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Background: Long-term survival after lung transplantation (LTx) remains limited by chronic lung allograft dysfunction (CLAD), which includes 2 main phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), with possible overlap. We aimed to detail and quantify pathological features of these CLAD sub-types., Methods: Peripheral and central paraffin-embedded explanted lung samples were obtained from 20 consecutive patients undergoing a second LTx for CLAD, from 3 lobes. Thirteen lung samples, collected from non-transplant lobectomies or donor lungs, were used as controls. Blinded semi-quantitative grading was performed to assess airway fibrotic changes, parenchymal and pleural fibrosis, and epithelial and vascular abnormalities., Results: CLAD lung samples had higher scores for all airway- and lung-related parameters compared to controls. There was a notable overlap in histologic scores between BOS and RAS, with a wide range of scores in both conditions. Parenchymal and vascular fibrosis scores were significantly higher in RAS compared to BOS (p = 0.003 for both). We observed a significant positive correlation between the degree of inflammation around each airway, the severity of epithelial changes, and airway fibrosis. Immunofluorescence staining demonstrated a trend toward a lower frequency of club cells in CLAD and a higher frequency of apoptotic club cells in BOS samples (p = 0.01)., Conclusions: CLAD is a spectrum of airway, parenchymal, and pleural fibrosis, as well as epithelial, vascular, and inflammatory pathologic changes, where BOS and RAS overlap significantly. Our semi-quantitative grading score showed a generally high inter-reader reliability and may be useful for future CLAD histologic assessments., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Acute allograft rejection is a well-known complication of liver transplantation (LT). The incidence, epidemiology, and outcomes of acute rejection have not been well described in Australia. We retrospectively studied consecutive adults who underwent deceased donor LT at a single center between 2010 and 2020. Donor and recipient data at the time of LT and recipient outcomes were collected from a prospective LT database. Liver biopsy reports were reviewed, and only a graft's first instance of biopsy-proven acute rejection was analyzed. During the study period, 796 liver transplants were performed in 770 patients. Biopsy-proven rejection occurred in 34.9% of transplants. There were no significant changes in the incidence of rejection over time (linear trend p =0.11). The median time to the first episode of rejection was 71 days after LT: 2.2% hyperacute, 50.4% early (≤90 d), and 47.5% late rejection (>90 d). Independent risk factors for rejection were younger recipient age at transplant (aHR 0.98 per year increase, 95% CI: 0.97-1.00, p =0.01), and ABO-incompatible grafts (aHR 2.55 vs. ABO-compatible, 95% CI: 1.27-5.09, p <0.01) while simultaneous multiorgan transplants were protective (aHR 0.21 vs. LT only, 95% CI: 0.08-0.58, p <0.01). Development of acute rejection (both early and late) was independently associated with significantly reduced graft (aHR 3.13, 95% CI: 2.21-4.42, p <0.001) and patient survival (aHR 3.42, 95% CI: 2.35-4.98, p <0.001). In this 11-year Australian study, acute LT rejection occurred in 35%, with independent risk factors of younger recipient age and ABO-incompatible transplant, while having a simultaneous multiorgan transplant was protective. Acute rejection was independently associated with reduced graft and patient survival after adjustment for other factors., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: The Banff Working Group has updated the histological classification of BK virus nephropathy (BKVN), highlighting the importance of early detection. However, an early detection strategy for BKVN using biopsy has not yet been established. Our investigation aimed to assess the efficacy of protocol biopsy for the diagnosis of BKVN., Methods: We performed a retrospective cohort study of 314 patients who had undergone kidney transplantation between 2006 and 2021. Kidney allograft biopsies were performed as part of a protocol biopsy at 3 months and 1 year post-transplantation. Following the diagnosis of BKVN, the immunosuppressant dose was reduced., Results: Twelve patients (3.8%) were diagnosed with BKVN by biopsy. Most diagnoses are established during the early stages of BKVN (polyomavirus nephropathy class 1 in six, class 2 in five, and class 3 in one). Following the reduction in immunosuppressant dose, kidney allograft function did not deteriorate in any patients. Additionally, test for BK virus DNA in the blood was negative. All but one patient demonstrated histological resolution of BKVN, and the other had a very slight positivity for the simian virus 40 large T antigen. The median follow-up time after BKVN diagnosis was 6 years. One patient developed de novo donor-specific antibody and subclinical acute antibody-mediated rejection that was successfully cured., Conclusions: Our analysis indicates that protocol biopsy may enable the early detection of BKVN, resulting in the preservation of kidney function., (© 2024 Wiley Periodicals LLC.)

Delayed graft function (DGF) is an early posttransplant complication predictive of adverse outcomes. This "acute kidney injury of transplantation" is often defined as allograft dysfunction requiring renal replacement within 7 d posttransplantation. DGF is an important area of study because it is emerging with efforts to expand the donor pool and address the supply-demand gap in kidney transplantation. DGF is often caused by severe kidney injury mechanisms because of multiple donors, recipients, and immunologic factors. The role of kidney biopsy, particularly in prolonged DGF, is an ongoing area of research and inquiry for clinicians and researchers alike to better define, manage, and predict outcomes of this early posttransplant event. This review aims to provide an in-depth, comprehensive summary of the literature to date on the histopathology of DGF and the role of kidney transplant biopsies in prolonged DGF., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The analytical renal pathology system (ARPS) based on convolutional neural networks has been used successfully in native IgA nephropathy (IgAN) patients. Considering the similarity of pathologic features, we aim to evaluate the performance of the ARPS in allograft IgAN patients and broaden its implementation., Methods: Biopsy-proven allograft IgAN patients from two different centers were enrolled for internal and external validation. We implemented the ARPS to identify glomerular lesions and intrinsic glomerular cells, and then evaluated its performance. Consistency between the ARPS and pathologists was assessed using intraclass correlation coefficients. The association of digital pathological features with clinical and pathological data was measured. Kaplan-Meier survival curve and cox proportional hazards model were applied to investigate prognosis prediction., Results: A total of 56 biopsy-proven allograft IgAN patients from the internal center and 17 biopsy-proven allograft IgAN patients from the external center were enrolled in this study. The ARPS was successfully applied to identify the glomerular lesions (F1-score, 0.696-0.959) and quantify intrinsic glomerular cells (F1-score, 0.888-0.968) in allograft IgAN patients rapidly and precisely. Furthermore, the mesangial hypercellularity score was positively correlated with all mesangial metrics provided by ARPS [Spearman's correlation coefficient ( r ), 0.439-0.472, and all p values < 0.001]. Besides, a higher allograft survival was noticed among patients in the high-level groups of the maximum and ratio of endothelial cells, as well as the maximum and density of podocytes., Conclusion: We propose that the ARPS could be implemented in future clinical practice with outstanding capability.

Background: Diagnosis of kidney transplant rejection currently relies on manual histopathological assessment, which is subjective and susceptible to inter-observer variability, leading to limited reproducibility. We aim to develop a deep learning system for automated assessment of whole-slide images (WSIs) from kidney allograft biopsies to enable detection and subtyping of rejection and to predict the prognosis of rejection., Method: We collected H&E-stained WSIs of kidney allograft biopsies at 400x magnification from January 2015 to September 2023 at two hospitals. These biopsy specimens were classified as T cell-mediated rejection, antibody-mediated rejection, and other lesions based on the consensus reached by two experienced transplant pathologists. To achieve feature extraction, feature aggregation, and global classification, we employed multi-instance learning and common convolution neural networks (CNNs). The performance of the developed models was evaluated using various metrics, including confusion matrix, receiver operating characteristic curves, the area under the curve (AUC), classification map, heat map, and pathologist-machine confrontations., Results: In total, 906 WSIs from 302 kidney allograft biopsies were included for analysis. The model based on multi-instance learning enables detection and subtyping of rejection, named renal rejection artificial intelligence model (RRAIM), with the overall 3-category AUC of 0.798 in the independent test set, which is superior to that of three transplant pathologists under nearly routine assessment conditions. Moreover, the prognosis models accurately predicted graft loss within 1 year following rejection and treatment response for rejection, achieving AUC of 0.936 and 0.756, respectively., Conclusion: We first developed deep-learning models utilizing multi-instance learning for the detection and subtyping of rejection and prediction of rejection prognosis in kidney allograft biopsies. These models performed well and may be useful in assisting the pathological diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ye, Xia, Yang, Luo, Tang, Li, Han, Xie, Ren and Na.)

