IKZF1 rs4132601 and rs11978267 gene polymorphisms and paediatric systemic lupus erythematosus; relation to lupus nephritis.

The demographic factors, the socioeconomic status and the ethnicity of populations are important players that determine the incidence, the prevalence and the spectrum of systemic lupus erythematosus (SLE) clinical presentations in different populations. Therefore, the purpose of the present research was to investigate the possible association between the Ikaros family zinc finger 1 gene (IKZF1) rs4132601 and rs11978267 single nucleotide polymorphisms (SNPs) and SLE susceptibility and clinical presentations including lupus nephritis (LN) among Egyptian paediatric patients. After DNA extraction from Ethylenediaminetetraacetic acid (EDTA) blood samples for 104 paediatric SLE (pSLE) patients and 286 healthy controls, the investigated SNPs (IKZF1 rs4132601 and rs11978267) were genotyped using TaqMan-Real-time Polymerase chain reaction (PCR). The G allele, GG and GT genotypes of IKZF1 rs4132601 were associated with pSLE (pc<.001, OR 2.97, 3.2 and 2.25, respectively). The GG and GA haplotype were more frequent in pSLE patients than other haplotypes (pc<.001, OR 3.47 and pc = .004, OR = 2.8, respectively). The studied SNPs have no impact on the distinctive features of pSLE. The rs4132601 TG genotype was significantly associated with proliferative LN (pc = .03) The IKZF1 rs4132601 can be considered a risk factor for SLE in the cohort of Egyptian children. The TG genotype of the IKZF1 rs4132601 may predispose to proliferative LN.

A retrospective analysis of acute kidney injury in children with post-COVID-19 multisystem inflammatory syndrome: insights into promising outcomes.

BACKGROUND: Acute kidney injury (AKI) in patients with multisystem inflammatory syndrome (MIS), COVID-19 related infection has been increasingly recognized with a paucity of data on AKI incidence, related mortality, and the requirement of renal replacement therapy in children with MIS (MIS-C). METHODS: This is a retrospective study evaluating the prevalence, severity, management and outcomes of AKI in a cohort of Egyptian children with MIS-children (MIS-C) post-COVID infection. Patients were included if they met the criteria for MIS-C based on CDC guidelines. All patients were evaluated for AKI diagnosis and staging according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Between March 2021 and June 2023, a total of 655 confirmed COVID-19 cases were admitted and then followed up in our hospital, of whom 138 (21%) were diagnosed with MIS-C. Fifty-one patients developed AKI associated with MIS-C post-COVID infection, 42 of whom were included in the analysis. Thirty-one patients had AKI in a formerly healthy kidney, of whom 51% (16 patients) were classified as KDIGO stage 3, 5 patients needed hemodialysis and 13 needed mechanical ventilation. Higher WBCs count, and serum ferritin on admission were associated with more severe AKI (KDIGO stage 3) (p = 0.04), while multivariate analysis showed high serum ferritin to be independent predictor of more severe AKI (p = 0.02). Two patients (2/31) died during hospital admission, while no residual renal impairment was reported at the time of discharge of patients with previously normal kidney functions. CONCLUSION: More than one-third of patients with MIS-C develop AKI. Avoidance of nephrotoxic drugs, early recognition, and prompt management of AKI, including well-timed commencement of dialysis in MIS-C cases, is associated with favorable outcomes.

In vitro evaluation of the potential immunosuppressive effect of panobinostat on cultured lymphocytes retrieved from childhood systemic lupus erythematosus patients.

Although many drugs are available for childhood systemic lupus erythematosus (SLE) treatment, the adverse effects and poor response in some cases make it crucial to find new drugs targeting various pathways in disease pathogenesis to improve overall outcomes. This study aimed to (i) investigate the effect of Panobinostat on cultured lymphocytes obtained from children with active SLE and (ii) to compare that effect with standard drugs used in SLE, such as Prednisone and hydroxychloroquine. The study included 24 SLE active patients, divided into four equal groups. Lymphocytes were isolated from blood samples of the study patients. According to the study group, cells were treated with either Panobinostat, Prednisolone, hydroxychloroquine, or not treated (control group). After cell culture, the response of lymphocytes upon drug treatment was analyzed in terms of the production of anti-dsDNA antibodies and levels of apoptosis as detected by flow cytometry using annexin V and propidium iodide (PI) staining. The Panobinostat group showed a significant decrease in the viable cell count (p < 0.001). Both Prednisone and hydroxychloroquine decreased anti-dsDNA expression more than the Panobinostat and control groups (p < 0.001 for both). PI was higher in the Prednisone group, and Annexin V was higher in the Panobinostat group compared to other groups; however, their increase did not reach statistically significant levels (p= 0.12 and 0.85, respectively). This is the first study of the Panobinostat effect on cultured lymphocytes of SLE. In conclusion, Panobinostat could be a prospective treatment for B-cell-driven autoimmune diseases such as SLE. However, its effect on autoantibodies levels and different clinical features of SLE still need a thorough evaluation.

