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.     

Risk factors for and outcomes of delayed graft function in live donor kidney transplantation – a retrospective study

Delayed graft function (DGF) in deceased donor kidney transplantation is associated with worse outcomes. DGF has been less well studied in live donor transplantation. We aimed to examine the risk factors for DGF, and associations between DGF and short‐ and long‐term outcomes in live donor kidney transplant recipients. Using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry, we included live donor kidney transplants performed in Australia and New Zealand over 2004–2015 and excluded pediatric recipients (n = 440), pathological donors (n = 97), grafts that failed in the first week (as a proxy for primary non function; n = 38), and grafts with missing DGF data (n = 46). We used multivariable logistic regression to identify the risk factors for DGF and the association between DGF and rejection at 6 months; Cox proportional hazards models to examine the relationship between DGF and patient and graft survival; and linear regression to examine the association between DGF and eGFR at 1 year. DGF occurred in 77 (2.3%) of 3358 transplants. Risk factors for DGF included right‐sided kidney [odds ratio (OR) 2.00 (95% CI 1.18, 3.40)], donor BMI [OR 1.06 per kg/m² (95% CI 1.01, 1.12)]; increasing time on dialysis and total ischemic time [OR 1.09 per hour (1.00, 1.17)]. DGF was associated with increased risk of rejection at 6 months [OR 2.37 (95% CI 1.41, 3.97)], worse patient survival [HR 2.14 (95% CI 1.21, 3.80)] and graft survival [HR 1.98 (95% CI 1.27, 3.10)], and worse renal function at 1 year [Coefficient ‐9.57 (95% CI ?13.5, ?5.64)]. DGF is uncommon after live donor kidney transplantation, but associated with significantly worse outcomes. The only modifiable risk factors identified were kidney side and total ischemic time.     

Kidney transplant outcomes associated with the use of increased risk donors in children

Increased risk donors (IRDs) may inadvertently transmit blood‐borne viruses to organ recipients through transplant. Rates of IRD kidney transplants in children and the associated outcomes are unknown. We used the Scientific Registry of Transplant Recipients to identify pediatric deceased donor kidney transplants that were performed in the United States between January 1, 2005 and December 31, 2015. We used the Cox regression analysis to compare patient and graft survival between IRD and non‐IRD recipients, and a sequential Cox approach to evaluate survival benefit after IRD transplants compared with remaining on the waitlist and never accepting an IRD kidney. We studied 328 recipients with and 4850 without IRD transplants. The annual IRD transplant rates ranged from 3.4% to 13.2%. IRDs were more likely to be male (P = .04), black (P < .001), and die from head trauma (P = .006). IRD recipients had higher mean cPRA (0.085 vs 0.065, P = .02). After multivariate adjustment, patient survival after IRD transplants was significantly higher compared with remaining on the waitlist (adjusted hazard ratio [aHR]: 0.48, 95% CI: 0.26‐0.88, P = .018); however, patient (aHR: 0.93, 95% CI: 0.54‐1.59, P = .79) and graft survival (aHR: 0.89, 95% CI: 0.70‐1.13, P = .32) were similar between IRD and non‐IRD recipients. We recommend that IRDs be considered for transplant in children.     

Lower tacrolimus exposure and time in therapeutic range increase the risk of de novo donor‐specific antibodies in the first year of kidney transplantation

De novo donor‐specific antibodies (dnDSAs) have been associated with reduced graft survival. Tacrolimus (TAC)–based regimens are the most common among immunosuppressive approaches used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSAs has not been established. We evaluated mean TAC C₀ (tacrolimus trough concentration) and TAC time in therapeutic range for the risk of dnDSAs in a cohort of 538 patients in the first year after kidney transplantation. A mean TAC C₀ < 8 ng/mL was associated with dnDSAs by 6 months (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.32–4.79, P = .005) and by 12 months (OR 2.32, 95% CI 1.30–4.15, P = .004), and there was a graded increase in risk with lower mean TAC C₀. TAC time in the therapeutic range of <60% was associated with dnDSAs (OR 2.05, 95% CI 1.28‐3.30, P = .003) and acute rejection (hazard ratio [HR] 4.18, 95% CI 2.31–7.58, P < .001) by 12 months and death‐censored graft loss by 5 years (HR 3.12, 95% CI 1.53–6.37, P = .002). TAC minimization may come at a cost of higher rates of dnDSAs, and TAC time in therapeutic range may be a valuable strategy to stratify patients at increased risk of adverse outcomes.     