Context.—: Respiratory infections complicate lung transplantation and increase the risk of allograft dysfunction. Allograft lungs may have different susceptibilities to infection than native lungs, potentially leading to different disease severity in lungs of single lung transplant recipients (SLTRs)., Objective.—: To study whether infections affect allograft and native lungs differently in SLTRs but similarly in double LTRs (DLTRs)., Design.—: Using an institutional database of LTRs, medical records were searched, chest computed tomography studies were systematically reviewed, and histopathologic features were recorded per lung lobe and graded semiquantitatively. A multilobar-histopathology score (MLHS) including histopathologic data from each lung and a bilateral ratio (MLHSratio) comparing histopathologies between both lungs were calculated in SLTRs and compared to DLTRs., Results.—: Six SLTRs died of infection involving the lungs. All allografts showed multifocal histopathologic evidence of infection, but at least 1 lobe of the native lung was uninvolved. In 4 of 5 DLTRs, histopathologic evidence of infection was seen in all lung lobes. On computed tomography, multifocal ground-glass and/or nodular opacities were found in a bilateral distribution in all DLTRs but in only 2 of 6 SLTRs. In SLTRs, the MLHSAllograft was higher than MLHSNative (P = .02). The MLHSratio values of SLTR and DLTR were significantly different (P < .001)., Conclusions.—: Allograft and native lungs appear to harbor different susceptibilities to infections. The results are important for the management of LTRs., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background: The Banff Foundation produces recommendations for classifying various lesions in renal allografts. Experts gather to update the classification every other year based on new scientific and clinical evidence., Objectives: This article presents the most important changes incorporated into the new recommendations after the last Banff conference., Materials and Methods: The author of this article personally took part in the Banff conference and the subsequent survey, reported on the activities of a Banff working group (peritubular capillaritis) on-site, and contributed to drafting the recently published meeting report., Results: Lesions of antibody-mediated kidney allograft rejection (AMR), especially microvascular inflammation, have been part of the diagnostic algorithm for over 20 years. Experts advocated for a simplified AMR algorithm and mindful inclusion of molecular pathological data in the clinicopathological reflection regarding therapeutic decision. A new, more descriptive diagnostic entity-microvascular inflammation, C4d negative and DSA negative-has been introduced into the AMR category to acknowledge this histological constellation and motivate research into this pathophysiologically and immunologically probably different phenotype., Conclusions: The Banff classification provides a structure for diagnosing kidney transplant pathology. Regular updates serve to adapt to ever-growing knowledge about alloimmunity. Particular challenges are capturing the complexity of various immunological scenarios and ensuring an understandable representation of these in a pathology report., (© 2024. The Author(s).)

Objectives: Pathologists interpreting kidney allograft biopsies using the Banff system usually start by recording component scores (eg, i, t, cg) using histopathologic criteria committed to memory. Component scores are then melded into diagnoses using the same manual/mental processes. This approach to complex Banff rules during routine sign-out produces a lack of fidelity and needs improvement., Methods: We constructed a web-based "smart template" (software-assisted sign-out) system that uniquely starts with upstream Banff-defined additional diagnostic parameters (eg, infection) and histopathologic criteria (eg, percent interstitial inflammation) collectively referred to as feeder data that is then translated into component scores and integrated into final diagnoses using software-encoded decision trees., Results: Software-assisted sign-out enables pathologists to (1) accurately and uniformly apply Banff rules, thereby eliminating human inconsistencies (present in 25% of the cohort); (2) document areas of improvement; (3) show improved correlation with function; (4) examine t-Distributed Stochastic Neighbor Embedding clustering for diagnosis stratification; and (5) ready upstream incorporation of artificial intelligence-assisted scoring of biopsies., Conclusions: Compared with the legacy approach, software-assisted sign-out improves Banff accuracy and fidelity, more closely correlates with kidney function, is practical for routine clinical work and translational research studies, facilitates downstream integration with nonpathology data, and readies biopsy scoring for artificial intelligence algorithms., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies., Methods: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation., Results: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata., Conclusion: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T cell therapies include prevention of graft-vs-host disease (GvHD) and suppression of allograft rejection. Here, we describe preclinical data supporting the ongoing first-in-human clinical study, the CaMMouflage trial (NCT05722418), evaluating CB-011 in patients with relapsed/refractory multiple myeloma. CB-011 is a hypoimmunogenic, allogeneic anti-B-cell maturation antigen (BCMA) CAR T cell therapy candidate. CB-011 cells feature 4 genomic alterations and were engineered from healthy donor-derived T cells using a Cas12a CRISPR hybrid RNA-DNA (chRDNA) genome-editing technology platform. To address allograft rejection, CAR T cells were engineered to prevent endogenous HLA class I complex expression and overexpress a single-chain polyprotein complex composed of beta-2 microglobulin (B2M) tethered to HLA-E. In addition, T-cell receptor (TCR) expression was disrupted at the TCR alpha constant locus in combination with the site-specific insertion of a humanized BCMA-specific CAR. CB-011 cells exhibited robust plasmablast cytotoxicity in vitro in a mixed lymphocyte reaction in cell cocultures derived from patients with multiple myeloma. In addition, CB-011 cells demonstrated suppressed recognition by and cytotoxicity from HLA-mismatched T cells. CB-011 cells were protected from natural killer cell-mediated cytotoxicity in vitro and in vivo due to endogenous promoter-driven expression of B2M-HLA-E. Potent antitumor efficacy, when combined with an immune-cloaking armoring strategy to dampen allograft rejection, offers optimized therapeutic potential in multiple myeloma. See related Spotlight by Caimi and Melenhorst, p. 385., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Perivascular aggregates (PVAs) often occur in kidney allografts; however, their significance needs to be re-evaluated in light of changes in the concept and criteria of allograft rejection., Methods: We reviewed 1-year protocol biopsies in 258 patients with kidney transplants to identify PVAs and concurrent pathology based on the Banff 2017 classification, including revised criteria for chronic active T-cell mediated rejection (CA-TCMR). We investigated the incidence of PVA, concurrent allograft lesions, diagnosis, and graft survival. No prisoners were used in this study, and no participants were coerced or paid., Results: We identified PVA in 81 biopsies (31.4%). The incidence of previous rejection (32.1% vs 12.4%, P= .0003) and total inflammation (1.3 ± 0.8 vs 0.6 ± 0.8, P < .0001), inflammation (0.7 ± 0.8 vs 0.2 ± 0.5, P < .0001), inflammation in the area of interstitial fibrosis and tubular atrophy (1.3 ± 1.2 vs 0.7 ± 0.9, P < .0001), tubulitis (1.4 ± 1.1 vs 0.6 ± 0.9, P < .0001), and interstitial fibrosis scores (1.2 ± 0.9 vs 0.9 ± 0.9, P= .01) were higher in PVA-positive compared with patients with PVA-negative. Diagnoses in the PVA-positive group revealed no rejection in 49.4%, CA-TCMR in 21.0%, borderline changes in 18.5%, and acute TCMR in 6.2%. CA-TCMR was more frequent in patients with PVA-positive (21.0% vs 4.0%, P < .0001). Graft survival was similar in both groups among all patients, no-rejection, any type of rejection, and CA-TCMR subgroups., Conclusions: PVAs occur heterogeneously and are associated with previous rejection or concurrent CA-TCMR. The prognostic significance of PVAs in kidney transplantation is inconclusive, and further investigations are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Delineation of T-cell genes, gene sets, pathways, and T-cell subtypes associated with acute T cell-mediated rejection (TCMR) may improve its management., Methods: We performed bulk RNA-sequencing of 34 kidney allograft biopsies (16 Banff TCMR and 18 no rejection [NR] biopsies) from 34 adult recipients of human kidneys. Computational analysis was performed to determine the differential intragraft expression of T-cell genes at the level of single-gene, gene set, and pathways., Results: T-cell signaling pathway gene sets for plenary T-cell activation were overrepresented in TCMR biopsies compared with NR biopsies. Heightened expression of T-cell signaling genes was validated using external TCMR biopsies. Pro- and anti-inflammatory immune gene sets were enriched, and metabolism gene sets were depleted in TCMR biopsies compared with NR biopsies. Gene signatures of regulatory T cells, Th1 cells, Th2 cells, Th17 cells, T follicular helper cells, CD4 tissue-resident memory T cells, and CD8 tissue-resident memory T cells were enriched in TCMR biopsies compared with NR biopsies. T-cell exhaustion and anergy were also molecular attributes of TCMR. Gene sets associated with antigen processing and presentation, and leukocyte transendothelial migration were overexpressed in TCMR biopsies compared with NR biopsies. Cellular deconvolution of graft infiltrating cells by gene expression patterns identified CD8 T cell to be the most abundant T-cell subtype infiltrating the allograft during TCMR., Conclusions: Our delineation of intragraft T-cell gene expression patterns, in addition to yielding new biological insights, may help prioritize T-cell genes and T-cell subtypes for therapeutic targeting., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Kidney allograft inflammation, mostly attributed to rejection and infection, is an important cause of graft injury and loss. Standard histopathological assessment of allograft inflammation provides limited insights into biological processes and the immune landscape. Here, using imaging mass cytometry with a panel of 28 validated biomarkers, we explored the single-cell landscape of kidney allograft inflammation in 32 kidney transplant biopsies and 247 high-dimensional histopathology images of various phenotypes of allograft inflammation (antibody-mediated rejection, T cell-mediated rejection, BK nephropathy, and chronic pyelonephritis). Using novel analytical tools, for cell segmentation, we segmented over 900 000 cells and developed a tissue-based classifier using over 3000 manually annotated kidney microstructures (glomeruli, tubules, interstitium, and arteries). Using PhenoGraph, we identified 11 immune and 9 nonimmune clusters and found a high prevalence of memory T cell and macrophage-enriched immune populations across phenotypes. Additionally, we trained a machine learning classifier to identify spatial biomarkers that could discriminate between the different allograft inflammatory phenotypes. Further validation of imaging mass cytometry in larger cohorts and with more biomarkers will likely help interrogate kidney allograft inflammation in more depth than has been possible to date., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: As there is no specific antiviral treatment currently available for BK polyomavirus associated nephropathy (BKVAN), its management relies on immunosuppression reduction in kidney transplant patients. Data on efficacy of steroid pulses in this indication are lacking., Methods: We performed a retrospective monocenter study on 64 patients diagnosed with biopsy-proven BKVAN. Patients within the "pulse group" (n = 37) received IV methylprednisolone 10 mg/kg 3 days consecutively. In the "low dose" steroid group (n = 27), patients were continued oral prednisone 5 mg daily., Results: Mean follow up was 78 months in the steroid pulse group and 56 months in the low dose group (p = 0.15). Mean eGFR values at diagnosis were comparable, as well as other demographic characteristics. Mean BK plasma viral load was higher in "pulse" than in "low dose" steroid group. Pulse group had higher inflammation and tubulitis (p < 0.05). Graft loss reached 57% in the "pulse" group versus 41% in the "low dose" group, p = 0.20. Rejection events were similar. No major adverse event was statistically associated with steroid pulse, including infections, cancer, and de novo diabetes., Conclusion: No significant differences were found in the evolution of both groups of patients, despite patients receiving "pulse" steroids were identified as the most severe sharing higher BK viral load and more frequent active lesions on histology., (© 2024 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

