Monocyte-Derived Dendritic Cells Impair Early Graft Function following Allogeneic Islet Transplantation

Islet transplantation can cure type 1 diabetes but is limited by lack of donor organs and early graft dysfunction, such that many patients require multiple transplants to achieve insulin independence. Monocyte-derived dendritic cells (moDCs) arise during inflammation and allograft encounters where they can promote various innate and adaptive immune responses. To determine whether moDCs impair early graft function following allogeneic islet transplantation, we transplanted MHC-mismatched BALB/c (H-2d) islets into diabetic C57BL/6-CCR2. DTR recipients (H-2b) treated with either saline (control) or diphtheria toxin (DT) to deplete moDCs. Graft function was assessed by blood glucose (BG) measurement. DT treatment resulted in specific depletion of graft site moDCs posttransplant. Despite equivalent pretransplant BG levels [27.0 ± 1.3 vs. 29.6 ± 1.1 mM, not significant (ns)], DT recipients achieved lower posttransplant BG levels and better rates of normoglycemia than control recipients (11.0 ± 1.9 vs. 19.1 ± 1.4 mM, p = 0.004) at 1 day posttransplant in diabetic recipients. When a suboptimal donor dose of 200 islets was transplanted, DT-induced moDC depletion resulted in normoglycemia in 78% compared to 25% of control recipients ( p = 0.03). As well as amelioration of graft dysfunction in the immediate peritransplant period, prolonged DT administration (15 days posttransplant) resulted in improved graft survival (21 vs. 11 days, p = 0.005). moDCs impair early graft function post-allogeneic islet transplantation. moDC depletion may allow for improved early graft function, permit transplantation with lower islet masses, and enhance graft survival.

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Value of Plasmatic Villin-1 in the prediction of early graft dysfunction in kidney transplant recipients among Egyptian population

QJM ◽

10.1093/qjmed/hcab100.116 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

M.A Ezzat ◽

M El Tayeb ◽

H Abou Ellail ◽

W Anwar ◽

N Teama

Keyword(s):

Serum Creatinine ◽

Kidney Transplant ◽

Reference Range ◽

Normal Population ◽

Graft Function ◽

Delayed Graft Function ◽

Graft Dysfunction ◽

Early Graft ◽

Esrd Patients ◽

Early Graft Dysfunction

Abstract Background One of the main complications of kidney transplantation is delayed graft function (DGF). There has been enormous growing research interest in the potential for the rapidly expanding fields of medical technology to generate new biomarkers with the aim of early prediction of DGF and modifying its therapy accordingly. Villin-1 has been detected in urine of patients with AKI. Additionally, it is redistributed during AKI from the brush borders of the proximal tubular cells toward the basolateral membrane which positions villin-1 closer to the renal vasculature and suggests that it could be released in the blood as well, so can be as a novel biomarker for DGF. Methods Of 70 patients with end-stage renal disease with one or more risk factor for developing delayed graft function attending renal transplantation preparation clinics in ASUSH, IMC and NILE Badrawi hospital in Egypt from May 2016 to July 2019, 41 patients were eligible and assigned into two groups according to the correlation with the serum creatinine levels in the first two days post-transplantation after signed informed consent for participation in our study into group 1 (DGF group) and group 2 (NGF group). We measured the presence of villin-1 by ELISA technique (quantitative) in comparison to serum creatinine levels in plasma at the time of declamping (zero level), 1st, 3rd, 5th, 7th, 12th, 24th, 48th, 72th 96th, 120th hour post declamping, also samples from normal population and chronic kidney disease stage V patients have been collected to establish reference range guide for plasmatic villin-1 in both groups. Results Statistically significant differences were noted in the comparison between both groups as regard the plasmatic villin-1 levels at the same measurement points in both groups, also plasmatic villin-1 started to rise above its reference range in the ESRD patients at the 5th hour post declamping while its peak was at the 7th hour in the DGF group’s recipients then started to decrease after that but didn’t settle down between the reference range guide during the regular follow up of its level till the 120th hour post declamping. the reference range guide was from 0.08 and 0.35 ng\ml in males and from 0.055 to 0.35 ng\ml in females in normal population while from 0.38 and 1.4 ng\ml in males and from 0.28 to 1.1 ng\ml in females in the ESRD patients. Conclusions Plasmatic villin-1 is a promising novel biomarker for detection of early graft dysfunction in kidney transplant. Due to restrictions of the study design these observations need further confirmation by prospective studies.

