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Advances in Kidney Transplantation

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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 (20 August 2025) | Viewed by 8091

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Dr. Pedro Ruiz-Esteban

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Nephrology Department, Hospital Universitario Regional de Málaga, Universidad de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, RICORS2040-renal (RD24/0004/0026), E-29010 Malaga, Spain
Interests: kidney transplantation; immunosuppression; acute rejection; subclinical inflammation; cardiovascular complications; metabolic complications; graft survival
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Prof. Dr. Domingo Hernández

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Nephrology Department, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas-Universidad La Laguna, RICORS2040-renal (RD24/0004/0025), E-38320 Tenerife, Spain
Interests: kidney transplant; immunosuppression; acute rejection; subclinical inflammation; cardiovascular complications; metabolic complications; graft survival
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Dr. Veronica López

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Nephrology Department, Hospital Universitario Regional de Málaga, Universidad de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, RICORS2040-renal (RD24/0004/0026), E-29010 Malaga, Spain
Interests: kidney transplant; immunosuppression; acute rejection; subclinical inflammation; cardiovascular complications; metabolic complications; graft survival
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The medical practice is moving toward precision medicine in the field of renal transplantation. Advancements in our understanding of the pathophysiology of graft rejection and other post-transplant complications have enabled the identification of implications in clinical features, the development of precise diagnostic methods and targeted therapies, and the accurate prediction of prognosis. Research on biomarkers has revealed new indicators for monitoring graft function and the early detection of rejection and subclinical graft inflammation. These biomarkers are being used as diagnostic tools and therapeutic targets, significantly improving post-transplant outcomes.

Artificial intelligence is being applied to our medical practice for identifying, classifying, and predicting important features of renal transplantation and is expected to have a significant impact on our clinical practice.

All these efforts have improved the clinician’s approach to diagnosis, treatment, and prognosis prediction in renal transplantation. The aim of this Special Issue is to highlight recent advances in the context of diagnosis, treatment, and prognosis prediction in renal transplantation, emphasizing how these developments are improving long-term outcomes for transplant recipients.

Dr. Pedro Ruiz-Esteban
Prof. Dr. Domingo Hernández
Dr. Veronica López
Guest Editors

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Keywords

kidney transplant
acute rejection
biomarkers
artificial intelligence
post-transplant complications
graft survival

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Related Special Issue

Advances in Kidney Transplantation: 2nd Edition in Journal of Clinical Medicine

Published Papers (7 papers)

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Research

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14 pages, 1012 KB

Open AccessArticle

Selection Patterns and Outcomes of Kidney Transplantation Versus Dialysis in Lung Recipients with End-Stage Renal Disease: A Single-Center Retrospective-Observational Study

by Fahim Kanani, Mordechai R. Kramer, Mohamad Atamna, Abed Elrahman Dahly, Aviad Gravets, Wladimir Tennak, Sigal Eisner and Eviatar Nesher

J. Clin. Med. 2025, 14(19), 7017; https://doi.org/10.3390/jcm14197017 - 3 Oct 2025

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Abstract

Background: End-stage renal disease (ESRD) affects up to 25% of lung transplant recipients within 10 years. The selection process for kidney transplantation versus dialysis reflects complex clinical decision-making that has not been systematically characterized. Methods: This retrospective observational study analyzed all lung transplant recipients who developed ESRD at our center from 2010 to 2024 (n=32), comparing those receiving kidney transplantation (n = 18) versus those remaining on dialysis (n = 14). We developed an exploratory Clinical Selection Score to retrospectively characterize observed selection patterns and calculated E-values to assess robustness to unmeasured confounding. Results: Kidney transplant recipients were younger (35.7 ± 12.9 vs. 48.4 ± 14.8 years, p = 0.013) with better selection characteristics quantified by our Clinical Selection Score (4.1 ± 0.8 vs. 1.6 ± 1.1 points, p < 0.001). The score showed excellent discrimination (C-statistic 0.82). Living donors were available for 88.9% of transplanted patients versus 0% of dialysis patients. In our selected cohorts, mortality was 22.2% in kidney transplant recipients vs. 78.6% in dialysis patients (p = 0.002), with median survival of 161.6 vs. 126.6 months (p = 0.021). After adjustment for age, kidney transplantation was observed to be associated with 72% lower mortality risk (HR 0.28, 95% CI 0.09–0.89, p = 0.031), though selection bias limits causal interpretation. The E-value of 6.61 suggests robustness to unmeasured confounding. Conclusions: This observational study describes real-world selection patterns and their associated outcomes in lung transplant recipients with ESRD. While carefully selected patients receiving kidney transplantation experienced favorable results, many patients were appropriately managed with dialysis based on medical and non-medical factors. Our analysis provides transparency about selection criteria and outcomes to inform clinical decision-making. Larger multicenter studies are needed to validate these findings and develop prediction tools. Full article