Background: Inhibition of the mammalian target of rapamycin (mTor) pathway after heart transplantation has been associated with reduced progression of coronary allograft vasculopathy (CAV). The application of low-dose mTOR inhibition in the setting of modern immunosuppression, including tacrolimus, remains an area of limited exploration., Methods: This retrospective study included patients who received heart transplantation between January 2009 and January 2019 and had baseline, 1-year and 2-3-year coronary angiography with intravascular ultrasound (IVUS). Intimal thickness in 5 segments along the left anterior descending artery was compared across imaging time points in patients who were transitioned to low-dose mTOR inhibitor (sirolimus) vs standard treatment with mycophenolate on a background of tacrolimus. Long-term adverse cardiovascular outcomes (revascularization, severe CAV, retransplant, and cardiovascular death) were also assessed., Results: Among 216 patients (mean age 51.5 ± 11.9 years, 77.8% men, 80.1% white), 81 individuals (37.5%) were switched to mTOR inhibition. mTOR inhibition was associated with a reduction in intimal thickness by 0.05 mm (95% CI 0.02-0.07; P < 0.001). This reduction was driven by patients who met the criteria for rapidly progressive CAV 1-year post-transplant (0.12 mm; P = 0.016 for interaction). After a median follow-up of 8.6 (IQR 6.6-11) years, 40 patients had major adverse cardiovascular outcomes. The use of mTOR inhibitors was not significantly associated with cardiovascular outcomes (P = 0.669)., Conclusion: Transitioning patients after heart transplantation to an immunosuppression regimen composed of low-dose mTOR inhibition and tacrolimus was associated with a lack of progression of CAV, particularly in those with rapidly progressive CAV at 1 year, but not with long-term cardiovascular outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Intestinal transplantation (IT) is the final treatment option for intestinal failure. Static cold storage (CS) is the standard preservation method used for intestinal allografts. However, CS and subsequent transplantation induce ischemia-reperfusion injury (IRI). Severe IRI impairs epithelial barrier function, including loss of intestinal stem cells (ISC), critical to epithelial regeneration. Normothermic machine perfusion (NMP) preservation of kidney and liver allografts minimizes CS-associated IRI; however, it has not been used clinically for IT. We hypothesized that intestine NMP would induce less epithelial injury and better protect the intestine's regenerative ability when compared with CS. Full-length porcine jejunum and ileum were procured, stored at 4 °C, or perfused at 34 °C for 6 hours (T6), and transplanted. Histology was assessed following procurement (T0), T6, and 1 hour after reperfusion. Real-time quantitative reverse transcription polymerase chain reaction, immunofluorescence, and crypt culture measured ISC viability and proliferative potential. A greater number of NMP-preserved intestine recipients survived posttransplant, which correlated with significantly decreased tissue injury following 1-hour reperfusion in NMP compared with CS samples. Additionally, ISC gene expression, spheroid area, and cellular proliferation were significantly increased in NMP-T6 compared with CS-T6 intestine. NMP appears to reduce IRI and improve graft regeneration with improved ISC viability and proliferation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Achilles tendon is composed of dense connective tissue and is one of the largest tendons in the body. In veterinary medicine, acute ruptures are associated with impact injury or sharp trauma. Healing of the ruptured tendon is challenging because of poor blood and nerve supply as well as the residual cell population. Platelet-rich plasma (PRP) contains numerous bioactive agents and growth factors and has been utilized to promote healing in bone, soft tissue, and tendons., Objective: The purpose of this study was to evaluate the healing effect of PRP injected into the surrounding fascia of the Achilles tendon after allograft in rabbits., Methods: Donor rabbits (n = 8) were anesthetized and 16 lateral gastrocnemius tendons were fully transected bilaterally. Transected tendons were decellularized and stored at -80°C prior to allograft. The allograft was placed on the partially transected medial gastrocnemius tendon in the left hindlimb of 16 rabbits. The allograft PRP group (n = 8) had 0.3 mL of PRP administered in the tendon and the allograft control group (n = 8) did not receive any treatment. After 8 weeks, rabbits were euthanatized and allograft tendons were transected for macroscopic, biomechanical, and histological assessment., Results: The allograft PRP group exhibited superior macroscopic assessment scores, greater tensile strength, and a histologically enhanced healing process compared to those in the allograft control group., Conclusions: Our results suggest administration of PRP on an allograft tendon has a positive effect on the healing process in a ruptured Achilles tendon., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Background: There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV)., Methods: A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors., Results: In total, 175 patients (mean age 52 ± 12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p = .013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p = .002), while having no impact on layered fibrotic plaque (p = .224), calcification (p = .231), macrophage infiltration (p = .197), or the absolute coronary artery risk score (p = .277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p = .699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

MRI plays an important role in the evaluation of kidney allografts for vascular complications as well as parenchymal insults. Transplant renal artery stenosis, the most common vascular complication of kidney transplant, can be evaluated by MRA using gadolinium and nongadolinium contrast agents as well as by unenhanced MRA techniques. Parenchymal injury occurs through a variety of pathways, including graft rejection, acute tubular injury, BK polyomavirus infection, drug-induced interstitial nephritis, and pyelonephritis. Investigational MRI techniques have sought to differentiate among these causes of dysfunction as well as to assess the degree of interstitial fibrosis or tubular atrophy (IFTA)-the common end pathway for all of these processes-which is currently evaluated by invasively obtained core biopsies. Some of these MRI sequences have shown promise in not only assessing the cause of parenchymal injury but also assessing IFTA noninvasively. This review describes current clinically used MRI techniques and previews promising investigational MRI techniques for assessing complications of kidney grafts.

