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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 (15 December 2021) | Viewed by 24008

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Prof. Dr. Eytan Mor

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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
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Special Issue Information

Dear Colleagues,

I would like to ask for your contribution 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 80s and early 90s 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 that limits graft survival and limited organ supply that makes kidney transplantation unavailable to many patients.

The following issue will focus on new advances that may answer some of these needs. First, in respect to prolonging graft survival in recent years, there has been an increased interest to improve organ quality by using machine preservation for marginal kidneys, especially those that are coming from donors after cardiac death (DCD). 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 using those to direct immunosuppressive therapy in a personalized manner. Tolerance induction has recently been a new target of clinical research with several protocols of combined kidney and bone marrow derived cells transplantation. This approach aims to lessen drug nephrotoxicity and prolong graft survival.

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

Prof. Eytan Mor
Guest Editor

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Keywords

Kidney transplantation
Machine perfusion
Tolerance
Biomarkers
Organ engineering
Altruistic donation

Published Papers (11 papers)

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Editorial

Jump to: Research, Review

3 pages, 168 KiB

Open AccessEditorial

Special Issue: New Advances in Kidney Transplantation

by Eytan Mor

J. Clin. Med. 2022, 11(14), 4190; https://doi.org/10.3390/jcm11144190 - 19 Jul 2022

Viewed by 1044

Abstract

This Special Issue in renal transplantation covers a variety of clinical and research areas in kidney transplantation [...] Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

Research

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13 pages, 3461 KiB

Open AccessArticle

Sildenafil Citrate Enhances Renal Organogenesis Following Metanephroi Allotransplantation into Non-Immunosuppressed Hosts

by Ximo Garcia-Dominguez, César D. Vera-Donoso, Eric Lopez-Moncholi, Victoria Moreno-Manzano, José S. Vicente and Francisco Marco-Jiménez

J. Clin. Med. 2022, 11(11), 3068; https://doi.org/10.3390/jcm11113068 - 29 May 2022

Cited by 1 | Viewed by 1858

Abstract

In order to harness the potential of metanephroi allotransplantation to the generation of a functional kidney graft on demand, we must achieve further growth post-transplantation. Sildenafil citrate (SC) is widely known as a useful inductor of angiogenesis, offering renoprotective properties due to its anti-inflammatory, antifibrotic, and antiapoptotic effects. Here, we performed a laparoscopic metanephroi allotransplantation after embedding sildenafil citrate into the retroperitoneal fat of non-immunosuppressed adult rabbit hosts. Histology and histomorphometry were used to examine the morphofunctional changes in new kidneys 21 days post-transplantation. Immunofluorescence of E-cadherin and renin and erythropoietin gene expression were used to assess the tubule integrity and endocrine functionality. After the metanephroi were embedded in a 10 µM SC solution, the new kidneys’ weights become increased significantly. The E-cadherin expression together with the renin and erythropoietin gene expression revealed its functionality, while histological mature glomeruli and hydronephrosis proved the new kidneys’ excretory function. Thus, we have described a procedure through the use of SC that improves the outcomes after a metanephroi transplantation. This study gives hope to a pathway that could offer a handsome opportunity to overcome the kidney shortage. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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11 pages, 2717 KiB

Open AccessArticle

Impact of the Type of Dialysis on Time to Transplantation: Is It Just a Matter of Immunity?

by Matteo Righini, Irene Capelli, Marco Busutti, Concettina Raimondi, Giorgia Comai, Gabriele Donati, Maria Laura Cappuccilli, Matteo Ravaioli, Pasquale Chieco and Gaetano La Manna

