<p>Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after transplantation (Tx). The incidence pattern appears to be divided into two groups, depending on the onset time, as with...<p>Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after transplantation (Tx). The incidence pattern appears to be divided into two groups, depending on the onset time, as within 1 or 2 years after Tx and thereafter (early and late, respectively). We report very early onset and rapid progression of PTLD after kidney Tx. Case Presentation: A 49-year-old man with a 12-year history of hemodialysis underwent deceased donor kidney Tx from a 62-year-old male donor. Serological examination revealed negative antibodies in the recipient for viral capsid and Epstein-Barr virus (EBV)-associated nuclear antigens. Graft function recovery was delayed, possibly because of recurrent bacterial urinary tract infections, and the patient was weaned from dialysis on day 17. The protocol biopsy on day 37 showed moderate mononuclear cell infiltration in the interstitium with tubulitis. Urine output decreased, and the serum creatinine level rose abruptly at approximately the same time as we initiated steroid pulse therapy. The allograft biopsy was repeated on day 52 and demonstrated large atypical lymphoid cells in the parenchyma. Tumor cells were positive for CD20 and negative for CD3 with immunostaining and positive on EBV-encoded RNA in situ hybridization. The diagnosis was EBV-associated PTLD, histologically diffuse large B-cell lymphoma. Hemodialysis was resumed, and graftectomy was performed on day 58. At 12 months post-graftectomy, the patient was alive on dialysis, and imaging studies had revealed no extra-graft lesions. Conclusion: Early onset and rapid progression of PTLD after Tx should be considered by transplant surgeons and physicians. </p>.
AIM: Reduced kidney function is a known risk amplifier for atherosclerotic cardiovascular disease (ASCVD) and adverse kidney events. Accurate assessment of kidney function using estimated glomerular filtration rate (eGFR...AIM: Reduced kidney function is a known risk amplifier for atherosclerotic cardiovascular disease (ASCVD) and adverse kidney events. Accurate assessment of kidney function using estimated glomerular filtration rate (eGFR) is therefore essential for evaluating ASCVD risk and kidney prognosis. We aimed to compare the revised 2021 Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) [2021-eGFRcr(AS)] and European Kidney Function Consortium (EKFCcr) with the 2009 CKD-EPI [2009-eGFRcr(ASR)] equations in predicting the risk of hospitalisations for acute myocardial infarction (AMI), acute kidney disease (AKD), and chronic kidney disease (CKD) in a multi-ethnic Asian cohort. METHODS: This was a multi-centre, retrospective cohort study of adults who attended the ambulatory clinics at the Singapore General Hospital and SingHealth Polyclinics. Individuals were included if they had at least one serum creatinine and albuminuria result in 2014 and at least one follow-up visit between 2015 and 2018. Demographic data, comorbidities, biochemistry, and hospitalisations were retrieved from electronic medical records. eGFR was calculated using the 2009-eGFRcr(ASR) and 2021-eGFRcr(AS) and EKFCcr equations. Multivariable logistic regression models for the associations between eGFR categories and hospitalisations for AMI, AKD, and CKD were evaluated for their goodness-of-fit and discrimination. RESULTS: Among 10,137 individuals in the study, the mean age was 65.5 (10.8) years. The mean eGFRs were 85.6 (20.4), 89.3 (20.0), and 79.6 (19.5) mL/min/1.73 m2 according to the 2009-eGFRcr(ASR), 2021-eGFRcr(AS), and EKFCcr equations, respectively. Compared to the 2009-eGFRcr(ASR) equation, 28.8-33.3% of individuals were reclassified to a less severe eGFR category by the 2021-eGFRcr(AS) equation, while 1.6%-36.6% were reclassified to a more severe eGFR category by the EKFCcr equation. Over a mean follow-up of 44.9 (12.6) months, hospitalisations for AMI, AKD, and CKD occurred in 42 (0.4%), 228 (2.4%), and 189 (2.0%) of patients, respectively. More severe eGFR categories were independently associated with all the outcomes. For hospitalisation for CKD, the model with the 2021-eGFRcr(AS) equation had significantly better discrimination (area under the receiver operating characteristic curve difference +0.010 (p = 0.016) and better fit (Vuong Z statistic = -2.175, p = 0.015) compared to the model with the 2009-eGFR(ASR). However, the discrimination and fit of models for predicting AMI and AKI hospitalisations were similar between 2021-eGFRcr(AS) and 2009-eGFR(ASR) equations were similar. The EKFCcr-based models did not demonstrate improved discrimination or fit for hospitalisation for AMI, AKD, and CKD, compared to 2009-eGFRcr(ASR)-based model. CONCLUSION: Lower eGFR ascertained by the 2009-eGFRcr(ASR), 2021-eGFRcr(AS), and EKFCcr equations were independently associated with greater risks of hospitalisation for cardiovascular and kidney disease in a multi-ethnic Asian cohort. Adoption of the race-free 2021-eGFRcr(AS) equation improved prediction of hospitalisation for CKD compared to the 2009-eGFRcr(ASR) and was non-inferior in predicting hospitalisation for AMI and AKD. These findings support the use of the 2021-eGFRcr(AS) equation in clinical practice, to predict health service utilisation for hospitalisations for cardiovascular and kidney disease, aligning with global initiatives for race-neutral kidney function evaluation.
