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Advances in Kidney Transplantation

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 June 2026) | Viewed by 5347

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Editor

Dr. Zeljko Kikic

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Guest Editor

Department of Urology, Medical University of Vienna, Vienna, Austria
Interests: kidney transplantation; hemodialysis; transplantation; nephrology

Special Issue Information

Dear Colleagues,

Kidney transplantation (KTX) is considered the best treatment for end-stage renal disease (ESRD). Despite excellent short-term results in KTX, organ survival has not changed significantly over the past decades, with a significant number of transplants failing within 10–15 years. This is accompanied by several unmet medical challenges. Chronic rejection, particularly antibody-mediated rejection, is a significant contributor to up to 50% of late graft loss. However, we still face diagnostic challenges as biopsy-based diagnostics are limited by non-specific lesions with significant overlap in diagnostic categories. Tailoring immunosuppression is also challenging, as immunosuppressive drugs are essential to prevent rejection but are associated with serious side effects, including increased risk of infection, cancer, and metabolic complications such as diabetes and cardiovascular disease. Some infections, including BK virus nephropathy, can lead to early graft loss despite current attempts to reduce IS to control BK infection.

This Special Issue dedicated to Advances in Kidney Transplantation will cover the full spectrum of research questions related to diagnostic and prognostic challenges in kidney transplantation, including treatment, with a focus on unresolved medical issues. This includes, but is not limited to, chronic rejection, BKVAN, immunosuppressive regimens, and selection of kidney transplant candidates. Original research, mini and full reviews, and commentaries are all welcome. IJMS is a journal of molecular science, so submitted clinical studies should cover biomolecular findings and their role in unresolved questions in renal transplantation.

Dr. Zeljko Kikic
Guest Editor

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Keywords

chronic rejection
antibody-mediated rejection
immunosuppression
BK virus nephropathy (BKVAN)
diagnostic challenges

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Published Papers (6 papers)

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Research

Jump to: Review

16 pages, 575 KB

Open AccessArticle

Population-Specific Exploration of MIR146A Gene Polymorphism in Acute Renal Rejection: A Cross-Sectional, Case–Control Study

by Nor Elhouda Nacer, Soumia Missoum, Houssem Eddine Ouarhlent, Seddam Hares, Asma Ribouh and Ghania Belaaloui

Int. J. Mol. Sci. 2026, 27(11), 5105; https://doi.org/10.3390/ijms27115105 - 4 Jun 2026

Viewed by 467

Abstract

Acute renal allograft rejection (AR) is immune-mediated. Recent evidence highlights some microRNAs as immune modulators. Few and conflicting studies have studied the impact of the MIR146A gene single-nucleotide polymorphism rs2910164 (C>G) on AR. We explored the association of rs2910164 with AR in a single-center cohort of 533 kidney transplant recipients (KTRs) by genotyping cases with biopsy-proven late AR (AR group, n = 35) and matched control KTRs without AR (non-AR group, n = 60). Genotyping was performed with real-time PCR. Multivariable logistic regression and Firth penalized logistic regression, as a sensitivity analysis, were used to adjust for confounding factors. Donor–recipient age difference was significantly higher in the AR group than in the non-AR group (23.37 ± 11.29 vs. 14.83 ± 10.54, p < 0.001). Recipient mean age in the AR group is lower than in the non-AR group (27.51 ± 10.34 vs. 32.83 ± 9.76 years, p = 0.014), while the opposite is observed with the donor mean age (49.57 ± 10.37 vs. 43.27 ± 10.27 years, p = 0.005). AR was associated with preformed donor-specific antibodies (DSAs) (45.7% vs. 8.3%, p = 0.000, OR = 9.263, 95% CI (2.988–28.720)), and with two HLA-A* mismatches (17.1% vs. 3.3%, p = 0.048, OR = 6.000, 95% CI (1.139–31.595)). Moreover, post-transplant viral infections, particularly with CMV and SARS-CoV-2, were associated with AR (p < 0.05). However, rs2910164 was not associated with AR across all the tested genetic models (p > 0.05). Our study provides population-specific negative association data on rs2910164 and AR. Larger multicentric studies and future meta-analyses are needed to clarify whether any effect is modest or context-dependent. Full article

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

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10 pages, 747 KB

Open AccessArticle

Finerenone as a Third-Line Therapy for Persistent Proteinuria in Diabetic Kidney Transplant Recipients

by Carmine Secondulfo, Dora Russo, Nicoletta Vecchione, Gianmarco Minelli, Luca Apicella, Candida Iacuzzo, Chiara Crescenzo, Maristella Minco, Anna Sannino, Gennaro Clemente, Antonio Pisani, Massimo Cirillo and Giancarlo Bilancio

Int. J. Mol. Sci. 2026, 27(11), 4832; https://doi.org/10.3390/ijms27114832 - 27 May 2026