Influence of epidemiology,immunosuppressive regimens,clinical presentation,and treatment on kidney transplant outcomes of patients diagnosed with tuberculosis: A retrospective cohort analysis

Tuberculosis (TB) mortality is high among kidney transplant (KT) recipients. Although local epidemiology is an important factor, diagnostic/therapeutic challenges and immunosuppressive therapy (ISS) may influence outcomes. We analyzed the cumulative incidence (CumI) of TB in KT recipients receiving a variety of ISS with long‐term follow‐up. Our retrospective single‐center cohort study included all KT procedures performed between January 1, 1998, and August 31, 2014, with follow‐up until August 31, 2014. Induction therapy was based on perceived immunological risk; maintenance ISS included prednisone and calcineurin inhibitor (CNI) plus azathioprine (AZA), and mycophenolic acid (MPA) or mechanistic target of rapamycin inhibitor (mTORi). Thirty‐four patients received belatacept/MPA. KT was performed on 11 453 patients and followed for 1989 (IQR 932 to 3632) days. Among these, 152 patients were diagnosed with TB (CumI 1.32%). Median time from KT to TB was 18.8 (IQR 7.2 to 60) months, with 59% of patients diagnosed after the first year. Unadjusted analysis revealed an increasing confidence interval (CI) of TB (0.94% CNI/AZA vs 1.6% CNI/MPA [HR = 1.62, 95% CI = 1.13 to 2.34, P = .009] vs 2.85% CNI/mTORi [HR = 2.45, 95% CI = 1.49 to 4.32, P < .001] vs 14.7% belatacept/MPA [HR = 13.14, 95% CI = 5.27 to 32.79, P < .001]). Thirty‐seven (24%) patients died, and 39 (25.6%) patients experienced graft loss. Cytomegalovirus infection (P = .02) and definitive ISS discontinuation (P < .001) were associated with death. Rejection (P = .018) and ISS discontinuation (P = .005) occurred with graft loss. TB occurred at any time after KT and was influenced by ISS.     

Short‐term outcomes of deceased donor renal transplants of HCV uninfected recipients from HCV seropositive nonviremic donors and viremic donors in the era of direct‐acting antivirals

The United States opioid use epidemic over the past decade has coincided with an increase in hepatitis C virus  (HCV) positive donors. Using propensity score matching, and the Organ Procurement Transplant Network data files from January 2015 to June 2019, we analyzed the short‐term outcomes of adult deceased donor kidney transplants of HCV uninfected recipients with two distinct groups of HCV positive donors (HCV seropositive, nonviremic n = 352 and viremic n = 196) compared to those performed using HCV uninfected donors (n = 36 934). Compared to the reference group, the transplants performed using HCV seropositive, nonviremic and viremic donors experienced a lower proportion of delayed graft function (35.2 vs 18.9%; P < .001 [HCV seropositive, nonviremic donors] and 36.2 vs 16.8% ;  P < .001[HCV viremic donors]). The recipients of HCV viremic donors had better allograft function at 6 months posttransplant (eGFR [54.1 vs 68.3 mL/min/1.73 m2; P = .004]. Furthermore, there was no statistical difference in the overall graft failure risk at 12 months posttransplant by propensity score matched multivariable Cox proportional analysis (HR =  0.60, 95% CI  0.23 to  1.29 [HCV seropositive, nonviremic donors] and HR =  0.85, 95% CI 0.25 to  2.96 [HCV viremic donors]). Further studies are required to determine the long‐term outcomes of these transplants and address unanswered questions regarding the use of HCV viremic donors.     