J. Clin. Med. 2022, 11(4), 1054; https://doi.org/10.3390/jcm11041054 - 17 Feb 2022

Cited by 2 | Viewed by 1284

Abstract

Background: Renal transplantation represents the therapeutic gold standard in patients with end stage renal disease (ESRD). Still the role of pre-transplant dialysis in affecting time to transplantation has yet to be determined. We wanted to verify whether the type of renal replacement therapy (hemodialysis vs. peritoneal dialysis) affects time to transplantation and to identify clinical features related to the longer time to transplantation. Methods: We performed a retrospective single-center observational study on patients who had received a transplant in the Bologna Transplant Unit from 1991 to 2019, described through the analysis of digital transplant list documents for sex, age, body mass index (BMI), blood group, comorbidities, underlying disease, serology, type of dialysis, time to transplantation, Panel Reactive Antibodies (PRA) max, number of preformed anti Human Leukocyte Antigens (HLA) antibodies. A p-value < 0.05 was considered statistically significant. Results: In the 1619 patients analyzed, we observed a significant difference in time to transplant, PRA max and Preformed Antibodies Number between patients who received Hemodialysis (HD) and Peritoneal dialysis (PD). Then we performed a multiple regression analysis with all the considered factors in order to identify features that support these differences. The clinical variables that independently and directly correlate with longer time to transplantation are PRA max (p < 0.0001), Antibodies number (p < 0.0001) and HD (p < 0.0001); though AB blood group (p < 0.0001), age (p < 0.003) and PD (p < 0.0001) inversely correlate with time to transplantation. Conclusions: In our work, PD population received renal transplants in a shorter period of time compared to HD and turned out to be less immunized. Considering immunization, the type of dialysis impacts both on PRA max and on anti HLA antibodies. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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12 pages, 1115 KiB

Open AccessArticle

Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study

by Ryoichi Imamura, Ryo Tanaka, Ayumu Taniguchi, Shigeaki Nakazawa, Taigo Kato, Kazuaki Yamanaka, Tomoko Namba-Hamano, Yoichi Kakuta, Toyofumi Abe, Koichi Tsutahara, Tetsuya Takao, Hidefumi Kishikawa and Norio Nonomura

J. Clin. Med. 2022, 11(1), 249; https://doi.org/10.3390/jcm11010249 - 04 Jan 2022

Cited by 3 | Viewed by 1911

Abstract

Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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16 pages, 2232 KiB

Open AccessArticle

Long-Term Results of Kidney Transplantation in the Elderly: Comparison between Different Donor Settings

by Renana Yemini, Ruth Rahamimov, Ronen Ghinea and Eytan Mor

J. Clin. Med. 2021, 10(22), 5308; https://doi.org/10.3390/jcm10225308 - 15 Nov 2021

Cited by 10 | Viewed by 1624

Abstract

With scarce organ supply, a selection of suitable elderly candidates for transplant is needed, as well as auditing the long-term outcomes after transplant. We conducted an observational cohort study among our patient cohort >60 years old with a long follow up. (1). Patients and Methods: We used our database to study the results after transplant for 593 patients >60 years old who underwent a transplant between 2000–2017. The outcome was compared between live donor (LD; n = 257) recipients, an old-to-old (OTO, n = 215) group using an extended criteria donor (ECD) kidney, and a young-to-old (YTO, n = 123) group using a standard-criteria donor. The Kaplan−Meir method was used to calculate the patient and graft survival and Cox regression analysis in order to find risk factors associated with death. (2). Results: The 5- and 10-year patient survival was significantly better in the LD group (92.7% and 66.9%) compared with the OTO group (73.3% and 42.8%) and YTO group (70.9% and 40.6%) (p < 0.0001). The 5- and 10-year graft survival rates were 90.3% and 68.5% (LD), 61.7% and 30.9% (OTO), and 64.1% and 39.9%, respectively (YTO group; p < 0.0001 between the LD and the two DD groups). There was no difference in outcome between patients in their 60’s and their 70’s. Factors associated with mortality included: age (HR-1.060), DM (HR-1.773), IHD (HR-1.510), and LD/DD (HR-2.865). (3). Conclusions: Our 17-years of experience seems to justify the rational of an old-to-old allocation policy in the elderly population. Live-donor transplant should be encouraged whenever possible. Each individual decision of elderly candidates for transplant should be based on the patient’s comorbidity and predicted life expectancy. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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13 pages, 8352 KiB

