Decrease of renal resistance during hypothermic oxygenated machine perfusion is associated with early allograft function in extended criteria donation kidney transplantation

Abstract Hypothermic oxygenated machine perfusion (HOPE) was recently tested in preclinical trials in kidney transplantation (KT). Here we investigate the effects of HOPE on extended-criteria-donation (ECD) kidney allografts (KA). Fifteen ECD-KA were submitted to 152 ± 92 min of end-ischemic HOPE and were compared to a matched group undergoing conventional-cold-storage (CCS) KT (n = 30). Primary (delayed graft function-DGF) and secondary (e.g. postoperative complications, perfusion parameters) endpoints were analyzed within 6-months follow-up. There was no difference in the development of DGF between the HOPE and CCS groups (53% vs. 33%, respectively; p = 0.197). Serum urea was lower following HOPE compared to CCS (p = 0.003), whereas the CCS group displayed lower serum creatinine and higher eGFR rates on postoperative days (POD) 7 and 14. The relative decrease of renal vascular resistance (RR) following HOPE showed a significant inverse association with serum creatinine on POD1 (r = − 0.682; p = 0.006) as well as with serum urea and eGFR. Besides, the relative RR decrease was more prominent in KA with primary function when compared to KA with DGF (p = 0.013). Here we provide clinical evidence on HOPE in ECD-KT after brain death donation. Relative RR may be a useful predictive marker for KA function. Further validation in randomized controlled trials is warranted. Trial registration: clinicaltrials.gov (NCT03378817, Date of first registration: 20/12/2017).

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The Use of the Oxygenated AirdriveTM Machine Perfusion System in Kidney Graft Preservation: A Clinical Pilot Study

European Surgical Research ◽

10.1159/000513493 ◽

2020 ◽

Vol 61 (6) ◽

pp. 153-162

Author(s):

Julia H.E. Houtzager ◽

Sebastiaan David Hemelrijk ◽

Ivo C.J.H. Post ◽

Mirza M Idu ◽

Frederike J. Bemelman ◽

...

Keyword(s):

Kidney Transplantation ◽

Pilot Study ◽

Adverse Events ◽

Deceased Donor ◽

Kidney Graft ◽

Machine Perfusion ◽

End Points ◽

Viable Solution ◽

Technical Failures

Background: The shortage of donor kidneys has led to the use of marginal donors, e.g., those whose kidneys are donated after circulatory death. Preservation of the graft by hypothermic machine perfusion (HMP) provides a viable solution to reduce warm ischemic damage. This pilot study was undertaken to assess the feasibility and patient safety of the AirdriveTM HMP system in clinical kidney transplantation. Methods: Five deceased-donor kidneys were preserved using the oxygenated Airdrive HMP system between arrival at the recipient center (Amsterdam UMC) and implantation in the patient. The main study end-points were adverse effects due to the use of Airdrive HMP. Secondary end-points were clinical outcomes and perfusion parameters. All events occurring during the transplantation procedure or within 1 month of follow-up were monitored. Results: Five patients were included in this pilot study. No technical failures were observed during the preservation period using the Airdrive HMP. Mean perfusion parameters were: duration 8.5 h (3–15 h), pressure 25 mm Hg (18–25 mm Hg), flow 49.77 mL/min (19–58 mL/min), resistance 0.57 mm Hg/min/mL (0.34–1.3 mm Hg/min/mL), and temperature 8.2 °C (2–13°C). Mean cold ischemia time (CIT) was 20.2 h (11–29.5 h). No adverse events or technical failures were observed during preservation and transplantation or during the 1-month follow-up. Conclusions: This pilot study showed the feasibility of the use of the Airdrive HMP system with no adverse events in clinical kidney transplantation.

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Conversion from calcineurin inhibitors to sirolimus of recipients with chronic kidney graft disease grade iii for a period 2003-2011

Vojnosanitetski pregled ◽

10.2298/vsp1309848i ◽

2013 ◽

Vol 70 (9) ◽

pp. 848-853 ◽

Cited By ~ 1

Author(s):

Ljiljana Ignjatovic ◽

Rajko Hrvacevic ◽

Dragan Jovanovic ◽

Zoran Kovacevic ◽

Neven Vavic ◽

...

