scholarly journals SO031ANGIOTENSIN II TYPE 1 RECEPTOR (AT1R) EXPRESSION IN RENAL TRANSPLANT BIOPSIES AND ANTI-AT1R ANTIBODIES IN SERUM AS AN INDICATOR OF THE RISK OF TRANSPLANT LOSS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Agnieszka Sas-Strózik ◽  
Piotr Donizy ◽  
Katarzyna Kościelska-Kasprzak ◽  
Dorota Kamińska ◽  
Kamila Gawlik ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Loss ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Positive Staining ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries ◽  
One Year ◽  
Transplant Biopsy

Abstract Background and Aims The manifestation of anti-angiotensin II type 1 receptor (AT1R) antibodies is considered a risk factor for transplant injury, however, the occurrence of AT1-Receptor expression in renal transplant biopsy may be an additional feature which can help to predict transplant loss. The aim of our study was to evaluate the expression of AT1R together with their antibodies and assess the risk of transplant loss in patients who had a renal transplant indication biopsy. Method AT1-Receptor immunoreactivity was analyzed in renal transplant biopsies. Additionally, we analyzed the presence of anti-AT1R antibodies in these patients using ELISA method. The result of more than 10 was assessed as positive. Immunohistochemical evaluation of AT1-Receptor expression was performed on 4 μm-thick paraffin sections mounted on silanized slides. AT1-Receptor expression was analyzed in five compartments: 1.tubular epithelium, 2.glomeruli, 3.peritubular capillaries, 4.interstitium and 5.renal blood vessels (small and intermediate arteries) based on a 3-step scale. Results We checked 156 samples of biopsies for the immunoreactivity of the AT1-Receptor. In all these patients we were able to access the presence of anti-AT1R antibodies. A group of 67 patients had positive AT1-Receptor expression (R+) and 16 patients had positive anti-AT1R antibodies (R+Ab+) results. A group of 89 patients had no expression of AT1-Receptor (R-), among which 51 had also no anti-AT1R (R-Ab-). One-year post-biopsy graft loss in the R+Ab+ patients was 37% (6/16) compared to 10% (7/69) in the R-Ab- patients (p = 0.006). Two-year and three-year graft loss was 43% vs. 17% (p=0.02) and 50% vs. 21% (p=0.02) respectively. Moreover, six patients had positive staining of AT1-Receptors in microcirculation (glomeruli and peritubular capillaries), which was associated with antibody mediated rejection. Conclusion The presence of anti-AT1R antibodies in serum together with the expression of AT1-Receptor in transplant biopsy was associated with a significantly higher graft loss. The relevance of AT1-Receptor expression analyzed together with anti-AT1R antibodies should be considered for better transplant immunological risk assessment.

scholarly journals Endothelin A Receptors Expressed in Glomeruli of Renal Transplant Patients May Be Associated with Antibody-Mediated Rejection

2021 ◽  
Vol 10 (3) ◽  
pp. 422
Author(s):  
Katarzyna Nowańska ◽  
Mirosław Banasik ◽  
Piotr Donizy ◽  
Katarzyna Kościelska-Kasprzak ◽  
Sławomir Zmonarski ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Loss ◽  
Human Leukocyte ◽  
Positive Staining ◽  
Antibody Mediated Rejection ◽  
Transplant Patients ◽  
Endothelin A Receptor ◽  
Microscopic Evaluation ◽  
Eta Receptor ◽  
Endothelin A

