Persistent secondary hyperparathyroidism and vertebral fractures in kidney transplantation: Role of calcium-sensing receptor polymorphisms and vitamin D deficiency

Abstract

Bone morbidity remains a major problem even after successful renal transplantation. We investigated the role of calcium-sensing receptor (CaSR) polymorphisms and 25-hydroxyvitamin D levels on the persistence of secondary hyperparathyroidism (SHPT) and their relationships with vertebral fractures (VFx) in 125 renal allograft recipients transplanted 44 AE 23 months before. All patients underwent evaluation of the main biochemical parameters of calcium metabolism as well as vertebral and femoral bone density. In 87 patients, CaSR polymorphisms (A986S, R990G, and Q1011E) also were assessed. X-ray images of the lateral spine were obtained in 102 subjects to perform vertebral morphometry. High parathyroid hormone (PTH) and 25-hydroxyvitamin D lower than 80 nmol/L were found in 54% and 97% of patients, respectively, with 40% of these showing vitamin D levels lower than 30 nmol/L. VFx were detected in 57% of the subjects. After multiple adjustments, 25-hydroxyvitamin D, age, and hemodialysis duration, but not CaSR polymorphisms, were found to be significant predictors of high PTH, whereas age and time since transplant were positively related with lower 25-hydroxyvitamin D values. PTH and time since transplant were significantly associated with VFx. Patients with two or more VFx showed serum PTH levels 50% higher than patients without fractures. We therefore conclude that persistent SHPT is a very common feature after renal transplantation and that, unlike CaSR polymorphisms, low 25-hydroxyvitamin D is involved in its pathogenesis. High PTH levels, in turn, are associated with an increased VFx risk, which confirms the need for strategies aimed at lowering serum PTH in this setting as well. ß

Polimorfismo A986S del receptor sensor del calcio y fracturas clínicas osteoporóticas

“…This possible relationship has been analysed in other populations. Thus, Gianini et al 18 , studied 87 women subject to renal transplant and with persistent secondary hyperparathyroidism and found negative results similar to our group. Recently, an Italian group studied risk factors for vertebral fractures in a population with primary hyperparathyroidism.…”

Kidney Transplantation with Early Corticosteroid Withdrawal

“…Data from our group and others suggest that the KDIGO guidelines may require revisiting and modification. In recipients managed with corticosteroids, both low 33 and high [34][35][36] PTH concentrations correlated with post-transplantation bone loss by DXA, and Giannini et al 37 found that each 1-pg/ml higher increment in PTH was associated with a significant 1% increased odds of vertebral fracture. These data suggest that optimal target levels of PTH and BTMs, based on fracture outcomes, need to be defined, that measurement of areal BMD should be obtained in kidney transplant recipients (regardless of whether they are managed with corticosteroids), and that the forearm may be the best site to assess BMD in recipients managed with ECSW.…”

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

“…Steroids directly worsen bone formation by impaired genesis and increased apoptosis of osteoblasts and enhanced osteoclastogenesis through an increased RANKL/OPG ratio [30] . Both cyclosporin and tacrolimus similarly promote bone loss via direct osteoclast activation [58] , but sirolimus is administered as a bone-sparing immunosuppressive agent due to its capability to inhibit osteoclast generation [57,59] .…”