Keyword(s):

Serum Creatinine ◽

Immunosuppressive Therapy ◽

Graft Function ◽

Solid Organ Transplantation ◽

Calcineurin Inhibitors ◽

Solid Organ ◽

Kidney Graft ◽

Group I ◽

Grade Iii

Background/Aim. Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI). At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNIbased immunosuppressive protocol to sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD) grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011 24 patients (6 famale and 18 male), mean age 41 ? 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL and followe-up for 76 ? 13 months. Nine patients (the group I) had early postransplant conversion after 4 ? 3 months and 15 patients (the group II) late conversion after 46 ? 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR), proteinuria, lipidemia and side effects. Results. Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and they were successfully treated with standard therapy. After 21 ? 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients) and double immunosuppressive therapy (3 patients), return to hemodialysis (1 patient) and death (1 patient). Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 ? 12.7 to 69 ? 15 mL/min), while the increase in proteinuria (from 265 ? 239 to 530.6 ? 416.7 mg/day) and lipidemia (cholesterol from 4.71 ? 0.98 to 5.61 ? 1.6 mmol/L and triglycerides from 2.04 ? 1.18 to 2.1 ? 0.72 mmol/L) were not significant. They were stable during the whole follow-up period. Ten patients were reconverted from SRL to CNI due to the abrupt increase of proteinuria (from 298 ? 232 to 1639 ? 1641/mg day in 7 patients), rapid growth of multiple ovarian cysts (2 patients) and operative treatment of persisted hematoma (1 patient). Thirty days after reconversion they were stable with an insignificant decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/min) and significantly improved proteinuria (from 1639 ? 1641 to 529 ? 688 mg/day). By the end of the follow-up these patients showed nonsignificant increase in the serum creatinine (from 172 ? 88 to 202 ? 91 mmol/L), decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/day) and increased proteinuria (from 528.9 ? 688 to 850 ? 1083 mg/min). Conclusion. In this small descriptive study, conversion from CNI to SRL was followed by an increased incidence of infections and consecutive 25-50% dose reduction in the second antiproliferative agent (AZA, MMF), with a possible influence on the development of glomerulopathy in some patients, which was the major reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine (37.5%) of the patients experienced the greatest benefit of CIN to SRL conversion without serious post-conversion complications.

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Machine perfusion versus static cold storage in expanded criteria donor kidney transplantation: 3-year follow-up data

Transplant International ◽

10.1111/tri.12094 ◽

2013 ◽

Vol 26 (6) ◽

pp. E52-E53 ◽

Cited By ~ 27

Author(s):

Anja Gallinat ◽

Cyril Moers ◽

Jacqueline M. Smits ◽

Agita Strelniece ◽

Jacques Pirenne ◽

...

Keyword(s):

Kidney Transplantation ◽

Cold Storage ◽

Machine Perfusion ◽

Donor Kidney ◽

Expanded Criteria Donor ◽

Expanded Criteria ◽

Donor Kidney Transplantation

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Hypothermic Machine Perfusion in DCD Kidney Transplantation: A Single Center Experience

Urologia Internationalis ◽

10.1159/000431025 ◽

2015 ◽

Vol 96 (2) ◽

pp. 148-151 ◽

Cited By ~ 5

Author(s):

Liyu Yao ◽

Honglan Zhou ◽

Yuantao Wang ◽

Gang Wang ◽

Weigang Wang ◽

...

Keyword(s):

Kidney Transplantation ◽

Graft Function ◽

Postoperative Recovery ◽

Donation After Cardiac Death ◽

Machine Perfusion ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Single Center Experience ◽

Hypothermic Machine Perfusion ◽

Significant Difference

Introduction: Donation after cardiac death (DCD) began in 2011 after the program hosted by the First Affiliated Hospital of Sun Yat-sen University in China. The aim of this study is to report on our experience regarding the method of preserving donated kidneys for DCD kidney transplantation. Material and Methods: A total of 37 donors and 73 primary kidney transplant recipients during the period 2011-2014 in the Urology Center of the First Hospital of Jilin University were enrolled in the study. Recipients were assigned to traditional static cold storage (SCS) group and hypothermic machine perfusion (HMP) group based on the preservation environment of donated kidneys after organ harvest. Clinical data were collected for each group. Result: The HMP group had a lower rate of delayed graft function (DGF), better postoperative recovery and kidney function compared with that of SCS group. There is no significant difference in postoperative rejection incidence between the 2 groups. Conclusions: DCD kidneys stored by hypothermic machine contribute to a lower rate of DGF and promoted the rehabilitation progress.