Health Related Quality of Life in Juvenile-Onset Systemic Lupus Erythematosus: A Questionnaire-Based Study.

OBJECTIVES: This study aimed to evaluate health related quality of life (HRQOL) in Egyptian children with systemic lupus erythematosus (SLE) using 3 different tools. METHODS: In this questionnaire-based study, 100 children with SLE were included. HRQOL was assessed using the Pediatric Quality of Life Inventory Generic Core Scales (PedsQL™ 4.0 GCS), PedsQL™ 3.0 Rheumatology Module (PedsQL3-RM) and the Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY). SLE disease activity index (SLEDAI) was used to evaluate activity and SLE International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI) was used to evaluate chronic damage. RESULTS: All mean scores of PedsQLTM4.0 GCS domains in SLE patients were lower than published normative data and previously published results of Egyptian healthy controls (p < 0.001). All mean scores of PedsQL-3RM domains were significantly lower than published normative data except for the treatment and pain and hurt domains (p = 0.1, 0.2 respectively). SMILEY scores were low and the lowest domain scores was "Burden of SLE". Longer duration of illness, higher cumulative steroid doses, higher SLEDAI and SDI scores and presence of obesity were associated with lower scores for all 3 tools (p < 0.001). CONCLUSION FOR PRACTICE: The Arabic copies of PedsQL™ 4.0 GCS, PedsQL3-RM and SMILEY are easily used for Arabic speaking subjects and easily interpreted by physician and can be implemented for frequent monitoring of SLE HRQOL. Controlling the disease activity and using lowest doses of steroids and other immunosuppressive drugs are the corner stone strategies for improving HRQOL in SLE children.

This is the first study to evaluate HRQOL scores in Egyptian children with SLE which were found to be lower than published data with long disease duration, high cumulative disease activity, use of steroids and presence of obesity are the main influential factors related to low QoL scores. Generic and disease specific questionnaires are easily used for Arabic speaking subjects and easily interpreted by physician and can be implemented for frequent monitoring of SLE HRQOL. Controlling the disease activity and using lowest doses of steroids and other immunosuppressive drugs are the corner stone strategies for improving HRQOL in SLE children.

Multidrug resistant 1 (MDR1) C3435T and G2677T gene polymorphism: impact on the risk of acute rejection in pediatric kidney transplant recipients.

BACKGROUND: Tacrolimus is the backbone drug in kidney transplantation. Single nucleotide polymorphism of Multidrug resistant 1 gene can affect tacrolimus metabolism consequently it can affect tacrolimus trough level and incidence of acute rejection. The aim of this study is to investigate the impact of Multidrug resistant 1 gene, C3435T and G2677T Single nucleotide polymorphisms on tacrolimus pharmacokinetics and on the risk of acute rejection in pediatric kidney transplant recipients. METHODS: Typing of Multidrug resistant 1 gene, C3435T and G2677T gene polymorphism was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for 83 pediatric kidney transplant recipients and 80 matched healthy controls. RESULTS: In Multidrug resistant 1 gene (C3435T), CC, CT genotypes and C allele were significantly associated with risk of acute rejection when compared to none acute rejection group (P = 0.008, 0.001 and 0.01 respectively). The required tacrolimus doses to achieve trough level were significantly higher among CC than CT than TT genotypes through the 1st 6 months after kidney transplantation. While, in Multidrug resistant 1 gene (G2677T), GT, TT genotypes and T allele were associated with acute rejection when compared to none acute rejection (P = 0.023, 0.033 and 0.028 respectively). The required tacrolimus doses to achieve trough level were significantly higher among TT than GT than GG genotypes through the 1st 6 months after kidney transplantation. CONCLUSION: The C allele, CC and CT genotypes of Multidrug resistant 1 gene (C3435T) and the T allele, GT and TT genotypes of Multidrug resistant 1 gene (G2677T) gene polymorphism may be risk factors for acute rejection and this can be attributed to their effect on tacrolimus pharmacokinetics. Tacrolimus therapy may be tailored according to the recipient genotype for better outcome.