Open AccessArticle

Intraoperative Near-Infrared Spectroscopy Monitoring of Renal Allograft Reperfusion in Kidney Transplant Recipients: A Feasibility and Proof-of-Concept Study

by Hien Lau, Alberto Jarrin Lopez, Natsuki Eguchi, Akihiro Shimomura, Antoney Ferrey, Ekamol Tantisattamo, Uttam Reddy, Donald Dafoe and Hirohito Ichii

J. Clin. Med. 2021, 10(19), 4292; https://doi.org/10.3390/jcm10194292 - 22 Sep 2021

Cited by 4 | Viewed by 1346

Abstract

Conventional renal function markers are unable to measure renal allograft perfusion intraoperatively, leading to delayed recognition of initial allograft function. A handheld near-infrared spectroscopy (NIRS) device that can provide real-time assessment of renal allograft perfusion by quantifying regional tissue oxygen saturation levels (rSO₂) was approved by the FDA. This pilot study evaluated the feasibility of intraoperative NIRS monitoring of allograft reperfusion in renal transplant recipients (RTR). Intraoperative renal allograft rSO₂ and perfusion rates were measured in living (LDRT, n = 3) and deceased donor RTR (DDRT, n = 4) during the first 50 min post-reperfusion and correlated with renal function markers 30 days post-transplantation. Intraoperative renal allograft rSO₂ for the DDRT group remained significantly lower than the LDRT group throughout the 50 min. Reperfusion rates were significantly faster in the LDRT group during the first 5 min post-reperfusion but remained stable thereafter in both groups. Intraoperative rSO₂ were similar among the upper pole, renal hilum, and lower pole, and strongly correlated with allograft function and hemodynamic parameters up to 14 days post-transplantation. NIRS successfully detected differences in intraoperative renal allograft rSO₂, warranting future studies to evaluate it as an objective method to measure ischemic injury and perfusion for the optimization of preservation/reperfusion protocols and early prediction of allograft function. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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11 pages, 723 KiB

Open AccessArticle

Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study

by Stephan Kemmner, Christopher Holzmann-Littig, Helene Sandberger, Quirin Bachmann, Flora Haberfellner, Carlos Torrez, Christoph Schmaderer, Uwe Heemann, Lutz Renders, Volker Assfalg, Tarek M. El-Achkar, Pranav S. Garimella, Jürgen Scherberich and Dominik Steubl

J. Clin. Med. 2021, 10(12), 2586; https://doi.org/10.3390/jcm10122586 - 11 Jun 2021

Cited by 7 | Viewed by 2049

Abstract

Delayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipients and its association with DGF. We included 239 kidney transplant recipients and measured sUMOD pretransplant and on postoperative Day 1 (POD1) as independent variables. The primary outcome was DGF, defined as need for dialysis within one week after transplantation. In total, 64 patients (27%) experienced DGF. In multivariable logistic regression analysis adjusting for recipient, donor and transplant associated risk factors each 10 ng/mL higher pretransplant sUMOD was associated with 47% lower odds for DGF (odds ratio (OR) 0.53, 95% confidence interval (95%-CI) 0.30–0.82). When categorizing pretransplant sUMOD into quartiles, the quartile with the lowest values had 4.4-fold higher odds for DGF compared to the highest quartile (OR 4.41, 95%-CI 1.54–13.93). Adding pretransplant sUMOD to a model containing established risk factors for DGF in multivariable receiver-operating-characteristics (ROC) curve analysis, the area-under-the-curve improved from 0.786 [95%-CI 0.723–0.848] to 0.813 [95%-CI 0.755–0.871, p = 0.05]. SUMOD on POD1 was not associated with DGF. In conclusion, higher pretransplant sUMOD was independently associated with lower odds for DGF, potentially serving as a non-invasive marker to stratify patients according to their risk for developing DGF early in the setting of kidney transplantation. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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11 pages, 1041 KiB

