DIARRA Danielle

Parathyroid Hormone Resistance After Kidney Transplantation

Background: During progression of chronic renal failure different renal and non-renal factors lead to development of osseous PTH resistance. One major cause seems to be down-regulation of the PTH1/PTH related peptide receptor. Down-regulation of the PTH receptor can also be found in parathyroidectomized uremic rats and seems therefore to be unrelated to hyperparathyroidism. Although kidney transplantation leads to a near normal kidney function PTH resistance seems to persist after effective engraftment. In recent studies we found low-turnover renal osteodystrophy in patients with tertiary hyperparathyroidism, as well as a lack of response to recombinant PTH therapy. Resistance towards PTH, however, implies that iPTH levels should be higher in transplant recipients than in patients with native kidney disease, which, due the lack of adequate data, is not being recommended. Inadequately low PTH levels might lead to relative hypoparathyroidism and decreased bone turnover.

Aim of the study: The aim of this study is to evaluate the presence of PTH resistance in kidney transplant recipients. Furthermore, the necessary intact PTH levels needed for normal posttransplant bone formation shall be determined. <//span>

Significance: Identification of the optimal posttransplant intact PTH level may lead to a decrease in fracture incidence, thus positively influencing patient quality of life and possibly overall outcome.

Methods: Cross sectional analysis of patients with different stages of kidney transplant function. The primary endpoint is the evaluation of bone biopsies by histomorphometry, immunohistochemistry and quantitative real time PCR and correlation to iPTH levels. Secondary endpoints include: (1) Serum measurements of osteocalcin, bone alkaline phosphatase and c-telopeptide cross-links as surrogate parameters for osteoblast and osteoclast activity. (2) Dual-energy X-ray absorptiometry and high resolution CT to measure bone mineral density, volume and bone stability.

Methods and Skills:

histomorphometry; immune histochemistry; laser capture microdissection; clinical studies