Donor organ biomarkers with sufficient predictive value in liver transplantation (LT) are lacking. We herein evaluate liver viability and mitochondrial bioenergetics for their predictive capacity towards the outcome in LT. We enrolled 43 consecutive patients undergoing LT. Liver biopsy samples taken upon arrival after static cold storage were assessed by histology, real-time confocal imaging analysis (RTCA), and high-resolution respirometry (HRR) for mitochondrial respiration of tissue homogenates. Early allograft dysfunction (EAD) served as primary endpoint. HRR data were analysed with a focus on the efficacy of ATP production or P - L control efficiency, calculated as 1- L / P from the capacity of oxidative phosphorylation P and non-phosphorylating respiration L . Twenty-two recipients experienced EAD. Pre-transplant histology was not predictive of EAD. The mean RTCA score was significantly lower in the EAD cohort (-0.75 ± 2.27) compared to the IF cohort (0.70 ± 2.08; p = 0.01), indicating decreased cell viability. P - L control efficiency was predictive of EAD (0.76 ± 0.06 in IF vs. 0.70 ± 0.08 in EAD-livers; p = 0.02) and correlated with the RTCA score. Both RTCA and P - L control efficiency in biopsy samples taken during cold storage have predictive capacity towards the outcome in LT. Therefore, RTCA and HRR should be considered for risk stratification, viability assessment, and bioenergetic testing in liver transplantation., Competing Interests: EG is founder and CEO of Oroboros Instruments. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Meszaros, Weissenbacher, Schartner, Egelseer-Bruendl, Hermann, Unterweger, Mittelberger, Reyer, Hofmann, Zelger, Hautz, Resch, Margreiter, Maglione, Komlódi, Ulmer, Cardini, Troppmair, Öfner, Gnaiger, Schneeberger and Oberhuber.)

Background: Interstitial fibrosis and tubular atrophy (IF/TA), a histologic feature of kidney allograft destruction, is linked to decreased allograft survival. The role of lipid metabolism is well-acknowledged in the area of chronic kidney diseases; however, its role in kidney allograft fibrosis is still unclarified. In this study, how lipid metabolism contributes to kidney allografts fibrosis was examined., Methods: A comprehensive bioinformatic comparison between IF/TA and normal kidney allograft in the Gene Expression Omnibus (GEO) database was conducted. Further validations through transcriptome profiling or pathological staining of human recipient biopsy samples and in rat models of kidney transplantation were performed. Additionally, the effects of enhanced lipid metabolism on changes in the fibrotic phenotype induced by TGF-β1 were examined in HK-2 cell., Results: In-depth analysis of the GEO dataset revealed a notable downregulation of lipid metabolism pathways in human kidney allografts with IF/TA. This decrease was associated with increased level of allograft rejection, inflammatory responses, and epithelial mesenchymal transition (EMT). Pathway enrichment analysis showed the downregulation in mitochondrial LC-fatty acid beta-oxidation, fatty acid beta-oxidation (FAO), and fatty acid biosynthesis. Dysregulated fatty acid metabolism was also observed in biopsy samples from human kidney transplants and in fibrotic rat kidney allografts. Notably, the areas affected by IF/TA had increased immune cell infiltration, during which increased EMT biomarkers and reduced CPT1A expression, a key FAO enzyme, were shown by immunohistochemistry. Moreover, under TGF-β1 induction, activating CPT1A with the compound C75 effectively inhibited migration and EMT process in HK-2 cells., Conclusions: This study reveal a critical correlation between dysregulated lipid metabolism and kidney allograft fibrosis. Enhancing lipid metabolism with CPT1A agonists could be a therapeutic approach to mitigate kidney allografts fibrosis., (© 2024. The Author(s).)

Purpose: To compare the clinical outcomes and tendon integrity after rotator cuff repair combined with anterior cable reconstruction (ACR) using the proximal biceps tendon and patch augmentation (PA) using a human dermal allograft (HDA) in a large retracted anterior rotator cuff tear., Methods: Patients who underwent arthroscopic rotator cuff repair with 2 different augmentation procedures between January 2017 and December 2020 were enrolled. The inclusion criteria were patients who were treated by arthroscopic rotator cuff repair with ACR using the proximal biceps tendon (ACR group) or patch augmentation using a an HDA (PA group) and follow-up for at least 2 years. Clinical outcomes were assessed using American Shoulder and Elbow Surgeons (ASES) score, Constant score, and the number of patients who achieved minimal clinically important differences (MCID). Magnetic resonance imaging was performed to evaluate tendon integrity after surgery., Results: A total of 92 patients were enrolled (ACR group = 55 patients and PA group = 37 patients). The mean ASES and Constant scores significantly improved in the ACR group (68.8 ± 15.3 and 58.4 ± 16.9 before surgery vs 91.4 ± 6.3 and 87.8 ± 6.0 after surgery, P < .001) and in the PA group (63.7 ± 16.7 and 57.9 ± 15.4 before surgery vs 93.1 ± 6.3 and 88.3 ± 6.2 after surgery, P < .001). Overall, 78 patients (84.8%) achieved the MCID with 81.8% in the ACR group and 89.2% in the PA group, with no significant differences between the 2 groups (P = .638). Ten patients (18.2%) had retear in the ACR group, and three patients (8.1%) had retear in the PA group (P = .174)., Conclusions: In large retracted anterior rotator cuff tears, both augmentation techniques using biceps tendon autograft and HDA provided satisfactory clinical outcomes that achieved the MCID in 84.8%, range of motion restoration, and lower retear rates with no significant differences between the two groups., Level of Evidence: Level III, retrospective case-control study., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Osteochondritis dissecans (OCD) of the capitellum occurs relatively infrequently but can be found in young overhead-throwing athletes, most commonly in baseball players and gymnasts. Although non-operative management can effectively treat stable lesions, unstable lesions can lead to debilitating symptoms of the elbow and diminished quality of life without surgical intervention. This article reviews methods of treating OCD of the capitellum categorized by stability, size, and patient characteristics, and seeks to familiarize the reader with the appropriate selection of osteochondral allograft versus autograft in treating large, unstable lesions. We complement this review with 3 case examples, each using either an osteochondral autograft or allograft, and discuss the decision-making methodology used in each case., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this study is to assess the effectiveness of horizontal ridge augmentation using FDBA in combination with injectable-platelet rich fibrin (i-PRF) versus FDBA alone. To fulfill this aim, the radiographic and histomorphometric outcomes are compared., Method: The study involved 41 patients who had horizontal alveolar ridge defects categorized as either B (2.5-7 mm) or C (0-2.5 mm). The control group received FDBA alone (n = 20), while the test group received FDBA in combination with i-PRF (n = 21). The horizontal dimensions of the alveolar ridge were measured at 0, 2, 4, and 6 mm from the bone crest using CBCT before and 6 months after alveolar ridge augmentation. In the second-stage surgery, 24 biopsies were taken from the augmented bone - 13 from the control group and 11 from the test group, and were examined histologically and histomorphometrically. The data were analyzed using Pearson correlation coefficient, chi-square, paired-t, and two-sample t tests., Results: There was no significant difference (p > 0.05) in the increase of mean ridge width between the test group and the control group after 6 months at distances of 0, 2, 4, and 6 mm from the crest, with differences of -0.28, 0.12, 0.52, and 1.04 mm, respectively. However, the amount of newly formed bone and material residues was significantly higher in the FDBA + i-PRF group compared to the FDBA alone group (45.01% and 13.06% vs 54.03% and 8.48%, respectively). There was no significant difference in the amount of soft tissue between the two groups (41.02% and 37.5%, p > 0.05)., Conclusion: The study found that there was no statistically significant difference in the increase of horizontal ridge width between the FDBA + i-PRF group and the FDBA group. However, the histomorphometric analysis revealed that the FDBA + i-PRF group had a higher proportion of newly formed bone, less connective tissue, and fewer residual particles. This suggests a superior quality of bone formation compared to the FDBA group., (© 2023 Wiley Periodicals LLC.)

