scholarly journals Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier

2020 ◽  
Vol 32 (10) ◽  
pp. 653-662
Author(s):  
Yusuke Takada ◽  
Daisuke Kamimura ◽  
Jing-Jing Jiang ◽  
Haruka Higuchi ◽  
Daiki Iwami ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Clinical Laboratory ◽  
Interstitial Fibrosis ◽  
Inflammatory Diseases ◽  
Laboratory Data ◽  
Calcineurin Inhibitors ◽  
Tubular Atrophy ◽  
Antibody Mediated Rejection ◽  
Co Activation ◽  
Whole Urine

Abstract Chronic active antibody-mediated rejection (CAAMR) is a particular problem in kidney transplantation (KTx), and ~25% of grafts are lost by CAAMR. Further, the pathogenesis remains unclear, and there is no effective cure or marker. We previously found that a hyper NFκB-activating mechanism in non-immune cells, called the IL-6 amplifier, is induced by the co-activation of NFκB and STAT3, and that this activation can develop various chronic inflammatory diseases. Here, we show that synaptotagmin-17 (SYT17) is increased in an exosomal fraction of the urine from CAAMR patients, and that this increase is associated with activation of the IL-6 amplifier. Immunohistochemistry showed that SYT17 protein expression was increased in renal tubule cells of the CAAMR group. While SYT17 protein was not detectable in whole-urine samples by western blotting, urinary exosomal SYT17 levels were significantly elevated in the CAAMR group compared to three other histology groups (normal, interstitial fibrosis and tubular atrophy, and calcineurin inhibitors toxicity) after KTx. On the other hand, current clinical laboratory data could not differentiate the CAAMR group from these groups. These data suggest that urinary exosomal SYT17 is a potential diagnostic marker for CAAMR.

scholarly journals Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Marco Cattalini ◽  
◽  
Sara Della Paolera ◽  
Fiammetta Zunica ◽  
Claudia Bracaglia ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Clinical Laboratory ◽  
Troponin T ◽  
Inflammatory Diseases ◽  
Age At Onset ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Chi Square ◽  
Pediatric Society ◽  
Multicenter Survey

Abstract Background There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group – KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients’ outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

scholarly journals Ischemia and Reperfusion Injury in Kidney Transplantation: Relevant Mechanisms in Injury and Repair

2020 ◽  
Vol 9 (1) ◽  
pp. 253 ◽  
Author(s):  
Gertrude J. Nieuwenhuijs-Moeke ◽  
Søren E. Pischke ◽  
Stefan P. Berger ◽  
Jan Stephan F. Sanders ◽  
Robert A. Pol ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Reperfusion Injury ◽  
Interstitial Fibrosis ◽  
Molecular Pathways ◽  
Ischemia And Reperfusion ◽  
Ischemia And Reperfusion Injury ◽  
Tubular Atrophy ◽  
Chronic Graft Dysfunction ◽  
Injury And Repair

Ischemia and reperfusion injury (IRI) is a complex pathophysiological phenomenon, inevitable in kidney transplantation and one of the most important mechanisms for non- or delayed function immediately after transplantation. Long term, it is associated with acute rejection and chronic graft dysfunction due to interstitial fibrosis and tubular atrophy. Recently, more insight has been gained in the underlying molecular pathways and signalling cascades involved, which opens the door to new therapeutic opportunities aiming to reduce IRI and improve graft survival. This review systemically discusses the specific molecular pathways involved in the pathophysiology of IRI and highlights new therapeutic strategies targeting these pathways.

scholarly journals Alveolar echinococcosis in patient after cadaveric kidney transplantation

2011 ◽  
Vol 48 (4) ◽  
pp. 229-236 ◽  
Author(s):  
S. Dražilová ◽  
J. Kinčeková ◽  
Ľ. Beňa ◽  
M. Zachar ◽  
M. Švajdler ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Ct Scan ◽  
Alveolar Echinococcosis ◽  
Clinical Symptoms ◽  
Interstitial Fibrosis ◽  
Graft Function ◽  
Deceased Donor ◽  
Chronic Haemodialysis ◽  
Tubular Atrophy ◽  
Long Term Treatment

