Evidence of antibody-mediated injury (DSA or C4d) is common (57%) in patients with new onset late kidney allograft dysfunction. The risk of subsequent graft failure is significantly worse in the presence of C4d+ staining.

We are studying two cohorts of kidney transplant recipients, with the goal of defining specific clinicopathologic entities that cause late graft dysfunction: (1) prevalent patients with new onset late graft dysfunction (Cross-Sectional Cohort); and (2) newly transplanted patients (Prospective Cohort). For the cross-sectional cohort (n=440), mean time from transplant to biopsy was 7.5±6.1 years. Local pathology diagnoses included CAN (48%), CNI toxicity (30%), and, perhaps surprisingly, acute rejection (cellular- or Ab-mediated) (23%). Actuarial rate of death-censored graft loss at 1 year post-biopsy was 17.7%; at 2 years, 29.8%. There was no difference in post-biopsy graft survival for recipients with vs. without CAN (p=0.9). Prospective cohort patients (n=2427) developing graft dysfunction >3 months posttransplant undergo “index” biopsy. The rate of index biopsy was 8.8% between months 3 and 12, and 18.2% by 2 years. Mean time from transplant to index biopsy was 1.0 ± 0.6 years. Local pathology diagnoses included CAN (27%), and acute rejection (39%). Intervention to halt late graft deterioration cannot be developed in the absence of meaningful diagnostic entities. We found CAN in late posttransplant biopsies to be of no prognostic value. The DeKAF study will provide broadly applicable diagnostic information to serve as the basis for future trials.

The nonspecific diagnoses 'chronic rejection' 'CAN' , or 'IF/TA' suggest neither identifiable pathophysiologic mechanisms nor possible treatments. As a first step to developing a more useful taxonomy for causes of newonset late kidney allograft dysfunction, we used cluster analysis of individual Banff score components to define subgroups. In this multicenter study, eligibility included being transplanted prior to October 1, 2005, having a 'baseline' serum creatinine ≤2.0 mg/dL before January 1, 2006, and subsequently developing deterioration of graft function leading to a biopsy. Mean time from transplant to biopsy was 7.5 ± 6.1 years. Of the 265 biopsies (all with blinded central pathology interpretation), 240 grouped into six large (n > 13) clusters. There were no major differences between clusters in recipient demographics. The actuarial postbiopsy graft survival varied by cluster (p = 0.002). CAN and CNI toxicity were common diagnoses in each cluster (and did not differentiate clusters). Similarly, C4d and presence of donor specific antibody were frequently observed across clusters. We conclude that for recipients with new-onset late graft dysfunction, cluster analysis of Banff scores distinguishes meaningful subgroups with differing outcomes.

Background The epidemiologic trends of hepatitis B virus (HBV) infection in HIV-infected patients over the last twenty years are largely unknown. Methods Prevalence and risk factors for HBV infection overall, at the time of HIV infection, and following HIV infection were examined in an ongoing observational HIV cohort study. Risk factors for HBV infection at the time of HIV diagnosis were evaluated using logistic regression, and risk for incident HBV infection following HIV diagnosis was evaluated using Cox proportional hazards models. Results Of the 2769 evaluable participants, 1078 (39%) had HBV infection, of which 117 (11%) had chronic HBV. The yearly cross-sectional prevalence of HBV infection decreased from a peak of 49% in 1995 to 36% in 2008 (p<0.001). HBV prevalence at the time of HIV diagnosis decreased between 1989 and 2008 from 34% to 9% (p<0.001). The incidence of HBV infection following HIV diagnosis decreased from 4.0/100 person-years in the pre-HAART era to 1.1/100 person-years in the HAART era (p<0.001), but has remained unchanged from 2000 through 2008 (p=0.49), with over 20% of incident HBV infections having chronic HBV. Decreased risk of HBV infection following HIV diagnosis was associated with higher CD4 cell counts and the use of HBV-active HAART. Receipt of ≥1 dose of HBV vaccine was not associated with reduced risk of HBV infection after HIV diagnosis. Conclusions While the burden of HBV infection overall is slowly decreasing among HIV-infected individuals, the persistent rate of HBV infection following HIV diagnosis raises concern that more effective prevention strategies may be needed to significantly reduce HBV infections in this patient population.