Obstructive nephropathy

Obstructive uropathy (OU) is a common condition in the elderly, particularly in men due to prostate disease. Besides the reversible effects of acute urinary tract obstruction on kidney function, with reduction of renal blood flow (RBF), glomerular filtration rate (GFR) and a tubular dysfunction, chronic obstruction can additionally cause permanent kidney injury. In this context, prolonged and untreated OU results in obstructive nephropathy (ON). ON is a nonspecific tubulointerstitial nephropathy, which can lead to chronic kidney disease (CKD) and to end-stage renal disease (ESRD). ON is one of the leading causes of ESRD in the elderly. Experimental ON models ureteral obstruction-mediated kidney injury and helps unravel key processes of the CKD pathogenesis. Apart from reversing obstruction, treatment strategies of ON consist of selective targeting on molecular mechanisms implicated in apoptosis, inflammation, and renal fibrosis. © 2019 Elsevier Inc. All rights reserved

Pathogenesis and management of intradialytic hypertension

Hypertension is common in chronic kidney disease patients especially in those undergoing hemodialysis (HD). Usually, blood pressure falls after the HD session but in some patients a paradoxical increase has been observed during or immediately after HD. This phenomenon is referred as intradialytic hypertension. HD patients with intradialytic hypertension or increased blood pressure during HD present higher cardiovascular (CV) morbidity and mortality rates. The underlying mechanism of intradialytic hypertension is multifactorial. Activation both of renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, volume and sodium overload with concomitant increase in cardiac output, and endothelial dysfunction have been implicated in the pathogenesis of intradialytic hypertension. Given the lack of clinical trials regarding the pathophysiology and management of intradialytic hypertension, current treatment strategies are based mainly on experts’ opinion. The purpose of this review is to describe the pathophysiology of intradialytic hypertension and discuss current strategies in order to improve intradialytic blood pressure management and concomitant HD patients’ outcomes. © 2014 Bentham Science Publishers

Evaluation of the Paris System in atypical urinary cytology

Objective Methods Our aim was to evaluate the Paris System for reporting urinary cytology, especially in the field of atypia. During the last year, 104 urinary cases had atypical cytology. These cases were reviewed and reclassified by three cytopathologists using the Paris criteria. Cyto-histological correlation was performed in 47 cases. Additionally, all cytology diagnoses were correlated with double immunocytochemistry for p53 and CK20 result. Interobserver consistency was also evaluated. Results Conclusions Out of 104 atypical cases, 30 were classified as benign, 49 atypical and 25 suspicious for high-grade urothelial carcinoma (HGUC). Diagnostic consistency between the three observers reached 93.27%. Using the new criteria, only 47.1% of the cases remained in the atypical category. The rate of HGUC histology was 14.3%, 26.7% and 96% in the benign, atypical and suspicious for HGUC cytological categories, respectively. Immunocytochemistry positivity was observed in 25.9%, 41.8% and 80% of the cases in the three diagnostic groups. The Paris System for reporting urinary cytology provides clear, easy to adopt criteria, which lead to diagnostic categories with clinical significance, facilitating patient management decisions

Evaluation of double immunocytochemical staining for CK20 and P53 as a potential adjunct to cytology for urothelial cancer diagnosis

Objective: To evaluate double immunocytochemical staining with p53 and CK20, as a tool for improving the accuracy of urinary cytology. The aim of the present study was to clarify the diagnostic significance of the expression of these markers and to investigate the possibility of using this information for better monitoring of bladder cancer patients during follow-up. Material and methods: One hundred and twenty-five urine cytology cases were retrieved with corresponding histology from our files. One ThinPrep (R) smear was available for each of them and dual immunocytological staining for p53 and CK20 was performed. Eleven cases were excluded from the study because of hypocellularity. The material comprised 58 malignant, 36 atypical and 20 negative for malignancy cases. Immunocytochemistry was evaluated by two cytopathologists, blinded to the histological diagnosis or follow-up data. A cut-off threshold of five stained atypical cells, according to the literature, was used for evaluation. Results: Fifty-two out of 58 malignant cases were positive for at least one of the markers (89.6%). In the atypical and negative groups, 18 (50%) and 5 (25%) cases were positive, respectively. Accuracy parameters evaluation for cytology versus the combination of cytology with immunocytological staining were: sensitivity 73.4% versus 91.1%, specificity 100% versus 74.3%, positive predictive value (PPV) 100% versus 88.9% and negative predictive value (NPV) 62.5% versus 78.8%. Conclusions: Double immunocytochemical staining for p53 and CK20 is easy to perform and evaluate and can improve cytology sensitivity. It is helpful in establishing a diagnosis of malignancy and may be used as a triage tool to select patients that require cystoscopy during clinical follow-up

