Faculty Bibliography

The updated Banff classification allows for the diagnosis of antibody-mediated rejection (AMR) in the absence of peritubular capillary C4d staining. Our objective was to quantify allograft loss risk in patients with consistently C4d-negative AMR (n = 51) compared with C4d-positive AMR patients (n = 156) and matched control subjects without AMR. All first-year posttransplant biopsy results from January 2004 through June 2014 were reviewed and correlated with the presence of donor-specific antibody (DSA). C4d-negative AMR patients were not different from C4d-positive AMR patients on any baseline characteristics, including immunologic risk factors (panel reactive antibody, prior transplant, HLA mismatch, donor type, DSA class, and anti-HLA/ABO-incompatibility). C4d-positive AMR patients were significantly more likely to have a clinical presentation (85.3% vs. 54.9%, p < 0.001), and those patients presented substantially earlier posttransplantation (median 14 [interquartile range 8-32] days vs. 46 [interquartile range 20-191], p < 0.001) and were three times more common (7.8% vs 2.5%). One- and 2-year post-AMR-defining biopsy graft survival in C4d-negative AMR patients was 93.4% and 90.2% versus 86.8% and 82.6% in C4d-positive AMR patients, respectively (p = 0.4). C4d-negative AMR was associated with a 2.56-fold (95% confidence interval, 1.08-6.05, p = 0.033) increased risk of graft loss compared with AMR-free matched controls. No clinical characteristics were identified that reliably distinguished C4d-negative from C4d-positive AMR. However, both phenotypes are associated with increased graft loss and thus warrant consideration for intervention.

BACKGROUND: Frailty is associated with worse health-related quality of life (HRQOL) in older adults and worse clinical outcomes in adults of all ages with end stage renal disease (ESRD). It is unclear whether frail adults of all ages with ESRD are more likely to experience worse HRQOL. OBJECTIVE: The goal of this study was to identify factors associated with worsening HRQOL in this population. DESIGN, SETTING AND MEASUREMENTS: We studied 233 adults of all ages with ESRD enrolled (11/2009-11/2013) in a longitudinal cohort study. Frailty status was measured at enrollment and HRQOL was reported (Excellent, Very Good, Good, Fair or Poor) at the initial assessment and follow-up (median follow-up 9.4 months). We studied factors associated with Fair/Poor HRQOL at follow-up using logistic regression and factors associated with HRQOL change using multinomial regression. All models were adjusted for age, sex, race, education, BMI, diabetes status, history of a previous transplant, type of dialysis and time between assessments. RESULTS: Fair/Poor HRQOL was reported by 28% at initial assessment and 33% at follow-up. 47.2% of participants had stable HRQOL, 22.8% better HRQOL, and 30.0% worse HRQOL at follow-up (P<0.001). In adjusted models, only frailty was associated with Fair/Poor HRQOL at follow-up (OR: 2.79, 95% CI: 1.32-5.90) and worsening HRQOL at follow-up (RR: 2.91, 95%CI: 1.08-7.80). CONCLUSIONS: Frail adults of all ages with ESRD are more likely to experience fair/poor HRQOL and worsening HRQOL over time. Frailty represents a state of decreased physiologic reserve that impacts not only clinical outcomes but also the patient-centered outcome of HRQOL.