Diffuse C4d staining of peritubular capillaries in renal allograft following bamlanivimab therapy

2021 ◽  
Author(s):  
Nattawat Klomjit ◽  
Mireille El Ters ◽  
Benjamin A. Adam ◽  
Priya Sampathkumar ◽  
Raymund R. Razonable ◽  
...  
Keyword(s):  
Renal Allograft ◽  
Peritubular Capillaries ◽  
C4d Staining

scholarly journals Acute Humoral Rejection in Kidney Transplantation: II. Morphology, Immunopathology, and Pathologic Classification

2002 ◽  
Vol 13 (3) ◽  
pp. 779-787 ◽  
Author(s):  
Shamila Mauiyyedi ◽  
Marta Crespo ◽  
A. Bernard Collins ◽  
Eveline E. Schneeberger ◽  
Manuel A. Pascual ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Graft Failure ◽  
Renal Allograft ◽  
Periodic Acid ◽  
Fibrinoid Necrosis ◽  
Humoral Rejection ◽  
Peritubular Capillaries ◽  
Significant Difference ◽  
Pathologic Classification ◽  
C4d Staining

ABSTRACT. The incidence of acute humoral rejection (AHR) in renal allograft biopsies has been difficult to determine because widely accepted diagnostic criteria have not been established. C4d deposition in peritubular capillaries (PTC) of renal allografts has been proposed as a useful marker for AHR. This study was designed to test the relative value of C4d staining, histology, and serology in the diagnosis of AHR. Of 232 consecutive kidney transplants performed at a single institution from July 1995 to July 1999, all patients (n = 67) who developed acute rejection within the first 3 mo and had a renal biopsy with available frozen tissue at acute rejection onset, as well as posttransplant sera within 30 d of the biopsy, were included in this study. Hematoxylin and eosin and periodic acid-Schiff stained sections were scored for glomerular, vascular, and tubulointerstitial pathology. C4d staining of cryostat sections was done by a sensitive three-layer immunofluorescence method. Donor-specific antibodies (DSA) were detected in posttransplant recipient sera using antihuman-globulin–enhanced T cell and B cell cytotoxicity assays and/or flow cytometry. Widespread C4d staining in PTC was present in 30% (20 of 67) of all acute rejection biopsies. The initial histologic diagnoses of the C4d+ acute rejection cases were as follows: AHR only, 30%; acute cellular rejection (ACR) and AHR, 45%; ACR (CCTT types 1 or 2) alone, 15%; and acute tubular injury (ATI), 10%. The distinguishing morphologic features in C4d+versus C4d− acute rejection cases included the following: neutrophils in PTC, 65% versus 9%; neutrophilic glomerulitis, 55% versus 4%; neutrophilic tubulitis, 55% versus 9%; severe ATI, 75% versus 9%; and fibrinoid necrosis in glomeruli, 20% versus 0%, or arteries, 25% versus 0%; all P < 0.01. Mononuclear cell tubulitis was more common in the C4d− group (70% versus 100%; P < 0.01). No significant difference between C4d+ and C4d− acute rejection was noted for endarteritis, 25% versus 32%; interstitial inflammation (mean % cortex), 27.2 ± 27% versus 38 ± 21%; interstitial hemorrhage, 25% versus 15%; or infarcts, 5% versus 2%. DSA were present in 90% (18 of 20) of the C4d+ cases compared with 2% (1 of 47) in the C4d− acute rejection cases (P < 0.001). The pathology of the C4d+ but DSA− cases was not distinguishable from the C4d+, DSA+ cases. The C4d+ DSA− cases may be due to non-HLA antibodies or subthreshold levels of DSA. The sensitivity of C4d staining is 95% in the diagnosis of AHR compared with the donor-specific antibody test (90%). Overall, eight grafts were lost to acute rejection in the first year, of which 75% (6 of 8) had AHR. The 1-yr graft failure rate was 27% (4 of 15) for those AHR cases with only capillary neutrophils versus 40% (2 of 5) for those who also had fibrinoid necrosis of arteries. In comparison, the 1-yr graft failure rates were 3% and 7%, respectively, in ACR 1 (Banff/CCTT type 1) and ACR 2 (Banff/CCTT type 2) C4d− groups. A substantial fraction (30%) of biopsy-confirmed acute rejection episodes have a component of AHR as judged by C4d staining; most (90%), but not all, have detectable DSA. AHR may be overlooked in the presence of ACR or ATI by histology or negative serology, arguing for routine C4d staining of renal allograft biopsies. Because AHR has a distinct therapy and prognosis, we propose that it should be classified separately from ACR, with further sub-classification into AHR 1 (neutrophilic capillary involvement) and AHR 2 (arterial fibrinoid necrosis).