INTRODUCTION: There is limited evidence regarding collapsing focal segmental glomerulosclerosis (cFSGS) after kidney transplantation. The aim of this study was to clarify the clinicopathological character of cFSGS. METHO...INTRODUCTION: There is limited evidence regarding collapsing focal segmental glomerulosclerosis (cFSGS) after kidney transplantation. The aim of this study was to clarify the clinicopathological character of cFSGS. METHODS: Forty-two biopsies from 35 patients with cFSGS were included in the study. The cFSGS variant was determined according to the Colombia classification. The scoring of arteriosclerosis was evaluated as a score of 0-3 on the basis of the intimal fibrous thickening divided by the media, and other histological scoring was evaluated using the Banff score. Biopsies with a sclerosis score ≥3/4 were excluded from the study. Multivariate analysis was performed by a forward selection method using covariates significantly associated with cFSGS biopsies. RESULTS: Of 42 biopsies diagnosed with FSGS, 19 (45.2%) biopsies were cFSGS and 23 (54.8%) were non-collapsing FSGS (ncFSGS). The cFSGS group had a longer time after transplantation, lower eGFR, higher urine protein levels, and higher systolic blood pressure (all statistically significant) compared with the ncFSGS group. The Banff aah, ci, and arteriosclerosis scores were significantly higher in the cFSGS group compared with the ncFSGS group. There were no significant differences in the donor age or arteriosclerosis in 1-h biopsies between groups. Multivariate analysis showed that the arteriosclerosis score and Banff ci score were significantly associated with cFSGS using covariates that were statistically significant-related factors including systolic blood pressure, eGFR, proteinuria, ci score, aah score, and arteriosclerosis score. Graft survival after the time of biopsy was significantly worse in the cFSGS group compared with the ncFSGS group. CONCLUSION: Collapsing FSGS was poor prognostic factor for allograft survival. Arteriosclerosis and chronic interstitial fibrosis may be related to cFSGS after kidney transplantation.
BACKGROUND: Thrombotic microangiopathy (TMA) encompasses a group of rare, life-threatening disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage, most commonly affecting the kid...BACKGROUND: Thrombotic microangiopathy (TMA) encompasses a group of rare, life-threatening disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage, most commonly affecting the kidneys. Complement-mediated TMA (CM-TMA), a subtype of TMA, is often associated with dysregulation of the complement system due to genetic mutations. Dengue virus has been recognized as a potential trigger of secondary TMA and may precipitate CM-TMA in genetically predisposed individuals. CASE PRESENTATION: We report the case of a 47-year-old woman with a history of thrombotic thrombocytopenic purpura (TTP) who presented with fever, gastrointestinal symptoms, anemia, thrombocytopenia, and acute kidney injury. Dengue infection was confirmed by a positive NS1 antigen. Laboratory and peripheral smear findings indicated TMA. Therapeutic plasma exchange was started due to previous history of TTP, with partial clinical response. ADAMTS13 activity was preserved at 60.7%. Kidney biopsy demonstrated features of TMA. Genetic testing identified a heterozygous pathogenic variant in the CD46 gene, supporting the diagnosis of CM-TMA. Notably, the patient showed sustained clinical improvement without the use of eculizumab. CONCLUSION: This case illustrates the diagnostic challenges of TMA in patients with overlapping clinical features and potential infectious triggers. In dengue-endemic regions, the virus should be recognized as a possible precipitating factor for TMA, particularly in individuals harboring complement gene mutations. A multidisciplinary approach - integrating clinical, laboratory, histopathological, and genetic data - is essential for accurate diagnosis and personalized management of TMA syndromes.
