E8

Table E8.1. Percent of kidney transplant recipients with an acute rejection episode who do not develop chronic rejection

% Chronic Rejection-Free Living Donor Cadaver Donor

1 Rejection Episode 88% 86%

>1 Rejection Episode 44% 46%

rejection episode were divided by their histopathologic assessment: mild, moderate, or severe tubular infiltrate with or without a vascular component.3 Those with a mild or moderate infiltrate but without a vascular component (n=164) had a 17% incidence of biopsy-proven chronic rejection and a 78% five-year graft survival rate. In contrast, those with a severe infiltrate or with a vascular component (n=65) had a 27% incidence of biopsy-proven chronic rejection (p=0.02) and a 64% five-year graft survival rate (p=0.005).

Other measures of the severity of the rejection episode (e.g., changing glomerular filtration rate, steroid-sensitive vs. -resistant, and lack of return of creati-nine to baseline) have also been associated with worse outcome.1

Thus, kidney transplant recipients with each of these characteristics could be targeted for changes in immunosuppressive therapy. Prospective studies are necessary to determine whether such changes will result in a decreased incidence of chronic rejection.

The role of noncompliance in recipients with multiple rejection episodes or late rejection needs to be considered. Noncompliance is discussed elsewhere in this volume. In our series of kidney transplant recipients, noncompliance was increased in recipients with late acute rejection episodes and in those with >1 acute rejection episodes (that is, the two groups at greatest risk for chronic rejection). Other investigators have noted this same finding. Thus, noncompliance should be considered in all recipients with rejection. Only if noncompliance is suspected can appropriate attempts at intervention take place.

While the above discussion on the relationship between acute and chronic rejection is concerned specifically with kidney transplant recipients, similar findings may or may not hold true for other organ transplant recipients. For example, chronic rejection after liver transplantation is relatively uncommon with modern day immunosuppression, and there is no good data to support a significant association between acute rejection episodes and eventual development of chronic rejection in these patients.

Pancreas transplant recipients, however, show a very strong association between episodes of acute rejection and eventual graft loss to chronic rejection 4. Short-term results with pancreas transplants have improved dramatically in the last 10 years due to improvements in surgical techniques and immunosuppressive agents. As an increasing number of grafts continue to function beyond the first year posttransplant, chronic rejection is becoming the major cause of graft loss in these cases. Chronic rejection in pancreas transplant recipients is defined by a typical clinical course coupled with characteristic histologic findings. The clinical course is characterized by a gradual deterioration in pancreas graft function beginning at least 2 months posttransplant. The exocrine component is usually affected first (manifested by falling urine amylase levels in bladder-drained grafts), followed by the endocrine component (manifested by episodes of hyperglycemia and the need for insulin therapy). Histologically, the process is characterized by arteriopathy with concentric narrowing of the small vessels and parenchymal fibrosis with atrophy of acini.

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