scholarly journals Activation of final complement components after kidney transplantation as a marker of delayed graft function severity

2020 ◽  
Author(s):  
Carlos E Arias-Cabrales ◽  
Marta Riera ◽  
María José Pérez-Sáez ◽  
Javier Gimeno ◽  
David Benito ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Graft Function ◽  
Basal Membrane ◽  
Factor H ◽  
Delayed Graft Function ◽  
Control Group ◽  
Complement Factor ◽  
Tubular Epithelial Cells ◽  
Complement Components ◽  
Protocol Biopsies

Abstract Background Ischaemia–reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available from kidney transplant (KT) patients. We studied the dynamics of membrane attack complex (C5b-9) as a soluble fraction (SC5b-9) and the histological deposit pattern of C3b, complement Factor H (FH) and C5b-9 in DGF patients. Methods We evaluated SC5b-9 levels in 59 recipients: 38 with immediate graft function and 21 with DGF. The SC5b-9 was measured at admission for KT and 7 days after KT. DGF-kidney biopsies (n = 12) and a control group of 1-year protocol biopsies without tissue damage (n = 4) were stained for C5b-9, C3b and FH. Results SC5b-9 increased significantly in DGF patients (Day 0: 6621 ± 2202 mAU/L versus Day 7: 9626 ± 4142  mAU/L; P = 0.006), while it remained stable in non-DGF patients. Days 0–7 increase >5% was the better cut-off associated with DGF versus non-DGF patient discrimination (sensitivity = 81%). In addition, SC5b-9 increase was related to DGF duration and worse graft function, and independently associated with DGF occurrence. SC5b-9, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed a more frequently high-intensity stain, a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for SC5b-9, C3b and FH than control patients. Conclusions Both SC5b-9 levels and SC5b-9, C3b and FH deposits in tubular epithelial cells basal membrane are highly expressed in patients experiencing DGF. SC5b-9 levels increase could be useful as a marker of DGF severity.

scholarly journals P1601COMPLEMENT MEMBRANE ATTACK COMPLEX DURING THE FIRST WEEK AFTER KIDNEY TRANSPLANTATION AS SEVERITY BIOMARKER TO DELAYED GRAFT FUNCTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Carlos Arias-Cabrales ◽  
Marta Riera ◽  
Maria José Pérez-Sáez ◽  
Javier Gimeno ◽  
Carla Burballa ◽  
...  
Keyword(s):  
Renal Function ◽  
Serum Creatinine ◽  
Complement Activation ◽  
Graft Function ◽  
Membrane Attack Complex ◽  
Factor H ◽  
Delayed Graft Function ◽  
Positive Staining ◽  
Complement Factor ◽  
Protocol Biopsies

Abstract Background and Aims Ischemia-reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available about the expression of the complement cascade final component -membrane attack complex (MAC)- and I/R injury in KT patients. We studied the dynamics of membrane attack complex (MAC) as plasma fraction (pMAC) and the histological deposit pattern of C3b, complement factor H (FH) and MAC in DGF patients. Method We evaluated pMAC levels in 59 recipients, 38 with immediate graft function and 21 without serum creatinine decreased at day 7 (DGF). pMAC was measured at admission for KT (day 0) and 7 days after KT (day 7). Sandwich ELISAs were used to measure MAC. Additionally, we performed imunohistoquimical stained for MAC, C3b and kidney biopsies (KB) with DGF (n=12) and a control group of one-year protocol biopsies without damage (n=4) Results Patients in the DGF group were older, more frequently diabetics and received kidneys from older donors and more frequently controlled cardio-circulatory death type. Day0 and day7 post-KT pMAC levels were similar in non-DGF patients 5902±3049 mAu/L vs 6178±2882 mAu/L; p=0.686). However, patients with DGF showed a significant increase of pMAC levels between day0 and day7 (6621±2202 mAu/L vs 9625±4142 mAu/L; p=0.006. Figure 1 Percentage pMAC levels increase (Δ0-7 pMAC%) discriminative assessment analyzed by ROC curve showed a good discriminative value for DGF with an AUC of 0.78; p<0.001 (sensitivity 81%, specificity 66% by cut-off point of 5%). In patients with DGF longer than ten days, we found more frequently patients with a Δ0-7 pMAC >5% (83% vs 17% Δ0-7 pMAC <5% ; p=0.003).Patients with DGF showed renal function at 3 and 6 months, but worse renal function 1 year after KT (serum creatinine 1.78±0.61 vs 1.35±0.30 mg/dl in non-DGF patients). DGF patients with Δ0-7 pMAC >5% displayed worse renal function 1 and 2 year after KT compared to DGF patients with Δ0-7 pMAC <5%. MAC, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed more frequently high-intensity stain for MAC and FH than controls, without differences to C3b stain. DGF-kidney biopsies also showed a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for MAC, C3b and FH than the controls. Figure 2. Among the 12 patients with DGF-biopsies, three (25%) never recovered renal function, all of them presented Δ0-7 pMAC >5% and intense, diffuse and positive staining in more than 50% of tubular perimeter for MAC, FH and C3b Conclusion Complement activation during peritrasplant period could be related with the severity of graft injury and the presence of DGF. Therefore, the determination of MAC levels could be useful to identify patients with possible complement dependent graft injury that might benefit from complement inhibitor therapies

