Ahmedabad tolerance induction protocol and chronic renal allograft dysfunction: pathologic observations and clinical implications

<p>Abstract</p> <p>Background</p> <p>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 transplantatio...

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Bibliographic Details
Main Authors: Trivedi Hargovind L, Shah Pankaj R, Aziz Feroz A, Vanikar Aruna V, Patel Rashmi D
Format: Article
Language:English
Published: BMC 2009-01-01
Series:Diagnostic Pathology
Online Access:http://www.diagnosticpathology.org/content/4/1/4
Description
Summary:<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Materials and methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>Chronic immune injury was less with ATIP vs controls as compared to a higher incidence of chronic calcineurin inhibitor toxicity in the former.</p>
ISSN:1746-1596