A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

Abstract

Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m(2) The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.

Keywords: calcium; hyperparathyroidism; renal transplantation.

Figure 1.

The iPTH decline early after subtotal parathyroidectomy was higher than 75%. Assessment of iPTH decline early after subtotal parathyroidectomy. iPTH was measured at baseline and 10 minutes after surgery to assure that enough parathyroid gland tissue had been removed.

Figure 2.

Subtotal parathyroidectomy was associated with a higher proportion of patients achieving normocalcemia and iPTH normalization. (A) Serum calcium, (B) iPTH, and (C) phosphate evolution in the cinacalcet and subtotal parathyroidectomy groups. Both treatments was associated with correction of calcium and phosphate, although the reduction of iPTH was greater in the parathyroidectomy group than in the cinacalcet group.

Figure 3.

There was some degree of eGFR loss in the cinacalcet and subtotal parathyroidectomy groups. eGFR at baseline and month 12 in the cinacalcet and subtotal parathyroidectomy groups. Decline in renal function was greater in the cinacalcet group than in the parathyroidectomy group.

Figure 4.

Vascular calcification score remained unchanged in the cinacalcet and subtotal parathyroidectomy groups. A representative patient to assess changes in vascular calcification. Unenhanced CT scan at the level of the aortic arch in the same patient at (A) baseline, (B) 6 months, and (C) 12 months. Multiple plaques are seen (arrows), with no variation during the follow-up. Calcification value at this level was three at all three time points.