Abstract52-years old man years following the kidney transplantation from deceased donor was admitted to the hospital with fever and progressive abdominal pain. The patient was diagnosed with chronic hepatitis C seven years before admission. Graft function in posttransplant period was stable and optimal, the patient was treated with standard maintenance immunosupresive protocol (cyclosporine A, mycophenolate mofetil and low-dose prednison), metylprednisolon bolus therapy (1 g/m2 body surface area), was administered two months prior to admission due to creeping creatinine (suspection of acute rejection was not confirmed by biopsy). Empiric antibiotic treatment due to febrile status was ineffective. Abdominal ultrasound and computer tomography (CT) scan revealed three tumorous lesions in the liver, radical surgical intervention was not executable. Histological examination of the tissue from the lesions demostrated alveolar echinococcosis, serology for Echinoccocus multilocularis was positive. Long-term treatment by mebendazol 200 mg twice daily led to disappearance of the clinical symptoms, but after the therapy cessasion patient was again hospitalized with fever and progression of cystic lesions in CT scan. Following the mebendazol therapy reinstalation the clinical course of echinococcosis was improved and remained stable, transplant kidney failure occurred due to progression of interstitial fibrosis/tubular atrophy and chronic haemodialysis was initiated one year later.

scholarly journals Pilot Analysis of Late Conversion to Belatacept in Kidney Transplant Recipients for Biopsy-Proven Chronic Tacrolimus Toxicity

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shruti Gupta ◽  
Ivy Rosales ◽  
David Wojciechowski
Keyword(s):  
Interstitial Fibrosis ◽  
Calcineurin Inhibitors ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Tubular Atrophy ◽  
Transplant Patients ◽  
Number Of Patients ◽  
Allograft Function ◽  
The Mean ◽  
Arteriolar Hyalinosis

Background. Calcineurin inhibitors are associated with chronic nephrotoxicity, manifesting as interstitial fibrosis/tubular atrophy (IF/TA) and arteriolar hyalinosis. Conversion from tacrolimus to belatacept may be one strategy to preserve renal function. Methods. We conducted a retrospective review of renal transplant patients followed at our institution who were converted to belatacept and found to have chronic tacrolimus toxicity on biopsy. The primary outcome was eGFR at conversion as compared to eGFR at 3, 6, 12, and 24 months after conversion. We also assessed incidence of infection and rates of allograft survival at 1 year. Results. The average time between transplant and conversion was 11.9 years. There was no decrease in eGFR at any postconversion time point as compared with preconversion. The mean eGFR at time of preconversion was 32.9 mL/min, as compared with 35.6 mL/min at 3 months (p=0.09), 34.1 mL/min at 6 months (p=0.63), 34.9 mL/min at 12 months (p=0.57), and 39.6 mL/min at 24 months after conversion (p=0.92). Four of 7 patients had increases in their eGFR after conversion. All grafts were functioning at 1 year after conversion. Conclusion. While this study was limited by a small number of patients, belatacept conversion stabilized eGFR at all time points in patients with late allograft function due to chronic tacrolimus toxicity, with a trend towards increased eGFR at 3 months.

scholarly journals Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial

2020 ◽  
Vol 9 (10) ◽  
pp. 3216
Author(s):  
Manuela Yepes-Calderón ◽  
Camilo G. Sotomayor ◽  
Daniel Guldager Kring Rasmussen ◽  
Ryanne S. Hijmans ◽  
Charlotte A. te Velde-Keyzer ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Collagen Type ◽  
Interstitial Fibrosis ◽  
Controlled Trial ◽  
Kidney Transplant Recipients ◽  
Tubular Atrophy ◽  
Post Hoc Analysis ◽  
Non Invasive ◽  
Collagen Type Vi ◽  
Post Hoc

The PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The current study is a post-hoc analysis of 94 participants of the MECANO trial, a 24-month prospective, multicenter, open-label, randomized, controlled trial aimed at comparing everolimus-based vs. cyclosporine-based immunosuppression. PRO-C6 was measured in plasma and urine samples collected 6 and 24 months post-transplantation. Fibrosis was evaluated in biopsies collected at the same time points by Banff interstitial fibrosis/tubular atrophy (IF/TA) scoring and collagen staining (Picro Sirius Red; PSR); inflammation was evaluated by the tubulo-interstitial inflammation score (ti-score). Linear regression analyses were performed. Six-month plasma PRO-C6 was cross-sectionally associated with IF/TA score (Std. β = 0.34), and prospectively with 24-month IF/TA score and ti-score (Std. β = 0.24 and 0.23, respectively) (p < 0.05 for all). No significant associations were found between urine PRO-C6 and any of the biopsy findings. Fibrotic changes and urine PRO-C6 behaved differentially over time according to immunosuppressive therapy. These results are a first step towards non-invasive fibrosis detection after kidney transplantation by means of collagen VI synthesis measurement, and further research is required.

scholarly journals Oxford MEST classification in Iranian patients with IgA nephropathy, with regards to extracapillary proliferation; a single center experience

