Altered renal calcium handling in hypercalcemia of malignancy

Katherine R. Tuttle, Robert T. Kunau, Nigel Loveridge, Gregory R. Mundy

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


It has been controversial whether increased renal tubular calcium reabsorption contributes to hypercalcemia in patients with malignancies. Moreover, whether this abnormality is associated with volume depletion, a parathyroid hormone-like effect, or other mechanisms has not been clarified. Eight consecutive patients with hypercalcemia due to a variety of tumor types were studied in detail. The glomerular filtration rate (iothalamate clearance) was reduced in all patients (0.98 ± 0.10 (mean ± SE) mL/ s·173 m2; P<0.001) compared with normal controls (N=9) (1.93 ± 0.08 mL/s·1.73 m2), but it was similar to that in controls matched for renal insufficiency (N = 6) (1.15 ± 0.05 mL/s·1.73 m2). During hypercalcemia produced by calcium infusion, urinary calcium excretion (millimoles of calcium per liter of glomerular filtrate) was increased in controls with renal insufficiency compared to those with normal renal function (P= 0.028). In all patients with hypercalcemia of malignancy, urinary calcium excretion was decreased compared with controls with renal insufficiency, but it was low in only five of eight patients compared with normal controls. Extracellular fluid volume (iothalamate volume of distribution) was not decreased in any patient, and urinary cAMP and/ or plasma parathyroid hormone-like bioactivity were increased in six of eight patients. After treatment with an inhibitor of bone resorption, aminopropylidene 1,1 diphosphonate, abnormal renal calcium handling was not detected if the serum calcium normalized. It was concluded that increased renal tubular calcium reabsorption was consistently present in patients with hypercalcemia of malignancy compared with controls matched for renal insufficiency, but the proportion with the abnormality was underestimated if normal controls were used. Because volume depletion was not observed and parathyroid hormone-like activity was not always demonstrated, hypercalcemia perse or other humoral factors may alter renal calcium handling.

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalJournal of the American Society of Nephrology
Issue number2
StatePublished - Aug 1991
Externally publishedYes


  • Extracellular fluid volume
  • Glomerular filtration rate
  • Renal tubular calcium reabsorption
  • Urinary calcium excretion

ASJC Scopus subject areas

  • Nephrology


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