Complement Blockade in Recipients Prevents Delayed Graft Function and Delays Antibody-mediated Rejection in a Nonhuman Primate Model of Kidney Transplantation.

BACKGROUND: Complement activation in kidney transplantation is implicated in the pathogenesis of delayed graft function (DGF). This study evaluated the therapeutic efficacy of high-dose recombinant human C1 esterase inhibitor (rhC1INH) to prevent DGF in a nonhuman primate model of kidney transplantation after brain death and prolonged cold ischemia. METHODS: Brain death donors underwent 20 h of conventional management. Procured kidneys were stored on ice for 44-48 h, then transplanted into ABO-compatible major histocompatibility complex-mismatched recipients. Recipients were treated with vehicle (n = 5) or rhC1INH 500 U/kg plus heparin 40 U/kg (n = 8) before reperfusion, 12 h, and 24 h posttransplant. Recipients were followed up for 120 d. RESULTS: Of vehicle-treated recipients, 80% (4 of 5) developed DGF versus 12.5% (1 of 8) rhC1INH-treated recipients (P = 0.015). rhC1INH-treated recipients had faster creatinine recovery, superior urinary output, and reduced urinary neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloproteinases 2-insulin-like growth factor-binding protein 7 throughout the first week, indicating reduced allograft injury. Treated recipients presented lower postreperfusion plasma interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and IL-18, lower day 4 monocyte chemoattractant protein 1, and trended toward lower C5. Treated recipients exhibited less C3b/C5b-9 deposition on day 7 biopsies. rhC1INH-treated animals also trended toward prolonged mediated rejection-free survival. CONCLUSIONS: Our results recommend high-dose C1INH complement blockade in transplant recipients as an effective strategy to reduce kidney injury and inflammation, prevent DGF, delay antibody-mediated rejection development, and improve transplant outcomes.

Kidney After Liver Transplantation Matched-pair Analysis: Are Kidneys Allocated to Appropriate Patients to Maximize Their Survival?

BACKGROUND: Kidney after liver transplantation (KALT) is the best therapeutic option for patients with end-stage renal disease after orthotopic liver transplantation (OLT). New allocation policies prioritize kidneys to patients in renal failure within the first year following OLT. There is little data on how kidney quality, measured by kidney donor profile index (KDPI), impacts KALT survival outcomes. METHODS: The United Network for Organ Sharing database was queried for adult KALT recipients from 1988 to 2015 and compared to their paired kidney transplant alone (KTA) recipients. Seven hundred forty-five pairs were stratified into 3 KDPI subgroups and compared patient survival, graft survival, and death-censored graft survival among matched-paired recipients. RESULTS: Overall, KTA recipients had superior patient and graft survival compared with the KALT group. KTA patient survival was superior for all 3 KDPI subgroups analysis. KTA graft survival was superior compared with KALT recipients of KDPI 21%-85% kidneys. Inferior graft half-life was observed in KALT versus KTA recipients with KDPI 21%-85% and >85%. CONCLUSIONS: From a utilitarian perspective, it is important that kidneys are allocated to recipients that are able to maximize their benefit from the full life of the organ. In KTA recipients, graft quality correlates directly to graft survival. However, in KALT patients receiving the matched-pair kidneys of the KTA recipients, patient mortality, rather than kidney quality, dictates graft survival significantly. As allocation practices continue developing, utilization of expanded criteria kidneys that better match anticipated patient and graft survival should be strongly considered to maximize the benefits of limited resources for the greatest number of patients.