AIM: The aim of the study was to elucidate the clinical and histological significance of glomerular capillary C4d (GC-C4d) deposition in allograft biopsies with microvascular inflammation (MVI), indicating antibody-media...AIM: The aim of the study was to elucidate the clinical and histological significance of glomerular capillary C4d (GC-C4d) deposition in allograft biopsies with microvascular inflammation (MVI), indicating antibody-mediated rejection (AMR). METHODS: The study included MVI biopsies defined as Banff g score ≥1 and/or peritubular capillary (ptc) score ≥1, with available HLA class I and/or class II single antigen test results. Biopsies with ABO-incompatible transplantation and diagnosis of T-cell-mediated rejection without AMR were excluded. We analyzed 84 allograft MVI biopsies obtained from January 2017 to May 2023. GC-C4d positivity was evaluated by immunofluorescence. RESULTS: GC-C4d positivity was determined in 46 of 84 (54.8%) MVI biopsies. Multivariate logistic analysis identified Banff g score and ptc-C4d score as factors significantly related to GC-C4d positivity in MVI biopsies with Banff cg score 0-3, and ptc score and ptc-C4d score as significantly related to GC-C4d positivity in MVI biopsies with cg0. Multivariate linear regression analysis identified Banff cg score and ptc-C4d score as factors significantly related to GC-C4d score in MVI biopsies with Banff cg0-3, and cadaver and Banff ptc-C4d score were significantly related to GC-C4d score in MVI biopsies with cg0. In MVI biopsies with cg0-3, evaluation of GC-C4d and/or ptc-C4d positivity decreased the specificity from 100.0% to 76.9% but increased the sensitivity from 67.2% to 84.5%, compared with the evaluation of ptc-C4d positivity alone for the diagnosis of Banff 2022 AMR. Ten of 19 biopsies (52.6%) with ptc-C4d-negative AMR showed ptc-C4d-negative but GC-C4d-positive AMR. CONCLUSION: GC-C4d-positive findings in MVI biopsies may reflect active lesions as well as ptc-C4d scoring, while a high GC-C4d score may reflect advanced cg lesions in MVI biopsies with cg0-3. The combined evaluation of GC-C4d and ptc-C4d in MVI biopsies may increase the diagnostic sensitivity for Banff 2022 AMR by reducing the diagnosis of "C4d-negative AMR."
INTRODUCTION: Renal involvement in TAFRO syndrome usually is present as acute kidney injury with oligoproteinuria. Renal pathology is typically characterized by glomerular microangiopathy without immune deposits, and the...INTRODUCTION: Renal involvement in TAFRO syndrome usually is present as acute kidney injury with oligoproteinuria. Renal pathology is typically characterized by glomerular microangiopathy without immune deposits, and there have been no reports of membranous nephropathy. While idiopathic multicentric Castleman disease (iMCD), which shares a similar pathophysiology with TAFRO syndrome, has documented several cases of membranous nephropathy, the underlying mechanisms remain unclear. CASE PRESENTATION: We present a case of TAFRO syndrome presenting with nephrotic syndrome, and kidney biopsy revealed exostosin 1/exostosin 2 (EXT1/EXT2)-associated membranous nephropathy. EXT1/EXT2 is considered a potential target antigen in autoimmune membranous nephropathy, suggesting their potential pathogenic role in this case. In iMCD cases with membranous nephropathy, IL-6 levels tend to be slightly low, while VEGF levels are significantly elevated, as seen in the present case. This cytokine profile may contribute to the differences in renal pathological findings and may also be involved in the response to treatment. CONCLUSION: This case may enhance our understanding of the pathophysiology of membranous nephropathy in TAFRO syndrome and iMCD.
