1. Improving the histologic detection of DSA-negative antibody-mediated rejection in kidney transplantsLuis G. Hidalgo, Katelynn Madill-Thomsen, Jeff Reeve, Martina Mackova, Philippe Gauthier, Zachary Demko, Adam Prewett, Miha Arnol, Nika Kojc, Željka Večerić-Haler, 2026, izvirni znanstveni članek Povzetek: Emerging treatments for antibody-mediated rejection (ABMR, NEJM391(2):122-132) have increased the importance of ABMR detection when donor-specific antibody (DSA) is negative. We addressed this issue in the Trifecta-Kidney study (ClinicalTrials.gov #NCT04239703) using three centralized tests in 690 kidney transplant biopsies: DSA (One Lambda Inc.), blood donor-derived cell-free DNA (dd-cfDNA, Prospera™ test, Natera, Inc.), and molecular biopsy assessment (MMDx). We used an “AutoBanff 2022” algorithm to model the impact of alternative DSA interpretations on the histologic diagnosis of “DSA-negative” ABMR following Banff guidelines, including agreement with dd-cfDNA and molecular ABMR. Lowering MFI cutoffs for DSA-positivity did not improve detection of DSA-negative ABMR. However, simply calling all DSA positive allowed Banff 2022 guidelines to identify 46% more ABMR cases with no measurable DSA, and per Net Reclassification Improvement increased agreement between histologic diagnoses and both dd-cfDNA (P=7.72E-7) and molecular ABMR (P=7.69E-7). New ABMR cases were as strongly positive for dd-cfDNA and molecular ABMR as those found using the conventional DSA interpretation. A validation set analysis using INTERCOMEX study data (ClinicalTrials.gov NCT#01299168) confirmed these findings, and found that the new DSA-negative ABMR cases identified by calling all DSA positive had the same risk for graft loss as those found with conventional DSA interpretation.
Ključne besede: donor-derived cell-free DNA, kidney biopsy, donor-specific antibody, microarrays antibody-mediated rejection, kidney transplant rejection
Objavljeno v DiRROS: 13.01.2026; Ogledov: 53; Prenosov: 26
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2. The use of machine learning in the diagnosis of kidney allograft rejection : current knowledge and applicationsTanja Belčič Mikič, Miha Arnol, 2024, pregledni znanstveni članek Povzetek: Abstract: Kidney allograft rejection is one of the main limitations to long-term kidney transplant survival. The diagnostic gold standard for detecting rejection is a kidney biopsy, an invasive procedure that can often give imprecise results due to complex diagnostic criteria and high interobserver variability. In recent years, several additional diagnostic approaches to rejection have been investigated, some of them with the aid of machine learning (ML). In this review, we addressed studies that investigated the detection of kidney allograft rejection over the last decade using various ML algorithms. Various ML techniques were used in three main categories: (a) histopathologic assessment of kidney tissue with the aim to improve the diagnostic accuracy of a kidney biopsy, (b) assessment of gene expression in rejected kidney tissue or peripheral blood and the development of diagnostic classifiers based on these data, (c) radiologic assessment of kidney tissue using diffusion-weighted magnetic resonance imaging and the construction of a computer-aided diagnostic system. In histopathology, ML algorithms could serve as a support to the pathologist to avoid misclassifications and overcome interobserver variability. Diagnostic platforms based on biopsy-based transcripts serve as a supplement to a kidney biopsy, especially in cases where histopathologic diagnosis is inconclusive. ML models based on radiologic evaluation or gene signature in peripheral blood may be useful in cases where kidney biopsy is contraindicated in addition to other non-invasive biomarkers. The implementation of ML-based diagnostic methods is usually slow and undertaken with caution considering ethical and legal issues. In summary, the approach to the diagnosis of rejection should be individualized and based on all available diagnostic tools (including ML-based), leaving the responsibility for over- and under-treatment in the hands of the clinician.
