Quantifying Donor Effects on Transplant Outcomes Using Kidney Pairs from Deceased Donors

Background and objectivesIn kidney transplantation, the relative contribution of donor versus other factors on clinical outcomes is unknown. We sought to quantify overall donor effects on transplant outcomes for kidney donations from deceased donors.Design, setting, participants, & measurementsFor paired donations from deceased donors resulting in transplants to different recipients, the magnitude of donor effects can be quantified by examining the excess of concordant outcomes within kidney pairs beyond chance concordance. Using data from the Organ Procurement and Transplantation Network between the years 2013 and 2017, we examined concordance measures for delayed graft function, death-censored 1-year graft failure, and death-censored 3-year graft failure. The concordance measures were excess relative risk, excess absolute risk, and the fixation index (where zero is no concordance and one is perfect concordance). We further examined concordance in strata of kidneys with similar values of the Kidney Donor Profile Index, a common metric of organ quality.ResultsIf the transplant of the kidney mate resulted in delayed graft function, risk for delayed graft function was 19% higher (95% confidence interval [95% CI], 18% to 20%), or 1.76-fold higher (95% CI, 1.73- to 1.80-fold), than baseline. If a kidney graft failed within 1 year, then the kidney mate’s risk of failure was 6% higher (95% CI, 4% to 9%), or 2.85-fold higher (95% CI, 2.25- to 3.48-fold), than baseline. For 3-year graft failure, the excess absolute risk was 7% (95% CI, 4% to 10%) but excess relative risk was smaller, 1.91-fold (95% CI, 1.56- to 2.28-fold). Fixation indices were 0.25 for delayed graft function (95% CI, 0.24 to 0.27), 0.07 for 1-year graft failure (95% CI, 0.04 to 0.09), and 0.07 for 3-year graft failure (95% CI, 0.04 to 0.10). Results were similar in strata of kidneys with a similar Kidney Donor Profile Index.ConclusionsOverall results indicated that the donor constitution has small or moderate effect on post-transplant clinical outcomes.

Download Full-text

Rate, Factors, and Outcome of Delayed Graft Function After Kidney Transplantation of Deceased Donors

Transplantation Proceedings ◽

10.1016/j.transproceed.2021.01.006 ◽

2021 ◽

Author(s):

Laura Jahn ◽

Christiane Rüster ◽

Mandy Schlosser ◽

Yvonne Winkler ◽

Susan Foller ◽

...

Keyword(s):

Kidney Transplantation ◽

Graft Function ◽

Delayed Graft Function ◽

Deceased Donors

Download Full-text

MO941CLINICAL OUTCOMES IN KIDNEY RE-TRANSPLANTATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab110.0020 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Clara Pardinhas ◽

Rita Leal ◽

Francisco Caramelo ◽

Teofilo Yan ◽

Carolina Figueiredo ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Graft Survival ◽

Graft Failure ◽

Graft Function ◽

Delayed Graft Function ◽

First Year ◽

Kidney Transplant Recipients ◽

Post Transplant

Abstract Background and Aims As kidney transplants are growing in absolute numbers, so are patients with failed allografts and thus potential candidates for re-transplantation. Re-transplantation is challenging due to immunological barriers, surgical difficulties and clinical complexities but it has been proven that successful second transplantation improves life expectancy over dialysis. It is important to evaluate re-transplantation outcomes since 20% of patients on the waiting list are waiting for a second graft. Our aim was to compare major clinical outcomes such as acute rejection, graft and patient survival, between patients receiving a first or a second kidney transplant. Method We performed a retrospective study, that included 1552 patients submitted to a first (N=1443, 93%) or a second kidney transplant (N=109, 7%), between January 2008 and December 2018. Patients with more than 2 grafts or multi-organ transplant were excluded. Demographic, clinical and histocompatibility characteristics of both groups were registered from our unit database and compared. Delayed graft function was defined has the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up time was defined at 1st June 2020 for functioning grafts or at graft failure (including death with a functioning graft). Results Recipients of a second graft were significantly younger (43 ±12 vs 50 ± 13 years old, p<0.001) and there were significantly fewer expanded-criteria donors in the second transplant group (31.5% vs 57.5%, p<0.001). The waiting time for a second graft was longer (63±50 vs 48±29 months, p=0.011). HLA mismatch was similar for both groups but PRA was significantly higher for second KT patients (21.6±25% versus 3±9%; p<0.001). All patients submitted to a second KT had thymoglobulin as induction therapy compared to 16% of the first KT group (p<0.001). We found no difference in primary dysfunction or delayed graft function between groups. Acute rejection was significantly more frequent in second kidney transplant recipients (19% vs 5%, p<0.001), being 10 acute cellular rejections, 7 were antibody mediated and 3 were borderline changes. For the majority of the patients (85%), acute rejection occurred in the first-year post-transplant. Death censored graft failure occurred in 236 (16.4%) patients with first kidney transplant and 25 (23%) patients with a second graft, p=0.08. Survival analysis showed similar graft survival for both groups (log-rank p=0.392). We found no difference in patients’ mortality at follow up for both groups. Conclusion Although second graft patients presented more episodes of biopsy proven acute rejection, especially at the first-year post-transplant, we found no differences in death censored graft survival or patients’ mortality for patients with a second kidney transplant. Second transplants should be offered to patients whenever feasible.

