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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: 266; Prenosov: 101
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Povzetek: Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune necrotizing small vessel vasculitis, frequently resulting in severe renal manifestations such as rapidly progressive glomerulonephritis (AAV-GN). Monitoring disease activity and determining ongoing renal involvement remain significant clinical challenges due to the limitations associated with traditional biomarkers. This study focused on the potential of circulating microRNA (miRNA) as supplementary noninvasive biomarkers for disease activity in AAV-GN. Methods: This prospective follow-up study involved serum samples from 60 patients with biopsy-proven AAV-GN, collected at renal biopsy and at 3-, 6-, 12-, and 24-month intervals post-biopsy. Nine miRNAs (miR-21-3p, miR-30b/d/e-5p, miR-142-5p, miR-150-5p, miR-181a-5p, miR-181b-5p, and let-7a-5p) were selected based on the differential expressions in renal tissue and corresponding serum samples identified in the previous research phases. Expression analysis was performed using quantitative real-time polymerase chain reaction and correlated with disease activity based on the Birmingham Vasculitis Activity Score and other clinical parameters. Results: A significant correlation was identified between disease activity and the expression levels of the miR-30 family members and let-7a. Specifically, these miRNAs demonstrated consistent correlation patterns across follow-up samples independent of the time elapsed post-biopsy, with down-regulation correlating with the presence of active disease. Notably, the miRNA expression profile in partial remission appeared analogous to that of complete remission, suggesting that many patients categorized as having partial remission may, in fact, be considered in true clinical remission. Conclusion: This study supports serum miRNA profiling as an adjunct noninvasive biomarker for assessing disease activity in AAV-GN. Such an approach could provide complementary information alongside traditional biomarkers and refine the future management of AAV-GN. However, it is important to acknowledge that our actual study cohort was small due to challenging technical aspects of miRNA expression analysis in the serum. Therefore, further research with larger cohorts is required to validate these results and assess their clinical applicability.
Ključne besede: ANCA, vasculitis, glomerulonephritis, microRNA, biomarker, BVAS, epigenetics, follow-up
Objavljeno v DiRROS: 26.11.2025; Ogledov: 247; Prenosov: 126
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Povzetek: Mycoplasma arginini is a bacterium primarily found in animals and is seldom reported in human infections. We identified M. arginini infection in a severely immunocompromised kidney transplant recipient in Slovenia. Clinicians should be aware of M. arginini's potential as a pathogen in immunocompromised persons with animal contact.
Ključne besede: Mycoplasma arginini, Slovenia, arthritis, bacteria, cellulitis, immunocompromised, kidney transplant recipient, zoonoses
Objavljeno v DiRROS: 13.11.2025; Ogledov: 246; Prenosov: 143
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Povzetek: Background. Many investigators have observed differences in the susceptibilityto induce intestinal tumors by 1,2-dimethylhydrazine (DMH) between various strains of rodents. The results are difficult to compare because of the different regimes used for induction. The purpose of our study was to evaluate the influence of strain on DMH-induced intestinal tumors between Wistar and Fischer rats. Materials and rreethods. We used 29 Fischer and 30 Wistar male rats that were injected subcutaneously DMH, weekly, at a dosage of 25 mg/kg-body weight for 20 weeks. After 25 weeks from the beginningof the experiment, the animals were sacrificed and autopsied. The complete length of colorectum and all macroscopic changes were examined histologically. Results. The induction of intestinal tumors was 97% in Fischerrats and 100% in Wistar rats. In Wistar rats 184 tumors were found: 133adenomas, 50 tubular adenocarcinomas and 1 signet-cell carcinoma. 77% of careinamas were found in colorectum and 23% in the small intestine. In Fiseherrats, 126 tumors were found: 94 adenomas, 26 tubular adenocarcinomas, 5signet-cell carcinomas and 1 mucinous carcinoma; 42% of carcinomas were foundin the colorectum and 58% in the small intestine. The strain difference in the incidence of all induced tumors was statistically significant (P=0.001). The differences in the occurrence of the malignant and benign tumors was also significant (P<0.001; P=0.011). Extra intestinal tumors were not found. Conclusions. Wistar rats showed greater percentage of colorectal tumors, and also the distribution of tumors in colorectum resembled more the distribution found in human pathology. That is why we reeommend Wistar rat rather than Fischer rat for the research work on the colorectal tumors.
Objavljeno v DiRROS: 13.02.2024; Ogledov: 1079; Prenosov: 278
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