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Advances in Kidney Transplantation

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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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Research

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

Viewed by 370

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 2 | Viewed by 1495

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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