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Background While opportunistic infections are a frequent and challenging problem in kidney transplant recipients, their long-term epidemiology remains hardly known. Methods Opportunistic infections were recorded in 1144 recipients transplanted in our center between 2004 and 2015. Incidence rates and baseline risk factors were determined using joint frailty models. Results After a median follow-up of 5.6 years, 544 opportunistic infections occurred in 373/1144 (33%) patients, dominated by viral infections (396/544, 72%), especially cytomegalovirus (CMV) syndromes and diseases (213/544, 39%). One-third of the infected patients experienced at least two opportunistic infections. The incidence of opportunistic infections was 10 times higher during the first year post-transplantation than after that (34.7 infections for 100 patient-years vs 3.64). Opportunistic infections associated with the age of the donor (P  = .032), the age of the recipient (P  = .049), the CMV serostatus (P  < 10−6), a higher class II HLA mismatch (P  = .032) and an induction treatment including rabbit anti-thymocyte globulins (P  = .026). Repeated opportunistic infections associated with each other (P  < 10−6) and with renal death (P  < 10−6). Conclusion Opportunistic infections occur with a two-period incidence pattern and many susceptible patients suffer from repeated episodes. This knowledge may help tailor new prevention and follow-up strategies to reduce the burden of opportunistic infections and their impact on transplantation outcome. [ABSTRACT FROM AUTHOR]

The impact of immunosuppressive therapy (IS) strategies after kidney transplant failure (KTF) on potential future new grafts is poorly established. We assessed the potential benefit of calcineurin inhibitor (CNI)-based IS maintenance throughout the dialysis period on the outcome of the second kidney transplant (KT). We identified 407 patients who underwent a second KT between January 2008 and December 2018 at four French KT centers. Inverse probability of treatment weighting was used to control for potential confounding. We included 205 patients with similar baseline characteristics at KTF: a total of 53 received at least CNIs on the retransplant day (G-CNI), and 152 did not receive any IS (G-STOP). On the retransplant date, G-STOP patients experienced a longer pretransplant dialysis time, were more often hyperimmunized, and underwent more expanded-criteria donor KTs than G-CNI patients. During the second KT follow-up period, rejection episodes were similar in both groups. The 10-year survival rates without death and dialysis were 98.7% and 59.5% in G-CNI and G-STOP patients, respectively. In the multivariable analysis, CNI-based IS maintenance was associated with better survival (hazard ratio: 0.08; 95% confidence interval: 0.01-0.58, p = 0.01). CNI-based IS maintenance throughout the dialysis period after KTF may improve retransplantation outcomes. [ABSTRACT FROM AUTHOR]

We report a 35-year-old man who suffered from recurrent macroscopic haematuria after intensive exercise. One episode was associated with bilateral loin (flank) pain and severe acute kidney injury. His kidney biopsy revealed an atypical anti-glomerular basement membrane (GBM) disease typified by bright linear GBM staining for monotypic immunoglobulin G but without a diffuse crescentic phenotype and no circulating anti-GBM antibody. Outcome was spontaneously favourable. The patient had no recurrence or urine abnormality without running. The original presentation emphasized that exercise could reveal an underlying glomerulopathy. [ABSTRACT FROM AUTHOR]

Background: The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear., Methods: We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023. We integrated clinical and pathological data to classify biopsy specimens according to the 2022 Banff Classification of Renal Allograft Pathology, which includes two new diagnostic categories: probable antibody-mediated rejection and microvascular inflammation without evidence of an antibody-mediated response. We then assessed the association between the newly recognized microvascular inflammation phenotypes and allograft survival and disease progression., Results: A total of 16,293 kidney-transplant biopsy specimens from 6798 patients were assessed. We identified the newly recognized microvascular inflammation phenotypes in 788 specimens, of which 641 were previously categorized as specimens with no evidence of rejection. As compared with patients without rejection, the hazard ratio for graft loss was 2.1 (95% confidence interval [CI], 1.5 to 3.1) among patients with microvascular inflammation without evidence of an antibody-mediated response and 2.7 (95% CI, 2.2 to 3.3) among patients with antibody-mediated rejection. Patients with a diagnosis of probable antibody-mediated rejection had a higher risk of graft failure beyond year 5 after biopsy than those without rejection (hazard ratio, 1.7; 95% CI, 0.8 to 3.5). Patients with a diagnosis of either newly recognized microvascular inflammation phenotype had a higher risk of progression of transplant glomerulopathy during follow-up than patients without microvascular inflammation., Conclusions: Microvascular inflammation in kidney allografts includes distinct phenotypes, with various disease progression and allograft outcomes. Our findings support the clinical use of additional rejection phenotypes to standardize diagnostics for kidney allografts. (Funded by OrganX. ClinicalTrials.gov number, NCT06496269.)., (Copyright © 2024 Massachusetts Medical Society.)

The Banff classification is regularly updated to integrate recent advances in the characterization of kidney allograft rejection, gathering novel diagnostic, prognostic, and theragnostic data into a diagnostic and pathogenesis-based framework. Despite ongoing research on noninvasive biomarkers of kidney rejection, the Banff classification remains, to date, biopsy-centered, primarily relying on a semiquantitative histological scoring system that overall lacks reproducibility and granularity. Besides, the ability of histopathological injuries and transcriptomics analyses from bulk tissue to accurately infer the pathogenesis of rejection is questioned. This review discusses findings from past, current, and emerging innovative tools that have the potential to enhance the characterization of allograft rejection from tissue samples. First, the digitalization of pathological workflows and the rise of deep learning should yield more reproducible and quantitative results from routine slides. Additionally, novel histomorphometric features of kidney rejection could be discovered with an overall genuine clinical implementation perspective. Second, multiplex immunohistochemistry enables in-depth in situ phenotyping of cells from formalin-fixed samples, which can decipher the heterogeneity of the immune infiltrate during kidney allograft rejection. Third, transcriptomics from bulk tissue is gradually integrated into the Banff classification, and its specific context of use is currently under extensive consideration. Finally, single-cell transcriptomics and spatial transcriptomics from formalin-fixed and paraffin-embedded samples are emerging techniques capable of producing up to genome-wide data with unprecedented precision levels. Combining all these approaches gives us hope for novel advances that will address the current blind spots of the Banff system., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Herein we report the case of a 41-year-old woman who presented with pelvic pain. Magnetic Resonance Imaging exhibited a single pelvic mass, measuring 50mm long axis, alongside the right iliac vessels. Histological examination of the excision specimen showed a lymphoid tumor with features of localized Castleman disease, hyaline vascular type. Moreover we identified multiple interfollicular dark clusters, composed of cells morphologically resembling cortical thymocytes. Their immunophenotype was consistent with an intermediate stage of T-cell differentiation, with the expression of CD3, CD4, CD8, TdT, CD1a, CD99, CD2, CD5, CD7 and CD10, with 40% Ki67. After integration of clinical and molecular data, the retained diagnosis was an indolent T-cell lymphoblastic proliferation associated with hyaline vascular localized Castleman disease. The clinical course confirmed the indolent nature of the proliferation, despite a late local recurrence at 7 years of the initial diagnosis, without histological modification, due to an incomplete initial resection surgery., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)