Cytomegalovirus mismatch still negatively affects patient and graft survival in the era of routine prophylactic and preemptive therapy: A paired kidney analysis

The impact of cytomegalovirus (CMV) serostatus on kidney transplant outcomes in an era when CMV prophylactic and preemptive strategies are used routinely is not clearly established. Using United Network for Organ Sharing/Organ Procurement and Transplantation Network data, recipients with first deceased donor kidney transplant (≥18 years, 2010‐2015) were stratified into 4 groups in the main cohort: CMV‐seronegative donor (D?)/CMV‐seronegative recipient (R?), CMV‐seropositive donor (D+)/R?, D+/CMV‐seropositive recipient (R+), and D?/R+. In a paired kidney cohort, we identified 2899 pairs of D? kidney transplant with discordance of recipient serostatus (D?/R? vs D?/R+) and 4567 pairs of D+ kidney transplant with discordance of recipient serostatus (D+/R? vs D+/R+). In the main cohort, D+/R? was associated with a higher risk of graft failure (hazard ratio [HR] = 1.17, P = .01), all‐cause mortality (HR = 1.18, P < .001), and infection‐related mortality (HR = 1.38, P = .03) compared with D?/R?. In the paired kidney analysis, D+/R? was an independent risk factor for all‐cause mortality (HR = 1.21, P = .003) and infection‐related mortality (HR = 1.47, P = .04) compared with D+/R+. No difference in graft loss between D+/R? and D+/R+. CMV mismatch is still an independent risk factor for graft loss and patient mortality. The negative impact of D+/R? serostatus on mortality persists after fully matching for donor factors.     

Preemptive kidney transplantation in systemic lupus erythematosus

Preemptive kidney transplantation is associated with superior outcomes. Patients who have kidney failure due to systemic lupus erythematosus (SLE) may not receive a preemptive kidney transplant because of the concern for risk of disease recurrence with shortened graft and patient survival. We identified 8001 patients in the United Network for Organ Sharing dataset who underwent kidney transplantation between October 1987 and February 2009 with kidney failure due to SLE. Seven hundred thirty patients received a preemptive kidney transplant with 7271 patients who were on dialysis before transplantation; their mean ages were 40.0 ± 11.6 years and 36.9 ± 11.7 years, respectively, (P < .01). Women constituted 82.5% of preemptive and 81.4% of non-preemptive groups (P = .47). Preemptive transplant recipients were more likely to receive a living donor kidney transplant (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 3.3–4.5; P < .01). In unadjusted analyses, preemptive transplantation was associated with lower risk of recipient death (hazard ratio [HR] = 0.52; 95% CI = 0.38–0.70; P < .01). The difference remained significant after adjustment fr covariates (HR = 0.55; 95% CI = 0.36–0.84; P < .01). Graft survival was also superior among preemptive kidney transplant recipients in both unadjusted (HR = 0.56; 95% CI = 0.49–0.68; P < .01), and adjustment analyses (HR = 0.69; 95% CI = 0.55–0.86; P < .01). We concluded that preemptive kidney transplantation among patients with SLE was associated with superior patient and graft outcomes and should be considered when feasible.     

Early clinical experience using donor‐derived cell‐free DNA to detect rejection in kidney transplant recipients

Donor‐derived cell‐free DNA (dd‐cfDNA) became Medicare reimbursable in the United States in October 2017 for the detection of rejection in kidney transplant recipients based on results from its pivotal validation trial, but it has not yet been externally validated. We assessed 63 adult kidney transplant recipients with suspicion of rejection with dd‐cfDNA and allograft biopsy. Of these, 27 (43%) patients had donor–specific antibodies and 34 (54%) were found to have rejection by biopsy. The percentage of dd‐cfDNA was higher among patients with antibody–mediated rejection (ABMR; median 1.35%; interquartile range [IQR]: 1.10%‐1.90%) compared to those with no rejection (median 0.38%, IQR: 0.26%‐1.10%; P < .001) and cell–mediated rejection (CMR; median: 0.27%, IQR: 0.19%‐1.30%; P = .01). The dd‐cfDNA test did not discriminate patients with CMR from those without rejection. The area under the ROC curve (AUC) for CMR was 0.42 (95% CI: 0.17‐0.66). For ABMR, the AUC was 0.82 (95% CI: 0.71‐0.93) and a dd‐cfDNA ≥0.74% yielded a sensitivity of 100%, specificity 71.8%, PPV 68.6%, and NPV 100%. The dd‐cfDNA test did not discriminate CMR from no rejection among kidney transplant recipients, although performance characteristics were stronger for the discrimination of ABMR.     