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A triple-biomarker approach for the detection of delayed graft function after kidney transplantation using serum creatinine, cystatin C, and malondialdehyde

Clinical Biochemistry ◽

10.1016/j.clinbiochem.2015.07.007 ◽

2015 ◽

Vol 48 (16-17) ◽

pp. 1033-1038 ◽

Cited By ~ 8

Author(s):

Isabel Fonseca ◽

Henrique Reguengo ◽

José Carlos Oliveira ◽

La Salete Martins ◽

Jorge Malheiro ◽

...

Keyword(s):

Kidney Transplantation ◽

Serum Creatinine ◽

Cystatin C ◽

Graft Function ◽

Delayed Graft Function

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P1749DECEASED DONOR KIDNEY TRANSPLANTATION IN AHUS: A PROPHYLAXIS-FREE APPROACH EXPERIENCE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1749 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Anna Manonelles ◽

Alexandre Favà ◽

Nuria Montero ◽

Edoardo Melilli ◽

Oriol Bestard ◽

...

Keyword(s):

Kidney Transplantation ◽

High Risk ◽

Atypical Hemolytic Uremic Syndrome ◽

Graft Function ◽

Deceased Donor ◽

Donor Kidney ◽

Plasma Therapy ◽

Kidney Donors ◽

Donor Kidney Transplantation

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) has been associated with high risk for recurrence after kidney transplantation. In 2017, a consensus report on aHUS was published by KDIGO working group whereby eculizumab prophylaxis approach was recommended in renal transplantation. Here we report a series of 5 cases of successful deceased donor kidney transplantation in aHUS affected recipients following a preemptive approach free of Eculizumab treatment. Method Five patients with history of end stage kidney disease due to aHUS were eligible for kidney transplantation. All of them had a functional and genetic complement pathway evaluation, showing pathologic mutations to CFI, MCP, CFH and CFB respectively. All of them received a cadaveric donor after a selection of optimal donors with minimal delayed graft function risk and low immunological risk. They accomplished a therapeutic strategy of plasmapheresis prior and in 3 cases 5 days after transplantation. After that, an intensive follow-up was performed with hemolyitic parameters monitoring (blood cell count and extension, LDH, haptoglobin, C3 and C4) regularly. The immediate clinical course was uneventful, without hemodialysis requirements nor biochemical microangiophatic anemia signs. One patient received iMTOR maintenance treatment, three patients received a CNI-based therapy with tacrolimus, mycophenolate and steroids, and one patient was treated with belatacept, mycophenolate and steroids. Results Patients presented an uneventful immediate transplant follow-up, with early graft function recovery and without surgical nor infectious complications. 4 patients completed long follow-up without complications (6 months to 12 years respectively). The patient with belatacept treatment (CFI mutation and MCP risk polymorphism) presented acute aHUS recurrence at 90 days after transplantation, with hypertension, hemolytic anemia, plaquetopenia and acute kidney injury (serum creatinine raised from 115µmol/L to 190µmol/L), but thanks to an early diagnose received immediate treatment with Eculizumab with complete resolution of the event, and with a current optimal outcome of 9 years follow up with normal GFR without proteinuria. Conclusion It has recently been described the potential benefits from living kidney donors and low tacrolimus use to minimize recurrence rates in aSHU, thereby averting endothelial injury. However, deceased donor transplantation is a beneficial option to patients affected of aHUS CKD without living donors. According to our experience, preemptive plasma therapy could be effective in the prevention of immediate disease recurrence in patients with high risk mutations with deceased kidney donors. Precocious diagnose of recurrence is mandatory and a rapid establishment of treatment with eculizumab brings optimal outcomes. A preemptive approach is safe when intensive clinical and analytical controls are performed, and represent a better cost-effective strategy. More evidence to define risk groups and tailor individualized treatments represent a future prospect in these patients.