A deeper look into the functions of right ventricle using three-dimensional echocardiography: the forgotten ventricle in children with systemic lupus erythematosus.

Studies on the right ventricular dysfunction (RV) in systemic lupus erythematosus (SLE) patients are limited, particularly in the pediatric age group. The study aimed to identify subclinical RV alterations in childhood-onset SLE (c-SLE) using conventional and three-dimensional echocardiography (3DE). Forty SLE pediatric patients and 40 healthy controls were included. Disease activity and chronicity were evaluated by SLE disease activity index (SLEDAI) score and SLE damage index (SDI). Participants underwent detailed RV echocardiographic examination with conventional and 3DE assessment using 3D auto RV software. Patients included 35/40 (87.5%) females with mean age of 15.6 ± 1.7 years. Using conventional pulmonary artery systolic pressure echocardiography-derived measurement, none of the c-SLE patients had pulmonary hypertension. By 3DE, RV end-systolic and end-diastolic volumes (p = < 0.001, 0.02, respectively) were greater, whereas 3D-derived RV ejection fraction (p < 0.001), septal, and lateral longitudinal strain (both p < 0.001) were lower in SLE. SDI displayed a significant correlation with 3D auto RV ejection fraction (EF), tricuspid annular plane systolic excursion (TAPSE), fractional area change, and RV longitudinal strain (RVLS)-free wall (p = 0.01, 0.003, 0.007, and < 0.001, respectively). Cumulative SLEDAI score also showed a significant correlation with RV EF, TAPSE, FAC, and RVLS-free wall (p = 0.03, 0.007, 0.002, and < 0.001, respectively). By multivariate regression analysis, SDI remained an independent predictor of RVLS-free wall (ß coefficient - 0.4, p = 0.03) and TAPSE (ß - 0.5, p = 0.02).  Conclusion: Subtle right ventricular myocardial dysfunction could be detected in childhood-onset SLE patients, especially via 3D-derived auto RV echocardiographic parameters, despite the absence of evident pulmonary hypertension. These parameters correlate with the SLE disease activity and chronicity scores. What is Known: •Diseases of the cardiovascular system are one of the most common causes of morbidity and mortality in SLE patients. •RV labeled the forgotten ventricle in many diseases, was also forgotten in SLE patients and has been rarely addressed in adults, with scarce research in pediatrics. What is New: •Right ventricular functions are affected in children with SLE in comparison to healthy controls, especially three-dimensional echocardiography-derived parameters, which is an aspect that has not been investigated in previous research in the pediatric age group. •Some of the detected myocardial dysfunctions of the right ventricle correlated with SLE disease activity and chronicity-related scores.

Effect of Uncomplicated Diabetes Mellitus on Acute Respiratory Distress Syndrome Among COVID-19 Patients in Aseer Region, Saudi Arabia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; an ssRNA virus), which mainly affects the respiratory system but can also cause damage to other body systems. Acute respiratory distress syndrome (ARDS) is a serious complication of COVID-19 that requires early recognition and comprehensive management. ARDS is a diffuse inflammatory process that causes diffuse alveolar damage in the lung.  Aim: The study aimed to assess the effect of uncomplicated diabetes mellitus on ARDS among COVID-19 patients in the Aseer region. METHODOLOGY:  A retrospective cohort study was conducted in Aseer Central Hospital between July 10, 2021 to Jan 15, 2022 where confirmed inpatient COVID-19 cases in the Aseer region were classified into two groups. The first group was diabetic patients without any diabetes-related complications and confirmed for COVID-19 infection (diabetes group). The second group was confirmed COVID-19 patients free from any chronic disease. Extracted data included patients' diabetes status, medical history, socio-demographic data, COVID-19 infection data and vaccination, experienced signs and symptoms, tachypnea, use of accessory muscles of respiration, nasal flaring, grunting, cyanosis, need for hospitalization, need for mechanical ventilation and ICU admission.  Results: The study included 144 patients with uncomplicated diabetes and 323 healthy patients with COVID-19 infection. The mean age of the diabetic group was 65.4 ± 12.9 years old compared to 40.2 ± 11.9 years old for the healthy group. Only one case of the diabetic group was vaccinated against COVID-19 at the study period versus two cases of the healthy group (P=.925). Also, 14 (9.7%) of the diabetic group were contacted with confirmed COVID-19 cases in comparison to 44 (13.6%) healthy cases (P=.238). A total of five (3.5%) diabetic cases needed mechanical ventilation during hospitalization compared to 23 (7.1%) healthy cases with no statistical significance (P=.125). Also, 12 (8.3%) diabetic cases admitted to ICU versus 42 (13%) of healthy cases (P=.145).  Conclusions: In conclusion, there is a great controversy regarding the effect of diabetes on the progression of COVID-19 infection to ARDS. The current study showed that there was no significant difference between diabetic and healthy COVID-19 infected cases regarding ARDS related clinical factors mainly need of ICU admission and mechanical ventilation.