Risk factors and outcomes for delayed kidney graft function in simultaneous heart and kidney transplant recipients: A UNOS/OPTN database analysis

There are no prior studies assessing the risk factors and outcomes for kidney delayed graft function (K-DGF) in simultaneous heart and kidney (SHK) transplant recipients. Using the OPTN/UNOS database, we sought to identify risk factors associated with the development of K-DGF in this unique population, as well as outcomes associated with K-DGF. A total of 1161 SHK transplanted between 1998 and 2018 were included in the analysis, of which 311 (27%) were in the K-DGF (+) group and 850 in the K-DGF (−) group. In the multivariable analysis, history of pretransplant dialysis (OR: 3.95; 95% CI: 2.94 to 5.29; p < .001) was significantly associated with the development of K-DGF, as was donor death from cerebrovascular accident and longer cold ischemia time of either organ. SHK recipients with K-DGF had increased mortality (HR: 1.99; 95% CI: 1.52 to 2.60; p < .001) and death censored kidney graft failure (HR: 3.51; 95% CI: 2.29 to 5.36; p < .001) in the multivariable analysis. Similar outcomes were obtained when limiting our study to 2008–2018. Similar to kidney-only recipients, K-DGF in SHK recipients is associated with worse outcomes. Careful matching of recipients and donors, as well as peri-operative management, may help reduce the risk of K-DGF and the associated detrimental effects.     

Prolonged Ischemic Time,Delayed Graft Function,and Graft and Patient Outcomes in Live Donor Kidney Transplant Recipients

The association between prolonged cold ischemic time (CIT) and graft and patient outcomes in live donor kidney transplant recipients remains unclear. The aims of this study were to examine the association of CIT with delayed graft function and graft loss in live donor kidney transplant recipients and those who participated in the Australian Paired Kidney Exchange program using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Of 3717 live donor transplant recipients between 1997 and 2012 who were followed for a median of 6.6 years (25 977 person‐years), 224 (25%) experienced CIT >4–8 h. Donor age was an effect modifier between CIT and graft outcomes. In recipients who received kidneys from older donors aged >50 years, every hour of increase in CIT was associated with adjusted odds of 1.28 (95% confidence interval [CI] 1.07–1.53, p = 0.007) for delayed graft function, whereas CIT >4–8 h was associated with adjusted hazards of 1.93 (95% CI 1.21–3.09, p = 0.006) and 1.91 (95% CI 1.05–3.49, p = 0.035) for overall and death‐censored graft loss, respectively, compared with CIT of 1–2 h. Attempts to reduce CIT in live donor kidney transplants involving older donor kidneys may lead to improvement of graft outcomes.     

Renal resistance thresholds during hypothermic machine perfusion and transplantation outcomes – a retrospective cohort study

Renal resistance (RR), of allografts undergoing hypothermic machine perfusion (HMP), is considered a measure of organ quality. We conducted a retrospective cohort study of adult deceased donor kidney transplant (KT) recipients whose grafts underwent HMP. Our aim was to evaluate whether RR is predictive of death‐censored graft failure (DCGF). Of 274 KT eligible for analysis, 59% were from expanded criteria donor. RR was modeled as a categorical variable, using a previously identified terminal threshold of 0.4, and 0.2 mmHg/ml/min (median in our cohort). Hazard ratios (HR) of DCGF were 3.23 [95% confidence interval (CI): 1.12–9.34, P = 0.03] and 2.67 [95% CI: 1.14–6.31, P = 0.02] in univariable models, and 2.67 [95% CI: 0.91–7.86, P = 0.07] and 2.42 [95% CI: 1.02–5.72, P = 0.04] in multivariable models, when RR threshold was 0.4 and 0.2, respectively. Increasing risk of DCGF was observed when RR over the course of HMP was modeled using mixed linear regression models: HR of 1.31 [95% CI: 1.07–1.59, P < 0.01] and 1.25 [95% CI: 1.00–1.55, P = 0.05], in univariable and multivariable models, respectively. This suggests that RR during HMP is a predictor of long‐term KT outcomes. Prospective studies are needed to assess the survival benefit of patients receiving KT with higher RR in comparison with staying wait‐listed.     