Background: The overall cancer risk increases in transplant patients, including in kidney allografts. This study aimed to analyze the outcome of patients with kidney allograft malignant tumors who underwent percutaneous thermal ablation., Methods: We included 26 renal allograft tumors, including 7 clear-cell renal cell carcinoma (RCCs), 16 papillary RCCs, 1 clear-cell papillary RCC, and 2 tubulocystic RCCs, treated in 19 ablation sessions. Outcomes of thermal ablation therapy were assessed, including technical success, adverse events, local tumor progression, development of metastases, survival after thermal ablation, and changes in renal function., Results: Success rate was achieved in all ablation sessions (primary success rate: 96%; secondary success rate: 100%). No adverse events were observed in grades 3, 4, or 5. The median follow-up period was of 34 mo (15-69 mo). Two patients died during follow-up from a cause independent of renal cancer. The median decrease in estimated glomerular filtration rate 1 y after procedure was -4 (interquartile range, -7 to 0) mL/min/1.73 m 2 . One patient returned to dialysis within the year of the procedure., Conclusions: Percutaneous thermal ablation shows convincing results for treating malignant renal graft tumors and should be a useful treatment option. The shorter hospitalization time, the advantage of avoiding a potentially challenging dissection of the transplant, and the excellent preservation of allograft function appear encouraging to extend this indication., Competing Interests: J.-M.C. received honoraria from Canon Medical Systems, Bracco, Guerbet; support for attending meetings and travel: Canon Medical Systems, Bracco, Guerbet; receipt of materials and equipment: Canon Medical Systems (loan of an US equipment). The other authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims and Background: To describe the prevalence of IgA deposits (IgAD) in renal allografts in a cohort of renal transplant recipients and to analyze their management strategies and histopathology. To assess graft function and proteinuria after 1 year of follow-up., Materials and Methods: A prospective longitudinal follow-up study was carried out in VPS Lakeshore Hospital and Research Centre, Kochi, Kerala, over a period of 5 years (July 2015 to June 2020). Kidney transplant recipients with allograft biopsies that reported IgAD on immunofluorescence were included in the study. Light microscopy and immunofluorescence studies were performed. Mesangial hypercellularity (M); segmental glomerulosclerosis (S); endocapillary hypercellularity (E); tubular atrophy/interstitial fibrosis (T); crescents (C) (MEST-C) Scoring was done in patients with pathogenic IgAD. Treatment strategies included increased baseline steroid dosage, rituximab administration, and plasma exchange. Clinical details and management strategies were analyzed, and patients were followed up for 1 year after diagnosis. Changes in graft function (S. Creatinine) and proteinuria (Urine Protein/Creatinine ratio) were analyzed. Clinico-pathologic correlation with the MEST-C scores was also done., Results: Out of 1036 kidney transplants done in the study period, 760 graft biopsies were performed. Sixty-four cases had post-transplant deposition of IgA (8%). The mean age was 45 ± 11.25SD years. The study had 51 men and 13 women. Induction immunosuppression comprised rabbit antithymocyte globulin in 29 (45%) patients and basiliximab in 35 (54%). Maintenance immunosuppression in all comprised tacrolimus, mycophenolate mofetil, and steroids. There were 2 groups: group A (pathogenic IgAD) and group B (incidental IgAD). Group A had 46 cases (71.9%), out of which 8 had "active" IgA nephropathy (endocapillary proliferation, crescents, and IgA vasculitis), and 38 had "inactive" IgAD. In patients with active deposits, 3 had cellular crescents (18%, 30%, and 23%), all 8 had endocapillary proliferation, and 2 had vasculitis. Group B had 18 cases (28.1%), comprising T cell-mediated rejections (5), antibody-mediated rejection (8), BK virus nephropathy (1), and interstitial fibrosis and tubular atrophy (4). In group A, 22 (47.8%) presented with graft dysfunction, 8 (17.3%) with isolated proteinuria, and 14 (30.4%) patients presented with a combination. Two (4.3%) patients had neither. Fourteen (30.4%) patients presented within 1 month of renal transplant. In patients of group A, at the end of 1 year of treatment, the mean S. Creatinine reduced to 1.68 mg/dL from 1.84 mg/dL, and the mean protein/creatinine ratio reduced from 1.2 to 0.5 (±1.17). In patients with "active IgA" lesions, at the end of 1 year of treatment, the mean S. Creatinine increased slightly to 1.68 mg/dL (±0.47SD) from 1.48 mg/dL (±0.52SD), and the mean protein/creatinine ratio reduced from 2.32 (±1.56SD) to 1.05 (±1.70SD). In the 16 patients with IgAD and proteinuria, at the end of 1 year of treatment, the mean S. Creatinine decreased to 1.41 ± 0.32 SD mg/dL from 1.47±0.37SD mg/dL and the mean protein/creatinine ratio reduced from 1.12 ± 1.31 SD to 0.39±0.75 SD. In the remaining 22 patients with acute tubular injury, at the end of 1 year, the mean S. Creatinine decreased to 1.920.32 SD mg/dL from 2.10.8SD mg/dL, and the mean protein/creatinine ratio reduced from 1.1 ± 1.31 SD to 0.66 ± 1.45 SD. In the MEST-C scoring analysis, all scores were 0 in 20 (43.4%) biopsies, only M1 score in 11 (23.9%) biopsies, only E1 score in 10 biopsies (21.7%), S1 in 13 (28.2%) cases., Conclusion: Immunoglobulin A deposits occur commonly after transplant; these may represent recurrence, de novo IgA, or donor-derived IgAD. Although commonly benign, some may cause significant graft dysfunction and graft loss. IgAD can present as varying combinations of graft dysfunction and proteinuria. Active IgA pathologies may occur early in the post-transplant course, may have significant graft dysfunction, and need proactive management. There is a correlation between segmental sclerosis and proteinuria. Evidence for the efficacy of Rituximab, plasma exchange, and prolonged courses of steroids is wanting; however, some benefits are possible. Long-term follow-up is essential., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The study aimed to determine the association of chronic graft-versus-host disease (cGVHD) diagnosis and severity with the development of subsequent neoplasms (SN) and nonmalignant late effects (NM-LE) in 2-year disease-free adult survivors following hematopoietic cell transplantation (HCT) for a hematologic malignancy. To do so, we conducted a retrospective analysis of 3884 survivors of HCT for hematologic malignancy in the Center of International Blood and Marrow Transplant Research database. We conducted a landmark analysis at the 2-year post-transplantation date, comparing first SN and NM-LE in survivors with and without cGVHD. The cumulative incidence (CuI) of SN and NM-LE were estimated through 10 years post-HCT in both groups, with death or disease relapse as a competing risk. Cox proportional hazards models were used to evaluate the associations of cGVHD and its related characteristics with the development of SN and NM-LE. The estimated 10-year CuI of SN in patients with GVHD (n = 2669) and patients without cGVHD (n = 1215) was 15% (95% confidence interval [CI], 14% to 17%) versus 9% (7.2% to 11%) (P < .001). cGVHD by 2 years post-HCT was independently associated with SN (hazard ratio [HR], 1.94; 95% CI, 1.53 to 2.46; P < .0001) with a standardized incidence ratio of 3.2 (95% CI, 2.9 to 3.5; P < .0001). Increasing severity of cGVHD was associated with an increased risk of SN. The estimated 10-year CuI of first NM-LE in patients with and without cGVHD was 28 (95% CI, 26% to 30%) versus 13% (95% CI, 11% to 15%) (P < .001). cGVHD by 2 years post-HCT was independently associated with NM-LE (HR, 2.23; 95% CI, 1.81 to 2.76; P < .0001). Multivariate analysis of cGVHD-related factors showed that increasing severity of cGVHD, extensive grade, having both mucocutaneous and visceral involvement, and receiving cGVHD treatment for >12 months were associated with the greatest magnitude of risk for NM-LE. cGVHD was closely associated with both SN and NM-LE in adult survivors of HCT for hematologic malignancy. Patients identified as having more severe involvement and both mucocutaneous and visceral organ involvement may warrant enhanced monitoring and screening for SNs and NM-LEs. However, caution is warranted when interpreting these results, as patients with cGVHD may have more vigilant post-transplantation health care and surveillance for late effects., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Fibronectin glomerulopathy is a rare genetic nephropathy with only a few cases of post-transplant recurrence being reported previously. We highlight a case that was initially misdiagnosed and emphasize the importance of full immunofluorescence and electron microscopy evaluation in allograft biopsies., Case Presentation: A 36-year-old male with a history of end-stage kidney disease secondary to biopsy-proven type 1 membranoproliferative glomerulonephritis (MPGN) status-post living unrelated donor kidney transplant 12 years prior, presented with increasing creatinine and proteinuria. Biopsy was performed and was consistent with fibronectin glomerulopathy. Subsequent genetic testing revealed an FN1 mutation, the primary gene associated with this condition., Conclusions: Full histologic evaluation of the allograft biopsy corrected the diagnosis and additionally suggested that the patient's mother, who had expired in her 30s and had received a diagnosis of type 1 MPGN on autopsy, likely also had fibronectin glomerulopathy, enabling appropriate genetic counseling for the family., (© 2023. The Author(s).)

