survival for this group was 92%, suggesting that, in kidney transplantation, nonimmunologic factors are responsible for only a small percent of graft loss.

Numerous studies have demonstrated the association between acute rejection, chronic rejection, and graft loss.1,2 This data may suggest that eliminating acute rejection could potentially eliminate chronic rejection and much late graft loss. Certainly, there has been a significant decrease in the incidence of chronic rejection, which has paralleled a decrease in the acute rejection rates. With our current immunosuppressive regimens, rates for acute rejection have fallen below 10%; yet, a similar substantial decrease has not been seen in chronic rejection rates. Of 701 recipients transplanted at our center between 1992-1996, the 6-month incidence of acute rejection was 31%, and the 5-year incidence of chronic rejection was 15%. Amongst 741 recipients transplanted more recently, from 1997 to 2001, 6-month acute rejection rates had decreased to 8% (p=0.001) but 5-year chronic rejection rates had remained stable at 14% (p=ns). By multivariate analysis, however, acute rejection remained the major risk factor for the development of chronic rejection in both or these time groups. A number of possible factors may explain these findings. It is possible that we have reached the limits of our current pharmacologic immunosuppression with regards to acute rejection rates and total elimination of rejection may be associated with unacceptable morbidity and mortality. The absence of a more significant drop in the chronic rejection rate suggests either that non-immunologic factors are having more of an impact or that the consequences of breaking through on modern-day immunosuppression (i.e. having an acute rejection episode) may be more significant than breaking through with lesser degrees of immunosuppression.

But, not all patients with acute rejection develop chronic rejection. In fact, most patients with a single acute rejection episode do not develop chronic rejection. Data from our center is shown in Table E8.1. For first transplant recipients who have a single early acute rejection episode, <10% develop chronic rejection; for those with late rejection or multiple rejection episodes, the rate of chronic rejection is higher.

What, then, are the risk factors for development of chronic rejection within the subgroup having an acute rejection episode? As shown in Table E8.1, a late rejection episode or multiple acute rejection episodes are significant risk factors. In addition, we and others have shown that the kidney biopsy at the time of the rejection episode is prognostic. In our series, 229 recipients with a single acute

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