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

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11 pages, 225 KB

Open AccessArticle

Long-Term Outcomes of Living Kidney Donors Left with Multiple Renal Arteries: A Retrospective Cohort Study from a Single Center

by Thomas Kurz, Jacob Schmidt, Isabel Lichy, Irena Goranova, Jonathan Jeutner, Nadine Biernath, Lukas Kurz, Thorsten Schlomm, Robert Peters, Frank Friedersdorff, Henning Plage and Bernhard Ralla

J. Clin. Med. 2025, 14(17), 6121; https://doi.org/10.3390/jcm14176121 - 29 Aug 2025

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Background: The presence of multiple renal arteries (MRAs) is a common anatomical variant in living kidney donors. While MRAs are not considered a contraindication to donation, it remains uncertain whether leaving the donor with a kidney containing MRAs affects long-term outcomes. This study aimed to evaluate renal and clinical outcomes in donors based on the vascular anatomy of the remnant kidney. Methods: We conducted a retrospective cohort study of living kidney donors who underwent nephrectomy at our institution between 2011 and 2016. Donors were categorized according to the vascular anatomy of the remaining kidney: single renal artery (SRA) vs. multiple renal arteries (MRAs). Data on renal function, hypertension, diabetes mellitus, and cardiovascular events were collected at baseline and follow-up. The primary outcome was long-term renal function, which was measured by the estimated glomerular filtration rate (eGFR). Secondary outcomes included clinical comorbidities and postoperative complications. Results: Among 190 donors, 132 had a remaining kidney with a single artery and 58 had MRAs. Over a median follow-up of 89.5 months (SRA) and 74.5 months (MRA), there were no significant differences in eGFR (SRA: 66 mL/min vs. MRA: 65 mL/min, p = 0.60), serum creatinine (p = 0.86), or the incidence of hypertension (31.8% vs. 34.5%, p = 0.35). Rates of diabetes mellitus and cardiovascular events were similarly low and comparable between groups. Conclusions: Living kidney donors left with a remnant kidney containing multiple renal arteries have similar long-term renal function and clinical outcomes as those with a single renal artery. These findings support the feasibility of MRA retention in donor selection and contribute to evidence-based surgical planning and donor counseling. Full article

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

10 pages, 225 KB

Open AccessArticle

Clinical Factors Influencing Tacrolimus Metabolism and Blood Level Early After Kidney Transplantation—A Comparison of Three Different Tacrolimus Formulations

by Aureliusz Kolonko and Andrzej Więcek

J. Clin. Med. 2025, 14(12), 4223; https://doi.org/10.3390/jcm14124223 - 13 Jun 2025

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Background: Optimal tacrolimus dosing in the early post-transplant period is still challenging. We prospectively studied the possible associations between selected parameters of recipient body composition, markers of intestinal permeability and tacrolimus dosing and blood level in kidney transplant recipients (KTRs) treated with three different tacrolimus formulations. Methods: When discharged from hospital immediately after kidney transplantation, markers of intestinal permeability, body composition parameters and tacrolimus blood level were assessed in 165 KTRs treated with Prograf, Advagraf or Envarsus. Results: In the stepwise multivariate analysis performed in patients treated with Prograf, only age independently influenced the tacrolimus exposure expressed as area under the curve (AUC). In patients treated with Advagraf, eGFR (r_partial = 0.291; p < 0.05), antithymocyte globulin (vs. basiliximab) induction (r_partial = 0.445; p < 0.001), lipopolysaccharide (LPS) level (r_partial = 0.393; p < 0.01) and drug dose (r_partial = 0.433; p < 0.01) were independently associated with tacrolimus AUC. In patients treated with Envarsus, only age (r_partial = −0.365; p < 0.05) and fatty-acid-binding protein (FABP-2) level (r_partial = −0.364; p < 0.05) were independently associated with the tacrolimus AUC. Conclusions: We confirmed the significant association between markers of intestinal permeability and tacrolimus exposure in KTRs who underwent early post-transplant conversion from Prograf to Advagraf or Envarsus. This may suggest that the planned tacrolimus conversion from the twice-daily to the once-daily formulation should be performed later (at least 3 months after transplantation) to avoid unnecessary tacrolimus blood level instability. Full article

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

13 pages, 1538 KB

Open AccessArticle

Exploring Net Immunosuppressive Status with Torque Teno Virus Viral Load in Kidney Transplant Recipients with High Molecular Injury

by Emilio Rodrigo, Elena González-López, Javier Gonzalo Ocejo-Vinyals, Enrique Pasache, Cristina García-Majado, Covadonga López del Moral, Ana García-Santiago, Adalberto Benito-Hernández, María Victoria Francia and Juan Carlos Ruiz