Background: Non-human leukocyte antigen (HLA) anti-endothelin A receptor antibodies are presented as being potentially important, but the expression of the endothelin A receptor in glomeruli (ETA receptor (g+)) has not yet been described. We decided to evaluate the presence and relevance of the ETA receptor in for-cause renal transplant biopsies. The aim of our study was to evaluate the immunoreactivity of the ETA receptor and its significance in patients who underwent a renal transplant biopsy due to the deterioration of transplant function, with detailed characterization of staining in glomeruli. Methods: The immunohistochemical expression of ETA receptor (ETAR) was analyzed in renal transplant biopsies. Microscopic evaluation was performed on paraffin sections in glomeruli. The analysis was performed using a two-step scale (0: lack of ETAR expression; 1: the presence of ETAR expression—mild to moderate immunoreactivity). Results: We analyzed 149 patients who underwent renal allograft biopsy after renal transplantation. Positive staining of ETA receptors in glomeruli (ETA receptor (g+)) was noticed in 13/149 (8.7%) patients. Five of these 13 (38.5%) patients with ETA receptor (g+) developed antibody-mediated rejection (AMR), while 13 of the remaining 136 (9.5%) ETA receptor (g-) patients developed AMR (p = 0.0022). Graft loss was noticed in all but one ETA receptor (g+) patient with AMR (4/5; 80%), but only in 2/13 (15%) ETA receptor (g-) patients with AMR (p = 0.009) during the first year after biopsy. Conclusions: The expression of endothelin A receptors in glomeruli seems to be a potentially important feature in the diagnosis of damage during antibody-mediated rejection. It may help to identify patients at a higher risk of allograft rejection and injury.

Abstract 309: Sp-3 But not the NF-kB Transcription Factor Causes the Up-regulation of Angiotensin Type 1 Receptor Expression and Contributes to Hypertension in Aging FBN rats.

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Mohammad Saleem ◽  
Mohammad Asghar
Keyword(s):  
Blood Pressure ◽  
Transcription Factors ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Receptor Function ◽  
Receptor Mrna ◽  
Hk2 Cells ◽  
Angiotensin Type

We recently reported that age-associated oxidative stress is causal to higher renal angiotensin Type 1 (AT1) receptor function and hypertension in aged Fisher 344 X Brown Norway (FBN) rats. We became interested in examining the mechanism of higher AT1 receptor function in the aging kidneys. Adult (3-month) and aging (21 month) FBN rats were subjected to conscious blood pressure measurement by telemetry approach. The levels of AT1 receptor mRNA in the kidney cortex was measured by qRT-PCR while nuclear Sp-3 and NF-kB-p65 redox-sensitive transcription factors were determined by western blotting. We found that blood pressure was higher in aged than in adult rats (adult vs. old: 110±1 vs. 130±1 mmHg) which was associated with higher AT1 receptor mRNA levels (adult vs. old: 1.51±0.72 vs. 7.86±1.03 DU), and nuclear levels of both Sp-3 (adult vs. old: 0.56±.01 vs. 1.54±.02 DU) and NF-kB-p65 (adult vs. old: 0.9±.01 vs. 1.5±0.01 DU). To further delineate whether sp-3 or NF-kB-p65 or both transcription factors are responsible for the up-regulation of AT1 receptor, human kidney (HK2) cells were transfected with Sp-3 and NF-kB-p65 plasmids. We found that Sp-3 plasmid but not NF-κB-p65 plasmid transfection caused an increase in the levels of AT1 receptor protein in HK2 cells (control vs. transfected: 135±22 vs. 235±10 DU). Furthermore, Sp-3 siRNA treatment resulted in the reduction of Sp-3 (control vs. transfected: 136±10 vs. 93±21 DU) and AT1 receptor protein levels (control vs. transfected: 270±38 vs. 172±201 DU) in HK2 cells. Our results suggest that sp-3 but not the NF-κB-p65 is involved in the up-regulation of renal AT1 receptor that may be contributing to hypertension in aging FBN rats.