2020 ◽  
Vol 5 (1) ◽  
pp. e14-e14
Author(s):  
Mohsen Akhavansepahi ◽  
Maryam Rafieyan ◽  
Hamid Nasri
Keyword(s):  
Iga Nephropathy ◽  
Interstitial Fibrosis ◽  
Laboratory Data ◽  
Clinical Findings ◽  
Reference Laboratory ◽  
Tubular Atrophy ◽  
Single Center Experience ◽  
Medical Centers ◽  
Two Samples ◽  
The Mean

Introduction: IgA nephropathy is the most common glomerulonephritis in the world. Objectives: In this study we aimed to find the relationship between morphological lesions of Oxford classification for IgA nephropathy with clinical findings and some laboratory data. Patients and Methods: All kidney biopsy conducted from 2009 to 2019 conducted in medical centers and were sent to a reference laboratory in Isfahan. All kidney biopsies included two samples for immunofluorescence and light microscopy. After definitive diagnosis of IgAN (IgA nephropathy), the slides were examined to classify the disease based on the Oxford-MEST (M; mesangial hypercellularity, E; endocapillary hypercellularity, S; segmental glomerulosclerosis, and T; tubular atrophy/interstitial fibrosis and also C; crescent) classification. Results: Our study on 238 biopsy proven IgA nephropathy patients showed that 78 patients (32.8%) were male. Mean ± SD of age individuals was 38.00 ±13.68 years. The mean± SD of serum creatinine level was 1.42 ± 0.79 mg/dL and the mean ± SD of proteinuria was 1780.94 ± 1168.75 mg/d. Our study showed no significant association between M, E and S variables with patients’ age. However, a statistically significant relationship between T variable and patients’ age (P=0.028) was detected. Furthermore, morphologic variables of M, E and S were not significantly associated with proteinuria while T variable was positively associated with the quantity of proteinuria (P=0.021). Conclusion: The association of tubular atrophy/interstitial fibrosis (T variable) with quantity of proteinuria showed significance of interstitial lesion on the prognosis IgA nephropathy.

scholarly journals Tocilizumab in the Treatment of Chronic Antibody-Mediated Rejection Post Kidney Transplantation: Clinical and Histological Monitoring

2021 ◽  
Vol 8 ◽  
Author(s):  
Johan Noble ◽  
Diane Giovannini ◽  
Reda Laamech ◽  
Farida Imerzoukene ◽  
Bénédicte Janbon ◽  
...  
Keyword(s):  
Renal Function ◽  
Statistical Difference ◽  
Interstitial Fibrosis ◽  
Therapeutic Option ◽  
Single Center ◽  
Tubular Atrophy ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaritis ◽  
Over Time

Introduction: Chronic antibody-mediated rejection (cAMR) has very few effective therapeutic options. Interleukin-6 is an attractive target because it is involved in inflammation and humoral immunity. Therefore, the use of tocilizumab (anti-IL6 receptor, TCZ) is a potential valuable therapeutic option to treat cABMR in kidney-transplant (KT) recipients.Materials and Methods: This single-center retrospective study included all KT recipients that received monthly TCZ infusions in the setting of cABMR, between August 2018 and July 2021. We assessed 12-month renal function and KT histology during follow-up.Results: Forty patients were included. At 12-months, eGFR was not significantly different, 41.6 ± 17 vs. 43 ± 17 mL/min/1.73 m2 (p = 0.102) in patients with functional graft. Six patients (15%) lost their graft: their condition was clinically more severe at the time of first TCZ infusion. Histological follow-up showed no statistical difference in the scores of glomerulitis, peritubular capillaritis, and interstitial fibrosis/tubular atrophy (IFTA). Chronic glomerulopathy score however, increased significantly over time; conversely arteritis and inflammation in IFTA ares improved in follow-up biopsies.Conclusion: In our study, the addition of TCZ prevented clinical and histological worsening of cABMR in KT recipients, except for more severely ill patients. Randomized studies are needed to clarify the risk/benefit of TCZ in cABMR.

scholarly journals MicroRNA regulation in blood cells of renal transplanted patients with interstitial fibrosis/tubular atrophy and antibody-mediated rejection

PLoS ONE ◽  
2018 ◽  
Vol 13 (8) ◽  
pp. e0201925 ◽  
Author(s):  
Mareen Matz ◽  
Frederik Heinrich ◽  
Christine Lorkowski ◽  
Kaiyin Wu ◽  
Jens Klotsche ◽  
...  
Keyword(s):  
Blood Cells ◽  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Microrna Regulation ◽  
Antibody Mediated Rejection
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