Predictors of decreased bone mineral density in childhood systemic lupus erythematosus: possible role of osteoprotegerin gene polymorphisms.

OBJECTIVES: This study aims to explore effects of osteoprotegerin (OPG) gene polymorphisms and other possible factors on bone mineral density (BMD) in children with systemic lupus erythematosus (SLE). METHODS: Osteoprotegerin gene rs2073617 and rs3134069 were evaluated in 74 SLE patients and 100 controls then genotypes, alleles and haplotypes' frequencies were compared between cases and controls and between patients with BMD z-scores above and below -2 evaluated by dual energy X-ray absorptiometry (DEXA). Disease activity was evaluated by SLE disease activity index (SLEDAI). RESULTS: The patients aged 14.01 ± 2.6 years and included 57 (77%) females and 27 (36%) patients with BMD z-score below -2. Genotypes, alleles, and haplotypes frequencies did not differ between patients and controls (p>0.05 for all). Rs3134069 GG genotype and G allele (p=0.001, 0.002) and rs2073617 TT genotype and T allele (p=0.01, 0.006) were significantly higher in patients with BMD below -2. Cumulative glucocorticoids dose, disease duration, and SLEDAI scores were higher in patients with BMD below -2 (p=0.01, 0.01, <0.001, respectively). Regression analysis showed T allele of rs2073617, duration of illness (above 36 months), and cumulative SLEDAI (above 10) as independent predictors of decreased BMD (p 0.02, 0.003, and 0.002, respectively). CONCLUSIONS: This is the first study to demonstrate OPG gene influence on BMD in children with SLE. The studied SNPs are not risk for developing SLE but, rs2073617 T allele is a possible predictor for reduced BMD in SLE. Other predictors include long disease duration and high activity supporting that osteoporosis in SLE is multifactorial.

Genetic variant in the 5' untranslated region of endothelin1 (EDN1) gene in children with primary nephrotic syndrome.

Endothelin-1 plays a crucial role in the pathophysiology of nephrotic syndrome (NS) in children. The primary purpose of this study is to evaluate the contribution of the EDN1 (3A/4A; rs1800997) variant to the risk of nephrotic syndrome. This study involves 200 participants (100 healthy controls, 50 steroid-sensitive nephrotic syndromes [SSNS] patients, and 50 steroid-resistant nephrotic syndromes [SRNS] patients]. Genomic DNA has been characterized using the PCR-RFLP technique. The predominant genotype that is common in this study population was the EDN1 3A/3A genotype (NS [75%] and healthy controls [88%]). The prevalence of EDN1 3A/4A genotype and EDN1 4A allele was significantly increased among NS patients compared with healthy subjects (p-value < 0.05). Furthermore, the frequency of the EDN1 (3A/4A; rs1800997) variant was statistically significant among SRNS patients (p-value < 0.05). The EDN1 3A/4A genotype and the EDN1 4A allele were identified as independent risk factors of the nephrotic syndrome among children.

Endothelin-1 RS5370 gene polymorphism in primary nephrotic syndrome: A case-control study.