Histopathological Relevance of Angiotensin II Type 1 Receptor in Renal Transplant Biopsy

2018 ◽  
Vol 50 (6) ◽  
pp. 1847-1849 ◽  
Author(s):  
A. Sas ◽  
P. Donizy ◽  
K. Kościelska-Kasprzak ◽  
D. Kamińska ◽  
O. Mazanowska ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Transplant ◽  
Transplant Biopsy

scholarly journals The causes and frequency of kidney allograft failure in a low-resource setting: Data from Iraqi Kurdistan

2021 ◽  
Author(s):  
Alaa Abbas Ali ◽  
Safaa E Almukhtar ◽  
Kais H Abd ◽  
Zana Sidiq M Saleem ◽  
Dana A Sharif ◽  
...  
Keyword(s):  
Graft Failure ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
The United States ◽  
Failure Rates ◽  
Antibody Mediated Rejection ◽  
Iraqi Kurdistan ◽  
Resource Setting ◽  
Long Term Treatment ◽  
One Year

Abstract Background In the developing world, transplantation is the most common long-term treatment for patients with end-stage renal disease, but rates and causes of graft failure are uncertain. Methods In 2019, in Iraqi Kurdistan, 301 of 871 renal transplant patients had indicated graft biopsies. Outcomes were followed over the subsequent year of 2020. Results The post-transplantation time ranged from one day to 18 years. All donors were living. Approximately 15% of transplants were preemptive. Pretransplant hemodialysis (HD) was twice weekly and less than one year. The median recipient age was 39 (IQR 28 to 48) years. 5.5% of recipients had previous transplants; 3.7% had pretransplant donor-specific antibodies (DSA). The Kaplan-Meier estimated graft failure rates for all-cause, return to HD, and death with functional graft (DWFG) were 9.1%, 6.3%, and 2.9% at one year and 23.8%, 6.3%, and 7.4% at five years. The median death-censored graft survival was 15 years. The most frequent biopsy diagnoses associated with graft failure were interstitial fibrosis and tubular atrophy (IF/TA) (23.1%), transplant glomerulopathy (13.7%), and acquired active antibody-mediated rejection (11.1%). The significant predictors of graft loss were C4d + biopsies (P < 0.01) and advanced IF/TA (P < 0.001). Conclusions These Iraqi patients had estimated graft failure rates similar to the United States (US) Renal Data System living-donor outcomes reported for the year 2000. The inability to approach recent US graft survivals may owe to inadequate pretransplant dialysis. Nevertheless, prolonged survival made chronic disorders and acquired DSA the leading causes of graft failure and is creating a need for second transplants.

scholarly journals The causes and frequency of kidney allograft failure in a low-resource setting: observational data from Iraqi Kurdistan

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alaa Abbas Ali ◽  
Safaa E. Almukhtar ◽  
Kais H. Abd ◽  
Zana Sidiq M. Saleem ◽  
Dana A. Sharif ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Failure ◽  
Graft Loss ◽  
Failure Rates ◽  
Antibody Mediated Rejection ◽  
Transplant Patients ◽  
Iraqi Kurdistan ◽  
Resource Setting ◽  
Long Term Treatment ◽  
Renal Transplant Patients

Abstract Background In the developing world, transplantation is the most common long-term treatment for patients with end-stage renal disease, but rates and causes of graft failure are uncertain. Methods This was a retrospective outcomes study of renal transplant patients seen in Iraqi Kurdistan nephrology clinics in the year 2019. In 2019, 871 renal transplant patients were registered and outcomes followed through 12/31/2020. Indicated renal biopsies were obtained on 431 patients at 1 day to 18 years post-transplantation. Outcomes were compared with United States Renal Data System (USRDS) living donor reports. Results All donors were living. The recipient age was 38.5 ± 13.3 years, 98.2% were < 65 years old, 3.7% had previous transplants, and 2.8% had pretransplant donor-specific antibodies (DSA). Gehan-Breslow estimated failure rates for all-cause, return to HD, and death with functional graft were 6.0, 4.2, and 1.9% at 1 year and 18.1, 13.7, and 5.1% at 5 years post-engraftment (USRDS 2000; 1 year: 7.0, 5.0, 2.6%; 5 year: 22.3, 15.2, 10.6%. USRDS 2010; 1 year: 3.7, 2.4, 1.4%; 5 year: 15.3, 9.6, 7.3%). The median graft survival was 15 years. Acute tubular injury (ATI), infarction, and acute T cell-mediated rejection accounted for 22.2% of graft loss, with > 75% of these failures taking place in the first year. Most graft failures occurred late, at a median post-transplant time of 1125 (interquartile range, 365–2555) days, and consisted of interstitial fibrosis and tubular atrophy (IF/TA) (23.8%), transplant glomerulopathy (13.7%), and acquired active antibody-mediated rejection (12.0%). The significant predictors of graft loss were C4d + biopsies (P < 0.01) and advanced IF/TA (P < 0.001). Conclusions Kurdistan transplant patients had graft failure rates similar to living donors reported by the USRDS for the year 2000 but higher than reported for 2010. Compared to USRDS 2010, Kurdistan patients had a moderate excess of HD failures at one and 5 years post-engraftment. Nevertheless, prolonged survival is the norm, with chronic disorders and acquired DSA being the leading causes of graft loss.