Open AccessArticle

Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation

by Johan Noble, Antoine Metzger, Hamza Naciri Bennani, Melanie Daligault, Dominique Masson, Florian Terrec, Farida Imerzoukene, Beatrice Bardy, Gaelle Fiard, Raphael Marlu, Eloi Chevallier, Benedicte Janbon, Paolo Malvezzi, Lionel Rostaing and Thomas Jouve

J. Clin. Med. 2021, 10(6), 1316; https://doi.org/10.3390/jcm10061316 - 23 Mar 2021

Cited by 16 | Viewed by 2836

Abstract

Nearly 18% of patients on a waiting list for kidney transplantation (KT) are highly sensitized, which make access to KT more difficult. We assessed the efficacy and tolerance of different techniques (plasma exchanges [PE], double-filtration plasmapheresis [DFPP], and immunoadsorption [IA]) to remove donor specific antibodies (DSA) in the setting of HLA-incompatible (HLAi) KT. All patients that underwent apheresis for HLAi KT within a single center were included. Intra-session and inter-session Mean Fluorescence Intensity (MFI) decrease in DSA, clinical and biological tolerances were assessed. A total of 881 sessions were performed for 45 patients: 107 DFPP, 54 PE, 720 IA. The procedures led to HLAi KT in 39 patients (87%) after 29 (15–51) days. A higher volume of treated plasma was associated with a greater decrease of inter-session class I and II DSA (p = 0.04, p = 0.02). IA, PE, and a lower maximal DSA MFI were associated with a greater decrease in intra-session class II DSA (p < 0.01). Safety was good: severe adverse events occurred in 17 sessions (1.9%), more frequently with DFPP (6.5%) p < 0.01. Hypotension occurred in 154 sessions (17.5%), more frequently with DFPP (p < 0.01). Apheresis is well tolerated (IA and PE > DFPP) and effective at removing HLA antibodies and allows HLAi KT for sensitized patients. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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18 pages, 1760 KiB

Open AccessArticle

Urinary NGAL Measured after the First Year Post Kidney Transplantation Predicts Changes in Glomerular Filtration over One-Year Follow-Up

by Małgorzata Kielar, Paulina Dumnicka, Agnieszka Gala-Błądzińska, Alina Będkowska-Prokop, Ewa Ignacak, Barbara Maziarz, Piotr Ceranowicz and Beata Kuśnierz-Cabala

J. Clin. Med. 2021, 10(1), 43; https://doi.org/10.3390/jcm10010043 - 25 Dec 2020

Cited by 11 | Viewed by 2152

Abstract

Currently, serum creatinine and estimated glomerular filtration rate (eGFR) together with albuminuria or proteinuria are laboratory markers used in long-term monitoring of kidney transplant recipients. There is a need for more sensitive markers that could serve as early warning signs of graft dysfunction. Our aim was to assess the urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of changes in kidney transplant function after the first year post-transplantation. We prospectively recruited 109 patients with functioning graft at least one year after the transplantation, with no acute conditions over the past three months, during their control visits in kidney transplant ambulatory. Urinary NGAL measured on recruitment was twice higher in patients with at least 10% decrease in eGFR over 1-year follow-up compared to those with stable or improving transplant function. Baseline NGAL significantly predicted the relative and absolute changes in eGFR and the mean eGFR during the follow-up independently of baseline eGFR and albuminuria. Moreover, baseline NGAL significantly predicted urinary tract infections during the follow-up, although the infections were not associated with decreasing eGFR. Additionally, we assessed urinary concentrations of matrix metalloproteinase 9—NGAL complex in a subgroup of 77 patients and found higher levels in patients who developed urinary tract infections during the follow-up but not in those with decreasing eGFR. High urinary NGAL in clinically stable kidney transplant recipients beyond the first year after transplantation may be interpreted as a warning and trigger the search for transient or chronic causes of graft dysfunction, or urinary tract infection. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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Review