INTRODUCTION: Primary nephrotic syndrome (NS) is a common glomerular disease in children. We assessed the genotypes and frequency of the rs5370 allelic variant of the EDN1 gene in children with primary NS. PATIENTS AND METHODS: We conducted a case-control study in Mansoura University Children's Hospital, Egypt between December 2015 and January 2018. We recruited 50 patients with steroid-sensitive NS (SSNS) and 50 patients with steroid-resistant NS (SRNS) in addition to 100 healthy controls. The patients underwent clinical evaluations and tests including measurement of serum albumin, cholesterol, creatinine and urea levels and a 24-h urinary protein test. We used polymerase chain reaction methods to assess the genotypes of rs5370 variants of the EDN1 gene (GG, GT and TT) and alleles (T and G) in the groups under study. RESULTS: The most frequent genotype of the EDN1 gene at the locus of interest in the control group was the GT genotype (88%; P=.001) while the GG genotype was more frequent in the NS group compared to the control group (P=.02). We did not find statistically significant differences between the NS and control groups in regard to the EDN1 rs5370 alleles (P=.69). The GG genotype was more frequent in the SSNS group compared to the SRNS and control groups (P=.03). When we compared allele frequencies between the control, SSNS and SRNS groups, we did not find significant differences (P=.89). The GT genotype was associated with normal blood pressure in children with NS (P=.007), while the GG genotype was associated with hypertension (P<.001). We did not find statistically significant differences in renal histopathology or serum cholesterol levels based on the genotype. CONCLUSIONS: The GG genotype at the rs5370 locus of the EDN1 gene may be associated with an increased risk of primary NS and a better response to steroid therapy.

Polimorfismo rs5370 del gen de la endotelina-1 en el síndrome nefrótico primario: estudio de casos y controles / Endothelin-1 rs5370 gene polymorphism in primary nephrotic syndrome: A case-control study

Introducción: El síndrome nefrótico (SN) primario es una glomerulopatía común en la edad pediátrica. Se evaluaron los genotipos y frecuencias alélicas del polimorfismo rs5370 del gen EDN1 en niños con SN primario.Pacientes y métodos: Estudio de casos y controles realizado en el Hospital Infantil Universitario de El Mansura, Egipto, de diciembre de 2015 a enero de 2018. Se seleccionó a 50 pacientes con SN corticosensible (SNCS) y a 50 con SN corticorresistente (SNCR), así como a 100 controles sanos. Además de una evaluación clínica de los pacientes, se hicieron pruebas de cuantificación de albúmina, colesterol, creatinina y urea séricas y de proteinuria en muestra de orina de 24 h. Se emplearon técnicas de reacción en cadena de la polimerasa para analizar los genotipos (GG, GT y TT) y los alelos (T y G) del polimorfismo rs5370 del gen EDN1 en los grupos en estudio.Resultados: El genotipo GT fue el más frecuente del polimorfismo rs5370 del gen EDN1 en el grupo de control (88%, p=0,001), mientras que el genotipo GG fue más frecuente en el grupo con SN que en el de control (p=0,02). No se encontraron diferencias estadísticamente significativas entre los grupos de SN y de control en los alelos del polimorfismo rs5370 (p=0,69). El genotipo GG fue más prevalente en el grupo de SNSC que en los grupos de SNRC y de control (p=0,03). Las diferencias en las frecuencias alélicas entre los grupos de SNRC, SNSC y de control no fueron significativas (p=0,89). El genotipo GT se asoció a una presión arterial normal en niños con SN (p=0,007) mientras que el genotipo GG se asoció a hipertensión (p<0,001). No se detectaron diferencias significativas en la histopatología renal ni en los niveles séricos de colesterol respecto al genotipo.Conclusiones: El genotipo GG del polimorfismo rs5370 del gen EDN1 podría asociarse a un riesgo mayor de desarrollar SN y a una respuesta más favorable al tratamiento con corticoides. (AU)

