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New Advances in Kidney Transplantation 2.0
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New Advances in Kidney Transplantation 2.0

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (25 October 2023) | Viewed by 5287

Special Issue Editor

Prof. Dr. Eytan Mor

E-Mail Website
Guest Editor
1. Transplant Center, Department of Surgery B, Sheba Medical Center, Ramat-Gan, Israel
2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Interests: organ transplantation; immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

You are invited to contribute to a Special Issue on advances in kidney transplantation. Kidney transplantation has evolved over the last 50 years to become the treatment of choice for patients with end-stage renal disease. The introduction of new immunosuppressive medications in the 1980s and early 1990s has been associated with a significant improvement in graft survival, reaching a median survival of 15 years. However, two major hurdles have yet to be overcome—one is the development of chronic allograft nephropathy, which limits graft survival, and the other is limited organ supply, which makes kidney transplantation unavailable to many patients.

This Special Issue will focus on new advances that may address these issues. First, in respect to prolonging graft survival, in recent years there has been an increased interest in improving organ quality by using machine preservation for marginal kidneys, especially those that are coming from donors after cardiac death (DCDs). Another innovative development that may be shortly introduced into the clinic are biomarkers in the peripheral blood or urine specimens of transplanted patients to better predict rejection, and the use of these biomarkers to direct immunosuppressive therapy in a personalized manner. Tolerance induction has recently been a new target of clinical research, with several protocols for combined kidney and bone-marrow-derived cells transplantation. This approach aims to lessen drug nephrotoxicity and prolong graft survival. Given the success obtained from the first edition of this Special Issue, we decided to repropose this topic.

Regarding the direction of expanding the number of kidneys for transplant, three topics will be discussed, including different approaches to increasing the number of live-donor kidney transplants by using ABO-incompatible transplants, desensitization protocols, and pair exchange programs. Lastly, in looking to the future, we will review current research to develop bioengineered and artificial kidneys.

Prof. Dr. Eytan Mor
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • kidney transplantation
  • machine perfusion
  • tolerance
  • biomarkers
  • organ engineering
  • altruistic donation

Published Papers (4 papers)

