title: Ahmedabad tolerance induction protocol and chronic renal allograft dysfunction: pathologic observations and clinical implications.
abstract: BACKGROUND
  Chronic Renal Allograft Dysfunction (CRAD) is responsible for a large number of graft failures. We have abrogated acute T-cell rejections using Ahmedabad Tolerance Induction Protocol (ATIP) with hematopoietic stem cell transplantation (HSCT) under non-myeloablative conditioning pre-transplant. However B-cell mediated rejections and CRAD continue to haunt us. We carried out retrospective analysis of renal allograft biopsies performed in the last 4 years to evaluate the effect of ATIP on CRAD.
  
  
  METHODS
  Biopsies diagnosed as per modified Banff criteria belonged to 2 groups: ATIP under low dose immunosuppression of cyclosporine/Azathioprine/Mycofenolate mofetil+ Prednisolone, subjected to donor leucocyte transfusion, anti-T/B cell antibodies, low dose target specific irradiation, cyclophosphamide, cyclosporin followed by HSCT pre-transplant; controls who opted out of ATIP were transplanted under standard triple drug immunosuppression. Demographics of both groups were comparable.
  
  
  RESULTS
  Incidence of chronic changes was higher in controls (17.5%) vs. 10.98% in ATIP over a mean follow up of 151.9 months in the former and 130.9 months in the latter. Proteinuria and hypertension were higher in controls (48.4%) vs. ATIP (32.7%) with chronic transplant glomerulopathy, focal global sclerosis in 67.7% in controls vs. 46.7% in ATIP, acute on chronic T/B cell rejection in 51.6% controls vs. 28.1% ATIP, with peritubular capillary C4d deposits in 19.4% controls vs. 1.9% ATIP biopsies. Acute on chronic calcineurin inhibitor toxicity was higher in ATIP (71.9%) vs. 48.4% in controls.
  
  
  CONCLUSIONS
  Chronic immune injury was less with ATIP vs controls as compared to a higher incidence of chronic calcineurin inhibitor toxicity in the former.
authors.affiliation: Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases, Ahmedabad, India. rashmi381@yahoo.co.in
authors.forename: Rashmi D
authors.initials: RD
authors.lastname: Patel
authors.forename: Aruna V
authors.initials: AV
authors.lastname: Vanikar
authors.forename: Feroz A
authors.initials: FA
authors.lastname: Aziz
authors.forename: Pankaj R
authors.initials: PR
authors.lastname: Shah
authors.forename: Hargovind L
authors.initials: HL
authors.lastname: Trivedi