Ključne besede: kidney transplantation, rejection, diagnosis, machine learning, kidney biopsy
Objavljeno v DiRROS: 08.12.2025; Ogledov: 208; Prenosov: 79
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3. Prophylactic treatment of hepatitis C virus infection after kidney transplantation with the combination of glecaprevir/pibrentasvir and sofosbuvir in a highly sensitized hepatitis c virus-negative recipient : a case report and review of the literatureTanja Belčič Mikič, Igor Sterle, Mojca Matičič, Miha Arnol, 2025, drugi znanstveni članki Povzetek: Background: Since the discovery of successful direct-acting antiviral (DAA) treatment, kidneys from hepatitis C virus (HCV) RNA-positive donors represent a new opportunity to expand the organ donor pool for HCV-negative recipients. Case presentation: In this paper, we describe a unique case of transplantation of an HCV genotype 3a-infected kidney into an HCV-negative recipient who was highly sensitized, with a virtual panel-reactive antibody level of 99.96%. Prior to the kidney transplantation, the recipient received DAA treatment with glecaprevir/pibrentasvir as a viable prophylactic strategy. Post-transplant, the recipient received a triple-combination DAA regimen with glecaprevir/pibrentasvir/sofosbuvir, which continued for 12 weeks. Subsequently, viral load was undetectable at 12 and 24 weeks after treatment, with no significant adverse events associated with DAA therapy. A 12-month post-transplantation biopsy revealed mixed rejection requiring treatment. The 19-month follow-up showed a favorable outcome regarding the function of the kidney allograft and the recipient’s quality of life. HCV-positive transplantation allowed our recipient to receive a kidney from an immunologically compatible donor without donor-specific antibodies and the need for desensitization strategies. Conclusions: Each transplant center should decide on the selection of candidates for kidney transplantation from HCV RNA-positive donors to HCV-negative recipients, the availability and choice of DAA treatment, and post-transplant follow-up. Our case emphasizes the need for early DAA treatment based on viral load and HCV genotyping, as well as for careful post-transplant surveillance including protocol biopsies.
Ključne besede: kidney transplantation, HCV RNA, direct-acting antiviral (DAA), glecaprevir/pibrentasvir, sensitization, case report
Objavljeno v DiRROS: 12.11.2025; Ogledov: 211; Prenosov: 100
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4. Extracellular vesicle-bound DNA in urine is indicative of kidney allograft injuryIvana Sedej, Maja Štalekar, Magda Tušek-Žnidarič, Katja Goričar, Nika Kojc, Polona Kogovšek, Vita Dolžan, Miha Arnol, Metka Lenassi, 2022, izvirni znanstveni članek Povzetek: Extracellular vesicle-bound DNA (evDNA) is an understudied extracellular vesicle (EV) cargo, particularly in cancer-unrelated research. Although evDNA has been detected in urine, little is known about its characteristics, localization, and biomarker potential for kidney pathologies. To address this, we enriched EVs from urine of well-characterized kidney transplant recipients undergoing allograft biopsy, characterized their evDNA and its association to allograft injury. The SEC-based method enriched pure EVs from urine of kidney transplant recipients, regardless of the allograft injury. Urinary evDNA represented up to 29.2 ± 8% (mean ± SD) of cell-free DNA (cfDNA) and correlated with cfDNA in several characteristics but was less fragmented (P < 0.001). Importantly, using DNase treatment and immunogold labelling TEM, we demonstrated that evDNA was bound to the surface of urinary EVs. Normalised evDNA yield (P = 0.042) and evDNA copy number (P = 0.027) significantly differed between patients with normal histology, rejection injury and non-rejection injury, the later groups having significantly larger uEVs (mean diameter, P = 0.045) and more DNA bound per uEV. ddDNA is detectable in uEV samples of kidney allograft recipients, but its quantity is highly variable. In a proof-of-principle study, several evDNA characteristics correlated with clinical and histological parameters (P = 0.040), supporting that the potential of evDNA as a biomarker for kidney allograft injury should be further investigated.
Ključne besede: DNA, donor-derived DNA, extracellular vesicles
Objavljeno v DiRROS: 26.02.2025; Ogledov: 734; Prenosov: 569
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5. Improved protective effect of umbilical cord stem cell transplantation on cisplatin-induced kidney injury in mice pretreated with antithymocyte globulinŽeljka Večerić-Haler, Andreja Erman, Anton Cerar, Helena Motaln, Katja Kološa, Tamara Lah Turnšek, Snežna Sodin-Šemrl, Katja Lakota, Katjuša Mrak Poljšak, Špela Škrajnar, Simona Kranjc Brezar, Miha Arnol, Martina Perše, 2016, izvirni znanstveni članek Povzetek: Mesenchymal stem cells (MSCs) are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG). We demonstrated that ATG pretreatment, when followed by MSC transplantation, significantly improved injured renal function parameters, as evidenced by decreased blood urea nitrogen and serum creatinine concentration, as well as improved renal morphology. This tissue restoration was also supported by increased survival of mice. The beneficial effects of ATG were associated with reduced level of inflammatory protein serum amyloid A3 and induced antioxidative expression of superoxide dismutase-1 (SOD-1), glutathione peroxidase (GPx), and hem oxygenase-1 (HO-1). Infused MSCs became localised predominantly in peritubular areas and acted to reduce renal cell death. In conclusion, these results show that ATG diminished in situ inflammation and oxidative stress associated with cisplatin-induced acute kidney injury, the effects that may provide more favourable microenvironment for MSC action, with consequential synergistic improvements in renal injury and animal survival as compared to MSC treatment alone.