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A Retrospective Propensity Score Matched Analysis Reveals Superiority of Hypothermic Machine Perfusion over Static Cold Storage in Deceased Donor Kidney Transplantation

Journal of Clinical Medicine ◽

10.3390/jcm9072311 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2311

Author(s):

Silvia Gasteiger ◽

Valeria Berchtold ◽

Claudia Bösmüller ◽

Lucie Dostal ◽

Hanno Ulmer ◽

...

Keyword(s):

Kidney Transplantation ◽

Propensity Score ◽

Graft Survival ◽

Cold Storage ◽

Strong Predictor ◽

Graft Function ◽

Machine Perfusion ◽

Hypothermic Machine Perfusion ◽

Increased Risk ◽

Matching Criteria

Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS in kidney transplantation. All kidney transplants performed between 08/2015 and 12/2019 (n = 347) were propensity score (PS) matched for cold ischemia time (CIT), extended criteria donor (ECD), gender mismatch, cytomegalovirus (CMV) mismatch, re-transplantation and Eurotransplant (ET) senior program. A total of 103 HMP and 103 SCS instances fitted the matching criteria. Prior to PS matching, the CIT was longer in the HMP group (17.5 h vs. 13.3 h; p < 0.001), while the delayed graft function (DGF) rates were 29.8% and 32.3% in HMP and SCS, respectively. In the PS matched groups, the DGF rate was 64.1% in SCS vs. 31.1% following HMP: equivalent to a 51.5% reduction of the DGF rate (OR 0.485, 95% CI 0.318–0.740). DGF was associated with decreased 1- and 3-year graft survival (100% and 96.3% vs. 90.8% and 86.7%, p = 0.001 and p = 0.008) or a 4.1-fold increased risk of graft failure (HR = 4.108; 95% CI: 1.336–12.631; p = 0.014). HMP significantly reduces DGF in kidney transplantation. DGF remains a strong predictor of graft survival.

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P1728FUROSEMIDE STRESS TEST PREDICTS DISCHARGE SERUM CREATININE AFTER KIDNEY TRANSPLANTATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1728 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Armando Coca ◽

Guadalupe Tabernero ◽

Carlos Arias-Cabrales ◽

Jimmy Reinaldo Sanchez Gil ◽

Jose Antonio Menacho Miguel ◽

...

Keyword(s):

Kidney Transplantation ◽

Serum Creatinine ◽

Stress Test ◽

Graft Function ◽

Deceased Donor ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Donor Kidney ◽

Deceased Donor Kidney ◽

Deceased Donor Kidney Transplant

Abstract Background and Aims Acute tubular necrosis is a common complication after kidney transplantation and is closely related to delayed graft function (DGF) and slower graft function recovery after surgery. The furosemide stress test (FST) uses a standardized dose of furosemide to evaluate the integrity of the renal tubule and determine which patients have developed severe tubular damage. We aimed to apply the FST to a sample of incident deceased-donor kidney transplant recipients and describe its association with DGF and serum creatinine (SCr) at discharge. Method Single-center prospective observational study of deceased-donor kidney transplant recipients. The FST, a standardized bolus dose of furosemide (1.5 mg/kg) was administered between the 3rd and 5th day after surgery. Patients were excluded if, during that time period, they presented evidence of active bleeding, obstructive uropathy or volume depletion. Urine output (UO) 60 and 120 min after FST was registered. To reduce the risk of hypovolemia, each ml of UO produced for six hours after FST was replaced with 1 ml of normal saline. Results 25 patients were included in the study. Mean 2h FST UO was 1012±570 ml. Demographic and clinical data are summarized in Table 1. Subjects that suffered DGF had a significantly lower 2h FST UO (534 vs 1164 ml; P=0.015). In adjusted linear regression analysis only a 2h FST UO<1000 ml (β=0.906; 95%CI: 0.04-1.772; P=0.041) and DGF (β=1.592; 95%CI: 0.488-2.696; P=0.008) were independent predictors of SCr at discharge (model adjusted for recipient age, cold ischemia time, number of HLA mismatches, donor SCr and donor hypertension). Conclusion Recipients with a 2h FST UO <1000 ml suffered DGF more frequently. FST and DGF were independent predictors of SCr at discharge. A standardized FST could help clinicians distinguish patients with more severe tubular dysfunction and higher risk of DGF.

