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Volker Kliem - One of the best experts on this subject based on the ideXlab platform.

  • long term kidney allograft survival in patients with transplant Glomerulitis
    Transplantation, 2015
    Co-Authors: Alexander Nabokow, Vladimir Dobronravov, Maria Khrabrova, Hermann Josef Grone, Elisabeth Grone, Michael Hallensleben, Daniela Kieneke, Peter Weithofer, Alexei V Smirnov, Volker Kliem
    Abstract:

    BACKGROUND: Renal transplant Glomerulitis (G) is associated with acute antibody-mediated rejection (ABMR) in the presence of donor-specific antibodies. However, the long-term prognosis of isolated G (isG) in the absence of donor-specific antibodies or G in combination with T cell-mediated rejection (TCMR) remains unexplored. METHODS: Seventy recipients with G were included in this retrospective study and subdivided into 3 groups: isG, G with TCMR (G+TCMR), and G with acute ABMR. The control groups were: patients with TCMR Banff type I or II without G (TCMR) and patients without rejection (NR). Kaplan-Meier death-censored survival plots and Cox regression were used to analyze graft survival. The combined graft survival endpoint was defined as a return to dialysis or estimated glomerular filtration rate less than 15 mL/min/1.73 m. The median follow-up was 37 (14; 77) months from biopsy. RESULTS: Graft survival was significantly lower in patients with G than in the NR and TCMR groups. No significant differences were observed among the isG, G+TCMR, and ABMR groups. Graft survival was lower in the G+TCMR group than in the TCMR group. Glomerulitis was independently associated with the risk of adverse graft outcome in a multivariate Cox regression model adjusted for other confounders (hazard ratio, 4.52 [95% confidence interval, 2.37-8.68] vs controls; P<0.001). CONCLUSIONS: Glomerulitis is strongly associated with increased risk of graft failure. Graft survival in patients with isG that do not meet the Banff criteria for acute/active ABMR and in patients with G accompanying TCMR is comparable to the ABMR group.

  • Long-term kidney allograft survival in patients with transplant Glomerulitis.
    Transplantation, 2015
    Co-Authors: Alexander Nabokow, Vladimir Dobronravov, Maria Khrabrova, Hermann Josef Grone, Elisabeth Grone, Michael Hallensleben, Daniela Kieneke, Peter Weithofer, Alexei V Smirnov, Volker Kliem
    Abstract:

    BACKGROUND: Renal transplant Glomerulitis (G) is associated with acute antibody-mediated rejection (ABMR) in the presence of donor-specific antibodies. However, the long-term prognosis of isolated G (isG) in the absence of donor-specific antibodies or G in combination with T cell-mediated rejection (TCMR) remains unexplored. METHODS: Seventy recipients with G were included in this retrospective study and subdivided into 3 groups: isG, G with TCMR (G+TCMR), and G with acute ABMR. The control groups were: patients with TCMR Banff type I or II without G (TCMR) and patients without rejection (NR). Kaplan-Meier death-censored survival plots and Cox regression were used to analyze graft survival. The combined graft survival endpoint was defined as a return to dialysis or estimated glomerular filtration rate less than 15 mL/min/1.73 m. The median follow-up was 37 (14; 77) months from biopsy. RESULTS: Graft survival was significantly lower in patients with G than in the NR and TCMR groups. No significant differences were observed among the isG, G+TCMR, and ABMR groups. Graft survival was lower in the G+TCMR group than in the TCMR group. Glomerulitis was independently associated with the risk of adverse graft outcome in a multivariate Cox regression model adjusted for other confounders (hazard ratio, 4.52 [95% confidence interval, 2.37-8.68] vs controls; P

Lorraine C Racusen - One of the best experts on this subject based on the ideXlab platform.

  • Peritubular capillaritis in the renal allograft takes center stage.
    Kidney International, 2015
    Co-Authors: Lorraine C Racusen, Serena M. Bagnasco
    Abstract:

    Capillaritis in the renal allograft is important for diagnosis and prognosis. Although Glomerulitis has been well studied, peritubular capillaritis has been defined only relatively recently. The finding that peritubular capillaritis severity score and extent may correlate independently with graft outcome mandates further prospective studies to confirm this finding, and to enhance recognition and quantitation of this important lesion.