J. Clin. Med. 2025, 14(7), 2417; https://doi.org/10.3390/jcm14072417 - 1 Apr 2025

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Abstract

Background/Objectives: New monitoring methods are being developed to improve the kidney transplant outcome. Among them, the measurement of Torque Teno virus load (TTV load) has been associated with the overall immunosuppressive status and the percentage of donor-derived circulating free DNA (dd-cfDNA) with molecular graft injury, mainly related to antibody-mediated rejection (AbMR). Both methods provide complementary information, but they have not been previously used together for the monitoring of kidney transplant recipients (KTx). Methods: A prospective study including 42 KTx performed in our centre was conducted, in which we monitored dd-cfDNA using a targeted NGS assay (AlloSeq cfDNA) in the first month and the TTV load with in-house PCR in the first and third months. Results: Eleven KTx with high molecular injury defined by dd-cfDNA ≥ 1.0% were selected. The TTV load showed a non-significant trend of being lower in AbMR patients (2.91, IQR 4.18 vs. 3.48, IQR 1.47 log10 copies/mL, p = 0.788). No overimmunosuppressed patient developed AbMR, whereas 40% of non-overimmunosuppressed patients showed AbMR (p = 0.428). The TTV load increased more in the AbMR-treated KTx (0.00, IQR 4.71 vs. +6.58, IQR 4.04 log10 copies/mL, p = 0.042) from months one to three, with all AbMR-treated KTx becoming overimmunosuppressed. KTx with opportunistic infections showed higher TTV loads in the third month (5.18, IQR 5.92 vs. 11.53, IQR 3.54 log10 copies/mL, p = 0.024). Conclusions: KTx with molecular injury secondary to rejection tended to be less immunosuppressed, as indicated by a low TTV load. After AbMR therapy, all KTx became overimmunosuppressed and suffered a higher risk of opportunistic infections. Dual monitoring provides useful complementary information for the follow-up of kidney transplant recipients. Full article

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

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13 pages, 1050 KB

Open AccessArticle

Efficacy of the Once-Daily Tacrolimus Formulation LCPT Compared to the Immediate-Release Formulation in Preventing Early Post-Transplant Diabetes in High-Risk Kidney Transplant Patients: A Randomized, Controlled, Open-Label Pilot Study (EUDRACT: 2017-000718-52)

by Armando Torres, Concepción Rodríguez-Adanero, Constantino Fernández-Rivera, Domingo Marrero-Miranda, Eduardo de Bonis-Redondo, Aurelio P. Rodríguez-Hernández, Lourdes Pérez-Tamajón, Ana González-Rinne, Diego Álvarez-Sosa, Alejandra Álvarez-González, Nuria Sanchez-Dorta, Estefanía Pérez-Carreño, Laura Díaz-Martín, Sergio Luis-Lima, Ana E. Rodríguez-Rodríguez, Antonia María de Vera González, Cristina Romero-Delgado, María Calvo-Rodríguez, Rocío Seijo-Bestilleiro, Consuelo Rodríguez-Jiménez, Manuel Arturo Prieto López, Antonio Manuel Rivero-González, Domingo Hernández-Marrero and Esteban Porrini Show full author list Hide full author list

J. Clin. Med. 2024, 13(24), 7802; https://doi.org/10.3390/jcm13247802 - 20 Dec 2024

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Abstract

Background/Objectives: Post-transplant diabetes mellitus (PTDM) and prediabetes (PreDM) are common after renal transplantation and increase the risk of cardiovascular events and mortality. Compared to immediate-release tacrolimus (IR-Tac), the LCPT formulation, with delayed absorption, offers higher bioavailability and a smoother time–concentration curve, potentially reducing beta-cell stress. Methods: This randomized pilot trial compared de novo immunosuppression with IR-Tac (twice daily) and LCPT (once daily). At-risk recipients (age ≥ 60 years or 18–59 years with metabolic syndrome) were enrolled and followed for 3 months. The primary and secondary outcomes were the incidence of PTDM and PreDM, respectively. Results: 27 patients were randomized to IR-Tac and 25 to LCPT. The incidence of PTDM was comparable between groups [IR Tac: 18.5% (95% CI: 8.2–36.7%) vs. LCPT: 24% (95% CI: 11.5–43.4%); p = 0.7]. Although not statistically significant, the LCPT group exhibited a trend toward a reduction in PreDM incidence [IR-Tac: 40.7% (95% CI: 25–59%) vs. LCPT: 20% (95% CI: 9–39%); p = 0.1]. A sensitivity analysis showed similar results, with no significant differences in cumulative corticosteroid doses or baseline body mass index (BMI) between groups. The LCPT group showed a trend toward higher tacrolimus exposure at the end of the study [trough levels: IR-Tac group 8.3 (6.9–9.2) vs. LCPT group 9.4 (7.4–11.4) ng/mL; p = 0.05)], as well as fewer acute rejection episodes (none vs. three). Delayed graft function was more common in the IR-Tac group (37% vs. 8%; p = 0.01), and the eGFR was lower. Adverse events were comparable between groups. Conclusions: The potential biological activity of LCPT in preventing glucose metabolic alterations in at-risk patients warrants further investigation. Full article

