Endothelin A Receptors Expressed in Renal Blood Vessels of Renal Transplant Patients Are Connected With Acute Tubular Necrosis or Antibody-Mediated Rejection.

BACKGROUND: The role of non-HLA antibodies named antiendothelin A receptor antibodies is potentially significant but not established. The significance of the endothelin A receptor (ETAR) and its expression in renal biopsy has not been defined. We decided to evaluate the presence and relevance of ETARs in renal transplant biopsy for cause. The aim of our study was to evaluate the immunoreactivity of the ETAR and its significance in patients who had a renal transplant biopsy due to deterioration of transplant function (biopsy for cause) with detailed characterization of staining in small and intermediate arteries of renal transplant biopsies. METHODS: Immunohistochemical expression of ETARs was analyzed in 162 renal transplant biopsies. Microscopic evaluation of ETAR expression (polyclonal antibody) was performed on paraffin sections. ETAR expression was analyzed in renal blood vessels (small and intermediate arteries) based on three-step scale. RESULTS: We analyzed 154 patients who had renal allograft biopsy between 6 days and 24 years (median 597 days) after transplantation. Positive staining of ETAR in small and intermediate arteries was noticed in 9 patients. Among these patients, 4 had early biopsies (<3 months after transplantation), all developed acute tubular necrosis, and 1 developed additionally acute humoral rejection. Further, 4 patients had late biopsy (1-8 years after transplantation) and all developed characteristics of antibody mediated rejection. Lastly, 1 patient had no characteristic changes in the biopsy 4 months after transplantation. Graft loss 1 year after biopsy was higher in patients who were ETAR-positive but statistical significance was not achieved. CONCLUSIONS: The expression of endothelin receptors in renal blood vessels (small and intermediate arteries) seems to be important in diagnosis of damage during acute tubular necrosis and antibody-mediated rejection.

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

The occurrence of anti-angiotensin II type 1 receptor (AT1R) antibodies is thought to be a risk factor for transplant injury, but the relationship of AT1R to graft loss in renal transplantation has not been assessed. The aim of our study was to evaluate the expression of AT1R and its relationship with graft loss in patients who had a renal transplant biopsy for cause. METHODS: AT1R immunoreactivity was analyzed in 170 renal transplant biopsies. Immunohistochemical evaluation of AT1R expression was performed on 4 µm-thick paraffin sections mounted on silanized slides. AT1R expression was analyzed in 5 compartments: 1. glomeruli, 2. renal blood vessels (small and intermediate arteries), 3. peritubular capillaries, 4. tubular epithelium, and 5. interstitium based on a 3-step scale. RESULTS: Initially we checked 170 consecutive samples of biopsies for the immunoreactivity of the AT1R. The study finally included 118 renal transplant patients in 1-year observation after the biopsy. The renal allograft biopsy was performed between 6 days and 24 years after transplantation and the diagnosis was based on Banff criteria. We observed positive immunostaining of AT1R in tubular epithelium in 26.3% (42/118) of patients. A total of 7 patients had staining assessed as 2 and 35 as 1. One year post-biopsy graft loss in the AT1R (+) patients was 35.7 % (15/42) compared to 14.5% (11/76) in the AT1R (-) group (P = .008). CONCLUSIONS: The expression of AT1R in tubular epithelium of the biopsy for cause was associated with significantly higher graft loss. The relevance of AT1R should be considered for better transplant immunological risk assessment.

Acute Brain Damage in a 56-Year-Old Woman With a 20-Year-Old Transplanted Kidney as a Complicated Differential Diagnostic Process: A Case Report.

INTRODUCTION: Acute central nervous system (CNS) damage in a patient who has received organ transplant is an extremely difficult and complex clinical issue that spans a wide spectrum of differential diagnoses with ischemia, post-transplant lymphoproliferative disorders (PTLDs), infections, lymphomas, and progressive multifocal leukoencephalopathy (PML). PTLDs are a clinically and histopathologically heterogeneous group of diseases that most often occur in heavily immunocompromised populations after solid organ transplantation (SOT), probably related to the infection or reactivation of Epstein-Barr virus (EBV) infection, whereas PML is an infectious disease caused by the John Cunningham virus (JCV). CASE DESCRIPTION: A 56-year-old female, 20 years after renal transplantation from a deceased donor, was admitted to the hospital as an emergency due to sensory aphasia and memory disorders. Computed tomography (CT) examination revealed a diffuse expansive process in the temporo-parieto-occipital and left frontal area. Magnetic resonance imaging (MRI) results suggested changes associated with PML; however, JCV was not found in the cerebrospinal fluid. The disorders progressed quickly, both clinically and radiologically-the patient developed central facial palsy, paresis of limbs, and positive Babinski sign on the left. A second radiological examination (CT) also suggested PML. Due to the rapid deterioration of the patient's general condition, further diagnostic examinations (magnetic resonance with contrast and brain stereotactic biopsy) could not be performed. After almost 2 months of the commencement of the diagnostic process, the patient died. Autopsy revealed that the cause of death was acute CNS damage in the course of monomorphic PTLD (CNS-PTLD). CONCLUSION: Rapid deterioration of mental status can be the first symptom of CNS-PTLD, a dangerous and life-threatening condition in immunocompromised patients after solid organ transplantation.

Correlation between PARP-1 immunoreactivity and cytomorphological features of parthanatos, a specific cellular death in breast cancer cells.

In parthanatos, a PARP-1 (poly (ADP-ribose) polymerase 1)-mediated cell death, dissipation of mitochondrial membrane potential, large-scale DNA fragmentation and chromatin condensation were observed. In contrast to apoptosis, it does not cause apoptotic bodies formation. Although PARP-1-mediated cell death presents loss of membrane integrity similar to necrosis, it does not induce cell swelling. The purpose of the study was to correlate the immunohistochemical parameters of PARP-1 reactivity and the selected cytomorphological features of parthanatos: the lack of apoptotic bodies and the absence of necrosis in breast cancer (BC) specimens. Immunohistochemistry for PARP-1 was performed on 83 BC specimens. Correlations between parameters of PARP-1 expression and sub-cellular localisation and the presence of apoptotic bodies and necrosis were evaluated. High expression of PARP-1 (ImmunoReactive Score ≥6) was associated with the lack of apoptotic bodies (P=0.013) and with the absence of necrosis (P=0.002). The presence of apoptotic bodies was correlated with re-distribution of PARP-1 from the nucleus to cytoplasm in BC cells (P=0.029). Additionally, a tendency was observed between necrosis and loss of nuclear PARP-1 expression (P=0.049). Our study suggests that PARP-1 may play a crucial role in induction and regulation of specific type of cellular death called parthanatos.