INTRODUCTION: Renal ciliopathy is a genetic disorder caused by abnormalities in primary cilia. Alström syndrome (AS) is a rare renal ciliopathy caused by mutations in the ALMS1 gene. The diagnostic criteria for AS includ...INTRODUCTION: Renal ciliopathy is a genetic disorder caused by abnormalities in primary cilia. Alström syndrome (AS) is a rare renal ciliopathy caused by mutations in the ALMS1 gene. The diagnostic criteria for AS include symptoms such as vision impairment, obesity, type 2 diabetes, hearing loss, and renal failure. The manifestations of these symptoms vary widely, making the diagnosis of AS difficult. CASE PRESENTATION: We report the case of a 31-year-old Japanese woman and her 1 year older brother with cone-rod dystrophy (retinal degeneration) and end-stage kidney disease (ESKD), who presented with a clinical course similar to that of AS. Exome sequencing revealed two shared missense variants in ALMS1: c.4334A>T in exon 8 and c.7976C>G in exon 10. In silico analysis suggested that c.4334A>T was likely benign, whereas c.7976C>G was interpreted as a variant of uncertain significance (VUS). A definitive diagnosis of AS could not be made because typical symptoms such as diabetes and obesity were absent. Renal pathological findings in the proband's brother showed tubulointerstitial nephritis and shortening of the proximal tubule cilia, consistent with the known pathological features of AS. The rare and shared clinical features observed in both siblings suggest that VUS is associated with a partial manifestation of AS. CONCLUSION: Both siblings presented with two rare clinical features, cone-rod dystrophy and ESKD, at a young age and carried the same VUS in ALMS1, suggesting the possibility of a partial AS.
Vassalotti JA, Francis A, Soares Dos Santos AC
… +10 more, Correa-Rotter R, Abdellatif D, Hsiao LL, Roumeliotis S, Haris A, Kumaraswami LA, Lui SF, Balducci A, Liakopoulos V, World Kidney Day Joint Steering Committee
INTRODUCTION: Adherence to fluid restriction is an essential component of haemodialysis (HD) self-management, although educational interventions are rarely adjusted to meet a person's health literacy abilities. This stud...INTRODUCTION: Adherence to fluid restriction is an essential component of haemodialysis (HD) self-management, although educational interventions are rarely adjusted to meet a person's health literacy abilities. This study aimed to evaluate the feasibility of a person-centred intervention to improve fluid adherence in adults receiving HD. METHODS: A pragmatic, clustered, randomised control feasibility trial involved adults receiving HD for at least 3 months. The control group received standard care while the intervention group received standard care plus a 12-week self-management program that included 4 face-to-face individual teach-back sessions. Randomisation was based on HD treatment shifts. Primary outcomes were acceptability and feasibility (recruitment, retention, and completion rates) and secondary outcomes included patient-reported measures (knowledge, self-efficacy, health literacy, health-related quality of life [HRQoL]) and clinical outcomes (interdialytic weight gain [IDWG] and blood pressure [BP]). RESULTS: The recruitment rate was 53.2% (50/94 screened) with participants (mean age 51 years, SD = 12.52) randomly allocated to intervention (n = 25) and control groups (n = 25). Overall, patient-reported outcome completion rates at baseline and 12 weeks were 88% and 90%, respectively. Retention rates for the intervention and control groups were 96% and 92%, respectively. There were no between group differences at baseline. At 12 weeks, significant improvements were found in the intervention group for knowledge, self-efficacy, health literacy, self-care index, and IDWG, but not HRQoL. The study found mixed results for BP. CONCLUSION: This intervention was feasible and acceptable to deliver in the clinical setting during HD treatment and has the potential to improve health outcomes for adults on HD.
Yonishi H, Namba-Hamano T, Nakazawa S
… +13 more, Yamanaka K, Kakuta Y, Hashiguchi H, Kawano Y, Kubota T, Tokuchi M, Okushima H, Sakai S, Takahashi A, Abe T, Imamura R, Nonomura N, Isaka Y
INTRODUCTION: Advances in immunosuppressive therapy have improved kidney transplant outcomes; however, antibody-mediated rejection (ABMR) still affects graft survival. Herein, we present a case of a 46-year-old woman who...INTRODUCTION: Advances in immunosuppressive therapy have improved kidney transplant outcomes; however, antibody-mediated rejection (ABMR) still affects graft survival. Herein, we present a case of a 46-year-old woman who experienced acute ABMR despite stable long-term graft function following kidney transplantation. CASE PRESENTATION: At 28 years of age, she underwent a blood-type-compatible living kidney transplant from her father. Eighteen years later, she was admitted to the hospital with a fever and sore throat, raising suspicion of a respiratory infection. Given the rapid deterioration of renal function following hospitalisation, a biopsy was conducted. The findings showed diffuse glomerulitis and peritubular capillaritis, along with focal observations of endoarteritis, glomerular thrombi, and interstitial haemorrhage, consistent with active ABMR. She was treated with methylprednisolone pulse therapy and intravenous immunoglobulin, which induced gradual recovery. Screening tests for anti-human leucocyte antigen (HLA) antibodies yielded negative results. However, tests for non-HLA antibodies detected the presence of anti-major histocompatibility complex class I chain-related gene A (MICA) antibodies in the blood sample prior to the onset of rejection. Notably, at the time of rejection, anti-MICA antibodies were not detectable in the blood; nevertheless, they were subsequently found to be positive 10 months later. These antibodies may have been sequestered within tissues, rendering them undetectable in the bloodstream. CONCLUSION: Anti-MICA antibodies have previously been implicated in ABMR; however, this case highlights their role in late-onset rejection after prolonged graft stability. This case underscores the importance of non-HLA donor-specific antibody tests when ABMR occurs in a recipient lacking anti-HLA antibodies.