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34 pages, 797 KiB

Open AccessEditor’s ChoiceReview

A Review of Current and Emerging Trends in Donor Graft-Quality Assessment Techniques

by Natalia Warmuzińska, Kamil Łuczykowski and Barbara Bojko

J. Clin. Med. 2022, 11(3), 487; https://doi.org/10.3390/jcm11030487 - 18 Jan 2022

Cited by 13 | Viewed by 3598

Abstract

The number of patients placed on kidney transplant waiting lists is rapidly increasing, resulting in a growing gap between organ demand and the availability of kidneys for transplantation. This organ shortage has forced medical professionals to utilize marginal kidneys from expanded criteria donors (ECD) to broaden the donor pool and shorten wait times for patients with end-stage renal disease. However, recipients of ECD kidney grafts tend to have worse outcomes compared to those receiving organs from standard criteria donors (SCD), specifically increased risks of delayed graft function (DGF) and primary nonfunction incidence. Thus, representative methods for graft-quality assessment are strongly needed, especially for ECDs. Currently, graft-quality evaluation is limited to interpreting the donor’s recent laboratory tests, clinical risk scores, the visual evaluation of the organ, and, in some cases, a biopsy and perfusion parameters. The last few years have seen the emergence of many new technologies designed to examine organ function, including new imaging techniques, transcriptomics, genomics, proteomics, metabolomics, lipidomics, and new solutions in organ perfusion, which has enabled a deeper understanding of the complex mechanisms associated with ischemia-reperfusion injury (IRI), inflammatory process, and graft rejection. This review summarizes and assesses the strengths and weaknesses of current conventional diagnostic methods and a wide range of new potential strategies (from the last five years) with respect to donor graft-quality assessment, the identification of IRI, perfusion control, and the prediction of DGF. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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19 pages, 5169 KiB

Open AccessReview

The Impact of Recipient Demographics on Outcomes from Living Donor Kidneys: Systematic Review and Meta-Analysis

by Maria Irene Bellini, Mikhail Nozdrin, Liset Pengel, Simon Knight and Vassilios Papalois

J. Clin. Med. 2021, 10(23), 5556; https://doi.org/10.3390/jcm10235556 - 26 Nov 2021

Cited by 7 | Viewed by 2481

Abstract

Background and Aims: Recipient demographics affect outcomes after kidney transplantation. The aim of this study was to assess, for kidneys retrieved from living donors, the effect of recipient sex, ethnicity, and body mass index (BMI) on delayed graft function (DGF) and one-year graft function, incidence of acute rejection (AR), and recipient and graft survivals. Methods: A systematic review and meta-analysis was performed. EMBASE and MEDLINE databases were searched using algorithms through Ovid. Web of Science collection, BIOSIS, CABI, Korean Journal database, Russian Science Citation Index, and SciELO were searched through Web of Science. Cochrane database was also searched. Risk of bias was assessed using the NHBLI tools. Data analysis was performed using Revman 5.4. Mean difference (MD) and risk ratio (RR) were used in analysis. Results: A total of 5129 studies were identified; 24 studies met the inclusion criteria and were analysed. Female recipients were found to have a significantly lower serum creatinine 1-year-post renal transplantation (MD: −0.24 mg/dL 95%CI: −0.18 to −0.29 p < 0.01) compared to male recipients. No significant difference in survival between male and female recipients nor between Caucasians and Africans was observed (p = 0.08). However, Caucasian recipients had a higher 1-year graft survival compared to African recipients (95% CI 0.52−0.98) with also a lower incidence of DGF (RR = 0.63 p < 0.01) and AR (RR = 0.55 p < 0.01). Recipient obesity (BMI > 30) was found to have no effect on 1-year recipient (p = 0.28) and graft survival (p = 0.93) compared to non-obese recipients although non-obese recipients had a lower rate of DGF (RR = 0.65 p < 0.01) and AR (RR = 0.81 p < 0.01) compared to obese recipients. Conclusions: Gender mismatch between male recipients and female donors has negative impact on graft survival. African ethnicity and obesity do not to influence recipient and graft survival but negatively affect DGF and AR rates. Full article

(This article belongs to the Special Issue New Advances in Kidney Transplantation)

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