CXCR3 renal expression in glomerulonephritis in children: is there a connection with the course of the disease?

Background: Glomerulonephritis (GN) is a common childhood disease that may represent a significant cause of chronic kidney disease at one point of its course. The role of chemokines in glomerulonephritis, has been long anticipated and studied and the possible link between certain chemokines and different renal pathologies, if proved, can pave the road for future use of such markers for early prognosis and possible therapies for this common disease.Objective: in this study, we aimed at detecting CXCR3 in the renal biopsies done for children with glomerulonephritis and to correlate it to the nature of renal pathology and response to therapy.Methods: The glomerular and interstitial expression of CXCR3 in renal biopsies done for 22 patients with glomerulonephritis was studied using immunohistochemical staining. Pathologies already diagnosed in these biopsies were proliferative GN (mesangioproliferative GN, diffuse proliferative GN, focal proliferative GN, IgA nephropathy and crescentic GN) as well as non-proliferative GN (Minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diffuse mesangial sclerosis and advanced hypertensive nephrosclerosis). History, clinical findings and laboratory investigations in the initial presentation and at the time of the study were obtained.Results: The degree of glomerular and interstitial CXCR3 expression did not vary with gender, age of presentation, response to steroids, or cumulative doses of steroids. Percentage of strong glomerular CXCR3 expression was much higher in proliferative GN compared to non-proliferative GN although the difference was not statistically significant, percentage of renal dysfunction was more among strong glomerular and mild/moderate interstitial CXCR3 expression with no statistically significant difference from the counterparts.Conclusion: Our study revealed that enhanced CXCR3 renal expression on glomerular and interstitial levels did not affect the response to steroids along the course of the disease and so can probably act as a therapeutic target rather than a prognostic marker.Keywords: glom. CXCR3, int. CXCR3, glomerulonephritis, renal biops

The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4

Background: Interferon therapy is used as a line of treatment of chronic hepatitis C virus (HCV) in several areas of the world including Egypt.Objective: Our aim was to investigate the value of hepatic progenitor cells (HPCs) in predicting response of patients with chronic HCV, genotype 4 to pegylated interferon (PEGIFN) plus ribavirin (RBV) therapy.Methods: Pre-treatment liver biopsies obtained from 110 patients with chronic HCV, genotype 4 were examined immunohisto- chemically for HPCs using cytokeratin19. The mean number of HPCs as ductular reaction (DR) and as isolated progenitor cells (IPCs) was counted in each case. The patients were classified into: those with sustained virological response (SVR) and those who did not achieve SVR. The results were compared between the two groups. Also, the relationships between HPCs and other clinico-pathologic variables were estimated using multivariate analysis.Results: The mean number of HPCs was the only independent predictor of therapeutic response, being significantly higher in non-responders (P = 0 for DR and P = 0.03 for IPCs). On the other hand, fibrosis stage and steatosis were the only independent factors which showed a significant direct association with the mean number of HPCs in the form of DR and IPCs (P = 0 for each).Conclusion: The number of HPCs provides prognostic information in chronic HCV since it is significantly associated with stage of fibrosis. More importantly, it can be used as a marker to predict response of patients with chronic HCV to PEGIFN plus RBV therapy.Keywords: Chronic hepatitis C, genotype 4, response to therapy, hepatic progenitor cells

CXCR 3 expression on CD4+T cells and in renal tissue of pediatric systemic lupus erythematosus patients

Background: Pediatric systemic lupus erythematosus (pSLE) accounts for about 20% of all cases of Systemic Lupus Erythematosus (SLE), with nephritis occurring in approximately 50% of the patients. Objective: to evaluate the expression of CXCR3 in the kidneys and on CD4+ T cells in pSLE. Methods: This study was conducted on 45 patients with pSLE following up at the Allergy and Immunology Clinic, Children’s Hospital, Ain Shams University and 45 age and sex matched healthy children as a control group. Medical history, clinical examination and routine laboratory investigations for assessment of disease activity were done for all patients, the frequency of CXCR3, CD4+ T cells was determined in all patients and controls. Twenty-five Paraffin blocks of patients with lupus nephritis (LN) (available at the time of the study) underwent immunohistochemistry staining for the frequencies of Chemokine C receptor (CXCR3). Results: The absolute level and percentage of serum CD4+CXCR3+ were significantly lower among our patients as compared to healthy controls. A significant direct correlation was found between serum CD4+CXCR3+ and both the lymphocytic count and quantitative Systemic Lupus erythematosus disease activity index (SLEDAI), as well as a significant inverse correlation between it and 24 hours urinary proteins. Variable degrees of CXCR3expression seemed to have no impact on laboratory tests, British Isles Lupus Assessment Group (BILAG) score and cumulative doses of Immunosuppressives. Conclusion: Serum CD4+CXCR3+ and not renal CXCR3 may be a potential marker of LN activity