  • Time course of pathologic changes in kidney allografts of positive crossmatch HLA-incompatible transplant recipients.
    Transplantation, 2014
    Co-Authors: Serena M. Bagnasco, Andrea A Zachary, Lorraine C Racusen, Lois J. Arend, Naima Carter-monroe, Nada Alachkar, Susanna M. Nazarian, Bonnie E. Lonze, Robert A. Montgomery, Edward S. Kraus
    Abstract:

    BACKGROUND: Recipients of incompatible allografts are at increased risk of graft loss. We hypothesized that analysis of sequential biopsies from these grafts could define progression of graft lesions and identify features predictive of progression. METHODS: We studied the time course of histologic injury in 745 kidney graft biopsies from 129 patients transplanted with a positive crossmatch human leukocyte antigen-incompatible kidney between 2000 and 2010 (follow-up of 1-9 years). RESULTS: Graft survival was 98% at 1 year and 80% at 5 years after transplantation. Throughout follow-up, 70% of patients experienced rejection, with 52% showing subclinical rejection in the first year. Cell-mediated rejection was more frequent than antibody-mediated rejection throughout follow-up. Transplant glomerulopathy (TxGN; cg≥1) developed in 47% of patients over the period of the study, as early as 3 months in a few patients. TxGN was preceded by Glomerulitis in more than 90% of cases, with a median time interval of 12 months. Glomerulitis and detectable posttransplantation donor-specific antibodies were risk factors for TxGN (P

  • cohort study of the prognostic significance of acute transplant Glomerulitis in acutely rejecting renal allografts
    Transplantation, 2001
    Co-Authors: Nidia C Messias, Joseph A Eustace, Andrea A Zachary, Pamela C Tucker, Douglas Charney, Lorraine C Racusen
    Abstract:

    Background. Acute transplant Glomerulitis is a unique lesion in renal allografts, the prognostic significance of which is controversial. We conducted this retrospective cohort study to examine the independent prognostic significance of moderate-to-severe transplant Glomerulitis in acute rejection. Methods. Renal allograft survival for patients with acute rejection were studied, comparing one group with significant Glomerulitis (G, n=28) with those with no Glomerulitis (NG, n=35). Clinical, biopsy, and demographic data and renal graft survival were compared, and the association of G with graft failure was examined. Results. In the G versus NG group, a greater percentage of patients were highly sensitized (peak panel reactive antibody value >80%;P =0.009), had had a previous renal transplant (40% vs. 11%;P =0.02), or had suffered from delayed graft function (P =0.03). The G group had a trend toward earlier rejection episodes (P =0.07), a significantly higher serum creatinine at the time of index biopsy (P =0.01), a higher prevalence of vascular rejection (P =0.02), and less improvement in mean reciprocal serum creatinine at 1–2 weeks after biopsy (P =0.02). Although there was a trend toward shorter allograft survival in the G group (P =0.09), the level of significance of which increased with adjustment for transplantation time period and the duration of the transplant-biopsy interval (P =0.06), the relative risk for graft loss was no longer significant when additionally adjusted for index biopsy Banff score (relative risk, 0.97;P =0.97). Conclusion. In this study, G was significantly more common in highly sensitized patients and was strongly associated with vascular rejection biopsies but was not an independent predictor of graft survival.

  • Reproducibility of the Banff classification of renal allograft pathology. Inter- and intraobserver variation.
    Transplantation, 1995
    Co-Authors: Niels Marcussen, Lorraine C Racusen, T. S. Olsen, Hallgrimur Benediktsson, Kim Solez
    Abstract:

    : The present study was undertaken to investigate the inter- and intraobserver variation in use of the scoring system for Glomerulitis, vasculitis, interstitial inflammation, tubulitis and arteriolar hyalinosis that is an essential part of the recently proposed Banff classification of renal allograft biopsies. Seventy-seven biopsies done less than 90 days after transplantation were included. The scoring was done blindly by five pathologists on biopsies stained with H&E and PAS. The volume fraction of interstitial inflammation was estimated. Spearman rank correlation coefficient and kappa values were used for the evaluation of reproducibility. The results of both inter- and intraobserver variability showed a good correlation and reasonable kappa values for vasculitis, interstitial inflammatory infiltration, and tubulitis. Less-good correlation was found for Glomerulitis and arteriolar hyalinosis. The interobserver kappa score for grading of the rejection severity was 0.40 overall but 0.56 when only presence or absence of acute rejection was considered and 0.66 for presence or absence of vasculitis. Weighted kappa values for interobserver vasculitis score and rejection grading were 0.58 and 0.55, respectively. A strong association existed between the volume fraction of interstitial inflammation and the semiquantitative scoring for interstitial inflammation. In conclusion, the good correlations for the key elements in the grading of the allograft biopsies in the present classification system, confirmed the utility of the defined criteria for grading rejection. More precisely defined criteria or simplification of the scoring system are needed for Glomerulitis and arteriolar hyalinosis--parameters not used in the diagnosis of rejection.