Download Full-text

Clinical significance of the Kidney Donor Profile Index in deceased donors for prediction of post-transplant clinical outcomes: A multicenter cohort study

PLoS ONE ◽

10.1371/journal.pone.0205011 ◽

2018 ◽

Vol 13 (10) ◽

pp. e0205011 ◽

Cited By ~ 3

Author(s):

Jong Hoon Lee ◽

Woo Yeong Park ◽

Young Soo Kim ◽

Bum Soon Choi ◽

Cheol Whee Park ◽

...

Keyword(s):

Cohort Study ◽

Clinical Outcomes ◽

Clinical Significance ◽

Kidney Donor ◽

Multicenter Cohort Study ◽

Post Transplant ◽

Multicenter Cohort ◽

Deceased Donors

Download Full-text

Three-Year Outcomes of a Randomized, Double-Blind, Placebo-Controlled Study Assessing Safety and Efficacy of C1 Esterase Inhibitor for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplant Recipients

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.04840419 ◽

2019 ◽

Vol 15 (1) ◽

pp. 109-116 ◽

Cited By ~ 6

Author(s):

Edmund Huang ◽

Ashley Vo ◽

Jua Choi ◽

Noriko Ammerman ◽

Kathlyn Lim ◽

...

Keyword(s):

Confidence Interval ◽

Graft Failure ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Controlled Trial ◽

Graft Function ◽

Deceased Donor ◽

Delayed Graft Function ◽

C1 Esterase Inhibitor ◽

Esterase Inhibitor

Background and objectivesDelayed graft function is related to ischemia-reperfusion injury and may be complement dependent. We previously reported from a randomized, placebo-controlled trial that treatment with C1 esterase inhibitor was associated with a shorter duration of delayed graft function and higher eGFR at 1 year. Here, we report longer-term outcomes from this trial.Design, setting, participants, & measurementsThis is a post hoc analysis of a phase 1/2, randomized, controlled trial enrolling 70 recipients of deceased donor kidney transplants at risk for delayed graft function (NCT02134314). Subjects were randomized to receive C1 esterase inhibitor 50 U/kg (n=35) or placebo (n=35) intraoperatively and at 24 hours. The cumulative incidence functions method was used to compare graft failure and death over 3.5 years. eGFR slopes were compared using a linear mixed effects model.ResultsThree deaths occurred among C1 esterase inhibitor–treated patients compared with none receiving placebo. Seven graft failures developed in the placebo group compared with one among C1 esterase inhibitor–treated recipients; the cumulative incidence of graft failure was lower over 3.5 years among C1 esterase inhibitor–treated recipients compared with placebo (P=0.03). Although no difference in eGFR slopes was observed between groups (P for group-time interaction =0.12), eGFR declined in placebo-treated recipients (−4 ml/min per 1.73 m2 per year; 95% confidence interval, −8 to −0.1) but was stable in C1 esterase inhibitor–treated patients (eGFR slope: 0.5 ml/min per 1.73 m2 per year; 95% confidence interval, −4 to 5). At 3.5 years, eGFR was 56 ml/min per 1.73 m2 (95% confidence interval, 42 to 70) in the C1 esterase inhibitor group versus 35 ml/min per 1.73 m2 (95% confidence interval, 21 to 48) in the placebo group, with an estimated mean eGFR difference of 21 ml/min per 1.73 m2 (95% confidence interval, 2 to 41 ml/min per 1.73 m2).ConclusionsTreatment of patients at risk for ischemia-reperfusion injury and delayed graft function with C1 esterase inhibitor was associated with a lower incidence of graft failure.

