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Increasing incidence of steroid resistant rejection in kidney transplantation
Increasing Incidence of Steroid Resistant Rejection in Kidney Transplantation L. Arrazola, H. Sozen, A. Humar, V. Papalois, M. Uknis, and A.J. Matas
F
OR THE LAST 15 years, the outcome of kidney transplantation have steadily improved. In the 1960s the 1-year graft survival for cadaver donor (CAD) and living donor (LD) recipients were 30% and 50%, respectively. However, in the 1990s, 86% of CAD and 93% of LD recipients have a functioning graft at 1-year posttransplant. These higher graft and patient survival rates have been associated with a parallel drop in the incidence of acute rejection (AR). Whether these episodes of rejection are more or less resistant to steroid therapy remains to be determined. To help answer this question, we studied the incidence of AR and steroid resistant rejection (SRR) in 1777 primary adult kidney transplants performed at the University of Minnesota between 1985 and 1998. We compared three eras. In era 1 (1/1/85–1/31/90) we did 366 LD and 330 CAD transplants. Immunosuppression for LD consisted of prednisone (PRE), cyclosporine (CsA), and azathioprine (AZA); for CAD, Minnesota antilymphocyte globulin (MALG), PRE, CSA, and AZA. In era 2 (1/1/91– 12/31/94) we did 313 LD and 210 CAD transplants. Immunosuppression for LD did not change except for maintaining higher CsA blood levels. For CAD, MALG was substituted by ATGAM. In era 3 (1/1/95–12/31/98) we did 354 LD and 204 CAD transplants. Higher CsA levels were targeted. The incidence of AR for CAD recipients in era 1,
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 32, 1767 (2000)
2, and 3 was 32%, 24% and 12%, respectively (P ⬍ .001); For LD recipients, 24%, 15%, and 11%, respectively (P ⬍ .001). The incidence of SRR for CAD recipients in era 1, 2, and 3 was 18%, 20%, and 8%, respectively (P ⬍ .001); for LD recipients, 19%, 24%, and 14%, respectively (P ⬍ .001). The percentage of acute rejection episodes that were steroid resistant in era 1, 2, and 3 for CAD recipients was 33%, 50%, and 48%, respectively (P ⬍ .069) and for LD recipients was 29%, 53%, and 43%, respectively (P ⬍ .009). In summary, we observed a significant decrease in the incidence of AR in primary CAD and LD kidney transplants. However, a higher percentage of these acute rejection episodes are now steroid resistant; this is most notable for living donor recipients. The use of more potent immunosuppressive drugs as well as modifications in the protocols has led to this drop in the incidence of A R. However, recipients who break through the newer protocols with an acute rejection episode are more likely to have steroidresistant rejection.
From the Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA. Address reprint requests to Luis Arrazola, MD, Box 328 Mayo, 420 Delaware Street SE, Minneapolis, Minnesota 55455.
0041-1345/00/$–see front matter PII S0041-1345(00)01384-1 1767
F
OR THE LAST 15 years, the outcome of kidney transplantation have steadily improved. In the 1960s the 1-year graft survival for cadaver donor (CAD) and living donor (LD) recipients were 30% and 50%, respectively. However, in the 1990s, 86% of CAD and 93% of LD recipients have a functioning graft at 1-year posttransplant. These higher graft and patient survival rates have been associated with a parallel drop in the incidence of acute rejection (AR). Whether these episodes of rejection are more or less resistant to steroid therapy remains to be determined. To help answer this question, we studied the incidence of AR and steroid resistant rejection (SRR) in 1777 primary adult kidney transplants performed at the University of Minnesota between 1985 and 1998. We compared three eras. In era 1 (1/1/85–1/31/90) we did 366 LD and 330 CAD transplants. Immunosuppression for LD consisted of prednisone (PRE), cyclosporine (CsA), and azathioprine (AZA); for CAD, Minnesota antilymphocyte globulin (MALG), PRE, CSA, and AZA. In era 2 (1/1/91– 12/31/94) we did 313 LD and 210 CAD transplants. Immunosuppression for LD did not change except for maintaining higher CsA blood levels. For CAD, MALG was substituted by ATGAM. In era 3 (1/1/95–12/31/98) we did 354 LD and 204 CAD transplants. Higher CsA levels were targeted. The incidence of AR for CAD recipients in era 1,
© 2000 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 32, 1767 (2000)
2, and 3 was 32%, 24% and 12%, respectively (P ⬍ .001); For LD recipients, 24%, 15%, and 11%, respectively (P ⬍ .001). The incidence of SRR for CAD recipients in era 1, 2, and 3 was 18%, 20%, and 8%, respectively (P ⬍ .001); for LD recipients, 19%, 24%, and 14%, respectively (P ⬍ .001). The percentage of acute rejection episodes that were steroid resistant in era 1, 2, and 3 for CAD recipients was 33%, 50%, and 48%, respectively (P ⬍ .069) and for LD recipients was 29%, 53%, and 43%, respectively (P ⬍ .009). In summary, we observed a significant decrease in the incidence of AR in primary CAD and LD kidney transplants. However, a higher percentage of these acute rejection episodes are now steroid resistant; this is most notable for living donor recipients. The use of more potent immunosuppressive drugs as well as modifications in the protocols has led to this drop in the incidence of A R. However, recipients who break through the newer protocols with an acute rejection episode are more likely to have steroidresistant rejection.
From the Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA. Address reprint requests to Luis Arrazola, MD, Box 328 Mayo, 420 Delaware Street SE, Minneapolis, Minnesota 55455.
0041-1345/00/$–see front matter PII S0041-1345(00)01384-1 1767