INTERFERON-γ INDUCES BIOSYNTHESIS OF COMPLEMENT COMPONENTS C2, C4 AND FACTOR H BY HUMAN PROXIMAL TUBULAR EPITHELIAL CELLS

Cytokine ◽  
1997 ◽  
Vol 9 (4) ◽  
pp. 276-283 ◽  
Author(s):  
Jort S.J. Gerritsma ◽  
Arnout F. Gerritsen ◽  
Marc De Ley ◽  
Leendert A. van Es ◽  
Mohamed R. Daha
Keyword(s):  
Epithelial Cells ◽  
Interferon Γ ◽  
Factor H ◽  
Tubular Epithelial Cells ◽  
Complement Components ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

scholarly journals GAMBARAN MIKROSKOPIK GINJAL TIKUS WISTAR (RATTUS NORVEGICUS) SETELAH DIINDUKSI DENGAN GENTAMISIN

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Poppy M Lintong ◽  
Carla F Kairupan ◽  
Priska L N Sondakh
Keyword(s):  
Body Weight ◽  
Epithelial Cells ◽  
Wistar Rats ◽  
Periodic Acid ◽  
Basal Membrane ◽  
Tubular Epithelial Cells ◽  
Periodic Acid Schiff ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Abstract: Gentamycin, a frequently used aminoglycoside antibiotics, has a nephrotoxic effect to human beings and animals. The purpose of this research was to find out the microscopic changes of wistar rat kidneys after gentamycin induction. This was an experimental study, using five adult wistar rats, divided into three groups. Group I was the control group; group II consisted of two rats, injected with gentamycin 0,3 ml/day (dose of 60 mg/kg body weight/day) intraperitoneally for seven days; and group III consisted of two rats, injected with gentamycin 0,3 ml/day intraperitoneally for 10 days. Group I and II were terminated at day-8, and group III at day-11. Their kidneys were processed for microscopic slides, stained with hematoxylin eosin and Periodic Acid Schiff. In microscopic evaluation, group II and III showed oedema, necrosis, apoptosis, and basal membrane destruction of tubular epithelial cells. Group III also showed fat vacuoles in these epithelial cells (macrovesicular fatty changes). Conclusion: wistar rats injected with gentamycin 60 mg/kg body weight/day for 7 and 10 days showed oedema, necrosis, apoptosis, and basal membrane destruction of tubular epithelial cells; and macrovesicular fatty changes after 10 days of gentamycin.Key words: gentamycin, necrosis tubular epithelial cells, fatty changesAbstrak: Gentamisin termasuk antibiotik golongan aminoglikosida berspektrum luas yang bersifat nefrotoksik terhadap manusia dan hewan. Tujuan penelitian ini untuk melihat perubahan mikroskopik struktur ginjal tikus Wistar setelah diberikan gentamisin. Metode penelitian eksperimental dengan menggunakan lima ekor tikus Wistar dewasa yang dibagi atas tiga kelompok. Kelompok I tanpa perlakuan; kelompok II terdiri dari dua ekor tikus perlakuan yang diinjeksi dengan gentamisin 0,3 ml/hari (dosis 60 mg/kgBB/hari) secara intraperitonial selama tujuh hari; dan kelompok III terdiri dari dua ekor tikus perlakuan yang diinjeksi dengan gentamisin 0,3 ml/hari secara intraperitonial selama 10 hari. Tikus Wistar kelompok I dan II diteminasi hari ke-8, sedangkan kelompok III diterminasi hari ke-11. Ginjal tikus kelompok I -III kemudian dibuat preparat histopatologik dengan pengecatan rutin hematoksilin eosin dan Periodic Acid Schiff (PAS). Hasil penelitian menunjukkan tikus Wistar perlakuan yang diberikan gentamisin 0,3 ml/hari selama 7 sampai 10 hari secara mikroskopik memperlihatkan pembengkakan, nekrosis, apoptosis, dan destruksi membrana basalis sel epitel tubulus; dan pada hari ke-10 terlihat vakuol-vakuol lemak pada sel epitel sehingga inti terdesak ke tepi (perlemakan makrovesikuler). Simpulan: pemberian gentamisin pada tikus Wistar dengan dosis 60 mg/kg BB/hari selama 7-10 hari menunjukkan pembengkakan, nekrosis, apoptosis sel epitel tubulus, dan membrana basalis tubulus rusak; dan setelah hari ke-10 juga terlihat perlemakan makrovesikuler.Kata kunci: gentamisin, nekrosis sel epitel tubulus, perlemakan makrovesikuler