scholarly journals Late Renal Allograft Rupture Associated with Cessation of Immunosuppression following Graft Failure

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Sumayah Askandarani ◽  
Noura Aloudah ◽  
Hanan Al Enazi ◽  
Khaled O. Alsaad ◽  
Abdulrahman Altamimi
Keyword(s):  
Graft Failure ◽  
Unusual Case ◽  
Renal Allograft ◽  
Time Interval ◽  
Antibody Mediated Rejection ◽  
Immunosuppressive Medications ◽  
Peritubular Capillaries ◽  
Long Time ◽  
Cellular Rejection ◽  
Marked Drop

A 29-year-old man developed chronic allograft nephropathy 63 months after renal transplantation. He became symptomatic with advanced chronic graft failure; his immunosuppressive medications were reduced and he was commenced on haemodialysis. Two months following the withdrawal of immunosuppression, he presented with abdominal pain, haematuria, and a marked drop in haemoglobin. The patient was taken to the operating room, where the renal allograft was found to be ruptured, and graft nephrectomy was subsequently performed. Histological examination of the graft specimen showed severe haemorrhagic acute vascular cellular rejection in a background of marked chronic allograft vasculopathy. Immunostaining for C4d showed diffuse, strong, linear circumferential staining of the peritubular capillaries, indicating a concurrent antibody-mediated rejection. We report herein an unusual case of spontaneous renal allograft rupture that occurred long time after transplantation due to severe acute rejection following cessation of immunosuppressive medications for advanced chronic allograft failure. To the best of our knowledge, the time interval between transplantation and the rupture of this allograft is the longest of those reported in the literature.

scholarly journals Evaluation of Early Renal Allograft Dysfunction from Living Donors among Egyptian Patients (Histopathological and Immunohistochemical Study)

2021 ◽  
Vol 9 (A) ◽  
pp. 328-335
Author(s):  
Maha Emad El-dein ◽  
Sawsan A. A. Fadda ◽  
Samia M. Gabal ◽  
Amr M. Shaker ◽  
Wael M. Mohamad
Keyword(s):  
Drug Toxicity ◽  
Renal Allograft ◽  
Single Case ◽  
The Other ◽  
Graft Dysfunction ◽  
Post Transplantation ◽  
Early Graft ◽  
Per Se ◽  
Early Graft Dysfunction ◽  
C4d Staining

BACKGROUND: Early renal graft dysfunction is a major problem in the early post-transplantation period and is considered a major cause of graft loss. Clinical diagnosis based on the clinical criteria alone is unreliable; therefore, biopsy remains the gold standard to differentiate between rejection and non-rejection causes. AIM: This study was designed to identify and differentiate between causes of early graft dysfunction during the first post-transplantation month and to correlate between histological lesions and immunohistochemistry (IHC) for accurate diagnosis and a better outcome. MATERIALS AND METHODS: A total of 163 renal allograft biopsies, performed in the first post-transplantation month over 6 years, were included in the study. New sections were prepared from the paraffin blocks and stained with conventional stains. Additional sections were prepared and treated by complement fragment 4d (C4d) and cluster differentiation 3 (CD3) antibodies for IHC evaluation. RESULTS: All the studied cases were from living donors. The mean patient age was 39 years with predominant males. The clinical indication for most biopsies (94.5%) was impaired graft function. Acute rejection (AR) was the main diagnostic category observed in (98/163, 60.1%); out of which, T cell-mediated rejection (TCMR) was observed in (62/98, 63.2%). Drug toxicity was suspected in (53/163, 32.5%), acute tubular injury (ATI) not otherwise specified (nos) in (21/163, 12.9%), and other lesions including thrombotic microangiopathy were observed in the remaining biopsies. The most common cause of graft dysfunction in the 1st and 2nd weeks was AR representing. A significant correlation was seen between mild glomerulitis (g1) and mild peritubular capillaritis (PTC) 1, on the one side, and negative C4d staining, on the other side. No significant correlation was seen between moderate glomerulitis (g2) and moderate ptc2 at one side and positive C4d staining at the other side reflecting the poor association between the microvascular inflammation (“g” and “ptc” scores) and C4d positivity (r = 0.2). Missed mild tubulitis (t1) was found in a single case and missed moderate tubulitis (t2) was found in a single case detected by CD3 IHC. CONCLUSION: AR and drug toxicity account for the majority of early graft dysfunction, however, other pathological lesions, per se or coincide with them may be the cause. The significance of g2 per se as a marker for diagnosis of antibody-mediated rejection requires further study. Considering C4d score 1 (by IHC) positive; also requires further study with follow-up.

