulates Ca absorption in the kidney. Interestingly, I learnt that PTH and PTHrP are very similar. PTH binds to PTHrP strongly and PTHrP binds to the same receptor with a low affinity. Both activate osteoclasts and increase bone resorption. Both increase absorption in the kidney of calcium and phos excretion. The main difference is that while PTH increases 1,25 vitamin D production, PTHrP has no effect on 1,25 production. In the GI tract as well, PTH increases Ca absorption in the ileum while PTHrP has no effect. Breast and lung cancers are the most common cancers producing PTHrP.
  2. Local osteolytic hypercalcemia: This is the second most common cause of HOM (15% of cases); destruction of bone via osteoclasts.
  3. Vitamin D-mediated 1,25 –dihydroxy vitamin D: Classically seen in lymphomas; response to steroids is amazing.
  4. Ectopic PTH: The rarest form, this is usually seen in small cell lung cancer.

Treatment options include IV hydration, stopping calcium meds, goal UO of 150-200 cc/hr, and furosemide only if volume overloaded.

  • Calcitonin: temporary measure
  • Corticosteroids: mainly for lymphomas and 1,25 vitamin D-mediated process
  • Bisphosphanates: best long-term agents, act in 2-4 days. Inhibit osteoclast activity (inhibit mevalonate pathway/ATP-dependent metabolic pathway/disrupt the osteoclast cytoskeleton and induce apoptosis), similar reason to cause lytic tubular damage in the kidney cells
  • Pamidronate: renal side effect- collapsing GN, FSGS, or MCD
  • Zoledronate: renal side effect- ATN
  • Denosumab: anti RANK ligand and inhibits maturation of osteoclasts. Not nephrotoxic. FDA-approved now for HOM.

Figure 1 from Reagan et al, Kidney International

Treatment algorithm proposal: See Figure 2 from Rosner MH and Dalkin AC.

Overall concept map of the talk:


Key References: Reagan P et al, 2014; Rosner MH and Dalkin AC, 2012.

– Post prepared by Kenar Jhaveri, AJKD Social Media Advisory Board member. Follow him @kdjhaveri.

The NKF Spring Clinical Meeting abstracts are available in the April 2018 issue of AJKD. Check out more AJKDBlog coverage of #NKFClinicals!


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