Viewed by 481

Abstract

Proteinuria is a strong predictor of graft failure in kidney transplant recipients (KTRs). While non-steroidal mineralocorticoid receptor antagonists (NS-MRAs), particularly finerenone, have demonstrated renoprotective benefits in chronic kidney disease, KTRs were excluded from pivotal trials. Evidence on finerenone’s safety and antiproteinuric effects in this population remains limited. This retrospective observational study evaluated 13 diabetic KTRs with persistent proteinuria despite optimized renin–angiotensin system blockade and sodium–glucose cotransporter 2 inhibitor therapy. Finerenone (10 mg/day) was added to standard care. Clinical and laboratory parameters, including estimated glomerular filtration rate (eGFR), serum electrolytes, total proteinuria, albuminuria, and their creatinine ratios, were assessed at baseline, 3 months, and 6 months. Safety outcomes focused on hyperkalemia and eGFR. Finerenone was discontinued in one patient due to hyperkalemia. In the remaining 12, 24-h proteinuria and urinary protein-to-creatinine ratio declined at 3 months and stabilized by 6 months. Conversely, no statistically significant changes were observed in albuminuria or the albumin-to-creatinine ratio. No clinically relevant changes occurred in eGFR, blood pressure, body weight, or serum electrolytes. This is the first study assessing finerenone in diabetic KTRs. Finerenone was well tolerated, was associated with an early reduction in proteinuria, and showed no adverse effects on graft function. These findings provide novel insights into the safety and potential role of finerenone in kidney transplant recipients. Full article

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

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12 pages, 1131 KB

Open AccessArticle

Molecular Diagnostics Supporting a ≥35% Diffuse Peritubular Capillaritis Extent Threshold for Diagnosis of AMR—A Retrospective Dual Center Study

by Michael Eder, Marian C. Clahsen-van Groningen, Michael Mengel, Haris Omic, Daniel Cejka, Benjamin Adam, Nicolas Kozakowski and Željko Kikić

Int. J. Mol. Sci. 2025, 26(22), 10945; https://doi.org/10.3390/ijms262210945 - 12 Nov 2025

Cited by 1 | Viewed by 784

Abstract

Peritubular capillaritis (ptc) is a hallmark lesion of antibody-mediated rejection (AMR), but the grading of its extent is historically based on arbitrary defined cut-offs. Molecular AMR diagnosis via intragraft gene expression measurements may provide evidence to challenge established ptc categories. We retrospectively included 38 renal allograft biopsies from clinical routine, performed because of suspicion of AMR. Biopsies were re-assessed by an experienced nephropathologist and intragraft gene expression was measured using the NanoString nCounter^® platform. Ptc categories were correlated with AMR gene expression to identify a ptc extent cut-off with optimal prediction of molecular diagnosis of AMR [gene expression levels above first quartile (AMR^Q>1)]. Finally, an independent validation cohort (n = 25, Erasmus MC, Rotterdam, The Netherlands) was included to reproduce the results. Re-assessment of biopsies revealed AMR in 26/68.4%, mixed rejection in 5/13.2%, and T-cell-mediated rejection in 3/7.9%. Biopsies with diffuse ptc had significantly higher AMR gene expression compared to biopsies with focal ptc and biopsies with no ptc (64.0/53.3–84.0 vs. 31.5/27.0–49.5, p = 0.023 and 27.0/14.3–31.8, p = 0.003, median/IQR). Sensitivity analysis revealed that a ≥35% ptc cut-off resulted in higher AUCs for predicting AMR^Q>1 compared to ptc^50% (AUC 0.78, 95% CI: 0.63–0.93, p = 0.009 versus AUC: 0.74, CI: 0.56–0.90, p = 0.03). In the validation cohort, only the ptc^35–, but not the ptc^50%, cut-off significantly predicted AMR^Q>1 (AUC 0.75, 95% CI: 0.54–0.96 p = 0.04 vs. AUC 0.69, CI: 0.46–0.93, p = 0.13). Using intragraft gene expression measurement, we identified a new ptc extent threshold with better prediction of molecular AMR. The newly proposed cut-off of ≥35% could potentially improve diagnostic evaluation and prognostication in cases with suspected or diagnosed AMR. Full article

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

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15 pages, 1059 KB

Open AccessArticle

Kidney Transplant Recipients with Acute Antibody-Mediated Rejection Show Altered Levels of Matrix Metalloproteinases and Their Inhibitors: Evaluation of Circulating MMP and TIMP Profiles

by Miguel A. Vázquez-Toledo, Fausto Sánchez-Muñoz, Iván Zepeda-Quiroz, Carlos A. Guzmán-Martín, Horacio Osorio-Alonso, Juárez-Villa Daniel, Ma. Virgilia Soto-Abraham, Bernardo Moguel-González, Rommel Chacón-Salinas, César Flores-Gama and Rashidi Springall