Aim: The aim of the present study was to clarify the relationship between the Banff score of the 7-year protocol biopsy and the allograft outcome., Methods: One-hundred-and-eighty-four patients received kidney transplantation from 2002 to 2008. We excluded patients aged <20 years at transplantation ( n  = 24), those who did not undergo a 7-year protocol biopsy ( n  = 66), and those who underwent for-cause biopsy ( n  = 5). Consequently, 89 patients who underwent a 7-year protocol biopsy were enrolled. We analyzed the relationship between the clinicopathological findings 7 years after transplantation and the estimated glomerular filtration rate (eGFR) change per year and allograft survival. Histological evaluation was performed using the Banff 2015 classification., Results: Among the clinicopathological findings, each Banff mesangial matrix increase (mm) score ≥1 and proteinuria ≥1+ was independently associated with the eGFR decline per year during a median follow-up of 73 months. Furthermore, in the model of the clinicopathological findings including the presence of mm with proteinuria, mm ≥1 alone and mm ≥1 with proteinuria were each independently associated with the eGFR decline. The graft survival was significantly worse for those with mm ≥1 with proteinuria than those with mm ≥1 without proteinuria., Conclusion: Among the 7-year protocol biopsy findings, the presence of mm alone and mm with proteinuria were each significant predictors of eGFR decline. The presence of both proteinuria and mm had a negative impact on graft survival. These results underscore the significance of the Banff mm score and proteinuria at the time of the 7-year protocol biopsy to predict the allograft outcome.

Primary focal segmental glomerulosclerosis (FSGS) is thought to be caused by circulating factors leading to podocytopathy, whereas segmental sclerotic lesions (FSGS lesions) have several causes. We studied the clinicopathological differences of FSGS-lesions in 258 cases of FSGS in renal allografts, depending on the following accompanying pathophysiology: recurrence of primary FSGS, calcineurin inhibitor (CNI)-induced arteriolopathy, antibody-mediated rejection (ABMR), and other conditions. All cases were categorized with the Columbia classification. Recurrent FSGS developed the earliest after transplantation and showed the highest percentage of the collapsing (COL) variant in which collapse of the glomerular capillaries with epithelial hypertrophy was apparent. FSGS accompanying CNI-induced arteriolopathy predominantly developed the not otherwise specified (NOS) variant, showing severe ultrastructural endothelial injury. On the contrary, approximately 7% of the cases showed the COL variant, presenting glomerular endothelial damage such as double contours of glomerular basement membrane and endothelial cell swelling as well as epithelial cell proliferation. FSGS with ABMR had the highest creatinine levels and cellular variant percentage, with marked inflammation and ultrastructural endothelial injury. Approximately two-thirds of the cases without ABMR, CNI-induced arteriopathy, or recurrent FSGS had other coexisting conditions such as glomerulonephritis, T cell-mediated rejection, and reflux nephropathy with progressive tubulointerstitial fibrosis. Most of these cases were of the NOS variant. The clinicopathologic features of post-transplant FSGS differed depending on the associated conditions, and endothelial injury was apparent especially in cases of CNI-induced arteriolopathy and ABMR. Precise observation of FSGS lesions may facilitate the diagnosis and clinical management of FSGS during renal transplantation., (© 2023. The Author(s).)

The primary aim of this study was to assess the histomorphometric outcomes of extraction sockets grafted with freeze-dried bone allograft (FDBA) and sealed with a collagen membrane after 3 months of healing in specific region of interest (ROI) areas. The secondary aims were to analyze the biomaterial resorption rate, the bone-to-biomaterial contact (BBC), and the area and perimeter of grafted particles compared with commercially available FDBA particles. Fifteen patients underwent tooth extractions and ridge preservation procedures performed with FDBA and a collagen membrane. Bone biopsy samples were harvested after 3 months at the time of implant placement for histologic and histomorphometric analysis. Two areas of concern (ROI1 and ROI2) with different histologic features were identified within the biopsy samples; ROI1, ROI2, and commercially available particles were analyzed and compared. The following parameters were analyzed: newly formed bone, marrow space, residual graft particles, perimeter and area of FDBA particles, and BBC. The histomorphometric analysis showed 35.22% ± 10.79% newly formed bone, 52.55% ± 16.06% marrow spaces, and 12.41% ± 7.87% residual graft particles. Moreover, the histologic data from ROI1 and ROI2 showed that (1) the mean percentage of BBC was 64.61% ± 27.14%; (2) the newly formed bone was significantly higher in ROI1 than in ROI2; (3) the marrow space was significantly lower in ROI1 than in ROI2; and (4) the FDBA particles in ROI1 sites showed significantly lower area and perimeter when compared to commercially available FDBA particles. This latter data led to the hypothesis that FDBA particles embedded in newly formed bone undergo a resorption/remodeling process.

Postinfantile giant cell hepatitis (PIGCH) is a rare hepatitis pattern in adults with variable etiologies and clinical outcomes. We conducted a multi-institutional retrospective study to define the clinicopathologic characteristics of patients with PIGCH. A total of 70 PIGCH cases were identified and reviewed for pathological features, including fibrosis, cholestasis, inflammation, steatosis, necrosis, and apoptosis, as well as the distribution of giant cells and the maximum number of giant cells per high-power field. Demographic and clinical data, including age, sex, laboratory results, etiologies, and follow-up results, were recorded. Among the 70 cases, 40% (28/70) were associated with autoimmune liver diseases, followed by 9 (13%) with unknown etiology, 8 (11%) with viral infection, 5 (7%) with medications, 5 with combined etiologies, and 4 (6%) with malignancies (mostly chronic lymphocytic leukemia). Notably, another 16% were de novo PIGCH in liver allografts, most of which occurred after a rejection event. During follow-up, 26 (37%) patients died of the disease and 44 (63%) were alive. Deceased patients were characterized by older age (mean age, 54.9 vs 45.5 years; P = .02), higher alkaline phosphatase level (mean value, 253.3U/L vs 166.3 U/L; P = .03), higher fibrosis stage (stage 3-4 vs stage 0-2, 57.7% vs 29.6%; P = .03), being more likely to have de novo PIGCH after transplantation (23.1% vs 11.4%; P = .04), and being less likely to have primary autoimmune liver disease etiology (26.9% vs 47.7%; P = .04). These results indicate that PIGCH is a rare pattern of liver injury associated with different etiologies and variable clinical outcomes. Autoimmune liver disease with PIGCH is associated with better survival, whereas de novo PIGCH in allografts is associated with poorer survival. Older age, higher alkaline phosphatase level, and advanced fibrosis are adverse prognostic factors., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Recurrence of immunoglobulin A nephropathy (IgAN) limits graft survival in kidney transplantation. However, predictors of a worse outcome are poorly understood., Methods: Among 442 kidney transplant recipients (KTRs) with IgAN, 83 (18.8%) KTRs exhibited biopsy-proven IgAN recurrence between 1994 and 2020 and were enrolled in the derivation cohort. A multivariable Cox model predicting allograft loss based on clinical data at the biopsy and a web-based nomogram were developed. The nomogram was externally validated using an independent cohort (n = 67)., Results: Patient age <43 years {hazard ratio [HR] 2.20 [95% confidence interval (CI) 1.41-3.43], P < .001}, female gender [HR 1.72 (95% CI 1.07-2.76), P = .026] and retransplantation status [HR 1.98 (95% CI 1.13-3.36), P = .016] were identified as independent risk factors for IgAN recurrence. Patient age <43 years [HR 2.77 (95% CI 1.17-6.56), P = .02], proteinuria >1 g/24 hours [HR 3.12 (95% CI 1.40-6.91), P = .005] and C4d positivity [HR 2.93 (95% CI 1.26-6.83), P = .013] were found to be associated with graft loss in patients with IgAN recurrence. A nomogram predicting graft loss was constructed based on clinical and histological variables, with a C statistic of 0.736 for the derivation cohort and 0.807 for the external validation cohort., Conclusions: The established nomogram identified patients with recurrent IgAN at risk for premature graft loss with good predictive performance., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Objective: To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection., Methods: Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded., Results: All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P <0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P >0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients., Conclusion: Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.