scholarly journals Binding of factor H to tubular epithelial cells limits interstitial complement activation in ischemic injury

2011 ◽  
Vol 80 (2) ◽  
pp. 165-173 ◽  
Author(s):  
Brandon Renner ◽  
Viviana P. Ferreira ◽  
Claudio Cortes ◽  
Ryan Goldberg ◽  
Danica Ljubanovic ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Complement Activation ◽  
Ischemic Injury ◽  
Factor H ◽  
Tubular Epithelial Cells

Association between thrombotic microangiopathy and activated alternative complement pathway in malignant nephrosclerosis

2020 ◽  
Author(s):  
Ying Zhang ◽  
Chaona Yang ◽  
Xinjin Zhou ◽  
Ruimin Hu ◽  
Songxia Quan ◽  
...  
Keyword(s):  
Thrombotic Microangiopathy ◽  
Alternative Pathway ◽  
Factor H ◽  
Complement Factor ◽  
Complement Alternative Pathway ◽  
Complement Components ◽  
Atypical Haemolytic Uraemic Syndrome ◽  
Urinary Levels ◽  
Normal Controls ◽  
Malignant Nephrosclerosis

Abstract Background Malignant nephrosclerosis, defined as renal microangiopathy in the setting of severe hypertension, remains a critical renal emergency leading to end-stage renal disease despite aggressive anti-hypertensive treatment. Recently, activation of the complement alternative pathway (AP) has been reported to play a prominent role in the pathogenesis of malignant nephrosclerosis. However, subsequent study failed to recapitulate the findings of genetic complement abnormalities in the disease. This study aimed to determine the presence of AP activation and genetic complement defects and establish their correlations to renal microangiopathy lesions, clinical features and prognosis in patients with malignant nephrosclerosis. Methods Fifty patients with malignant hypertension and concomitant thrombotic microangiopathy (TMA) proven by renal biopsy were investigated; 25 cases of kidney donors who received zero-hour allograft biopsies were used as normal controls. Various renal TMA lesions in patients with malignant nephrosclerosis were reviewed and evaluated using a semi-quantitative scoring system. Deposition of C5b-9, C3a, C5a, C4d and mannose-binding lectin was assessed by immunohistochemistry. Co-localization of C5b-9 and CD34 was detected by confocal microscopy. Complement factor B (FB), factor P (FP; properdin), factor D (FD), factor H (FH), C3a and C5a levels were quantified by enzyme-linked immonosorbent assay in plasma and urine samples of patients with malignant nephrosclerosis and controls. Genetic abnormalities of complement components were analysed by whole-exome sequencing. Results Renal biopsies of malignant nephrosclerosis showed identical histopathological and ultrastructural features to atypical haemolytic uraemic syndrome. C5b-9, C3a and C5a deposits were found along the walls of arteries/arterioles and glomerular capillaries and localized in the endothelial cells. Elevated plasma and urinary levels of FB, FP, FD, C3a and C5a as well as decreased FH levels were observed in patients with malignant nephrosclerosis compared with normal controls. The urinary levels of complement AP components, but not the plasma levels, were correlated with renal functions, prognosis and active TMA lesions except for arteriolar thrombi. Finally, mutations of the MCP, CFB, CFH and CFHR5 genes were identified in 8 of 20 patients with malignant nephrosclerosis. Conclusions Aberrant complement AP dysregulation was demonstrated and associated with the activity, severity and renal outcomes of malignant nephrosclerosis. This observation warrants screening for complement defects in patients with malignant nephrosclerosis for the potential use of complement regulators and also highlights the need for further investigation of the precise role of AP in the pathogenesis of the disease.

