title: Sequential protocol biopsies from renal transplant recipients show an increasing expression of active TGF beta.
abstract: Chronic allograft nephropathy (CAN) is a major cause of graft loss after renal transplantation. Implicated in the pathogenesis of this complication is overproduction of the cytokine transforming growth factor beta (TGF beta). In this study we measured changes in CAN's expression in stable patients early after transplantation, and studied links with established risk factors for CAN, such as delayed graft function, acute rejection, and cyclosporine exposure. We took biopsies from 40 renal allografts at time of transplantation (pre-perfusion), and then, using ultrasound guidance, at 1 week and 6 months after transplantation. An immunofluorescence technique was used to stain sections for active TGF beta. These were then assessed by semi-quantitative scanning laser confocal microscopy. There was very little variation in active TGF-beta expression among patients in their pre-perfusion biopsies. Expression had increased by 1 week and then very significantly by 6 months ( P<0.0001). Patients who suffered delayed graft function had increased TGF-beta expression at both time points. There was no difference regarding donor type, acute rejection, and immunosuppressive drug (cyclosporine or tacrolimus). There was no correlation between the amount of TGF-beta expression at any time-point and isotope glomerular filtration rate (GFR) at 12 months. This study demonstrated that in a group of stable renal allograft recipients, TGF-beta expression in the kidney increased after transplantation. As the study used protocol biopsies, this increase is unlikely to be due to acute events, and probably represents a genuine increase.
authors.affiliation: University Department of Surgery, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK. sj34@le.ac.uk
authors.forename: Sunjay
authors.initials: S
authors.lastname: Jain
authors.forename: Mostafa A S
authors.initials: MA
authors.lastname: Mohamed
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sandford
authors.forename: Peter N
authors.initials: PN
authors.lastname: Furness
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nicholson
authors.forename: David
authors.initials: D
authors.lastname: Talbot
mesh_terms: D000328:Adult; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006085:Graft Survival / Q000502:physiology; D006146:Guanidines / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D019520:Living Donors; D008297:Male; D013997:Time Factors; D014019:Tissue Donors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D006146:Guanidines; D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; C037258:gusperimus