Focal C4d Staining in Peritubular Capillaries and Kidney Graft Survival: Results of a Retrospective Study

2010 ◽  
Vol 42 (4) ◽  
pp. 1095-1097 ◽  
Author(s):  
F. Fior ◽  
F. Nacchia ◽  
A. Minicozzi ◽  
C. Ghimenton ◽  
L. Boschiero
Keyword(s):  
Retrospective Study ◽  
Graft Survival ◽  
Kidney Graft ◽  
Peritubular Capillaries ◽  
C4d Staining

scholarly journals Pathological diagnosis of antibody-mediated rejection in renal allograft without c4d staining, how much reliable?

2012 ◽  
Vol 1 (1) ◽  
pp. 40
Author(s):  
Diana Taheri ◽  
Maryam Taghaodi ◽  
Mojgan Mortazavi ◽  
Shahaboddin Dolatkhah ◽  
Mohsen Nasr ◽  
...  
Keyword(s):  
Renal Allograft ◽  
Pathological Diagnosis ◽  
Antibody Mediated Rejection ◽  
C4d Staining

53-P: Urinary C4d-containing complement components correlate with glomerular proteinuria but not with C4d-staining of peritubular capillaries

2007 ◽  
Vol 68 (1) ◽  
pp. S41
Author(s):  
Gideon Hoenger ◽  
Michael Mayr ◽  
Michael Dickenmann ◽  
Michael Mihatsch ◽  
Stefan Schaub
Keyword(s):  
Complement Components ◽  
Glomerular Proteinuria ◽  
Peritubular Capillaries ◽  
C4d Staining

Peritubular capillaries in chronic renal allograft rejection: A quantitative ultrastructural study

2000 ◽  
Vol 31 (9) ◽  
pp. 1129-1138 ◽  
Author(s):  
Béla Iványi ◽  
Hanan Fahmy ◽  
Holly Brown ◽  
Pál Szenohradszky ◽  
Phil F. Halloran ◽  
...  
Keyword(s):  
Ultrastructural Study ◽  
Allograft Rejection ◽  
Renal Allograft ◽  
Renal Allograft Rejection ◽  
Peritubular Capillaries

scholarly journals Chronic Humoral Rejection: Identification of Antibody-Mediated Chronic Renal Allograft Rejection by C4d Deposits in Peritubular Capillaries

2001 ◽  
Vol 12 (3) ◽  
pp. 574-582 ◽  
Author(s):  
SHAMILA MAUIYYEDI ◽  
PATRICIA DELLA PELLE ◽  
SUSAN SAIDMAN ◽  
A. BERNARD COLLINS ◽  
MANUEL PASCUAL ◽  
...  
Keyword(s):  
Graft Survival ◽  
Allograft Rejection ◽  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Survival Rates ◽  
Renal Allograft Rejection ◽  
Ulex Europaeus ◽  
Type Iv ◽  
Peritubular Capillaries ◽  
Hla Antibody

Abstract. The pathogenesis of chronic renal allograft rejection (CR) remains obscure. The hypothesis that a subset of CR is mediated by antidonor antibody was tested by determining whether C4d is deposited in peritubular capillaries (PTC) and whether it correlates with circulating antidonor antibodies. All cases (from January 1, 1990, to July 31, 1999) that met histologic criteria for CR and had frozen tissue (28 biopsies, 10 nephrectomies) were included. Controls were renal allograft biopsies with chronic cyclosporine toxicity (n = 21) or nonspecific interstitial fibrosis (n = 10), and native kidneys with end-stage renal disease (n = 10) or chronic interstitial fibrosis (n = 5). Frozen sections were stained by two-color immunofluorescence for C4d, type IV collagen and Ulex europaeus agglutinin I. Antidonor HLA antibody was sought by panel-reactive antibody analysis and/or donor cross matching in sera within 7 wk of biopsy. Overall, 23 of 38 CR cases (61%) had PTC staining for C4d, compared with 1 of 46 (2%) of controls (P < 0.001). C4d in PTC was localized at the interface of endothelium and basement membrane. Most of the C4d-positive CR tested had antidonor HLA antibody (15 of 17; 88%); none of the C4d-negative CR tested (0 of 8) had antidonor antibody (P < 0.0002). The histology of C4d-positive CR was similar to C4d-negative CR, and 1-yr graft survival rates were 62% and 25%, respectively (P = 0.05). Since August 1998, five of six C4d-positive CR cases have been treated with mycophenolate mofetil ± tacrolimus with a 100% 1-yr graft survival, versus 40% before August 1998 (P < 0.03). These data support the hypothesis that a substantial fraction of CR is mediated by antibody (immunologically active). C4d can be used to separate this group of CR from the nonspecific category of chronic allograft nephropathy and may have the potential to guide successful therapeutic intervention.

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