Geographic disparities in donor lung supply and lung transplant waitlist outcomes: A cohort study

Despite the Final Rule mandate for equitable organ allocation in the United States, geographic disparities exist in donor lung allocation, with the majority of donor lungs being allocated locally to lower‐priority candidates. We conducted a retrospective cohort study of 19 622 lung transplant candidates waitlisted between 2006 and 2015. We used multivariable adjusted competing risk survival models to examine the relationship between local lung availability and waitlist outcomes. The primary outcome was a composite of death and removal from the waitlist for clinical deterioration. Waitlist candidates in the lowest quartile of local lung availability had an 84% increased risk of death or removal compared with candidates in the highest (subdistribution hazard ratio [SHR]: 1.84, 95% confidence interval [CI]: 1.51‐2.24, P < .001). The transplantation rate was 57% lower in the lowest quartile compared with the highest (SHR: 0.43, 95% CI: 0.39‐0.47). The adjusted death or removal rate decreased by 11% with a 50% increase in local lung availability (SHR: 0.89, 95% CI: 0.85‐0.93, P < .001) and the adjusted transplantation rate increased by 19% (SHR: 1.19, 95% CI: 1.17‐1.22, P < .001). There are geographically disparate waitlist outcomes in the current lung allocation system. Candidates listed in areas of low local lung availability have worse waitlist outcomes.     

Racial/ethnic disparities in waitlisting for deceased donor kidney transplantation 1 year after implementation of the new national kidney allocation system

The impact of a new national kidney allocation system (KAS) on access to the national deceased‐donor waiting list (waitlisting) and racial/ethnic disparities in waitlisting among US end‐stage renal disease (ESRD) patients is unknown. We examined waitlisting pre‐ and post‐KAS among incident (N = 1 253 100) and prevalent (N = 1 556 954) ESRD patients from the United States Renal Data System database (2005‐2015) using multivariable time‐dependent Cox and interrupted time‐series models. The adjusted waitlisting rate among incident patients was 9% lower post‐KAS (hazard ratio [HR]: 0.91; 95% confidence interval [CI], 0.90‐0.93), although preemptive waitlisting increased from 30.2% to 35.1% (P < .0001). The waitlisting decrease is largely due to a decline in inactively waitlisted patients. Pre‐KAS, blacks had a 19% lower waitlisting rate vs whites (HR: 0.81; 95% CI, 0.80‐0.82); following KAS, disparity declined to 12% (HR: 0.88; 95% CI, 0.85‐0.90). In adjusted time‐series analyses of prevalent patients, waitlisting rates declined by 3.45/10 000 per month post‐KAS (P < .001), resulting in ≈146 fewer waitlisting events/month. Shorter dialysis vintage was associated with greater decreases in waitlisting post‐KAS (P < .001). Racial disparity reduction was due in part to a steeper decline in inactive waitlisting among minorities and a greater proportion of actively waitlisted minority patients. Waitlisting and racial disparity in waitlisting declined post‐KAS; however, disparity remains.     

The feared five fungal infections in kidney transplant recipients: A single‐center 20‐year experience

Invasive fungal infections are a feared complication in kidney transplant recipients (KTRs). Here we present the University of Wisconsin experience with 5 invasive fungal infections—aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis—in KTRs transplanted between 01/01/1994 and 06/30/2014. During this period, there were 128 cases of fungal infections; aspergillosis was the most common (72), followed by cryptococcosis (29), histoplasmosis (14), blastomycosis (10), and coccidioidomycosis (3). The mean interval from transplant to fungal infection was 3.19 ± 3.58 years (range 5 days‐15.8 years). By 6 months postinfection, there were 53 (41%) graft failures and 24 (19%) deaths. Graft failure occurred in 46%, 38%, 21%, 40%, and 67% of patients with aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis, respectively. Anti‐thymocyte globulin (ATG) induction (HR, 1.49; 95% CI, 1.03‐2.16; P = .04), diabetes (HR, 1.53; 95% CI, 1.05‐2.21; P = .03), and age (HR, 1.47; 95% CI, 1.27‐1.70; P ≤ .001) were associated with an increased risk for infection in univariate analysis. Multivariate adjustment retained ATG induction and older age. A large proportion of kidney transplant recipients with invasive fungal infections suffer graft failure within 3 years. Preventive, therapeutic, and monitoring strategies are needed to improve graft and patient outcomes.     

