Parathyroidectomy vs calcimimetics for treatment of persistent hyperparathyroidism after kidney transplantation

Ideally, a successful kidney transplantation corrects the abnormalities in mineral metabolism that, during uraemia, lead to secondary hyperparathyroidism (HPT) and renal osteodystrophy. This includes reversal of uraemia, abolition of hypocalcaemia, hyperphosphataemia and acidosis, and restoration of calcitriol production and reversal of skeletal resistance to parathyroid hormone (PTH) and vitamin D [1]. Elevated PTH levels persist in a significant number of renal transplant patients. In addition to its potential negative consequences on bone mineralization, persistent HPT might worsen hypercalcaemia, induce hypophosphataemia, and may be a risk factor for acute tubular necrosis in the renal allograft [2]. The incidence of hypercalcaemia after kidney transplantation is significant and varies between 8.5 and 65%. The natural evolution of hypercalcaemia after successful kidney transplantation is, however, in most cases a spontaneous resolution [3,4] and the pathogenesis of post-transplant hypercalcaemia is not necessarily due to persistent HPT. Several factors, such as resolution of soft tissue calcifications, immobilization, high doses of corticosteroids and hypophosphataemia, may all contribute to hypercalcaemia [4]. In the clinical situation, the majority of the patients with secondary HPT will, despite previous long-term uraemia, present a significant and gradual fall in plasma PTH after kidney transplantation. Some part of this fall might be due to clearance of C-terminal PTH fragments as a result of the improvement in the glomerular filtration rate (GFR), as the intact PTH assays, which have been used until recently, co-measure some long C-terminal PTH fragments [5]. In most cases, plasma PTH returns to near normal with time, although not all studies are confirmative [6]. The normalization of GFR seems, however, to be decisive for the normalization of the PTH levels [7]. In transplanted patients with reduced GFR, elevated PTH levels are to be expected, due to the degree of uraemia and, independently of whether the patients are transplanted or not. The risk for developing posttransplant HPT increases with the duration of dialysis [3,8] and with the severity of the pre-transplant HPT [8,9]. Among kidney-transplanted patients, between 1.3 and 20% (on average 5%) will later require parathyroidectomy (PTX) [3,4,7,10]. The general criteria for PTX after kidney transplantation are in most centres symptomatic or asymptomatic hypercalcaemia with inappropriately elevated levels of PTH, one or more years after a successful kidney transplantation resulting in normal kidney function [3,4]. The degree of parathyroid hyperplasia is believed to determine the ability of the parathyroid glandular function to involute after transplantation [11]. One would expect patients requiring PTX to have the most severe changes of the parathyroid glands, such as monoclonal nodular hyperplasia.