Effect of Delayed Graft Function on the Outcome and Allograft Survival of Kidney Transplanted Patients from a Deceased Donor

Abstract Background: African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. Methods: Outcomes from 3,872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. Results: Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR=0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. Conclusion: Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.

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Shorter Cold Ischemia Time in Deceased Donor Kidney Transplantation Reduces the Incidence of Delayed Graft Function Especially Among Highly Sensitized Patients and Kidneys From Older Donors

Transplantation Proceedings ◽

10.1016/j.transproceed.2019.11.025 ◽

2020 ◽

Vol 52 (1) ◽

pp. 42-49 ◽

Cited By ~ 1

Author(s):

Jouni Lauronen ◽

Juha P. Peräsaari ◽

Timo Saarinen ◽

Taina Jaatinen ◽

Marko Lempinen ◽

...

Keyword(s):

Kidney Transplantation ◽

Graft Function ◽

Deceased Donor ◽

Delayed Graft Function ◽

Cold Ischemia Time ◽

Cold Ischemia ◽

Donor Kidney ◽

Deceased Donor Kidney ◽

Donor Kidney Transplantation ◽

Deceased Donor Kidney Transplantation

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Endogenous intronic antisense long non-coding RNA, MGAT3-AS1, and kidney transplantation

Scientific Reports ◽

10.1038/s41598-019-51409-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Subagini Nagarajah ◽

Shengqiang Xia ◽

Marianne Rasmussen ◽

Martin Tepel

Keyword(s):

Kidney Transplantation ◽

Predictive Value ◽

Graft Function ◽

Deceased Donor ◽

Delayed Graft Function ◽

Transplant Recipients ◽

Donor Kidney ◽

Non Coding Rna ◽

Deceased Donor Kidney ◽

Long Non Coding Rna

Abstract β-1,4-mannosylglycoprotein 4-β-N-acetylglucosaminyltransferase (MGAT3) is a key molecule for the innate immune system. We tested the hypothesis that intronic antisense long non-coding RNA, MGAT3-AS1, can predict delayed allograft function after kidney transplantation. We prospectively assessed kidney function and MGAT3-AS1 in 129 incident deceased donor kidney transplant recipients before and after transplantation. MGAT3-AS1 levels were measured in mononuclear cells using qRT-PCR. Delayed graft function was defined by at least one dialysis session within 7 days of transplantation. Delayed graft function occurred in 22 out of 129 transplant recipients (17%). Median MGAT3-AS1 after transplantation was significantly lower in patients with delayed graft function compared to patients with immediate graft function (6.5 × 10−6, IQR 3.0 × 10−6 to 8.4 × 10−6; vs. 8.3 × 10−6, IQR 5.0 × 10−6 to 12.8 × 10−6; p < 0.05). The median preoperative MGAT3-AS1 was significantly lower in kidney recipients with delayed graft function (5.1 × 10−6, IQR, 2.4 × 10−6 to 6.8 × 10−6) compared to recipients with immediate graft function (8.9 × 10−6, IQR, 6.8 × 10−6 to 13.4 × 10−6; p < 0.05). Receiver-operator characteristics showed that preoperative MGAT3-AS1 predicted delayed graft function (area under curve, 0.83; 95% CI, 0.65 to 1.00; p < 0.01). We observed a positive predictive value of 0.57, and a negative predictive value of 0.95. Long non-coding RNA, MGAT3-AS1, indicates short-term outcome in patients with deceased donor kidney transplantation.

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Early Sirolimus Conversion as Rescue Therapy in Kidneys With Prolonged Delayed Graft Function in Deceased Donor Renal Transplant

Transplantation Proceedings ◽

10.1016/j.transproceed.2015.04.102 ◽

2015 ◽

Vol 47 (6) ◽

pp. 1610-1615 ◽

Cited By ~ 4

Author(s):

W. Tahir ◽

A. Hakeem ◽

M. Dawrant ◽

P. Prasad ◽

M. Lee ◽

...

Keyword(s):

Renal Transplant ◽

Rescue Therapy ◽

Graft Function ◽

Deceased Donor ◽

Delayed Graft Function

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Gene Expression Patterns in Deceased Donor Kidneys Developing Delayed Graft Function After Kidney Transplantation

Transplantation Journal ◽

10.1097/tp.0b013e318165491f ◽

2008 ◽

Vol 85 (4) ◽

pp. 626-635 ◽

Cited By ~ 25

Author(s):

Valeria R. Mas ◽

Kellie J. Archer ◽

Kenneth Yanek ◽

Catherine I. Dumur ◽

Maria I. Capparuccini ◽

...

Keyword(s):

Gene Expression ◽

Kidney Transplantation ◽

Expression Patterns ◽

Graft Function ◽

Deceased Donor ◽

Delayed Graft Function ◽

Gene Expression Patterns

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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.

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