BACKGROUND: Fabry disease is an inherited metabolic disease that is caused by an abnormal accumulation of sphingolipids, including globotriaosylceramide (Gb3), in lysosomes. Patients with Fabry disease have insufficient...BACKGROUND: Fabry disease is an inherited metabolic disease that is caused by an abnormal accumulation of sphingolipids, including globotriaosylceramide (Gb3), in lysosomes. Patients with Fabry disease have insufficient levels or no total activity of an enzyme called α-galactosidase A, which catalyzes the removal of terminal α-galactose saccharides from substrates such as Gb3. SUMMARY: Because of the monogenetic nature of Fabry disease, the levels of enzyme activity correlate with disease outcome in patients, and thus enable genotype-phenotype predictions in the disease. Although Fabry disease results from reduced α-galactosidase A activity in the lysosome, there are many different molecular mechanisms for the loss of α-galactosidase A activity in Fabry disease patients, so it is of utmost importance to understand the journey and maturation of α-galactosidase A inside the cell. The proper synthesis of α-galactosidase A requires many steps, including the folding of the polypeptide, posttranslational modifications, trafficking of the enzyme to the lysosome, and substrate binding. Furthermore, researchers and clinicians benefit from extensive clinical data, with over 1,000 different mutations identified in patients, many of which are investigated by researchers. Finally, the availability of a pharmacological chaperone, which enhances the enzymatic activity of many α-galactosidase A variants, allows us to understand the biology better. KEY MESSAGES: This review will focus on the molecular steps that must be precisely orchestrated to properly synthesize the α-galactosidase A enzyme, and how failures in different maturation steps of α-galactosidase A lead to Fabry disease. We also describe how different treatment options address the loss of α-galactosidase A activity in the lysosome of patients.
INTRODUCTION: Thrombotic microangiopathy (TMA) is a known complication in renal transplant recipients and is often associated with drugs like calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibit...INTRODUCTION: Thrombotic microangiopathy (TMA) is a known complication in renal transplant recipients and is often associated with drugs like calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors. Additionally, toxic levels of valproic acid have been implicated in systemic TMA. This report describes a case of pathologic TMA in a renal allograft that may be induced by the combined use of CNI, mTOR inhibitor, and valproic acid at standard doses. CASE PRESENTATION: A 37-year-old female diagnosed with glomerulonephritis underwent ABO-compatible living donor renal transplantation. Following the procedure, the blood concentrations of tacrolimus (CNI) and everolimus (mTOR inhibitor) were maintained at optimal levels. Two and a half years posttransplant, valproic acid therapy was initiated for migraine management and titrated within the therapeutic range. Despite the gradual decline in renal function, there was no evidence of anemia or thrombocytopenia. Four years posttransplant, a graft biopsy identified a necrotic thrombotic microvascular lesion suggestive of acute TMA, despite no signs of rejection. Renal function stabilized after the discontinuation of valproic acid. CONCLUSION: Pathological TMA may impair renal function in patients receiving multiple drugs known to induce TMA. Hence, an early graft biopsy may be crucial for diagnosis, even when blood levels of immunosuppressive drugs are within the therapeutic range.