Introduction: Primary nephrotic syndrome (NS) is a common glomerular disease in children. We assessed the genotypes and frequency of the rs5370 allelic variant of the EDN1 gene in children with primary NS.Patients and methods: We conducted a case-control study in Mansoura University Children's Hospital, Egypt, between December 2015 and January 2018. We recruited 50 patients with steroid-sensitive NS (SSNS) and 50 patients with steroid-resistant NS (SRNS) in addition to 100 healthy controls. The patients underwent clinical evaluations and tests including measurement of serum albumin, cholesterol, creatinine and urea levels and a 24-hour urinary protein test. We used polymerase chain reaction methods to assess the genotypes of rs5370 variants of the EDN1 gene (GG, GT and TT) and alleles (T and G) in the groups under study.Results: The most frequent genotype of the EDN1 gene at the locus of interest in the control group was the GT genotype (88%; P=.001) while the GG genotype was more frequent in the NS group compared to the control group (P=.02). We did not find statistically significant differences between the NS and control groups in regard to the EDN1 rs5370 alleles (P=.69). The GG genotype was more frequent in the SSNS group compared to the SRNS and control groups (P=.03). When we compared allele frequencies between the control, SSNS and SRNS groups, we did not find significant differences (P=.89). The GT genotype was associated with normal blood pressure in children with NS (P=.007), while the GG genotype was associated with hypertension (P<.001). We did not find statistically significant differences in renal histopathology or serum cholesterol levels based on the genotype.Conclusions: The GG genotype at the rs5370 locus of the EDN1 gene may be associated with an increased risk of primary NS and a better response to steroid therapy. (AU)

Tumor necrosis factor receptor II and PTPN22 genes polymorphisms and the risk of systemic lupus erythematosus in Egyptian children.

BACKGROUND: Many genes have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF) is a potent cytokine stimulator acting through 2 cell surface receptors (TNFR I and II). TNFRII gene which controls expression of these receptors has been linked to SLE susceptibility through promoting apoptosis. Also; Protein tyrosine phosphatase non receptor 22 (PTPN22) gene enhances intrinsic phosphatase activity of T lymphocytes leading to their dysregulation and stimulates autoimmune process of lupus and its rs2476601 has been linked to susceptibility to thyroiditis in SLE patients in few studies. OBJECTIVES: (i) to investigate the correlation between 2 SNPs of TNFR II and PTPN22 genes and SLE susceptibility in a cohort of Egyptian children compared to controls (ii) and to investigate their possible association with different clinical presentations of the disease in children. SUBJECTS AND METHODS: Typing of TNFR II rs1061622 and PTPN22 rs2476601 SNPs were done using polymerase chain reaction-restriction fragment length polymorphism for 74 children with SLE and 100 matched healthy controls. RESULTS: Children with SLE had more frequent G allele and GG genotype of TNFR II rs1061622 (p < 0.001) and more T allele and TT genotype of PTPN22 rs2476601 (p = 0.012 and <0.001, respectively) compared to controls. Only 6 patients (8%) had thyroiditis (hypothyroidism) with T allele and TT genotype of PTPN22 1858 T more prevalent in those patients versus those without thyroiditis (p ≤ 0.001). Apart from, thyroiditis, no significant association was found between genotypes and alleles frequencies of the 2 studied SNPs and other clinical manifestations of the disease. CONCLUSION: The G allele and GG genotype of TNFR II rs1061622 and T allele and TT genotype of PTPN22 rs2476601 genes polymorphism can be considered as risk factors for the development of SLE. The presence of the T allele of PTPN22 rs2476601 may increase the risk of concomitant thyroiditis in Egyptian children with SLE but further studies are required to confirm this finding as thyroiditis was reported only in few cases in this study.