The risk of cytomegalovirus infection after treatment of acute rejection in renal transplant recipients

The risk of cytomegalovirus infection (CMV) after rejection treatment is poorly understood. To investigate this, we conducted a case/control (1:2) analysis of adult renal transplant recipients between January 1, 2005 and December 31, 2015, via incidence density sampling and survival analysis. Our objective was to evaluate the association of prior acute rejection with subsequent CMV, including epidemiology and outcomes. There were 2481 eligible renal transplants within the study period and 251 distinct CMV infections. Despite the use of antiviral prophylaxis rejection was a significant risk factor for CMV on unadjusted (HR 1.73 [1.34, 2.24] P < 0.05) and adjusted analysis (HR 1.46 [1.06, 2.04] P < 0.05). When matching cases to controls patients with CMV had significantly more rejection prior to CMV diagnosis (26.7% vs 14.2%, P < 0.01). CMV was associated with a twofold increased risk of prior rejection on unadjusted (OR 1.94, 95%CI: 1.28‐2.96, P < 0.01) and adjusted analysis (OR 2.16, 95% CI: 1.31‐3.58, P < 0.01). Patients with rejection preceding CMV had significantly increased graft loss (HR 2.89, 95% CI: 1.65‐5.09, P < 0.01) and mortality (HR 1.82, 95% CI: 1.12‐4.24, P = 0.03) as compared to those CMV cases without rejection. In conclusion, rejection is a risk factor for CMV infection that appears to persist for 1 year. Preceding rejection events increased risk of graft loss and mortality in CMV patients. Given this, prolonged surveillance monitoring for CMV after rejection may be warranted. Studies are needed investigating optimal monitoring strategies.     

Graft and patient outcomes of zero‐human leucocyte‐antigen‐mismatched deceased and live donor kidney transplant recipients

Greater compatibility of human leucocyte antigen (HLA) alleles between kidney donors and recipients may lead to improved graft outcomes. This study aimed to compare the incidence of acute rejection and graft failure in zero‐HLA‐mismatched recipients of living‐related (LD) and deceased donor (DD) kidney transplants. Using data from the Australia and New Zealand Dialysis and Transplant Registry, we compared the risk of any acute rejection and biopsy‐proven acute rejection (BPAR) and graft failure in recipients of zero‐HLA‐mismatched kidneys between LD and DD using logistic and Cox regression models. Of the 931 zero‐HLA‐mismatched recipients transplanted between 1990 and 2012, 19 (2.0%) received kidneys from monozygotic/dizygotic twins (twin), 500 (53.7%) from nontwin LD and 412 (44.3%) from DD. Twin kidney transplant recipients did not experience rejection. Compared to DD transplant recipients, the risk of any acute rejection (adjusted odds ratio 0.52, 95%CI 0.34–0.79, P = 0.002) and overall graft failure (adjusted hazard ratio 0.55, 95%CI 0.41–0.73, P < 0.001) was significantly lower in LD recipients independent of initial immunosuppression, but not for BPAR (adjusted odds ratio 0.52, 95%CI 0.16–1.64, P = 0.263). Zero‐HLA‐mismatched DD kidney transplant recipients have a significantly higher risk of any acute rejection episodes and graft loss compared to zero‐HLA‐mismatched LD kidney transplant recipients. A cautious and careful approach in reducing immunosuppression appears to be warranted in this group of transplant recipients.     