David Buob - One of the best experts on this subject based on the ideXlab platform.

  • three year outcome of isolated Glomerulitis on 3 month protocol biopsies of donor hla antibody negative patients
    Transplant International, 2012
    Co-Authors: David Buob, Philippe Grimbert, Francois Glowacki, Myriam Labalette, Francoise Dufosse, Dominique Nochy, Mariechristine Copin, Emmanuel Boleslawski, C Noel, Marc Hazzan
    Abstract:

    Summary Transplant Glomerulitis (TG) can lead to the diagnosis of acute humoral rejection when associated with C4d. Recent data have shown that, in patients with donor-specific antibodies, TG is a sign of humoral rejection, even in the absence of C4d. However, the clinical significance of isolated TG, i.e. TG without C4d deposition or morphological evidence of rejection, has not been specifically studied in protocol biopsies of recipients without donor-specific antibodies. We compared 20 isolated TG-patients with 44 selected recipients without TG or any rejection-associated change. The two groups had similar baseline characteristics. After a 3 year follow-up, renal function, acute rejection rate, and development of HLA antibodies were not significantly different between the two groups. Isolated TG had no deleterious consequences on the 3 year graft outcome. Eleven patients of the Glomerulitis-group had another allograft biopsy during follow-up: glomerular lesions returned to normal in six patients whereas the persistence of Glomerulitis or features consistent with chronic transplant glomerulopathy were noticed in the remaining five patients. Four of these five patients had pretransplant non-donor specific HLA antibodies. In conclusion, although isolated TG had no impact on allograft function at 3 year, histological outcome could be related to patient sensitization.

  • intrarenal ifn γ mrna expression differentiates clinical and subclinical Glomerulitis in renal transplant recipients
    Transplantation, 2011
    Co-Authors: David Buob, Marc Hazan, Sebastien Homs, Marie Matignon, Hicham Mansour, Vincent Audard, Dominique Desvaux, Philippe Remy, Christian Noel, Sylvie Bastujigarin
    Abstract:

    BACKGROUND: Transplant Glomerulitis, characterized by mononuclear cell infiltration of glomeruli, is likely to occur during clinical or subclinical antibody-mediated rejection. METHODS: To determine whether T-cell phenotype influences the clinical presentation of this pathologic condition, we used reverse transcription quantitative polymerase chain reaction to analyze expression of Treg cells (Foxp3), cytotoxic CD8 T cells (Granzyme B), Th1 cells (INF-γ,T Bet), Th2 cells (GATA3, IL-4), and Th17 pathway (IL-17). Our study included 20 renal transplant recipients exhibiting subclinical Glomerulitis (SG) diagnosed after a routine 3-month posttransplant biopsy. Results were compared with those observed in 22 patients with normal routine biopsies at 3 months (N) and 17 patients with clinical Glomerulitis occurring during early acute renal dysfunction within the first year after transplantation in a context of acute antibody-mediated rejection. RESULTS: Our results show that expression of IL-4 mRNA was significantly higher in SG patients than in N patients (P = 0.02). Expression of IFN-γ was significantly higher in patients with clinical Glomerulitis than in patients with SG (P<0.001) and was associated with a clinical expression of Glomerulitis. CONCLUSION: Our results suggest that the balance of Th1/Th2 is likely to differentiate clinical expression of transplant glomerulopathy. They also indicate that therapeutic approaches in cases of SG should be defined with caution and take into account transcriptional criteria.

  • Intrarenal IFN-γ mRNA expression differentiates clinical and subclinical Glomerulitis in renal transplant recipients.
    Transplantation, 2011
    Co-Authors: David Buob, Marc Hazan, Sebastien Homs, Marie Matignon, Hicham Mansour, Vincent Audard, Dominique Desvaux, Philippe Remy, Christian Noel, Sylvie Bastuji-garin
    Abstract:

    BACKGROUND: Transplant Glomerulitis, characterized by mononuclear cell infiltration of glomeruli, is likely to occur during clinical or subclinical antibody-mediated rejection. METHODS: To determine whether T-cell phenotype influences the clinical presentation of this pathologic condition, we used reverse transcription quantitative polymerase chain reaction to analyze expression of Treg cells (Foxp3), cytotoxic CD8 T cells (Granzyme B), Th1 cells (INF-γ,T Bet), Th2 cells (GATA3, IL-4), and Th17 pathway (IL-17). Our study included 20 renal transplant recipients exhibiting subclinical Glomerulitis (SG) diagnosed after a routine 3-month posttransplant biopsy. Results were compared with those observed in 22 patients with normal routine biopsies at 3 months (N) and 17 patients with clinical Glomerulitis occurring during early acute renal dysfunction within the first year after transplantation in a context of acute antibody-mediated rejection. RESULTS: Our results show that expression of IL-4 mRNA was significantly higher in SG patients than in N patients (P = 0.02). Expression of IFN-γ was significantly higher in patients with clinical Glomerulitis than in patients with SG (P

