Ectopic soft tissue calcium deposition following liver transplantation

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Abstract
We observed ectopic soft tissue calcification affecting seven patients following orthotopic liver transplantation. The cause of such calcification is unknown, but potential pathogenetic factors include hyperparathyroidism, calcium administered during and following surgery, renal failure, acid-base changes and citrate in fresh frozen plasma. To investigate some of the mechanisms underlying ectopic calcification following liver transplantation, we determined preoperative levels of ionized serum calcium, phosphate, magnesium, parathyroid hormone (midmolecule assay) and 1,25-(OH)2 vitamin D in 20 patients who underwent 24 liver transplants. In addition, these parameters were measured weekly in 15 patients during the first month after liver transplantation. Preoperatively, 5 of the 20 patients had elevated serum levels of parathyroid hormone, and 9 others had low levels of 1,25-(OH)2 vitamin D. After liver transplantation, ectopic calcification was found in seven patients (47%). The organs affected in order of frequency were lungs, liver graft, colon, vascular walls, kidneys, adrenal glands and gastric mucosa. One patient with ectopic calcification of both lungs had markedly restricted pulmonary function as well as radiologic evidence of osteopenia and pathologic fractures of three vertebrae. Postoperatively, increased parathyroid hormone levels were found in all patients who developed soft tissue calcification. Parathyroid hormone levels peaked during the second week after transplantation and were higher at all times compared to subjects without calcification. Five of the seven patients with ectopic calcification had associated renal failure. Individuals who developed calcification had received significantly more fresh frozen plasma, red blood cells and elemental calcium postoperatively, but showed no difference in serum levels of calcium, magnesium, vitamin D, total plasma CO2 or phosphate levels when compared to patients without calcification. We conclude that multiorgan ectopic soft tissue calcification may complicate the postoperative course following liver transplantation. In one patient, calcifications were associated with respiratory insufficiency and bone fractures. Renal failure, secondary hyperparathyroidism and large amounts of transfused blood-derived products appear to be major factors associated with ectopic calcification. We speculate that renal failure and the citrate contained in massive fresh frozen plasma transfusions lead to transient hypocalcemia, which in turn stimulates parathyroid hormone secretion and secondary hyperparathyroidism. Under these conditions, local tissue injury and concomitant administration of exogenous calcium may result in soft tissue calcium deposition.