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

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26 pages, 597 KB

Open AccessReview

Recurrence of Glomerular Diseases (GN) After Kidney Transplantation: A Narrative Review

by Abbal Koirala, Aditi Singh and Duvuru Geetha

J. Clin. Med. 2025, 14(18), 6686; https://doi.org/10.3390/jcm14186686 - 22 Sep 2025

Viewed by 740

Abstract

Recurrence of the original glomerular disease (GN) poses a significant threat to kidney transplant function and longevity. The probability and severity of this recurrence vary, with C3 glomerulopathy and certain forms of FSGS exhibiting particularly high rates. Kidney transplant GN recurrence risk hinges on the characteristics of the initial GN, recipient/donor genetics, recipient age, donor type, end-stage kidney disease (ESRD) progression rate, and proteinuria levels. Standard immunosuppression has limited efficacy in preventing primary disease recurrence; however, agent selection and induction therapy can influence the risk for specific GNs. Diagnosing recurrent GN involves a comprehensive approach, including clinical evaluation, laboratory tests (such as proteinuria, hematuria, and specific biomarkers like anti-PLA2R for membranous nephropathy or complement for C3G), and, critically, an allograft biopsy analyzed with light, immunofluorescence, and electron microscopy. Treatment strategies are evolving towards targeted therapies, such as rituximab for antibody-mediated GN and complement inhibitors for C3G, moving away from broad immunosuppression. This narrative literature review provides practical monitoring algorithms for post-transplant settings, synthesizing information on the incidence, predictors, diagnostic strategies, and therapeutic options for various glomerular disease subtypes. The methodology involved searching MEDLINE, Embase, and Cochrane databases from 1996 to 2025, prioritizing systematic reviews, cohort studies, registries, and interventional reports. Eligibility criteria included adult transplant recipients and English-language reports on recurrent glomerular disease outcomes, excluding most single-patient case reports. Limitations include potential selection bias, omission of relevant studies, and the absence of a formal risk-of-bias assessment or meta-analysis. The evidence base is heterogeneous, with inconsistent outcome reporting and scarce randomized controlled trials. Future efforts should focus on developing predictive biomarkers, standardizing diagnostic and response criteria, conducting multicenter prospective cohorts and pragmatic trials, and creating shared registries with harmonized data. Full article

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

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21 pages, 703 KB

Open AccessReview

Compatibility of Post-Kidney Transplant Immunosuppression Therapy with Lactation

by Gema Gomez-Casado, Juana Alonso-Titos, Ernesto Gonzalez-Mesa and Almudena Ortega-Gomez

J. Clin. Med. 2025, 14(7), 2364; https://doi.org/10.3390/jcm14072364 - 29 Mar 2025

Viewed by 2092

Abstract

Breastfeeding after kidney transplantation remains a complex and underexplored topic, primarily due to concerns regarding the safety of immunosuppressive therapies during lactation. Individuals who have received kidney transplants face a higher likelihood of delivering preterm infants and giving birth to babies with a low birth weight when compared with the general population. In this context, breastfeeding is increasingly important because of its advantages for preterm infants. Despite the well-established benefits of breastfeeding for both the mother and infant, the traditional recommendation has been to avoid nursing due to potential drug transmission through breast milk. However, emerging evidence suggests that certain immunosuppressants may be compatible with breastfeeding, challenging long-standing clinical guidelines. In this review, we examine the current literature on the pharmacokinetics, safety profiles, and clinical outcomes associated with key immunosuppressive agents, including cyclosporine, tacrolimus, everolimus, azathioprine, corticosteroids, and belatacept. Our work highlights that all published reports to date on the studied treatments indicate that the amount of the drug reaching breast milk is considered safe for the child’s health. These conclusions, however, are derived from very short-term measurements and small numbers of patients. Therefore, we emphasize the need to design structured prospective studies to assess safety in the medium and long term. Our review aims to equip clinicians with the most up-to-date evidence on this topic, enabling them to make informed decisions regarding the compatibility of post-kidney transplant treatments with breastfeeding. Full article

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

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