Faculty Bibliography

New regulations require living kidney donor (LKD) follow-up for 2 years, but donor retention remains poor. Electronic communication (eg, text messaging and e-mail) might improve donor retention. To explore the possible impact of electronic communication, we recruited LKDs to participate in an exploratory study of communication via telephone, e-mail, or text messaging postdonation; communication through this study was purely optional and did not replace standard follow-up. Of 69 LKDs recruited, 3% requested telephone call, 52% e-mail, and 45% text messaging. Telephone response rate was 0%; these LKDs were subsequently excluded from analysis. Overall response rates with e-mail or text messaging at 1 week, 1 month, 6 months, 1 year, and 2 years were 94%, 87%, 81%, 72%, and 72%. Lower response rates were seen in African Americans, even after adjusting for age, sex, and contact method (incidence rate ratio (IRR) nonresponse _2.07 5.81_16.36 , P = .001). Text messaging had higher response rates than e-mail (IRR nonresponse _0.11 0.28_0.71 , P = .007). Rates of nonresponse were similar by sex (IRR 0.68, P = .4) and age (IRR 1.00, P > .9). In summary, LKDs strongly preferred electronic messaging over telephone and were highly responsive 2 years postdonation, even in this nonrequired, nonincentivized exploratory research study. These electronic communication tools can be automated and may improve regulatory compliance and postdonation care.

BACKGROUND:Antibody-mediated rejection (AMR) is a major barrier to the long-term function of renal allografts. White blood cells, which may be present in red blood cell (RBC) units, and platelets (PLTs) express HLA antigens that may increase the risk of AMR by inducing or increasing humoral sensitization to HLA. STUDY DESIGN AND METHODS/METHODS:A retrospective cohort study of HLA-incompatible (HLAi) renal transplant recipients between 2004 and 2015 was conducted. Data on apheresis PLT and leukoreduced RBC transfusions within 4 weeks of transplantation, demographic information, and biopsy-proven AMR were collected from medical records and the Scientific Registry of Transplant Recipients. Patients were evaluated until they showed evidence of AMR or until 1 year posttransplant, whichever came first. Multivariable analysis with Cox modeling was performed. RESULTS:Of 244 individuals, 182 (74.6%) received RBCs and 20 (8.2%) of those also received PLTs. During the first year posttransplant, 97 (39.8%) had AMR. RBC-alone or RBC and PLT transfusions were not associated with increased risk of AMR after adjustment for panel-reactive antibody, years on dialysis, HLA antibody strength, and number of therapeutic plasma exchange treatments (adjusted hazard ratio [adjHR] 1.00, 95% confidence interval [95% CI] 0.59-1.69; and adjHR 0.68, 95% CI 0.28-1.68, respectively). For each 1-unit increase in RBC transfusions, there was no association with AMR (adjHR 0.94, 95% CI 0.85-1.05). Only HLA antibody strength before transplantation was associated with AMR (adjHR 2.23, 95% CI 1.10-4.52; cytotoxic crossmatch compared to crossmatch negative but detectable donor-specific HLA antibodies). CONCLUSIONS:Patients who receive an HLAi transplant who are transfused with leukoreduced RBCs or PLTs in the peritransplant period are at no higher risk of AMR than nontransfused patients.

Kidney transplant recipients (KTR) have greater morbidity and length of stay (LOS) following certain surgical procedures than non-KTR. Given that appendectomy is one of the most common surgical procedures, we investigated differences in outcomes between 1336 KTR and 2,640,247 non-KTR post-appendectomy at transplant and non-transplant centers in the US from 2000-2011, using NIS data and adjusting for patient and hospital level factors. Postoperative complications were identified using ICD9 codes. Among KTR, there were no post-appendectomy in-hospital deaths, compared to a 0.2% in non-KTR (p=0.5). Overall complications were similar among KTR and non-KTR (17.0% vs 11.6%; aOR:_0.771.12_1.61). LOS and costs were greater for KTR compared to non-KTR (LOS ratio_1.191.31_1.45; cost ratio_1.111.17_1.26). Only 44.8% of KTR had laparoscopic approach compared to 54.5% of non-KTR, but had similar complication rates (10.6 vs 8.7%, p 0.5). When treated at transplant centers, KTR had similar complications (aOR_0.440.79_1.43), but longer LOS (ratio_1.211.37_1.55) and greater hospital-associated costs (ratio_1.191.29_1.41) than non-KTR. Conversely, at non-transplant centers, KTR and non-KTR had similar complications (aOR_0.751.23_2.0), LOS (ratio_0.840.96_1.09), and cost (ratio_0.931.01_1.10). Contrary to other procedures, KTR did not constitute a high-risk group for patients undergoing appendectomy.

Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNgamma response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.

30% of kidney transplant recipients are readmitted in the first month post-transplant. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95%CI: 1.13-1.46; P<0.001). Risk peaked at 6-12 months (RR 1.67; 95%CI: 1.49-1.87; P<0.001), attenuating by 24-36 months (RR 1.24; 95%CI: 1.10-1.40; P<0.001). ILDKTs had a 5.86-fold higher readmission risk (95%CI: 4.96-6.92; P<0.001) in the first month compared to waitlist-only controls. At 12-24 (RR 0.85; 95%CI: 0.77-0.95; P=0.002) and 24-36 months (RR 0.74; 95% CI: 0.66-0.84; P<0.001), ILDKTs had a lower risk than waitlist-only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist-only controls should be considered in regulatory/payment schemas and planning clinical care.

Excellent outcomes have been demonstrated in primary human immunodeficiency virus (HIV)-positive (HIV+) kidney transplant recipients, but a subset will lose their graft and seek retransplantation (re-KT). To date, no study has examined outcomes among HIV+ re-KT recipients. We studied risk for death and graft loss among 4149 (22 HIV+ vs. 4127 HIV-negative [HIV-]) adult re-KT recipients reported to the Scientific Registry of Transplant Recipients (SRTR) (2004-2013). Compared to HIV- re-KT recipients, HIV+ re-KT recipients were more commonly African American (63.6% vs. 26.7%, p < 0.001), infected with hepatitis C (31.8% vs. 5.0%, p < 0.001) and had longer median time on dialysis (4.8 years vs. 2.1 years, p = 0.02). There were no significant differences in length of time between the primary and re-KT events by HIV status (1.5 years vs. 1.4 years, p = 0.52). HIV+ re-KT recipients experienced a 3.11-fold increased risk of death (adjusted hazard ratio [aHR]: 3.11, 95% confidence interval [CI]: 1.82-5.34, p < 0.001) and a 1.96-fold increased risk of graft loss (aHR: 1.96, 95% CI: 1.14-3.36, p = 0.01) compared to HIV- re-KT recipients. Re-KT among HIV+ recipients was associated with increased risk for mortality and graft loss. Future research is needed to determine if a survival benefit is achieved with re-KT in this vulnerable population.

Excellent outcomes have been demonstrated among select HIV-positive kidney transplant (KT) recipients with well-controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01-10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre- and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non-PI-based ART (88 PI vs. 244 non-PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI-based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p = 0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with a 1.8-fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22-2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75-11.48, p = 0.002), and a 1.9-fold increased risk of death as compared to non-PI regimens (aHR 1.91, 95% CI 1.02-3.59, p = 0.05). These results suggest that whenever possible, recipients should be converted to a non-PI regimen prior to kidney transplantation.