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15 pages, 1793 KiB  
Article
Living Donors’ Age Modifies the Impact of Pre-Donation Estimated Glomerular Filtration Rate on Graft Survival
by Manuela Almeida, Catarina Ribeiro, José Silvano, Sofia Pedroso, Sandra Tafulo, La Salete Martins, Miguel Ramos and Jorge Malheiro
J. Clin. Med. 2023, 12(21), 6777; https://doi.org/10.3390/jcm12216777 - 26 Oct 2023
Viewed by 684
Abstract
Background: The global scarcity of organs for kidney transplants (KTs) has led to the increased acceptance of living donors (LDs) with minor abnormalities to increase the donor pool.. We sought to evaluate the effects of some of these LDs’ clinical characteristics (older age, [...] Read more.
Background: The global scarcity of organs for kidney transplants (KTs) has led to the increased acceptance of living donors (LDs) with minor abnormalities to increase the donor pool.. We sought to evaluate the effects of some of these LDs’ clinical characteristics (older age, borderline renal function, hypertension, dyslipidemia, smoking, and obesity) on graft outcomes. Methods: We studied 352 recipients of LDKTs (1998–2020). Firstly, considering the recipients and KT variables, we identified relevant predictors of overall and censored graft failure (GF). Then, adjusting for these predictors, we explored LD variables as predictors of overall and censored GF in a multivariable Cox model. Results: The recipients from LD with higher eGFR (≥90 mL/min/1.73 m2) had significantly better overall and censored graft survival GS) at 15 y after KT (respectively, 67 and 75% vs. 46 and 46%, p < 0.001). Importantly, none of the remaining LD factors which were evaluated (hypertension, dyslipidemia, smoking, proteinuria, and obesity) were independent predictors of GF. In recipients from LDs < 50 y, having an eGFR < 90 was an independent predictor of overall GF [adjusted HR (95%CI) of 2.578 (1.120–5.795)] and censored GF [adjusted HR (95%CI) of 3.216 (1.300–7.959)], compared to recipients from LDs with eGFR ≥ 90. Contrarily, when donors were older, no difference in the risk of GF was observed between eGFR categories. Conclusion: In our cohort, lower pre-donation eGFR had an impact on GS only in younger LDs. An age-adjusted eGFR cutoff may be pursued for improved donor admissibility. Full article
(This article belongs to the Special Issue New Advances in Kidney Transplantation 2.0)
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11 pages, 540 KiB  
Article
Differential Cytokine Levels during Normothermic Kidney Perfusion with Whole Blood- or Red Blood Cell-Based Perfusates—Results of a Scoping Review and Experimental Study
by Julie De Beule, Delphine Keppens, Hannelie Korf and Ina Jochmans
J. Clin. Med. 2022, 11(22), 6618; https://doi.org/10.3390/jcm11226618 - 8 Nov 2022
Cited by 2 | Viewed by 1182
Abstract
The ideal composition of the perfusate for normothermic kidney perfusion is unknown, though the perfusate commonly used to perfuse human kidneys contains leukocyte-depleted packed red blood cells (RBC), as this is believed to prevent excessive inflammation. We performed a systematic search identifying 19 [...] Read more.
The ideal composition of the perfusate for normothermic kidney perfusion is unknown, though the perfusate commonly used to perfuse human kidneys contains leukocyte-depleted packed red blood cells (RBC), as this is believed to prevent excessive inflammation. We performed a systematic search identifying 19 articles reporting on cytokine levels during normothermic pig or human kidney perfusion. Cytokine levels varied widely across the reported studies. No direct comparisons of perfusate cytokines during perfusion with RBC or whole blood were performed, and no data on how these levels are influenced by ischemia are available. Therefore, we compared perfusate IL-6, IL-1β, TNF-α, TGF-β, IL-10, IL-8, and CCL2 levels during 4 h normothermic pig kidney perfusion with a whole blood- or RBC-based perfusate. Kidneys were exposed to either 1 h of warm or 22 h of cold ischemia. We found no evidence of different perfusate cytokine or gene expression levels in whole blood or RBC perfusions. There was no clear evidence to suggest that cytokine concentrations differ between ischemically injured kidneys and controls. In conclusion, pro-inflammatory and anti-inflammatory cytokines and chemokines are detectable in the perfusate and urine of kidneys undergoing normothermic perfusion. It is unclear how cytokine levels change in different ischemic conditions and whether the use of a leukocyte filter plays a role. Full article
(This article belongs to the Special Issue New Advances in Kidney Transplantation 2.0)
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15 pages, 3551 KiB  
Article
The Impact of Obesity and Associated Comorbidities on the Outcomes after Renal Transplantation with a Living Donor vs. Deceased Donor Grafts
by Renana Yemini, Ruth Rahamimov, Eviatar Nesher, Roi Anteby, Ronen Ghinea, Tammy Hod and Eytan Mor
J. Clin. Med. 2022, 11(11), 3069; https://doi.org/10.3390/jcm11113069 - 29 May 2022
Cited by 7 | Viewed by 1689
Abstract
Background: Obesity among kidney transplant (KT) recipients can lead to metabolic comorbidity-associated deaths. This study compares post-KT survival between obese and non-obese patients and outcomes of living donor (LD) and deceased donor (DD) grafts. Methods: Between January 2005–May 2019, 1403 KT recipients from [...] Read more.
Background: Obesity among kidney transplant (KT) recipients can lead to metabolic comorbidity-associated deaths. This study compares post-KT survival between obese and non-obese patients and outcomes of living donor (LD) and deceased donor (DD) grafts. Methods: Between January 2005–May 2019, 1403 KT recipients from a single center were included in the study, as well as 314 patients (22.4%) with obesity (BMI > 30 kg/m2), 137 DD transplants, and 177 LD transplants. Of the 1089 (77.6%) in the control group (BMI ≤ 30 kg/m2), 384 were DD transplants and 705 LD transplants. The Kaplan–Meier method was used for survival analysis and a Cox regression was used to identify risk factors for graft loss and mortality. Propensity score matching analysis adjusting for age, IHD, and T2DM was performed. Results: The study group had higher incidence of obesity related comorbidities, delayed graft function and primary non function (p < 0.001). One-, 5-and 10-year patient and graft survival were lower in the study group (p < 0.001). Subgroup analysis of graft survival according to type of graft shows a difference in the DD (p = 0.002) but not in the LD group (p = 0.220). However, mortality was higher in both groups (LD, p = 0.045; DD, p = 0.004). Risk factors for mortality were age, T2DM, IHD, and DD, and for graft failure: IHD, BMI, donor age, re-transplant, and DD. Propensity score analysis shows an odds ratio of 0.81 for graft failure and 0.93 for death in the study group (95% CI = 0.55, 1.21, p = 0.3 and CI = 0.59, 1.46, p = 0.7, respectively). Conclusions: Recipient age and metabolic comorbidities should be emphasized when evaluating patients with obesity. We suggest considering weight loss interventions using the new GLP-1 inhibitors and bariatric procedures in selected patients to prepare overweight patients for transplant. Full article
(This article belongs to the Special Issue New Advances in Kidney Transplantation 2.0)
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21 pages, 709 KiB  
Systematic Review
Current Insights into the Metabolome during Hypothermic Kidney Perfusion—A Scoping Review
by Laurence Verstraeten, Rutger Den abt, Bart Ghesquière and Ina Jochmans
J. Clin. Med. 2023, 12(11), 3613; https://doi.org/10.3390/jcm12113613 - 23 May 2023
Viewed by 1198
Abstract
This scoping review summarizes what is known about kidney metabolism during hypothermic perfusion preservation. Papers studying kidney metabolism during hypothermic (<12 °C) perfusion were identified (PubMed, Embase, Web of Science, Cochrane). Out of 14,335 initially identified records, 52 were included [dog (26/52), rabbit [...] Read more.
This scoping review summarizes what is known about kidney metabolism during hypothermic perfusion preservation. Papers studying kidney metabolism during hypothermic (<12 °C) perfusion were identified (PubMed, Embase, Web of Science, Cochrane). Out of 14,335 initially identified records, 52 were included [dog (26/52), rabbit (2/52), pig (20/52), human (7/52)]. These were published between 1970–2023, partially explaining study heterogeneity. There is a considerable risk of bias in the reported studies. Studies used different perfusates, oxygenation levels, kidney injury levels, and devices and reported on perfusate and tissue metabolites. In 11 papers, (non)radioactively labeled metabolites (tracers) were used to study metabolic pathways. Together these studies show that kidneys are metabolically active during hypothermic perfusion, regardless of the perfusion setting. Although tracers give us more insight into active metabolic pathways, kidney metabolism during hypothermic perfusion is incompletely understood. Metabolism is influenced by perfusate composition, oxygenation levels, and likely also by pre-existing ischemic injury. In the modern era, with increasing donations after circulatory death and the emergence of hypothermic oxygenated perfusion, the focus should be on understanding metabolic perturbations caused by pre-existing injury levels and the effect of perfusate oxygen levels. The use of tracers is indispensable to understanding the kidney’s metabolism during perfusion, given the complexity of interactions between different metabolites. Full article
(This article belongs to the Special Issue New Advances in Kidney Transplantation 2.0)
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