Int. J. Mol. Sci. 2025, 26(13), 6011; https://doi.org/10.3390/ijms26136011 - 23 Jun 2025

Cited by 4 | Viewed by 2126

Abstract

Antibody-mediated rejection (ABMR) remains a major cause of renal graft dysfunction and loss. The histological hallmark of antibody-mediated rejection is progressive tissue damage, in which extracellular matrix turnover plays an important role. This turnover is mainly regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Recent studies suggest that MMP/TIMP imbalance may favor the progression of renal damage, inflammation, and fibrosis, but the utility of these molecules as a biomarker of antibody-mediated turnover has not been fully explored. We measured plasma MMP and TIMP levels by ELISA in 15 patients with antibody-mediated renal transplant rejection and 12 patients without rejection. There was a significant increase in MMP-1, MMP-2, and MMP-3 concentrations in the plasma of patients with rejection, directly correlating with the severity of different renal lesions. In contrast, TIMP-3 levels were elevated in patients without rejection, showing a negative correlation with the severity of histopathological lesions. The concentrations of these molecules demonstrated good diagnostic capacity for patients with rejection. Our results show that MMP-1, MMP-2, MMP-3, and TIMP-3 could be potential biomarkers of rejection. Full article

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

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Review

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28 pages, 1107 KB

Open AccessReview

Revolutionizing Renal Replacement: Current Advancements in Development and Transplantation of Bioengineered Kidneys

by Rune Brulez and Marijn M. Speeckaert

Int. J. Mol. Sci. 2026, 27(13), 5879; https://doi.org/10.3390/ijms27135879 - 30 Jun 2026

Viewed by 164

Abstract

The rising prevalence of chronic kidney disease represents a major global health burden. Limitations of current renal replacement therapies, including donor organ shortages, rejection, and dialysis-related complications, underscore the need for innovative treatment options. This narrative review assesses the feasibility of bioengineered kidneys as an alternative to current treatments by discussing advances in decellularization, recellularization, and the transplantation of cell-on-scaffold kidneys. We propose that the development of functional bioengineered kidneys follows a hierarchical, staged process, in which vascular patency is the primary prerequisite for graft survival, followed by partial restoration of glomerular filtration, with complete tubular function remaining the final and most challenging milestone. Perfusion-based whole-organ decellularization has made significant progress in preserving the extracellular matrix, enabling the production of acellular human kidney scaffolds. However, complete recellularization of whole kidneys has not yet been achieved. Nevertheless, partially repopulated kidney scaffolds have been shown to withstand physiological blood pressure, produce urine, and exhibit filtration in large-animal models. Complete endothelial coverage of the vascular network proved essential for preventing thrombosis after transplantation. Current work on bioengineered kidneys shows promising results regarding feasibility for clinical application. It is important to note that most of the included studies are proof-of-concept, characterized by small sample sizes and short observation periods. Although these findings are crucial for further research, they cannot be generalized, and larger trials are recommended. In addition to cell-on-scaffold kidneys, 3D bioprinting is a promising technique that could eliminate the need for donor scaffolds. Full article

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

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16 pages, 529 KB

Open AccessReview

Endothelial Glycocalyx in Kidney Transplantation: Molecular Mechanisms, Biomarkers, and Therapeutic Opportunities

by Pavel Navratil, Minh Nguyet Tranova, Adam Haluska, Michal Lesko, Igor Gunka and David Astapenko

Int. J. Mol. Sci. 2026, 27(10), 4332; https://doi.org/10.3390/ijms27104332 - 13 May 2026

Viewed by 523

Abstract

The endothelial glycocalyx (EG) is a dynamic endothelial surface layer composed of proteoglycans, glycosaminoglycans, glycoproteins, and adsorbed plasma proteins that regulates permeability, mechanotransduction, leukocyte trafficking, coagulation, and nitric oxide signaling. In kidney transplantation (KT), the EG is exposed to cumulative injury from recipient uremia, donor instability, preservation, machine perfusion, reperfusion, rejection, and immunosuppressive toxicity. This narrative review summarizes EG biology in KT, with emphasis on biomolecular findings relevant to ischemia–reperfusion injury, delayed graft function, rejection, and chronic allograft injury. Particular attention is given to syndecan-1, heparan sulfate, heparanase, soluble thrombomodulin, matrix metalloproteinases, angiopoietin-2/Tie2 signaling, selectins, miR-126, extracellular vesicles, and urinary or perfusate-derived readouts. Current evidence is biologically coherent but uneven: human data are largely observational, whereas many therapeutic concepts remain preclinical or exploratory. Glycocalyx-centered phenotyping may eventually improve risk stratification and trial enrichment, but clinical implementation will require standardized sampling, sample-source-aware biomarker panels, prospective validation, and clear separation between mechanistic plausibility and proven clinical utility. Full article

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

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