BACKGROUND: End-stage renal disease (ESRD) patients are at a higher risk of perioperative complications. Existing perioperative risk assessment tools have been mainly validated in the general population. Despite the heig...BACKGROUND: End-stage renal disease (ESRD) patients are at a higher risk of perioperative complications. Existing perioperative risk assessment tools have been mainly validated in the general population. Despite the heightened risk of postoperative complications in patients with ESRD, there is a significant gap in research dedicated to studying preoperative risk calculators for this vulnerable population. METHODS: We conducted a retrospective study of patients in the Acute Care Surgery National Surgical Quality Improvement Program database from 2008 to 2012. We compared the performance of the Revised Cardiac Risk Index (RCRI) and the American University of Beirut HAS2 (AUB-HAS2) in predicting cardiovascular events in patients with ESRD. RESULTS: We analyzed 32,337 ESRD patients. The cohort had a mean age of 61.1 years, with 43.2% females. Key comorbidities included diabetes (47.4%), hypertension (85.1%), and history of myocardial infarction (MI) (4.2%). Mortality was 9.9%, with a composite outcome of death, MI, or stroke occurring in 11.3% of the patients. The RCRI and AUB-HAS2 scores were significantly associated with increased mortality and composite outcome, with mortality rates rising from 4.4% to 19.2% across RCRI scores and 1.8% to 23% across AUB-HAS2 scores. ROC curve analysis demonstrated the superior predictive performance of the AUB-HAS2 score over the RCRI for both mortality and composite outcome. Regression analysis confirmed the AUB-HAS2 score's superior discrimination ability. CONCLUSION: Our findings suggest that the AUB-HAS2 score may be more effective than the RCRI in predicting cardiovascular events in patients with ESRD undergoing surgery.
Wu R, Hughes A, Recabarren Silva J
… +9 more, Guha C, Hawley CM, Scholes-Robertson N, Sluiter A, Torrisi LG, Viecelli A, van Zwieten A, Wong G, Jaure A
BACKGROUND: Patient and caregiver involvement in identifying and designing health interventions can enhance the acceptability and uptake of interventions for person-centered care and outcomes. Our aim was to describe the...BACKGROUND: Patient and caregiver involvement in identifying and designing health interventions can enhance the acceptability and uptake of interventions for person-centered care and outcomes. Our aim was to describe the approaches used to involve patients and caregivers in the identification and design of interventions in chronic kidney disease (CKD). METHODS: Electronic databases were searched to April 2024 for articles that described the involvement of patients and caregivers in the identification and design of interventions for research in CKD. The findings were synthesized using a framework that addressed the type of intervention, purpose and reason of involvement, population involved, mode of involvement, and impacts of patient/caregiver involvement on the intervention. RESULTS: We identified 14 studies that involved patients with CKD (n = 238) and/or caregivers (n = 36). The types of interventions included psychosocial, educational, lifestyle, and navigator programs. Patients and caregivers were involved to identify and prioritize features of the intervention, describe their lived experience to inform the intervention, provide feedback on intervention design, and identify potential facilitators and barriers to the uptake of the intervention. Patients and caregivers were involved as members of steering committees and advisory groups, and participated through workshops, interviews, focus groups, meetings, and an online messaging forum. The input of patients and caregivers resulted in the addition and changes to intervention features (e.g., content, structure, delivery, and materials) to personalize the intervention and to improve its inclusivity, accessibility, and suitability. CONCLUSION: Very few studies have described patient and caregiver involvement in the identification and design of interventions for research in CKD. Patients and caregivers were mostly involved in developing educational, lifestyle, and navigator interventions. Further efforts to involve patients and caregivers in developing interventions for research can help maximize the uptake and impact of person-centered interventions.