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Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality

Frontiers in Surgery ◽

10.3389/fsurg.2021.693288 ◽

2021 ◽

Vol 8 ◽

Author(s):

Margot Fodor ◽

Adriana Woerdehoff ◽

Wolfgang Peter ◽

Hannah Esser ◽

Rupert Oberhuber ◽

...

Keyword(s):

Liver Transplantation ◽

Graft Survival ◽

Predictive Value ◽

Liver Graft ◽

Rank Test ◽

Graft Dysfunction ◽

Log Rank Test ◽

Early Graft ◽

Early Graft Dysfunction ◽

Patient And Graft Survival

Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival.Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7.Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity.Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.

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Pretransplantation hemodialysis strategy influences early renal graft function.

Journal of the American Society of Nephrology ◽

10.1681/asn.v93473 ◽

1998 ◽

Vol 9 (3) ◽

pp. 473-481 ◽

Cited By ~ 1

Author(s):

A A Van Loo ◽

R C Vanholder ◽

P R Bernaert ◽

F E Vermassen ◽

M Van der Vennet ◽

...

Keyword(s):

Renal Failure ◽

Renal Function ◽

Kidney Transplantation ◽

Graft Function ◽

Graft Dysfunction ◽

Urinary Volume ◽

Renal Graft ◽

Functional Differences ◽

Early Graft ◽

Early Graft Dysfunction

The influence of the pretransplantation hemodialysis strategy on early renal graft function was evaluated in 44 patients receiving hemodialysis in the 24 h preceding kidney transplantation and in 13 patients receiving hemodialysis more than 24 h before transplantation. The patients dialyzed less than 24 h before transplantation were stratified according to treatment with or without complement-activating dialyzers (cuprophane, bioincompatible membrane [BICM] versus polysulfone, biocompatible membrane [BCM]) and with or without ultrafiltration (UF). Serum creatinine (Scr) at days 0, 2, 5, 10, and 30, the time for Scr to decrease 50% (T1/2Scr), the incidence of acute renal failure (ARF; defined as urinary volume < 500 ml/d and/or necessity for posttransplantation hemodialysis), and early graft dysfunction (defined as T1/2Scr > 3.5 d) were registered. Scr was higher in BCM- versus BICM-treated patients (P < 0.0001 by variance analysis) and in patients receiving UF versus those receiving no UF (P = 0.0009). T1/2Scr was higher in treatment with BICM versus BCM (7.4 +/- 7.9 versus 3.1 +/- 2.9 d; P < 0.05) and UF versus no UF (7.1 +/- 7.7 versus 2.7 +/- 2.0 d; P < 0.01). The evolution of Scr was markedly more favorable in the patient group treated with BCM without UF (T1/2Scr 1.7 +/- 0.8 d) compared with the group treated with BICM and UF (T1/2Scr 9.3 +/- 9.1 d; P < 0.01). The remaining groups (BICM without UF and BCM with UF) showed intermediate results. The incidence of ARF and early graft dysfunction was higher in the group on BICM with UF compared to BCM without UF. Functional differences persisted up to 1 mo after transplantation. Patients who underwent dialysis with UF more than 24 h before transplantation had a more beneficial evolution of renal function parameters than those who were dialyzed with UF less than 24 h before transplantation. In conclusion, the use of BICM and the application of UF within 24 h before kidney transplantation enhance the risk of posttransplantation ARF and early graft dysfunction.

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