scholarly journals Treatment of Chronic Active Antibody-mediated Rejection in Renal Transplant Recipients – A single center retrospective study

2019 ◽  
Author(s):  
Hsien-Fu Chiu ◽  
Mei-Chin Wen ◽  
Ming-Ju Wu ◽  
Cheng-Hsu Chen ◽  
Tung-Min Yu ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Loss ◽  
Rank Test ◽  
Renal Transplant Recipients ◽  
Supportive Treatment ◽  
Aggressive Treatment ◽  
Transplant Recipients ◽  
Antibody Mediated Rejection ◽  
Group 2 ◽  
Group 1

Abstract Background: Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there are no approved treatments. Methods: Computerized records from Taichung Veterans General Hospital were collected to identify the renal transplant biopsies performed in the past 7 years with the diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1: aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2: supportive treatment. Results: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 ( P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was no significant different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. Conclusions : Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for aggressive treatment patients.

Angiotensin II Type 1 Receptor Expression in Renal Transplant Biopsies and Anti-AT1R Antibodies in Serum Indicates the Risk of Transplant Loss

2020 ◽  
Vol 52 (8) ◽  
pp. 2299-2304
Author(s):  
Agnieszka Sas-Strózik ◽  
Piotr Donizy ◽  
Katarzyna Kościelska-Kasprzak ◽  
Dorota Kamińska ◽  
Kamila Gawlik ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Transplant ◽  
Receptor Expression

MO963GRAFT- AND PATIENT-SURVIVAL AFTER FIRST KIDNEY TRANSPLANT BIOPSY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Salmir Nasic ◽  
Johan Mölne ◽  
Bernd Stegmayr ◽  
Marie Felldin ◽  
Björn Peters
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Patient Survival ◽  
Graft Loss ◽  
Glomerular Diseases ◽  
Hematological Diseases ◽  
Antibody Mediated Rejection ◽  
Transplant Kidney ◽  
Grade Ii ◽  
Transplant Biopsy