Beneficial Effect of U-74389 G and Sildenafil in An Experimental Model of Flap Ischemia/Reperfusion Injury in Swine. Histological and Biochemical Evaluation of the Model

Purpose of the study: Tissue reconstruction after burns, tumor excisions, infections or injuries is a frequent surgical challenge to avoid Ischemia-reperfusion injury. Lazaroids and sildenafil, through their mechanisms of action, have been studied for their protective effects on various organs subjected to IRI. In this study, we aimed to evaluate the therapeutic potential of U-74389G and sildenafil in a swine model of ischemia and reperfusion injury of latissimus dorsi flap. Materials and methods: Forty-two Landrace male pigs, weighing 28–35 kg, were equally (n = 6) randomized into the following groups: (a) Group I: control, (b) Group II: administration of U-74389G after ischemia, (c) Group III: administration of sildenafil after ischemia, (d) Group IV: administration of U-74389G and sildenafil after ischemia, (e) Group V: administration of U-74389G prior to ischemia, (f) Group VI: administration of sildenafil prior to ischemia, and (g) Group VII: administration of U-74389G and sildenafil prior to ischemia. Blood and tissue sampling was conducted before ischemia, 15 and 30 min after occlusion, 30, 60, 90, and 120 min after reperfusion. Results: Statistically significant reduction (p < 0.05) was detected in lymphocytes and polymorphonuclear leukocytes concentrations as well as in the appearance of edema after histopathologic evaluation of the ischemic tissue, especially in the groups of combined treatment. Measurements of malondialdeyde and tumour necrosis factor alpha in tissues revealed a significant decrease (p < 0.001) of these markers in the treatment groups when compared to the control, particularly in the latest estimated timepoints. Conclusions: The synergistic action of U-74389G and sildenafil seems protective and promising in cases of flap IRI during tissue reconstruction surgery. © 2018, © 2018 Taylor & Francis Group, LLC

Experimental isolation and preservation of solid organs before transplantation: effects of pretreatment using four different molecules

Objectives: In transplantation surgery, the ischaemic organ and reperfusion impairment after cold storage remains a considerable risk factor for impaired function and potential failure of the grafted organ. Substantial logistical efforts have been undertaken to reduce the cold ischaemic time because the demand for available transplant organs and the periods of cold ischaemia are increasing. Methods: Four molecules were investigated (erythropoietin, sildenafil, lazaroid [U74389G], octreotide) in individual intravenous infusions 1 hour before the organ was harvested. This study was performed in 30 healthy landrace/large-white pigs (male; >10 weeks old; average weight, 22 ± 2 kg) in groups of six. The organs were studied at harvest, and at 8 and 24 hours post-harvest. Results: The lazaroid molecule increased malondialdehyde (MDA) levels in the liver and pancreas at 8 hours. Hepatic lazaroid molecules improved liver histology at 8 and 24 hours. For kidneys, erythropoietin had a positive effect at 24 hours post-harvest. For the pancreas, octreotide showed better performance. In the lungs, there was less interstitial oedema with erythropoietin and lazaroid compared with the control group at 8 hours post-harvest. Conclusion: All molecules had a positive effect and decreased ischaemia/reperfusion graft injury. Thus, pretreatment before organ harvest has a beneficial role. © The Author(s) 2020

Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients

Purpose: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. Methods: The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. Results: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). Conclusion: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed. © 2016, Springer-Verlag Berlin Heidelberg