Membrane endothelial protein C receptor expression in renal tissue of pediatric lupus nephritis patients

Background: Lupus nephritis (LN) is more common and more severe is pediatric systemic lupus erythematosus (pSLE). Endothelial protein C receptor (EPCR) is an inducer of anti-apoptotic pathways in endothelial cells. Recent studies have taken elevated anti-injury biomarkers as EPCR into consideration regarding their roles to antagonize LN.Objectives: to evaluate the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in pediatric patients with LN.Methods: This study was conducted on 25 patients with pSLE following up at the Allergy and Immunology Clinic, Children’s Hospital, Ain Shams University. The 25 patients have LN proved by a previous renal biopsy. Medical history, clinical examination and routine laboratory investigations for assessment of disease activity were done for all patients. Paraffin blocks of patients’ renal biopsies were subjected to immunohistochemistry staining for the frequency of mEPCR.Results: mEPCR was mainly expressed in the endothelium of the peritubular capillaries. Our results showed that an equal number of patients had nil and mild marker expression (8 patients each, 32%) while 9 patients (36%) showed moderate/strong marker expression. We found that 9 out of 10 (90%) of patients with class II had nil/mild marker expression, 5 patients out of 9 (55.5%) with class III had mild/moderate marker expression, while 5 patients 0ut of 6 (83.3%) with class IV and V had moderate/strong marker expression. We only found a significant statistical difference between the different degrees of mEPCR expression regarding 24 hours urinary proteins. No statistical significance was found between the different degrees of mEPCR expression and different immuno-suppressive therapy dose/kg or renal outcome using the renal British Isles Lupus Assessment Group (BILAG) score; in spite that most of the patients who got improved had nil/mild marker expression.Conclusion: mEPCR -bearing a statistically significant difference in relation to different LN classes- showed more expression in the more aggressive classes; a finding which might suggest a contribution of the endothelium of the renal parenchyma to the pathophysiology of more progressive LN. Hence the tissue marker might emerge as a potential new therapeutic target in the search for more selective treatment for SLE.Keywords: p SLE, mEPCR, renal biopsy, immunohistochemistry, BILAG, lupus nephriti

The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4

Background: Interferon therapy is used as a line of treatment of chronic hepatitis C virus (HCV) in several areas of the world including Egypt. Objective: Our aim was to investigate the value of hepatic progenitor cells (HPCs) in predicting response of patients with chronic HCV, genotype 4 to pegylated interferon (PEGIFN) plus ribavirin (RBV) therapy. Methods: Pre-treatment liver biopsies obtained from 110 patients with chronic HCV, genotype 4 were examined immunohistochemically for HPCs using cytokeratin19. The mean number of HPCs as ductular reaction (DR) and as isolated progenitor cells (IPCs) was counted in each case. The patients were classified into: those with sustained virological response (SVR) and those who did not achieve SVR. The results were compared between the two groups. Also, the relationships between HPCs and other clinico-pathologic variables were estimated using multivariate analysis. Results: The mean number of HPCs was the only independent predictor of therapeutic response, being significantly higher in non-responders (P = 0 for DR and P = 0.03 for IPCs). On the other hand, fibrosis stage and steatosis were the only independent factors which showed a significant direct association with the mean number of HPCs in the form of DR and IPCs (P = 0 for each). Conclusion: The number of HPCs provides prognostic information in chronic HCV since it is significantly associated with stage of fibrosis. More importantly, it can be used as a marker to predict response of patients with chronic HCV to PEGIFN plus RBV therapy. DOI: https://dx.doi.org/10.4314/ahs.v19i1.14 Cite as: Helal T El A, Radwan NA, Mahmoud HA, Zaki AME, Ahmed NS, Wahib AAA, et al. The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4. Afri Health Sci. 2019;19(1). 1411-1421. https://dx.doi.org/10.4314/ahs.v19i1.1