Ključne besede: mesenchymal stem cells, nephrotoxicity
Objavljeno v DiRROS: 25.07.2024; Ogledov: 927; Prenosov: 707
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6. Feasibility of droplet digital PCR analysis of plasma cell-free DNA from kidney transplant patientsBarbara Jerič Kokelj, Maja Štalekar, Sebastian Vencken, David Dobnik, Polona Kogovšek, Matjaž Stanonik, Miha Arnol, Maja Ravnikar, 2021, izvirni znanstveni članek Povzetek: Increasing research demonstrates the potential of donor-derived cell-free DNA (dd-cfDNA) as a biomarker for monitoring the health of various solid organ transplants. Several methods have been proposed for cfDNA analysis, including real-time PCR, digital PCR, and next generation sequencing-based approaches. We sought to revise the droplet digital PCR (ddPCR)-based approach to quantify relative dd-cfDNA in plasma from kidney transplant (KTx) patients using a novel pilot set of assays targeting single nucleotide polymorphisms that have a very high potential to distinguish cfDNA from two individuals. The assays are capable of accurate quantification of down to 0.1% minor allele content when analyzing 165 ng of human DNA. We found no significant differences in the yield of extracted cfDNA using the three different commercial kits tested. More cfDNA was extracted from the plasma of KTx patients than from healthy volunteers, especially early after transplantation. The median level of donor-derived minor alleles in KTx samples was 0.35%. We found that ddPCR using the evaluated assays within specific range is suitable for analysis of KTx patientsʼ plasma but recommend prior genotyping of donor DNA and performing reliable preamplification of cfDNA.
Ključne besede: kidney transplantation, droplet digital PCR, plasma cell-free DNA, minor allele quantification, assay evaluation, graft health monitoring
Objavljeno v DiRROS: 19.07.2024; Ogledov: 1480; Prenosov: 603
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9. Onko-nefrologija - pristop k obravnavi bolnikovTomaž Milanez, Janja Ocvirk, Miha Arnol, 2021, strokovni članek Povzetek: Onko-nefrologija je novo, multidisciplinarno področje, ki povezuje predvsem področji onkologije in nefrologije. Število bolnikov z rakom, ki imajo različno stopnjo ledvične okvare, narašča. Cilj celostne obravnave onko-nefrološkega bolnika je večja učinkovitost in varnost zdravljenja. Bolniki z ledvično okvaro višje stopnje so bili izključeni iz prospektivnih randomiziranih raziskav, tako da za njih ni na voljo podatkov z visoko dokazi visoke stopnje o učinkovitosti in varnosti zdravil ter mejnih vrednostih biooznačevalcev, ki so v pomoč pri vodenju zdravljenja. V klinični praksi se zato pri zdravljenju onko-nefrološkega bolnika opiramo na klinične izkušnje, podatke iz retrospektivnih analiz in posameznih objavljenih primerov ter priporočila, ki temeljijo na soglasju strokovnjakov. Pri zdravljenju onko-nefrološkega bolnika je ključno tesno sodelovanje med onkologom in nefrologom, mnogokrat je nujen multidisciplinarni posvet. Zdravnik, ki je odgovoren za načrt zdravljenja, potrebuje osnovno znanje nefrologije in dobro poznavanje omejitev onkološkega zdravljenja. Zaradi vedno večjega števila onko-nefroloških bolnikov in novih možnosti protirakavega zdravljenja je pred desetimi leti na Onkološkem inštitutu Ljubljana začela delovati onko-nefrološka ambulanta, za zahtevnejše bolnike, ki potrebujejo dodatno multidisciplinarno obravnavo, pa deluje onko-nefrološki konzilij. Delovna skupina za onko-nefrologijo v okviru Sekcije za internistično onkologijo vsako leto pripravi onko-nefrološko šolo, kjer svoj pogled na isti klinični problem predstavijo različni strokovnjaki. Ena izmed prioritet onko-nefrologije so raziskave. V prispevku so opisane pomembnejše teme s področja onko-nefrologije skupaj z izzivi iz klinične prakse.
Ključne besede: onko-nefrologija, ocena ledvičnega delovanja, nefrotoksičnost
Objavljeno v DiRROS: 10.06.2021; Ogledov: 2577; Prenosov: 639
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