Abstract Background and Aims Kidney transplantation is frequently used as a treatment in uremic patients. However, long term function is not easily predicted. The aim of this study was to investigate to what extent histological diagnosis in the first registered transplant kidney biopsy is related to clinical outcome. Method Included were data of 1463 patients (36.6 % women, 63.4 % men) that were merged from a kidney transplantation register and a biopsy register. These patients obtained their first registered transplant biopsy during the period January 1, 2007 until July 30, 2017. Fisher’s exact test and χ-2 analyses were used for cross-tabulation of data. Graft- and patient-survival analysis was performed by Kaplan-Meier analysis with log-rank tests comparing different groups and in next step age and gender adjusted analysis were performed by multivariate Cox-regression-analysis. Data are presented as Hazard Ratio (HR) and 95% Confidence Intervals (CI). A two-sided p-value of &lt;0.05 was considered as statistically significant. Results The graft-survival was shorter for patients with biopsy-proven glomerular diseases (HR 8.1, CI 3.1-20.7) and rejections (HR 4.3, CI 1.7 -10.5) compared to normal biopsy findings. Further, there was a shorter graft-survival for those with chronic damages (HR 3.2, CI 1.3-8.0), acute tubular injuries (HR 3.0, CI 1.2-7.8), and borderline changes (HR 2.9, CI 1.1-7.6). The patient-survival was reduced for patients with biopsy-proven hematological diseases (HR 9.6, CI 2.1-44.0). Sub analysis of all types of rejections showed shorter graft-survival for chronic T-cell-mediated rejection (TCMR) (HR 4.8, CI 2.1-11.7), active antibody-mediated rejection (ABMR) (HR 4.4, CI 2.1-9.3), chronic ABMR (HR 3.8, CI 2.2-6.7), combined chronic ABMR and TCMR (HR 4.0, CI 2.4-6.9) and other rejections (HR 3.3, CI 1.1-9.6) compared to acute TCMR. Patients with TCMR Banff grade II rejection had a better graft-survival (HR 0.35, CI 0.20-0.63) compared to other rejections as well as patients with TCMR Banff grade I (HR 0.52, CI 0.29-0.93). 265 patients had graft-loss and 42 of those patients died afterwards (15.8%). Of the 42 who died after graft-loss 9 patients died within 30 days after transplant failure (21.4%). Conclusion A shorter graft-survival was found in kidneys with glomerular diseases, rejections, acute tubular injuries, borderline changes and chronic damages. A shorter patient-survival was noted for patients with transplant kidney biopsies with hematological diseases. Patients with Banff grade II rejection had a better graft-survival compared to all other diagnosis and other rejections. Further, awareness should be given to patients the first month after graft-loss.

scholarly journals Enhanced hemodynamic responses to angiotensin II in diabetes are associated with increased expression and activity of AT1 receptors in the afferent arteriole

2017 ◽  
Vol 49 (10) ◽  
pp. 531-540 ◽  
Author(s):  
Jie Zhang ◽  
Helena Y. Qu ◽  
Jiangping Song ◽  
Jin Wei ◽  
Shan Jiang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mrna Level ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Ang Ii ◽  
Diabetic Mice ◽  
At1 Receptors ◽  
Enhanced Expression ◽  
Bolus Intravenous Injection

The prevalence of hypertension is about twofold higher in diabetic than in nondiabetic subjects. Hypertension aggravates the progression of diabetic complications, especially diabetic nephropathy. However, the mechanisms for the development of hypertension in diabetes have not been elucidated. We hypothesized that enhanced constrictive responsiveness of renal afferent arterioles (Af-Art) to angiotensin II (ANG II) mediated by ANG II type 1 (AT1) receptors contributes to the development of hypertension in diabetes. In response to an acute bolus intravenous injection of ANG II, alloxan-induced diabetic mice exhibited a higher mean arterial pressure (MAP) (119.1 ± 3.8 vs. 106.2 ± 3.5 mmHg) and a lower renal blood flow (0.25 ± 0.07 vs. 0.52 ± 0.14 ml/min) compared with nondiabetic mice. In response to chronic ANG II infusion, the MAP measured with telemetry increased by 55.8 ± 6.5 mmHg in diabetic mice, but only by 32.3 ± 3.8 mmHg in nondiabetic mice. The mRNA level of AT1 receptor increased by ~10-fold in isolated Af-Art of diabetic mice compared with nondiabetic mice, whereas ANG II type 2 (AT2) receptor expression did not change. The ANG II dose-response curve of the Af-Art was significantly enhanced in diabetic mice. Moreover, the AT1 receptor antagonist, losartan, blocked the ANG II-induced vasoconstriction in both diabetic mice and nondiabetic mice. In conclusion, we found enhanced expression of the AT1 receptor and exaggerated response to ANG II of the Af-Art in diabetes, which may contribute to the increased prevalence of hypertension in diabetes.

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