  • Premier épisode de rejet aigu après transplantation rénale : étude des caractéristiques histopathologiques en fonction du risque immunologique du patient
    Nephrologie & Therapeutique, 2008
    Co-Authors: Lidia Ghisdal, David Buob, Guy Touchard, Jean-michel Goujon, Dominique Durand, Georges Mourad, Philippe Lang, Michèle Kessler, Renaud Snanoudj, F. Berthoux
    Abstract:

    Summary Renal allograft biopsies ( n  = 34) of two different populations of patients according to the immunological risk (high versus low-risk) have been compared retrospectively. The presence of polymorphonuclear leukocytes in peritubular capillaries was more frequent in the high-risk group. The C4d staining was positive in 10% of the low-risk patients and in 50% of the high-risk patients ( P  = 0.03). There were more early graft loss, renal infarctions, interstitial hemorrhage, severe Glomerulitis, neutrophilic Glomerulitis and Banff III grade rejection in the positive C4d group. In conclusion, half of the immunized patients had a humoral rejection, patients with a C4d positive rejection had more early graft loss and more severe histological lesions.

Alexander Nabokow - One of the best experts on this subject based on the ideXlab platform.

  • long term kidney allograft survival in patients with transplant Glomerulitis
    Transplantation, 2015
    Co-Authors: Alexander Nabokow, Vladimir Dobronravov, Maria Khrabrova, Hermann Josef Grone, Elisabeth Grone, Michael Hallensleben, Daniela Kieneke, Peter Weithofer, Alexei V Smirnov, Volker Kliem
    Abstract:

    BACKGROUND: Renal transplant Glomerulitis (G) is associated with acute antibody-mediated rejection (ABMR) in the presence of donor-specific antibodies. However, the long-term prognosis of isolated G (isG) in the absence of donor-specific antibodies or G in combination with T cell-mediated rejection (TCMR) remains unexplored. METHODS: Seventy recipients with G were included in this retrospective study and subdivided into 3 groups: isG, G with TCMR (G+TCMR), and G with acute ABMR. The control groups were: patients with TCMR Banff type I or II without G (TCMR) and patients without rejection (NR). Kaplan-Meier death-censored survival plots and Cox regression were used to analyze graft survival. The combined graft survival endpoint was defined as a return to dialysis or estimated glomerular filtration rate less than 15 mL/min/1.73 m. The median follow-up was 37 (14; 77) months from biopsy. RESULTS: Graft survival was significantly lower in patients with G than in the NR and TCMR groups. No significant differences were observed among the isG, G+TCMR, and ABMR groups. Graft survival was lower in the G+TCMR group than in the TCMR group. Glomerulitis was independently associated with the risk of adverse graft outcome in a multivariate Cox regression model adjusted for other confounders (hazard ratio, 4.52 [95% confidence interval, 2.37-8.68] vs controls; P<0.001). CONCLUSIONS: Glomerulitis is strongly associated with increased risk of graft failure. Graft survival in patients with isG that do not meet the Banff criteria for acute/active ABMR and in patients with G accompanying TCMR is comparable to the ABMR group.

  • Long-term kidney allograft survival in patients with transplant Glomerulitis.
    Transplantation, 2015
    Co-Authors: Alexander Nabokow, Vladimir Dobronravov, Maria Khrabrova, Hermann Josef Grone, Elisabeth Grone, Michael Hallensleben, Daniela Kieneke, Peter Weithofer, Alexei V Smirnov, Volker Kliem
    Abstract:

