NEW ADVANCES IN THE MOLECULAR BIOLOGY OF ISCHEMIA/REPERFUSION: MAPK PATHWAYS

Elevated levels of intact parathyroid hormone (iPTH) are not uncommon after renal transplantation, and this disturbance may affect renal allograft function. This study investigated whether iPTH levels were related to histopathological findings of acute rejection in kidney graft biopsies. Thirty-eight renal transplant recipients (29 males, nine females; mean age 29.5±10.3years) were studied. Renal allograft biopsy was performed in each case to investigate increased creatinine levels. Lymphocyte and macrophage infiltration of the interstitium was evaluated immunohistochemically with monoclonal antibodies to CD3 and CD68. Expression of HLA-DR and fibronectin were also studied. The proportion of interstitial cell staining was graded semiquantitatively. Serum calcium, phosphorus and iPTH levels before and after the renal transplantation were compared. Patients were grouped according to their stabilized iPTH levels at 3 months post-transplantation. Group I ( n =13) exhibited persistently elevated iPTH levels (levels elevated since surgery), and Group II ( n =25) showed persistently low-normal iPTH levels. The mean age of the Group I patients was significantly lower, and their serum calcium levels post-transplantation were significantly higher than those in Group II ( P =0.02 and P =0.03, respectively). Persistent elevation of iPTH was strongly associated with interstitial T-cell density, macrophage density, and glomerular fibronectin expression in the renal allograft biopsies ( P <0.05). Also, the time to fibrosis was significantly shorter in Group I ( P =0.02). The study revealed that PTH has a potent immunomodulatory effect, and that persistent hyperparathyroidism has a significant impact on renal allograft outcome. The data indicate that the serum iPTH level is a valuable indicator of immune response, and that regular monitoring of serum iPTH levels is essential after renal transplantation.