Long-Term Graft and Patient Outcomes Following Kidney Transplantation in End-Stage Kidney Disease Secondary to Hyperoxaluria

BackgroundEnd-stage kidney disease secondary to hyperoxaluria presents a major challenge for transplant physicians given concern regarding disease recurrence. Few contemporary studies have reported long-term outcomes following transplantation in this population.MethodsThis study examined the outcomes of all adult patients with end-stage kidney disease secondary to hyperoxaluria who received a kidney or combined liver-kidney transplant in Australia and New Zealand between 1965 and 2015. Patients with hyperoxaluria were propensity score matched to control patients with reflux nephropathy. The primary outcome was graft survival. Secondary outcomes included graft function, acute rejection, and patient survival.ResultsNineteen transplants performed in 16 patients with hyperoxaluria were matched to 57 transplants in patients with reflux nephropathy. Graft survival was inferior in patients with hyperoxaluria receiving a kidney transplant alone (subhazard ratio [SHR] = 3.83, 95% confidence interval [CI], 1.22-12.08, P = .02) but not in those receiving a combined liver-kidney transplant (SHR = 0.63, 95% CI, 0.08-5.21, P = .67). Graft failure risk was particularly high in patients with hyperoxaluria receiving a kidney transplant alone after more than 1 year of renal replacement therapy (SHR = 8.90, 95% CI, 2.35-33.76, P = .001). Posttransplant estimated glomerular filtration rate was lower in patients with hyperoxaluria (10.97 mL/min/1.73 m², 95% CI, 0.53-21.42, P = .04). There was no difference between groups in the risk of acute rejection or death with a functioning graft.ConclusionCompared to reflux nephropathy, hyperoxaluria was associated with inferior graft survival in patients receiving a kidney transplant alone. Long-term graft function was lower in patients with hyperoxaluria, but the risks of acute rejection and death were not different.     

Transplanting kidneys from donation after cardiac death donors with acute kidney injury

Donation after cardiac death (DCD) and acute kidney injury (AKI) donors have historically been considered independent risk factors for delayed graft function (DGF), allograft failure, and inferior outcomes. With growing experience, updated analyses have shown good outcomes. There continues to be limited data, however, on outcomes specific to DCD donors who have AKI. Primary outcomes for this study were post–kidney transplant patient and allograft survival comparing two donor groups: DCD AKIN stage 2‐3 and DBD AKIN stage 2‐3. In comparing these groups, there were no short‐ or long‐term differences in patient (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.54‐1.93, P = .83) or allograft survival (HR 1.47, 95% CI 0.64‐2.97, P = .32). In multivariate models, the DCD/DBD status had no significant impact on the estimated GFR (eGFR) at 1 (P = .38), 2 (P = .60), and 3 years (P = .52). DGF (57.9% vs 67.9%, P = .09), rejection (12.1% vs 13.9%, P = .12), and progression of interstitial fibrosis/tubular atrophy (IFTA) on protocol biopsy (P = .16) were similar between the two groups. With careful selection, good outcomes can be achieved utilizing severe AKI DCD kidneys. Historic concerns regarding primary nonfunction, DGF resulting in interstitial fibrosis and rejection, and inferior outcomes were not observed. Given the ongoing organ shortage, increased effort should be undertaken to further utilize these donors.     

Machine perfusion of donor kidneys may reduce graft rejection

Recent evidence suggests that hypothermic machine perfusion of donor kidneys reduces delayed graft function (DGF). This study addresses the effect of machine perfusion (MP) on allograft rejection in the United States. We assembled a retrospective cohort of patients undergoing kidney‐alone transplants in the UNOS database from June 30, 2004 to May 31, 2017. DGF was defined as dialysis requirement in the first week post‐transplant; graft rejection was defined at 6 months and 1 year. Multivariable logistic regression adjusted for recipient and donor factors evaluated the effect of MP on DGF and graft rejection. Records for 79 300 kidney transplants meeting inclusion criteria were abstracted, 42% of which underwent MP. MP kidneys came from older donors, were more likely to have been obtained following donation after cardiac death, and had longer cold ischemic times. Rates of DGF and rejection were similar between MP and static storage kidneys. Following adjustment, recipients of MP kidneys were less likely to experience rejection at 1 year (OR 0.91 [95% CI 0.86‐0.97] P = .002), but not at 6 months post‐transplantation (OR 0.94 [0.88‐1.02] P = .07). This effect persisted following adjustment for cold ischemic time. This study adds to the accumulating evidence demonstrating improved outcomes following MP of kidneys. We encourage protocolized consideration of MP for kidney grafts.