    BACKGROUND: Renal transplant Glomerulitis (G) is associated with acute antibody-mediated rejection (ABMR) in the presence of donor-specific antibodies. However, the long-term prognosis of isolated G (isG) in the absence of donor-specific antibodies or G in combination with T cell-mediated rejection (TCMR) remains unexplored. METHODS: Seventy recipients with G were included in this retrospective study and subdivided into 3 groups: isG, G with TCMR (G+TCMR), and G with acute ABMR. The control groups were: patients with TCMR Banff type I or II without G (TCMR) and patients without rejection (NR). Kaplan-Meier death-censored survival plots and Cox regression were used to analyze graft survival. The combined graft survival endpoint was defined as a return to dialysis or estimated glomerular filtration rate less than 15 mL/min/1.73 m. The median follow-up was 37 (14; 77) months from biopsy. RESULTS: Graft survival was significantly lower in patients with G than in the NR and TCMR groups. No significant differences were observed among the isG, G+TCMR, and ABMR groups. Graft survival was lower in the G+TCMR group than in the TCMR group. Glomerulitis was independently associated with the risk of adverse graft outcome in a multivariate Cox regression model adjusted for other confounders (hazard ratio, 4.52 [95% confidence interval, 2.37-8.68] vs controls; P

Eizaburo Sasatomi - One of the best experts on this subject based on the ideXlab platform.

  • immunohistochemical markers of tissue injury in biopsies with transplant Glomerulitis
    Human Pathology, 2012
    Co-Authors: Ibrahim Batal, Jamil Azzi, Najib Elhaddad, Leonardo V Riella, John G Lunz, Adriana Zeevi, Eizaburo Sasatomi
    Abstract:

    Summary Transplant Glomerulitis is associated with suboptimal graft function. To understand its pathogenesis and to assess the parameters of potential prognostic value, we immunostained 25 paraffin-embedded allograft biopsies showing Glomerulitis for markers of complement activation (C4d), cytotoxicity (Granzyme-B), apoptosis (Bcl-XL, Bcl-2, and Fas-L), and endothelial injury (von Willebrand factor). Staining was semiquantitatively assessed in different anatomical compartments, and comparison was made with 40 control allograft biopsies without Glomerulitis. Biopsies with Glomerulitis had more frequent incidence of "mixed" T-cell and antibody-mediated rejection compared with controls [8/25 (32%) versus 4/40 (10%), P = .046]. Furthermore, they had higher glomerular capillary-C4d scores (1.9 ± 1.1 versus 1.2 ± 1.2, P = .015), which tended to persist when biopsies showing transplant glomerulopathy were excluded. Higher glomerular capillary-C4d scores were observed in samples with versus without donor-specific antibody (2.5 ± 0.9 versus 1.2 ± 1.2, P = .01). Compared with controls, biopsies with Glomerulitis had more intraglomerular (4.8 ± 4.5 versus 0.9± 0.8 cells/glomerulus, P P = .002) Granzyme-B + leukocytes. Higher mesangial–von Willebrand factor scores were noted in the Glomerulitis group (1.8 ± 1.0 versus 0.8 ± 0.8, P = .003) and correlated with the percentage of inflamed glomeruli ( r = 0.54, P P = .02). Glomerular capillary–Bcl-XL was not associated with accommodation. Finally, no difference in Bcl-2 or Fas-L was observed upon comparing Glomerulitis to controls. In conclusion, glomerular injury in transplant Glomerulitis appears to be mediated by complement activation and cellular cytotoxicity. Mesangial– or interstitial–von Willebrand factor identified cases with more severe microcirculation injury.

  • a critical appraisal of methods to grade transplant Glomerulitis in renal allograft biopsies
    American Journal of Transplantation, 2010
    Co-Authors: Ibrahim Batal, John G Lunz, Eizaburo Sasatomi, N Aggarwal, A Zeevi, Amit Basu, R Shapiro, Parmjeet Randhawa
    Abstract:

    Transplant Glomerulitis is an increasingly recognized lesion in renal transplant biopsies. To develop a refined grading system, we defined Glomerulitis by the presence of ≥5 leukocytes/glomerulus and evaluated 111 biopsies using three different grading systems: (i) percentage of glomerular involvement, (ii) peak inflammation in the most severely affected glomerulus and (iii) presence/absence of endocapillary occlusion by inflammatory cells. Endocapillary occlusion had no impact on graft survival, but was associated with increased serum creatinine, proteinuria and subsequent transplant glomerulopathy. Grading based on either percent or peak glomerular involvement correlated with graft failure and peritubular capillaritis. However, the percent glomerular involvement method had the additional advantage of displaying associations with: concurrent proteinuria, focal or diffuse immunoperoxidase peritubular capillary C4d staining, 1-year postbiopsy serum creatinine, subsequent detection of donor-specific antibody and development of transplant glomerulopathy. Patients with >75% glomerular involvement also revealed persistent high-grade Glomerulitis on follow-up biopsies despite antirejection treatment. In conclusion, grading of Glomerulitis is a meaningful exercise, and a quantification system based on percentage of glomerular involvement shows the most robust associations with clinical parameters and prognosis.