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Machine Perfusion Following Static Cold Storage in Kidney Transplantation Decreases the Duration of Delayed Graft Function and Time to Hospital Discharge.

Transplantation Journal ◽

10.1097/00007890-201407151-02019 ◽

2014 ◽

Vol 98 ◽

pp. 598

Author(s):

A. Pacheco-Silva ◽

Borrelli M. Junior ◽

L. Moura-Requiao ◽

Souza M. Durao Junior ◽

Nogueira M. Junior ◽

...

Keyword(s):

Kidney Transplantation ◽

Hospital Discharge ◽

Cold Storage ◽

Graft Function ◽

Delayed Graft Function ◽

Machine Perfusion

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MO975INFLUENCE OF THE TYPE OF DIALYSIS ON SHORT-TERM KIDNEY TRANSPLANT RESULTS. EXPERIENCE OF OUR CENTER

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab110.0054 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Maria Lanau Martinez ◽

Marta Artamendi Larrañaga ◽

Celia Garijo Pacheco ◽

Iñigo Gaston Najarro ◽

Guillermo Pereda Bengoa ◽

...

Keyword(s):

Renal Function ◽

Kidney Transplantation ◽

Acute Rejection ◽

Graft Function ◽

Vascular Complications ◽

Group Versus ◽

Infectious Complications ◽

Delayed Graft Function ◽

Dialysis Technique

Abstract Background and Aims Kidney transplantation (KT) is considered to be the best option for renal replacement therapy (RRT) in patients with advanced chronic kidney disease, surpassing any dialysis technique in quality and life expectancy. However, results in terms of how pre-KT dialysis technique influences graft and recipient survival are mixed. Some studies show a higher incidence of vascular complications in the immediate post-transplant period and higher rates of acute rejection in patients coming from peritoneal dialysis (PD) versus those coming from hemodialysis (HD) while others observe a lower incidence of delayed graft function in the PD group of patients versus those on HD. Our objective is to analyze if there are differences in immediate post-kidney transplantation and at 6 months of follow-up depending on the pre-KT dialysis technique, PD versus HD. Method Observational study of all patients with KT of cadaveric donor from the beginning of the KT program in our Center, from August 2011 to August 2019. We analyzed the characteristics of donors and recipients according to the technique (PD/HD), the evolution and complications in the immediate post-KT, as well as results at 6 months of follow-up in terms of complications, renal function and survival of the recipient and the graft. For statistical analysis we used SPSS 25. We compared qualitative variables by means of Xi2 test, and quantitative variables by t of Student, or U of Mann-Whitney if the variables did not follow a normal distribution. A value of p <0.05 was considered significant. Results 121 patients were included, 71 of whom were in the HD group, versus 50 who were in the PD group. The recipients in the HD group were significantly older (57.2 vs 51.6 years, p 0,02) and stayed on dialysis longer (33.8 vs 26.8 months). We observed no difference in the recipient's cardiovascular history, except for increased smoking in the HD group (52.1% vs. 24%). The donor-recipient immune profile was similar in both groups. As for the incidence of delayed graft function, it was significantly lower in the PD group (14.9% vs 34.3%), finding no difference in renal function at hospital discharge or in days of admission. In the first 6 months of follow-up, we found no differences in terms of vascular, urological or infectious complications. There were also no differences in the incidence of acute rejection, renal function measured by creatinine (HD 1.47 vs DP 1.50 mg/dl) and proteinuria (HD 200 vs DP 216 mg/24 hours). Graft and recipient survival at 6 months of TR follow-up were similar in both groups. Conclusion In our experience, we have not found differences in the evolution at 6 months of the KT according to the modality of dialysis , nor greater incidence of vascular, immunological or other complications, with a survival of graft and receptor superimposable between both groups, PD or HD.

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