Background: Porto-mesenteric vein (PMV) infiltration of pancreatic cancer is classified as borderline resectable cancer. For en-bloc resectability, the probability of PMV resection and reconstruction is the most decisive factor. The purpose of this study was to compare and analyze PMV resection and reconstruction during pancreatic cancer surgery using end-to-end anastomosis (EA) and a cryopreserved allograft (AG) and to verify the effectiveness of reconstruction using an AG., Methods: Between May 2012 and June 2021, 84 patients (65 underwent EA, and 19 received AG reconstruction) underwent pancreatic cancer surgery with PMV reconstruction. An AG is a cadaveric graft with a diameter of 8-12 mm and is obtained from a liver transplant donor. Patency after reconstruction, disease recurrence, overall survival, and perioperative factors were assessed., Results: The median age was higher in EA patients (p = .022) and neoadjuvant therapy (p = .02) was more in AG patients. Upon histopathological examination, the R0 resection margin did not show a significant difference by reconstruction method. During a 36-month survival analysis, primary patency was significantly superior in EA patients (p = .004), and there was no significant difference in recurrence-free survival (p = .628) or overall survival (p = .638) rates., Conclusion: Compared with EA, AG reconstruction after PMV resection during pancreatic cancer surgery showed a lower primary patency, but there was no difference in recurrence-free or overall survival rates. Therefore, the use of AG can be a viable option for borderline resectable pancreatic cancer surgery if the patient is properly followed-up postoperatively., Competing Interests: Declaration of competing interest The authors have no conflicts of interests or disclosures to report., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Thrombotic microangiopathy (TMA) on kidney biopsy shows a variable combination of features: arterial mucoid intimal thickening, acellular closure of glomerular capillary loops, fragmented red blood cells, fibrin thrombi, and arterial fibrinoid necrosis. However, some early post-transplant kidney biopsies show only arterial mucoid intimal thickening. We aimed to elucidate the importance of this finding., Methods: We identified 19 biopsies showing isolated arterial mucoid intimal thickening and compared them with 22 bona fide TMA biopsies identified based on the pathological findings (excluding rejection) (2011-2020). Additionally, delayed graft function (DGF) (n = 237), and no DGF (control, n = 1314) groups were included for survival analysis., Results: Seven of 19 cases with isolated arterial mucoid intimal thickening showed peripheral blood schistocytes but no other systemic features of TMA. Eight patients underwent adjustments in maintenance immunosuppression (mainly calcineurin inhibitors). None of the cases progressed to full-blown TMA on consecutive biopsies. The overall and death-censored graft survival rates in this group were comparable to the DGF group, but significantly better than the TMA group (P = .005 and .04, respectively)., Conclusions: Isolated arterial mucoid intimal thickening in early post-transplant biopsies may be an early/mild form of TMA, probably requiring adjustment in immunosuppressive regimen. Careful exclusion of known causes of TMA, and donor-derived arterial injury are important., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Purpose: To perform a preclinical histologic assessment of a biphasic acellular interpositional cancellous allograft in an ovine model of rotator cuff repair (RCR) designed to better understand its safety profile and effects on tendon healing after RCR., Methods: Thirty skeletally mature sheep with clinically normal shoulders with an artificially created degenerative infraspinatus tendon tear were randomized to control and treatment groups. Animals were euthanized at 3 weeks, 6 weeks, and 12 weeks. After gross dissection, rotator cuff specimens were fixed with formalin and polymerized for sectioning and staining. Blinded histologic scores evaluated inflammatory cell infiltrates, signs of degradation, particulate debris, collagen arrangement, neovascularization, and enthesis qualitative measures., Results: There were no treatment specimens that exhibited histologic signs of a significant infection, inflammatory infiltrate, or foreign body reaction such as granuloma or fibrous capsule formation. Histologic scores in all categories were not significantly different at all time points, including the primary end point mean cumulative inflammatory score (control: 3.66 ± 1.21 vs treated: 4.33 ± 1.51, P = .42), when comparing the treatment and control RCR groups. In general, the degree of tendon healing and host tissue response was essentially equivalent between the 2 groups with observation of low overall levels of inflammation and progressive improvements in collagen organization, reduced tenocyte activity, and fibrocartilaginous enthesis reformation., Conclusions: This histologic study demonstrated the use of a biphasic interpositional allograft for RCR augmentation in an ovine model does not generate an inflammatory response or foreign body reaction. Use of the biphasic interpositional allograft resulted in a histological profile that was essentially equivalent to that of a standard RCR at 3-, 6-, and 12-week postoperative timepoints. These findings suggest that a biphasic interpositional allograft is safe for further clinical investigation in humans before broader clinical application., Clinical Relevance: Patch augmentation of RCR is a popular technique that has shown clinical success in improving the likelihood of a successful repair in patients at elevated risk for retear. Newer augmentation technologies are being developed to address the biology at the interface between the bone and soft tissue where failure typically occurs., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Allograft reconstruction following the resection of malignant bone tumors is associated with high rates of complications and failures. This study aimed to evaluate the efficacy and current problems of allograft reconstruction techniques to optimize treatment strategies at our center., Materials and Methods: Thirty-eight cases (16 men and 22 women), who were diagnosed with malignant bone tumors and had undergone allograft reconstruction, were recruited. Allograft was fixed by intramedullary nail, single steel plate, double plate, and intramedullary nail combined plate in 2, 4, 17, and 15 cases, respectively. Allograft union, local recurrence, and complications were assessed with clinical and radiological tests. Tumor grade was assessed using the Enneking staging of malignant bone tumors. Functional prognosis was evaluated by the Musculoskeletal Tumor Society (MSTS) scoring system., Results: Intercalary and osteoarticular reconstructions were performed in 32 and 6 cases, respectively. Six patients underwent reoperation related to allograft complications, four patients had local recurrence, and three patients with allograft fracture underwent allograft removal. A total of eight host-donor junctions showed nonunion, including seven cases (18.4%) in diaphysis and one case (3.1%) in metaphysis (p < 0.01). Host rejection and secondary osteoarthritis occurred in nine and two cases, respectively. No deep infection and internal fixation device fracture occurred. The overall allograft survival rate was 81.6%. Postoperative MSTS score of patients with allograft survival was 26.8 ± 2.9, indicating a significant improvement as compared to their preoperative function., Conclusions: Allograft represents an excellent choice for intercalary bone defects after malignant bone tumor resection. Robust internal fixation protection across the whole length of the allograft is an important prerequisite for the survival of the allograft, while multidimensional osteotomy, intramedullary cement reinforcement, and pedicled muscle flap transfer can effectively improve the survival rate and healing rate of the allograft., (© 2023. The Author(s).)

Advances in immunosuppressive therapy; posttransplant management of allograft rejection; and measures against infectious diseases, cardiovascular diseases, and malignancy dramatically improved graft and patient survival after kidney transplantation (KT). Among them, kidney allograft biopsy is an important tool and the gold standard for the diagnosis of various kidney allograft injuries, including allograft rejection, virus-induced nephropathy, calcineurin inhibitor toxicity, and posttransplant glomerular diseases. The Banff Conference on Allograft Pathology has contributed to establishing the diagnostic criteria for kidney allograft rejection and polyomavirus-associated nephropathy that are used as a common standard worldwide. In addition to the for-cause biopsy, many transplant centers perform protocol biopsies in the early and late posttransplant periods to detect and treat allograft injury earlier. Preimplantation biopsy in deceased-donor KT has also been performed, especially in the marginal donor, and attempts have been made to predict the prognosis in combination with clinical information and the renal resistance of hypothermic machine perfusion. Regarding the preimplantation biopsy from a living kidney donor, it can provide useful information on aging and/or early changes in lifestyle diseases, such as glomerulosclerosis, tubulointerstitial changes, and arterial and arteriolar sclerosis, and be used as a reference for the subsequent management of living donors. In this review, morphologic features of important kidney allograft pathology, such as allograft rejection and polyomavirus-associated nephropathy, according to the latest Banff classification and additional information derived from protocol biopsy, and future perspectives with recently developed technologies are discussed.

Malakoplakia is an uncommon inflammatory disease that can involve many organ systems but is often encountered in the urogenital tract. Kidney allograft malakoplakia is even rarer and can have a diffuse parenchymal or a pseudotumoral presentation. We describe a case of grafi malakoplakia in an adult female, who presented with dull aching pain in the right loin, fever, and vomiting. Ultrasonography of the kidney graft showed a heterogeneous lesion (2.6 cm × 2.9 cm), raising suspicion of primary or metastatic renal tumors. The diagnosis was established after a histopathological examination of the kidney biopsy. This pseudotumoral presentation of malakoplakia can mimic renal cell carcinoma, lymphoma, fungal infections, or tuberculosis. It is essential to perform a biopsy for establishing the diagnosis., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Kidney Diseases and Transplantation.)

