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

Abstract

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.

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

“…Our observations inspired us to publish another article showing that the expression of ETA receptors in the glomeruli might be a feature in the diagnosis of damage during AMR [ 24 ]. Preformed IgG antibodies targeting non-HLA antigens expressed on glomerular endothelial cells were also described as associated with early acute microvascular rejection [ 29 ].…”

“…The results were described using a three-step scale (0: lack of expression, 1: mild to moderate immunoreactivity, 2: high expression). The method and figures were presented and described in our previous paper [ 24 ]. In addition, the results of each compartment (0, 1, 2) from a single biopsy were summarized and assessed in the context of AMR.…”

“…We noticed that anti-ETAR antibodies in renal transplant recipients might be associated with a worse transplant function compared to patients without such antibodies [ 10 ]. We presented that the expression of ETA receptors in glomeruli might be a feature in the description of injury during AMR [ 24 ]. We also described that the expression of ETA receptors in small and intermediate arteries of renal transplants was associated with acute tubular necrosis (ATN) or AMR [ 25 ].…”

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation

“…In our recent studies we described the role of AT1 receptors but also ETA receptors in different renal compartments [32][33][34][35]. The stimulated injury described by authors as vascular changes in microcirculation [23] creates the dangerous opportunity for further damage of the transplant.…”

Adherence to Immunosuppressive Therapies after Kidney Transplantation from a Biopsychosocial Perspective: A Cross-Sectional Study

“…Although the advantages of KT for the QoL in comparison to treatment for end-stage renal disease are well established [ 18 , 19 ], there are still many difficulties faced by KT recipients after transplant [ 20 , 21 , 22 ]. Patients’ lives after KT also presents negative aspects, such as a strict regimen of immunosuppressive drugs and their related side effects, frequent medical visits and hospitalizations, infections, and symptoms of anxiety and depression concerning rejection episodes and the potential loss of the graft [ 23 , 24 , 25 , 26 ]. It is worth noting that after KT and discharging the patients with a functioning transplant, their life with chronic illness is continued [ 27 ].…”