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.

scholarly journals The Summarized Assessment of Endothelin A Receptor Expression in Renal Transplant Compartments Associated with Antibody-Mediated Rejection

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2366
Author(s):  
Mirosław Banasik ◽  
Magdalena Kuriata-Kordek ◽  
Piotr Donizy ◽  
Katarzyna Nowańska ◽  
Krzysztof Wiśnicki ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Receptor Expression ◽  
Immunohistochemical Method ◽  
Antibody Mediated Rejection ◽  
Allograft Biopsy ◽  
Score Analysis ◽  
Endothelin A Receptor ◽  
Eta Receptor ◽  
Endothelin A ◽  
Expression Score

The occurrence of anti-endothelin A receptor antibodies may be useful in diagnosis of transplant damage. We noticed that the presence of the endothelin A receptor (ETA receptor) in biopsy compartments is yet to be defined. We decided therefore to analysed the presence and relevance of the ETA receptor in biopsy to define the cause. Our study aims to evaluate the expression of ETA receptors in renal recipients after a biopsy due to the worsening of transplant function. Methods: The expression of ETA receptors was analyzed in renal transplant biopsies using the immunohistochemical method. The evaluation of ETA receptors was performed on paraffin sections. ETA receptor expression was analyzed in four compartments of renal transplant biopsies: glomeruli; vessels; tubular epithelium; and interstitium. The assessment was presented using a three-step scale (0: lack of expression; 1: mild to moderate immunoreactivity; 2: high expression). The results of each compartment from a single biopsy were summarized and assessed in the context of antibody-mediated rejection (AMR). Results: We analyzed 156 patients who had a renal allograft biopsy after renal transplantation. For each patient, we created a summarized ETA receptor expression score. The summarized ETA receptor expression score analysis showed statistically significant differences in patients with and without AMR. In addition, we noticed that patients with AMR had a significantly higher mean summarized expression of ETA receptor score of 3.28 ± 1.56 compared to patients who had a biopsy for other reasons with a mean summarized ETA receptor expression score of 1.47 ± 1.35 (p < 0.000001). ROC analysis of the ETA receptor expression score for detecting AMR status showed that the most appropriate cut-off for the test of the chosen binary classifier is between 2 and 3 of the summarized ETA receptor expression score. Conclusions: The expression of endothelin A receptors in renal transplant compartments may be associated with antibody-mediated rejection. The positive ETA receptor staining might be a vital feature in the diagnosis of damage in AMR. The summarized ETA receptor expression score seems to be an exciting diagnostic tool in transplant injury assessment.

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 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.

Human BK Polyomavirus Nephropathy (BKVN) In Non- Kidney-Transplant Patients

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S118-S118
Author(s):  
Y Chen Wongworawat ◽  
C Zuppan
Keyword(s):  
Renal Transplant ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Transplant Patients ◽  
Bk Polyomavirus ◽  
Pathologic Features ◽  
Renal Biopsies ◽  
Renal Transplant Patients

Abstract Introduction/Objective Human BK polyomavirus nephropathy (BKVN) occurs in up to 10% of renal transplant recipients, and can result in graft loss. Transplant biopsy is the gold standard to diagnose BKVN, and SV40 immunohistochemical (IHC) staining is helpful in confirming the diagnosis. BKVN is uncommon outside the setting of renal transplantation. To understand more about its occurrence in other contexts, we reviewed our renal biopsies files for cases of BKVN. Methods Our renal biopsy files for the past 20 years were reviewed for all cases with a diagnosis of BKVN or polyoma virus infection, and the clinical characteristics of the affected patients noted. Results Evidence of BKVN was found in 44 renal biopsies, of which 39 (86%) were renal transplant patients. Of the remaining five patients (14%), two had undergone heart transplantation, one lung transplantation, one was undergoing chemotherapy for acute lymphoblastic leukemia, and one patient had active HIV infection. All patients had elevated serum creatinine, and four out of five patients had documented BK viremia. Four of the five biopsies showed typical tubular injury with viral nuclear cytopathic changes (inclusions). In the lung transplant patient, the biopsy showed advanced chronic tubulointerstitial injury without distinct viral inclusions, but SV40 staining confirmed the presence of BK virus antigen. Conclusion The BKVN is distinctly uncommon outside the context of kidney transplantation. In our series, 14% of patients with BKVN were not kidney transplant recipients, but all were immune compromised in some fashion. The pathologic features of BKVN appear similar, regardless of whether the host is a renal transplant recipient or not. Although uncommon, it is important to consider the possibility of BKVN in non-renal transplant patients with persistent or progressive renal dysfunction.

scholarly journals Understanding and using AlloSure donor derived cell-free DNA

2020 ◽  
Vol 12 (4) ◽  
pp. 917-924 ◽  
Author(s):  
R. K. Seeto ◽  
J. N. Fleming ◽  
S. Dholakia ◽  
B. L. Dale
Keyword(s):  
Renal Transplant ◽  
Graft Loss ◽  
Cost Effective ◽  
Low Grade ◽  
Cell Free Dna ◽  
Disease States ◽  
Transplant Patients ◽  
Free Dna ◽  
Obesity Hypertension ◽  
End Stage

Abstract Renal transplant is a lifesaving and cost-effective intervention for patients with End Stage Renal Failure. Yet it is often regarded as replacement therapy rather than a cure given the overall failure rate over time. With a shortage of organs, this global issue has been further compounded by increased incidences of obesity, hypertension and diabetes, such that the disease burden and need for transplantation continues to increase. Considering the lifetime of immunosupression in transplant patients, there will also be significant associated co-morbidities By leveraging the advances in innovation in Next Generation Sequencing, the field of transplant can now monitor patients with an optimized surveillance schedule, and change the care paradigm in the post-transplant landscape. Notably, low grade inflammation is an independent risk for mortality across different disease states. In transplantation, sub-clinical inflammation enhances acute and chronic rejection, as well as accelerates pathologies that leads to graft loss. Cell free DNA has been shown to be increased in inflammatory processes as we all as provide an independent predictor of all-cause mortality. This review considers the utility of AlloSure, a donor derived cell free DNA molecular surveillance tool, which has shown new clinical insights on how best to manage renal transplant patients, and how to improve patient outcomes.

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.

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