Calcium Balance in Rhabdomyolysis and Acute Kidney Injury: A Biphasic Disease

Calcium homeostasis is closely regulated mainly by the parathyroid hormone (PTH) and to a lesser degree by the activated form of vitamin D. Primary hyperparathyroidism and underlying malignancy are the two most common causes of hypercalcemia. Few cases of rebound hypercalcemia have been reported in the recovery period of rhabdomyolysis-induced acute kidney injury (AKI) despite the relatively high incidence from up to one third of cases. Here we report a case of severe and symptomatic hypercalcemia in the recovery period of rhabdomyolysis and AKI with low PTH, PTH-related peptide (PTHrP) and 1,25-dihydroxycholecalciferol levels, and normal 25-hydroxycholecalciferol.

Case Description :

A 37-year-old Caucasian male was transferred to our hospital for management of a previous hand fracture. Severe traumatic rhabdomyolysis was discovered on previous hospitalization with subsequent AKI and temporary hemodialysis. Calcium balance reached a nadir of 5.7 mg/dl by third day, with decision for intravenous calcium administration. No electrocardiographic changes were documented during this time. On day 24 of the hospital stay, endocrinology was consulted for hypercalcemia of new onset with levels recorded at 17.3 mg/dl. The patient was complaining of severe thirst and fatigue. No abdominal pain, nephrolithiasis, bone pain, previous hypercalcemia or exposure to exogenous vitamin D was reported. General physical examination showed a thin male lying supine in bed, slightly confused, with dry mucous membranes and an otherwise normal examination.

Laboratory tests, correlating with a corrected calcium of 17.3 mg/dl, showed a PTH of 5.5 pg/ml, 25-hydroxycholecalciferol of 35 ng/ml, 1,25 dihydroxycholecalciferol of 9.9 pg/dl and PTHrP less than 2 pmol/l. Serum and urine protein electrophoresis was negative for monoclonal protein. Imaging with chest and abdomen CT scan were negative for lymphadenopathies or masses. Patient was treated aggressively with normal saline and subcutaneous calcitonin for 48 hours with full resolution of his hypercalcemia within 5 days of therapy.

Discussion :

In rhabdomyolysis-induced AKI there are different listed hypotheses why calcium balance can range from hypo, normo or hypercalcemia. There is evidence of calcium shifting freely from extracellular to intracellular space, and vice versa; and a decrease in hydroxylation of vitamin D to its active form secondary to kidney failure. In our case, PTH levels were obtained with the highest calcium recorded, and it was found appropriately low. Interestingly, the 1,25 dihydroxycholecalciferol levels were found low in the recovery period of the AKI, pointing to a less likely cause of rebound hypercalcemia.
Additionally, with only normal saline infusion and calcitonin administration, we were able to control his hypercalcemia. This brings up new perspectives when choosing modalities of therapy in this clinical scenario. Another important point is that we need to avoid aggressive hypocalcemia correction initially seen in this condition, unless electrocardiographic or neuromuscular irritability is present, although more studies are needed to verify this hypothesis and to what degree.