Download Full-text

Delayed graft function requiring more than one-time dialysis treatment is associated with inferior clinical outcomes

Clinical Transplantation ◽

10.1111/ctr.12029 ◽

2012 ◽

Vol 26 (5) ◽

pp. E536-E543 ◽

Cited By ~ 21

Author(s):

Deepa Jayaram ◽

Mallika Kommareddi ◽

Randall S. Sung ◽

Fu L. Luan

Keyword(s):

Clinical Outcomes ◽

Graft Function ◽

Delayed Graft Function ◽

Dialysis Treatment

Download Full-text

Artificial Intelligence—A Tool for Risk Assessment of Delayed-Graft Function in Kidney Transplant

Journal of Clinical Medicine ◽

10.3390/jcm10225244 ◽

2021 ◽

Vol 10 (22) ◽

pp. 5244

Author(s):

Andrzej Konieczny ◽

Jakub Stojanowski ◽

Klaudia Rydzyńska ◽

Mariusz Kusztal ◽

Magdalena Krajewska

Keyword(s):

Machine Learning ◽

Risk Assessment ◽

Kidney Transplant ◽

Graft Function ◽

Deceased Donor ◽

Delayed Graft Function ◽

Clinical Tool ◽

Kidney Donor ◽

Common Input ◽

Discriminant Ability

Delayed-graft function (DGF) might be responsible for shorter graft survival. Therefore, a clinical tool predicting its occurrence is vital for the risk assessment of transplant outcomes. In a single-center study, we conducted data mining and machine learning experiments, resulting in DGF predictive models based on random forest classifiers (RF) and an artificial neural network called multi-layer perceptron (MLP). All designed models had four common input parameters, determining the best accuracy and discriminant ability: donor’s eGFR, recipient’s BMI, donor’s BMI, and recipient–donor weight difference. RF and MLP designs, using these parameters, achieved an accuracy of 84.38% and an area under curve (AUC) 0.84. The model additionally implementing a donor’s age, gender, and Kidney Donor Profile Index (KDPI) accomplished an accuracy of 93.75% and an AUC of 0.91. The other configuration with the estimated post-transplant survival (EPTS) and the kidney donor risk profile (KDRI) achieved an accuracy of 93.75% and an AUC of 0.92. Using machine learning, we were able to assess the risk of DGF in recipients after kidney transplant from a deceased donor. Our solution is scalable and can be improved during subsequent transplants. Based on the new data, the models can achieve better outcomes.

Download Full-text

Donor Age, Cold Ischemia Time, and Delayed Graft Function

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.13711119 ◽

2020 ◽

Vol 15 (6) ◽

pp. 813-821 ◽

Cited By ~ 1

Author(s):

Ilkka Helanterä ◽

Hassan N. Ibrahim ◽

Marko Lempinen ◽

Patrik Finne

Keyword(s):

Graft Function ◽

The United States ◽

Delayed Graft Function ◽

Cold Ischemia Time ◽

Donation After Circulatory Death ◽

Donor Age ◽

Cold Ischemia ◽

Kidney Donor ◽

Ischemia Time ◽

Circulatory Death

Background and objectivesIncreased donor age is one of the most important risk factors for delayed graft function (DGF), and previous studies suggest that the harmful effect of cold ischemia time is increased in kidneys from older donors. Our aim was to study the association of increased donor age and cold ischemia time with the risk of delayed graft function in a large cohort kidney transplants from the current era.Design, setting, participants, & measurementsThe Scientific Registry of Transplant Recipients was used for this observational, retrospective registry analysis to identify all deceased donor kidney transplantations in the United States between 2010 and September 2018, who were on dialysis pretransplantation (n=90,810). The association of donor age and cold ischemia time with the risk of DGF was analyzed in multivariable models adjusted for recipient characteristics (age, race, sex, diabetes, calculated panel-reactive antibodies, pretransplant dialysis duration) and donor characteristics (cause of death, sex, race, body mass index, creatinine, donation after circulatory death status, history of hypertension, and HLA mismatch).ResultsCold ischemia time and donor age were independently associated with the risk of DGF, but the risk of DGF was not statistically significantly lower in donor age categories between 50 and 64 years, compared with donors ≥65 years. The harmful association of cold ischemia time was not higher in kidneys from older donors in any age category, not even among donation after circulatory death donors. When donor risk was assessed with kidney donor profile index, although a statistically significant interaction with cold ischemia time was found, no practically meaningful increase in cold-ischemia susceptibility of kidneys with a high kidney donor profile index was found.ConclusionsWe were unable to demonstrate an association between donor age and DGF. The association of longer cold ischemia time with the risk of DGF was not magnified in older or more marginal donors.

Download Full-text