Sub-clinical acute rejection detected using protocol biopsies in patients with delayed graft function

2000 ◽  
Vol 13 (7) ◽  
pp. S52-S55 ◽  
Author(s):  
S. Jain ◽  
V. Curwood ◽  
S. A. White ◽  
P. N. Furness ◽  
M. L. Nicholson
Keyword(s):  
Acute Rejection ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Protocol Biopsies

Investigation of biochemical and histopathological effects of Mentha piperita L. and Mentha spicata L. on kidney tissue in rats

2003 ◽  
Vol 22 (4) ◽  
pp. 213-219 ◽  
Author(s):  
Mehmet Akdogan ◽  
Ibrahim KWlWnc ◽  
Meral Oncu ◽  
Erdal Karaoz ◽  
NamWk Delibas
Keyword(s):  
Epithelial Cells ◽  
Kidney Tissue ◽  
Group Iv ◽  
Mentha Piperita ◽  
Control Group ◽  
Tubular Epithelial Cells ◽  
Mentha Spicata ◽  
Plasma Urea ◽  
Hydropic Degeneration ◽  
Group I

Peppermint plants have been used as a herbal medicine for many conditions, including loss of appetite, common cold, bronchitis, sinusitis, fever, nausea, vomiting and indigestion. This study is aimed at investigating the biochemical and histological effects of Mentha piperita L., growing in the Yenisar Bademli town of Isparta City, and Mentha spicata L., growing on the Anamas high plateau of Isparta City, on rat kidney tissue. Forty-eight male Wistar albino rats weighing 200 / 250 g were used for this study. Animals were divided into four experimental groups, each with 12 rats, as follows: control group (group I); 20 g/L M. piperita tea (group II); 20 g/L M. spicata tea (group III); 40 g/L M. spicata tea (group IV). The control group rats were given commercial drinking water (Hayat DANONESA water). The tea for the other groups was prepared daily and provided at all times to the rats during 30 days as drinking water. Plasma urea and creatinine levels were determined, and the levels of thiobarbituric acid reactive substance (TBARS) and the activities of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. The levels of plasma urea and creatinine were increased significantly (P B-0.0033) in groups III and IV when compared with group I. The activities of SOD and GSHPx were decreased significantly (P B-0.0033) in group IV when compared with group I. The activities of CAT were decreased significantly in groups III and IV (P B-0.033,P B-0.0033, respectively) when compared with group I. TBARS levels were increased significantly (P B-0.0033) in groups III and IV when compared with group I. In groups II, III and IV, hydropic degeneration of tubular epithelial cells, the epithelial cells with picnotic nuclei and eosinophilic cytoplasm, tubular dilatation and enlargements in Bowman capsules were observed histologically. However, in group II histopathological changes were more slight than in groups III and IV. In group IV, in addition to these changes, extremely hydropic degeneration of tubular epithelial cells, some atrophic tubules and glomerules, and focal mononuclear cell infiltrations in the kidney tissues of the rats were observed. In conclusion, the results indicate that M. piperita does not show nephrotoxicity but M. spicata presents markedly nephrotoxic changes in rats.

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