Characterizing the risk of human leukocyte antigen-incompatible living donor kidney transplantation in older recipients.

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors.

BACKGROUND: A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or not a kidney from a deceased donor was received. The generalizability of that finding is unclear. METHODS: In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group). We analyzed the data with and without patients from the highest-volume center in the study. RESULTS: Recipients of kidney transplants from incompatible live donors had a higher survival rate than either control group at 1 year (95.0%, vs. 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%) (P<0.001 for all comparisons with the two control groups). The survival benefit was significant at 8 years across all levels of donor-specific antibody: 89.2% for recipients of kidney transplants from incompatible live donors who had a positive Luminex assay for anti-HLA antibody but a negative flow-cytometric cross-match versus 65.0% for the waiting-list-or-transplant control group and 47.1% for the waiting-list-only control group; 76.3% for recipients with a positive flow-cytometric cross-match but a negative cytotoxic cross-match versus 63.3% and 43.0% in the two control groups, respectively; and 71.0% for recipients with a positive cytotoxic cross-match versus 61.5% and 43.7%, respectively. The findings did not change when patients from the highest-volume center were excluded. CONCLUSIONS: This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

Hospital readmissions following HLA-incompatible live donor kidney transplantation: A multi-center study.

Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. 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% confidence interval [CI] 1.13-1.46; P < .001). Risk peaked at 6-12 months (relative risk [RR] 1.67, 95% CI 1.49-1.87; P < .001), attenuating by 24-36 months (RR 1.24, 95% CI 1.10-1.40; P < .001). ILDKTs had a 5.86-fold higher readmission risk (95% CI 4.96-6.92; P < .001) in the first month compared to waitlist-only controls. At 12-24 (RR 0.85, 95% CI 0.77-0.95; P = .002) and 24-36 months (RR 0.74, 95% CI 0.66-0.84; P < .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.

Prospective, Randomized, Concurrently-Controlled Study of a Stent Graft versus Balloon Angioplasty for Treatment of Arteriovenous Access Graft Stenosis: 2-Year Results of the RENOVA Study.

PURPOSE: To present final, 2-year data from randomized comparison of an expanded polytetrafluoroethylene stent graft (SG) and percutaneous transluminal angioplasty (PTA) for treatment of arteriovenous graft (AVG) anastomotic stenoses. MATERIALS AND METHODS: A 28-site, prospective, controlled US study enrolled 270 patients with malfunctioning AVG anastomotic stenoses of ≥ 50%; 138 patients underwent SG placement, and 132 underwent PTA alone. Follow-up imaging and intervention were event-driven. RESULTS: The study was completed by 191 patients (97 SG, 94 PTA). Five patients were lost to follow-up or withdrew; 74 patients died during the study (38 SG, 36 PTA). At 12 months, treatment area primary patency (TAPP) was SG 47.6% versus PTA 24.8% (P < .001), access circuit primary patency (ACPP) was SG 24% versus PTA 11% (P = .007), and index of patency function (IPF) was SG 5.2 months/intervention ± 4.1 versus PTA 4.4 months/intervention ± 3.5 (P = .009). At 24 months, TAPP was SG 26.9% versus PTA 13.5% (P < .001), ACPP was SG 9.5% versus PTA 5.5% (P = .01), and IPF was SG 7.1 months/intervention ± 7.0 versus PTA 5.3 months/intervention ± 5.2; estimated number of reinterventions before graft abandonment was 3.4 for SG patients versus 4.3 for PTA patients. There were no significant differences in adverse events (P > .05) except for restenosis requiring reintervention rates of 82.6% in PTA patients versus 63.0% in SG patients (P < .001). CONCLUSIONS: At 2 years, SG use provided a sustained, greater than 2-fold advantage over PTA in treatment area and overall access patency. Time to subsequent intervention was longer in the SG group.

Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes.

BACKGROUND: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.

Clinical results of an organ procurement organization effort to increase utilization of donors after cardiac death.

BACKGROUND: To stimulate organ donation, an organ procurement organization (OPO)-wide effort was undertaken to increase donors after cardiac death (DCD) over a 5-year period. This included commonality of protocols, pulsatile perfusion of kidneys, centralization of data and a regional allocation variance designed to minimize cold ischemia times and encourage adoption of DCD protocols at transplant centers. RESULTS: In one OPO, eight centers initiated DCD programs in 11 hospitals. A total of 52 DCD donors were procured, increasing from four in 1999 to 21 in 2003. Eleven donors had care withdrawn in the operating room, whereas 41 had care withdrawn in the ICU. In all, 91 patients received renal transplants from these 52 donors (12 kidneys discarded, one double transplant), whereas 5 patients received liver transplants. One-, two-, and three-year kidney graft survival rates were 90%, 90%, and 82%, respectively. Fifty-five percent of patients needed at least one session of hemodialysis postoperatively. Mean recipient hospital length of stay was 11.1+/-6 days. Mean creatinine levels at 3, 6, 12, and 24 months were 1.65, 1.40, 1.41, and 1.40, respectively. CONCLUSIONS: DCD donors can be an important source of donor organs and provide excellent overall outcomes. Regional cooperation and a prospectively considered allocation and distribution system are important considerations in stimulating DCD programs.

Effects of prolonged ethanol lock exposure to carbothane- and silicone-based hemodialysis catheters: a 26-week study.

PURPOSE: Antibiotic locks in catheter-dependent chronic hemodialysis patients reduce the rate of catheter-related bloodstream infections (CRBSIs), but may be associated with the development of resistant bacteria. Ethanol-based catheter locks may provide a better alternative; however, there are limited data on the long-term integrity of dialysis catheters exposed to ethanol. METHODS: We performed in vitro testing of two types of hemodialysis catheters­silicone (SLC) and carbothane (CBT) based­with a 70% ethanol lock (EL) versus heparin lock (HL) for 26 weeks. Lock solutions were changed thrice weekly to mimic a conventional hemodialysis schedule. We tested mechanical properties of the catheters at 0, 13 and 26 weeks by examining stress/strain relationships (SS400%) and modulus of elasticity (ME). Electron microscopy was performed to examine catheter ultrastructure at 0 and 26 weeks. RESULTS: Catheter integrity for HL versus EL in SLC (SS400%: 4.5 vs. 4.5 MPa, p = NS; ME: 4.6 vs. 4.7 MPa, p = NS) or CBT-based catheters (SS400%: 7.6 vs. 8.9 MPa, p = NS; ME: 9.6 vs. 12.2 MPa, p = NS) were all similar at 13 and 26 weeks. Scanning electron microscopy revealed no structural changes in the central and luminal wall internal surfaces of EL- versus HL-treated catheters. CONCLUSIONS: There were no significant differences in catheter integrity between SLC or CBT catheters exposed to a 70% EL for 26 weeks. Given its low cost, potential to avoid antibiotic resistance and structural integrity after 6 months of high-dose ethanol, ELs should be studied prospectively against antibiotic locks to assess the efficacy and safety in hemodialysis patients.