BACKGROUND: The 16th Banff Meeting for Allograft Pathology was held in Banff, Canada from September 19 to 23, 2022. The results were published in the American Journal of Transplantation in March this year as "The Banff 2...BACKGROUND: The 16th Banff Meeting for Allograft Pathology was held in Banff, Canada from September 19 to 23, 2022. The results were published in the American Journal of Transplantation in March this year as "The Banff 2022 Kidney Meeting Report: Reappraisal of Microvascular Inflammation and the Role of Biopsy-Based Transcript Diagnostics." SUMMARY: The changes in the Banff 2022 classification (Banff 2022) have four distinct features. The first was the modification of antibody-mediated rejection (AMR). The key points are microvascular inflammation/injury (MVI); the presence or absence of C4d deposition in the peritubular capillaries; and the presence or absence of donor-specific antibodies (DSAs). Even if the MVI is above the threshold, if C4d and DSA are negative, it is not classified as AMR but as "MVI, DSA-negative, and C4d-negative." Furthermore, if MVI is below the threshold, C4d is negative but DSA is positive, the patient is classified under "probable AMR." Second, patients with acute tubular injury (ATI) without other obvious causes such as ischemia are excluded from AMR. Third, the Banff cv score for "arterial intimal fibrosis of new onset" (AIFNO) is excluded from AMR when used alone. Fourth, non-human leukocyte antigen (HLA) antibodies, except for anti-blood group antibodies in ABO-incompatible kidney transplants, were excluded from DSA and included in the diagnostic criteria for AMR. KEY MESSAGES: The changes in Banff 2022 are as follows: implementation of new terminology, such as MVI, DSA-negative, and C4d-negative and probable AMR, ATI, and AIFNO are excluded from AMR, and non-HLA antibodies are excluded from DSA.
BACKGROUND: In contemporary kidney transplantation, the pathology is important for diagnosing various problems with an allograft. Striking a balance is essential to achieve accuracy and speed of a diagnosis. However, bec...BACKGROUND: In contemporary kidney transplantation, the pathology is important for diagnosing various problems with an allograft. Striking a balance is essential to achieve accuracy and speed of a diagnosis. However, because of the distinctive characteristics of renal allograft pathology, there is a lack of pathologists with expertise in this specific domain. SUMMARY: A telepathology system using digital pathology can facilitate the delivery of diagnostic outcomes even in settings where pathologists with expertise may not be continuously available. This system is equivalent in diagnostic ability and superior in speed to the method using conventional diagnosis by light microscopy with glass slides. The pathology guidelines of various countries have emphasized the importance of ensuring the quality of digital pathology. Although maintaining the quality of diagnosis is necessary, telepathology in renal allograft pathology is an innovative tool that can shorten the time to diagnosis and address the shortage of pathologists. Unfortunately, the routine use of telepathology is currently limited to only a few institutions in Japan. One of the reasons for this limited use is the heavy burden on facilities requesting biopsies to set up infrastructure, such as slide scanners and servers. KEY MESSAGE: Consequently, there is an urgent need for greater public support of telepathology.
UNLABELLED: <p>Background: The selective cytopheretic device (SCD) is an immunomodulatory cell-directed extracorporeal therapy that reprograms activated neutrophils and monocytes towards immune homeostasis in hyperinflam...UNLABELLED: <p>Background: The selective cytopheretic device (SCD) is an immunomodulatory cell-directed extracorporeal therapy that reprograms activated neutrophils and monocytes towards immune homeostasis in hyperinflammatory conditions such as acute kidney injury (AKI). However, clinical mechanisms remain unclear. METHODS: We examined the effect of SCD treatment from prior AKI adult clinical studies on systemic inflammation through neutrophil-to-lymphocyte ratios (NLR) and other hematological measures to gain insights into the mechanism of the SCD. Linear-mixed effects regression was used to estimate differences in NLR and other hematological measures between SCD-treated patients and controls over the first 6 days after initiating continuous kidney replacement therapy (CKRT). RESULTS: Hematological data were analyzed from 76 adult patients with AKI requiring CKRT treated with the SCD, and 32 CKRT-only control patients. SCD reduced NLR across all individual studies through day 6 of treatment, while the control group demonstrated upward trends in NLR past day 3. When analyzed as pooled groups, both cohorts displayed similar baseline NLRs (SCD = 23.6 vs. control = 21.7; p = 0.636). SCD-treated patients demonstrated a statistically significant reduction in NLR vs. control patients at day 6 (SCD = 13.3 vs. control = 25.7 at day 6; p = 0.011). This difference was maintained following sensitivity analysis upon exclusion of an ICU study due to a shorter follow-up period (SCD = 13.7 vs. control = 25.6; p = 0.013). NLR reductions in the SCD group were driven by decreases in neutrophils and increases in lymphocytes. No statistically significant differences were observed between groups for monocyte-to-lymphocyte ratio levels or platelets over the same treatment duration. CONCLUSIONS: In a pooled analysis of multiple AKI adult clinical studies, SCD treatment demonstrated reductions in NLR. This analysis provides further clinical mechanistic evidence of leukocyte immunomodulation in targeting the dysregulation of effector immune cells in hyperinflammatory conditions such as AKI and sepsis. </p>.