A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children

Background: Atopic dermatitis (AD) aetiology is not exactly identified, but it is characterized by pruritic skin reactions with elevation in the levels of inflammatory markers. Despite the fact that Corticosteroids are the mainstay therapy in the management of AD, they have many local and systemic adverse effects.Objective: The aim of this study is to evaluate the efficacy and safety of topical tacrolimus ointment in comparison to topical hydrocortisone cream in the management of the AD of children diagnosed with AD.Patients and Methods: This study was conducted on 200 children with AD. They were simply randomized into two groups, the tacrolimus group treated with 0.03% topical tacrolimus ointment and the hydrocortisone group treated with 1% hydrocortisone cream twice daily during the 3 weeks study period.Results: At the end of the study, both the tacrolimus and hydrocortisone groups showed a significant decline in the mean serum level of IL-10, IL-17, and IL-23 (p < 0.05) when compared to their baseline levels. However, the tacrolimus group showed a more significant decrease (p < 0.05) in the mean serum level of IL-10, IL-17, and IL-23 as compared to the hydrocortisone group [Mean differences = 1.600, 95% CI: 0.9858–2.214; 1.300, 95% CI: 1.086–1.514 and 4.200, 95% CI: 3.321–5.079]. Moreover, the median mEASI decreased similarly from 32 to 21 in the tacrolimus group and from 30 to 22 in the hydrocortisone group (p > 0.05) [Median difference = −2.000, 95% CI: −2.651 to −1.349; Median difference = 1.000, 95% CI: 0.3489–1.651]. Mild to moderate transient stinging and erythema were the main adverse effects that showed higher incidence in the tacrolimus group than in the hydrocortisone group (p < 0.05). In most cases, they resolved within 3–4 days. Besides, tacrolimus ointment did not cause skin atrophy as compared to the hydrocortisone group (p < 0.05).Conclusion: Tacrolimus ointment is more beneficial than hydrocortisone cream in managing AD in children in terms of lowering the inflammatory markers, however, there is no difference on the dermatitis severity scale. Moreover, tacrolimus is safer with a better side effect profile compared to hydrocortisone.Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05324618

Automated image analysis system for renal filtration barrier integrity of potassium bromate treated adult male albino rat

Potassium bromate (KBrO3) is a potent nephrotoxic agent that leads to a significant decrease in the activities of renal antioxidant capacity, antioxidant loss and restoration of the renal dysfunction. Several measurements are used to examine the kidney status, including the base width of the foot, the slit pore diameter, and the glomerular basement membrane thickness of the kidney. In this work, morphometric analysis based on image processing is carried out to assess the filtration barrier integrity parameters, which indicates the degree of recovery against the nephrotoxic effect of the KBrO3 on the renal cortex of adult male albino rat and assesses the capability of the renal cortex to recover after its cessation. The morphometric methods based proposed image analysis system enabled the identification of the renal status of different groups, namely the control, potassium bromate affected, and the recovered groups, according to the variation of the measured parameters is a powerful tool. The proposed image analysis system provided a radical geometric morphometrics, which includes morphological operations and structuring element processes in order to identify the glomerular filtration barrier and the feet for further measurements in each case study. The results established that the average lengths of the feet in the histological microscopic images are 465.2397 nm, 278.189 nm, and 393.2347 nm for the control, KBrO3 affected rats and the recovered rats; respectively

Effect of preoperative ureteral stenting on the surgical outcomes of patients with 1-2 cm renal stones managed by retrograde intrarenal surgery using a ureteral access sheath

Objective: To assess the surgical results of patients who underwent retrograde intrarenal surgery (RIRS) using a ureteral access sheath (UAS) for management of renal stones sized 1-2 cm compared between patients who did and did not undergo preoperative ureteral stenting. Materials and methods: This prospective study included 83 patients (aged ≥ 20 years) who underwent RIRS from July 2021 to January 2023. All patients had renal calculi (stone size: 1-2 cm) located within the pelvicalyceal system. 43 and 40 patients were allocated to the non-prestent (group A) and prestent (group B), respectively. Patient baseline characteristics, renal stone details, operative data, stone-free rate (SFR) at 4 weeks and 6 months, and perioperative complications were compared between groups. Results: The baseline characteristics of all patients were comparable across the groups. Four weeks after surgery, the overall stone-free rate (SFR) stood at 62.65%. In the non-prestent and prestent groups, the SFRs were 58.12% and 67.5%, respectively (p = 0.89). By the sixth month post-surgery, the overall SFR rose to 80.72%. In the non-prestent and prestent groups, the SFRs were 76.74% and 85%, respectively (p = 0.081). No notable differences emerged in other variables, including perioperative complications, between the two groups. Conclusions: The SFR showed no significant difference between the prestenting and non-prestenting groups at the 4-week and 6-month postoperative marks. Additionally, there were no substantial differences in complications during surgery and recovery between the groups. Notably, the SFR increased from 4 weeks to 6 months without any additional procedures in either group