BACKGROUND: This paper reports the histopathologic results of 2-year protocol biopsies from patients who were enrolled in the U.S. FK506 kidney transplant study . METHODS:Recipients of cadaveric kidney transplants were randomized to tacrolimus or cyclosporine therapy. Patients active in the trial at 2 years after transplantation were approached for a protocol biopsy. Biopsies were scored by the Banff classification in a blinded fashion by one pathologist. RESULTS: A total of 144 patients (41.3% of those active at 2 years) had a 2-year protocol biopsy performed; 79 patients were treated withtacrolimus and 65 patients were treated with cyclosporine. Evidence of acute rejection was found in seven (8.9%) of the 2-year biopsies in tacrolimus-treated patients and six (9.2%) cyclosporine-treated patients. Chronic allograft nephropathy was found in 49 (62.0%) tacrolimus biopsies and 47 (72.3%) cyclosporine biopsies (P=0.155). There were no apparent histopathologic differences between the tacrolimus and cyclosporine biopsies. The occurrence of chronic allograft nephropathy was significantly higher in patients who received a graft from an older donor (P<0.01), who experienced presumed cyclosporine or tacrolimus nephrotoxicity (P<0.001), who developed a cytomegalovirus infection (P=0.038), or who experienced acute rejection in the first year after transplantation (P=0.045). A multivariate analysis showed that nephrotoxicity and acute rejection were the most significant predictors for chronic allograft nephropathy. CONCLUSIONS: The occurrence of histologic acute rejection was rare at 2 years, confirming the absence of subclinical acute rejection in these late biopsies. A majority of the biopsies showed features consistent with chronic allograft nephropathy that was associated with acute rejection (particularly in cyclosporine-treated patients), nephrotoxicity, and cytomegalovirus infection in the first year. This suggests that nonimmunologic factors, such as drug-induced toxicity, may play an important role in chronic allograft nephropathy.
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BACKGROUND: This paper reports the histopathologic results of 2-year protocol biopsies from patients who were enrolled in the U.S. FK506 kidney transplant study . METHODS: Recipients of cadaveric kidney transplants were randomized to tacrolimus or cyclosporine therapy. Patients active in the trial at 2 years after transplantation were approached for a protocol biopsy. Biopsies were scored by the Banff classification in a blinded fashion by one pathologist. RESULTS: A total of 144 patients (41.3% of those active at 2 years) had a 2-year protocol biopsy performed; 79 patients were treated with tacrolimus and 65 patients were treated with cyclosporine. Evidence of acute rejection was found in seven (8.9%) of the 2-year biopsies in tacrolimus-treated patients and six (9.2%) cyclosporine-treated patients. Chronic allograft nephropathy was found in 49 (62.0%) tacrolimus biopsies and 47 (72.3%) cyclosporine biopsies (P=0.155). There were no apparent histopathologic differences between the tacrolimus and cyclosporine biopsies. The occurrence of chronic allograft nephropathy was significantly higher in patients who received a graft from an older donor (P<0.01), who experienced presumed cyclosporine or tacrolimus nephrotoxicity (P<0.001), who developed a cytomegalovirus infection (P=0.038), or who experienced acute rejection in the first year after transplantation (P=0.045). A multivariate analysis showed that nephrotoxicity and acute rejection were the most significant predictors for chronic allograft nephropathy. CONCLUSIONS: The occurrence of histologic acute rejection was rare at 2 years, confirming the absence of subclinical acute rejection in these late biopsies. A majority of the biopsies showed features consistent with chronic allograft nephropathy that was associated with acute rejection (particularly in cyclosporine-treated patients), nephrotoxicity, and cytomegalovirus infection in the first year. This suggests that nonimmunologic factors, such as drug-induced toxicity, may play an important role in chronic allograft nephropathy.
Authors: Darshika Chhabra; Anton I Skaro; Joseph R Leventhal; Pranav Dalal; Gaurav Shah; Edward Wang; Lorenzo Gallon Journal: Clin J Am Soc Nephrol Date: 2012-01-26 Impact factor: 8.237
Authors: A Basu; J L Falcone; H P Tan; D Hassan; I Dvorchik; K Bahri; N Thai; P S Randhawa; A Marcos; T E Starzl; R Shapiro Journal: Transplant Proc Date: 2007 Jan-Feb Impact factor: 1.066
Authors: Avram Z Traum; Tatsuo Kawai; Joseph P Vacanti; David H Sachs; A Benedict Cosimi; Joren C Madsen Journal: Pediatrics Date: 2008-06 Impact factor: 7.124
Authors: M D Pescovitz; J Rabkin; R M Merion; C V Paya; J Pirsch; R B Freeman; J O'Grady; C Robinson; Z To; K Wren; L Banken; W Buhles; F Brown Journal: Antimicrob Agents Chemother Date: 2000-10 Impact factor: 5.191
Authors: Daniel G Maluf; Valeria R Mas; Kellie J Archer; Kenneth Yanek; Eric M Gibney; Anne L King; Adrian Cotterell; Robert A Fisher; Marc P Posner Journal: Mol Med Date: 2008 May-Jun Impact factor: 6.354