Chronic allograft dysfunction (CAD), characterized histologically by interstitial fibrosis and tubular atrophy, is the major cause of kidney allograft loss. Here, using single nuclei RNA sequencing and transcriptome analysis, we identified the origin, functional heterogeneity, and regulation of fibrosis-forming cells in kidney allografts with CAD. A robust technique was used to isolate individual nuclei from kidney allograft biopsies and successfully profiled 23,980 nuclei from five kidney transplant recipients with CAD and 17,913 nuclei from three patients with normal allograft function. Our analysis revealed two distinct states of fibrosis in CAD; low and high extracellular matrix (ECM) with distinct kidney cell subclusters, immune cell types, and transcriptional profiles. Imaging mass cytometry analysis confirmed increased ECM deposition at the protein level. Proximal tubular cells transitioned to an injured mixed tubular (MT1) phenotype comprised of activated fibroblasts and myofibroblast markers, generated provisional ECM which recruited inflammatory cells, and served as the main driver of fibrosis. MT1 cells in the high ECM state achieved replicative repair evidenced by dedifferentiation and nephrogenic transcriptional signatures. MT1 in the low ECM state showed decreased apoptosis, decreased cycling tubular cells, and severe metabolic dysfunction, limiting the potential for repair. Activated B, T and plasma cells were increased in the high ECM state, while macrophage subtypes were increased in the low ECM state. Intercellular communication between kidney parenchymal cells and donor-derived macrophages, detected several years post-transplantation, played a key role in injury propagation. Thus, our study identified novel molecular targets for interventions aimed to ameliorate or prevent allograft fibrogenesis in kidney transplant recipients., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Surgery of primary malignant tumors involving the sacroiliac joint requires wide resection, which often interrupts the pelvic ring. Nowadays, restoration of the pelvic ring to provide stability and which technique is most fitting remain subject to debate. The aim of this study is to evaluate the results of pelvic reconstruction with pedicle screw instrumentation and tibial allograft following Enneking Type I-IV resections., Patients and Methods: All patients who underwent reconstruction with tibial allograft, screws and rods after resection of areas I and IV for primary bone tumors between 2017 and 2022 were reviewed. Clinical and radiological characteristics, fusion rate and functional results were analyzed. The MSTS score and the TESS were used to evaluate functional results., Results: Seven patients were included in the study. Chondrosarcoma was the most common histology. Only four patients reported pain. No fractures were observed at tumor diagnosis. Computer-assisted navigation was used in six cases. Reconstruction was performed in four cases with a screw inserted in the homolateral L5 pedicle and in the ischium, in two cases with a screw in the homolateral L4 pedicle and another in the homolateral L5 pedicle, in the last case with two screws inserted in L4 and L5, one screw in the ischium and another one in the residual iliac wing. In this case a contralateral stabilization was also carried out. The spine screws and the iliac screws were connected with a rod. The mean follow-up for all 7 patients was 37 months. One patient (16.6%) died due to general complications not directly related to the surgery; while the others are alive and apparently free of disease. Complete fusion was obtained in four out of seven patients and the average time for fusion was 9 months. The average MSTS score and TESS were 58.7% and 57.8%, respectively., Discussion: The need for reconstruction is thoroughly debated in literature. The advantages of restoring posterior pelvis stability are the prevention of long-term pain associated with limb shortening and secondary scoliosis. Re-establishment of the pelvic ring can be achieved through synthetic, biologic or hybrid reconstructions., Conclusions: More studies that assess the surgical consequences at long-term follow-up and help clarify the indications for reconstruction and the specific technique are necessary to confirm our preliminary results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

T cell-mediated rejection (TCMR) remains a significant cause of long-term kidney allograft loss, either indirectly through induction of donor-specific anti-HLA alloantibodies or directly through chronic active TCMR. Whether found by indication or protocol biopsy, Banff defined acute TCMR should be treated with antirejection therapy and maximized maintenance immunosuppression. Neither isolated interstitial inflammation in the absence of tubulitis nor isolated tubulitis in the absence of interstitial inflammation results in adverse outcomes, and neither requires antirejection treatment. RNA gene expression analysis of biopsy material may supplement conventional histology, especially in ambiguous cases. Lesser degrees of tubular and interstitial inflammation (Banff borderline) may portend adverse outcomes and should be treated when found on an indication biopsy. Borderline lesions on protocol biopsies may resolve spontaneously but require close follow-up if untreated. Following antirejection therapy of acute TCMR, surveillance protocol biopsies should be considered. Minimally invasive blood-borne assays (donor-derived cell-free DNA and gene expression profiling) are being increasingly studied as a means of following stable patients in lieu of biopsy. The clinical benefit and cost-effectiveness require confirmation in randomized controlled trials. Treatment of acute TCMR is not standardized but involves bolus corticosteroids with lymphocyte depleting antibodies for severe, refractory, or relapsing cases. Arteritis may be found with acute TCMR, active antibody-mediated rejection, or mixed rejections and should be treated accordingly. The optimal treatment ofchronic active TCMR is uncertain. Randomized controlled trials are necessary to optimally define therapy., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Despite many advances in the development of knowledge and application of new immunosuppressive medications over the past two decades, the improvement has only been seen in the short-term outcome of kidney transplantation while the long-term survival of kidney transplantation has not significantly improved. Allograft kidney biopsy may help to determine the causes of allograft dysfunction which may change the treatment strategy., Methods: In this retrospective study, kidney transplant recipients who underwent kidney biopsy in Shariati hospital during the years 2004 to 2015, at least three months after the kidney transplantation, were included for evaluation. Chi-square, ANOVA, post-hoc LSD, and T-test were used for data analysis., Results: A total number of 525 renal transplant biopsies were performed; 300 of them had complete medical records. The reported pathologies consisted of acute T-Cell mediated rejection (TCMR) (17%), interstitial fibrosis and tubular atrophy/chronic allograft nephropathy (IFTA/CAN) (15%), calcineurin inhibitor (CNI) nephrotoxicity (12.8%), borderline changes (10.3%), glomerulonephritis (GN) (8.9%), antibody mediated rejection (ABMR) (6.7%), transplant glomerulopathy (TG) (5.3%), normal (8.4%), and other pathologies (15.6%). C4d was positive in 19.9% of the biopsies. The pathology category had a significant correlation with allograft function (P < .001), but it had no significant relationship with age and gender of the recipient, donor and donor source (P > .05). Moreover, in about 50% of cases, treatment interventions were based on pathological results, which were effective in 77% of cases. The two-year graft and patient survival after kidney biopsy were 89% and 98%, respectively., Conclusion: Acute TCMR, IFTA/CAN, CNI nephrotoxicity were the most common causes of allograft dysfunction based on the transplanted kidney biopsy. In addition, pathologic reports were helpful for proper treatment.  DOI: 10.52547/ijkd.7256.

Few previous studies have reported immune-complex nephropathy that has not been classified as a specific phenotype in kidney allografts. We report a case of a de novo subclinical "full-house" pattern of deposition in a pediatric transplantation recipient with possible donor-derived IgA deposition. A five-year-old boy underwent living kidney transplantation due to congenital kidney and urinary tract anomalies. A one-hour implantation biopsy revealed IgA deposition. A four-month protocol biopsy finding showed less intense IgA deposition, in contrast with the one-hour biopsy, and trace para-mesangial deposits. A one-year protocol biopsy demonstrated a full-house deposition pattern and massive electron-dense deposits with minor glomerular changes. At the time of the one-year biopsy, kidney function was stable, with no urinalysis abnormalities. No evidence of systemic lupus erythematosus was observed in clinical and serologic examinations. Mesangial IgG, IgM, C3, and C1q deposition was codominant, and IgA deposition was weaker. We diagnosed this case as C1q nephropathy combined with remaining donor-derived IgA deposition. Few studies have reported C1q nephropathy in kidney allograft; further accumulation of cases is required. To distinguish between donor-derived and de novo glomerular lesions, it is important to assess the serial histologic findings of immunofluorescence and electron microscopy. Here, we report a rare case of subclinical C1q nephropathy with possible donor-derived IgA nephropathy., Competing Interests: DISCLOSURES Written informed consent for this publication was obtained from the patient. All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)