Left Ventricular Strain Analysis by Tissue Tracking- Cardiac Magnetic Resonance for early detection of Cardiac Dysfunction in children with End-Stage Renal Disease.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in end-stage renal disease (ESRD). Reduction in left ventricular ejection fraction (LVEF) represents late left ventricle (LV) dysfunction. Cardiac MRI myocardial strain analysis is an alternative method for assessment of LV function. PURPOSE: To investigate whether LV strain analysis is more sensitive than LVEF for early detection of systolic dysfunction in children with ESRD. STUDY TYPE: Case control. POPULATION: Thirty-two children with ESRD (median 14 years, 17 females) and 10 healthy control (median 12.5 years, 7 females). FIELD STRENGTH AND SEQUENCES: A 1.5 T /retrospective ECG-gated steady-state free precession (SSFP). ASSESSMENT: LVEF, and indexed LV mass (LVMi) and LV end-diastolic volume (LVEDVi) were measured. Using tissue tracking analysis, LV endocardial and epicardial contours were traced in short and long axes at end diastole to calculate global longitudinal (GLS), circumferential (GCS) and radial (GRS) strains. STATISTICAL ANALYSIS: Cardiac MRI and strain parameters were compared between patients and control, and between subgroup with preserved LVEF and control by Student t-test/Mann Whitney test. Diagnostic accuracy was assessed by Receiver operating characteristic analysis. Strain as predictor of poor outcome (mortality, pulmonary edema, and/or heart failure) within 1-year follow up was investigated by binary logistic regression. RESULTS: Compared to control, cardiac MRI LVEF, LVEDVi, LVMi, GLS, GCS and GRS were significantly impaired in patients. Patients with preserved LVEF had significantly higher LVEDVi, LVMi and significantly impaired GCS and GRS than control. Strain parameters were significantly correlated with LVEF, LVEDVi, and LVMi. GCS and GRS demonstrated greater diagnostic accuracy than GLS (area under curve: 0.89). LVEF, LVMi, GCS, and GRS were correlated with poor outcome. CONCLUSION: Cardiac MRI tissue tracking could identify subclinical LV dysfunction in children with ESRD and still preserved LVEF. Furthermore, LV strain parameters (GCS and GRS) were correlated with future cardiovascular events. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

ARID5B rs10821936 and rs10994982 gene polymorphism and susceptibility to juvenile systemic lupus erythematosus and lupus nephritis.

BACKGROUND: The prevalence of SLE and the spectrum of clinical manifestations vary widely in different races and geographical populations. OBJECTIVE: To investigate the possible role of ARID5B rs10821936 and rs10994982 polymorphism as a risk factor for the development of SLE in children (jSLE) and to evaluate their role in relation to clinical manifestations especially lupus nephritis (LN). METHODS: DNA extraction and Real-time PCR genotyping of ARID5B rs10821936 and rs10994982 were done for 104 jSLE and 282 healthy controls. RESULTS: The C allele and C containing genotypes (CC, CT and CC+CT) of ARID5B rs10821936 were higher in children with SLE (p = 0.009, OR = 1.56, 0.037, OR = 2.35, 0.016, OR = 1.81 and 0.008 OR = 1.88 respectively). ARID5B rs10994982 alleles, genotypes and haplotypes are not associated with jSLE (p > 0.05). The ARID5B rs10821936 and rs10994982 genotypes showed non-significant associations with LN, proliferative versus non proliferative and biopsy grades (p > 0.05). CONCLUSION: ARID5B rs10821936 SNP may be a susceptibility risk factor for juvenile SLE in the studied cohort of Egyptian children.

[Endothelin-1 rs5370 gene polymorphism in primary nephrotic syndrome: A case-control study]. / Polimorfismo rs5370 del gen de la endotelina-1 en el síndrome nefrótico primario: estudio de casos y controles.

INTRODUCTION: Primary nephrotic syndrome (NS) is a common glomerular disease in children. We assessed the genotypes and frequency of the rs5370 allelic variant of the EDN1 gene in children with primary NS. PATIENTS AND METHODS: We conducted a case-control study in Mansoura University Children's Hospital, Egypt, between December 2015 and January 2018. We recruited 50 patients with steroid-sensitive NS (SSNS) and 50 patients with steroid-resistant NS (SRNS) in addition to 100 healthy controls. The patients underwent clinical evaluations and tests including measurement of serum albumin, cholesterol, creatinine and urea levels and a 24-hour urinary protein test. We used polymerase chain reaction methods to assess the genotypes of rs5370 variants of the EDN1 gene (GG, GT and TT) and alleles (T and G) in the groups under study. RESULTS: The most frequent genotype of the EDN1 gene at the locus of interest in the control group was the GT genotype (88%; P=.001) while the GG genotype was more frequent in the NS group compared to the control group (P=.02). We did not find statistically significant differences between the NS and control groups in regard to the EDN1 rs5370 alleles (P=.69). The GG genotype was more frequent in the SSNS group compared to the SRNS and control groups (P=.03). When we compared allele frequencies between the control, SSNS and SRNS groups, we did not find significant differences (P=.89). The GT genotype was associated with normal blood pressure in children with NS (P=.007), while the GG genotype was associated with hypertension (P<.001). We did not find statistically significant differences in renal histopathology or serum cholesterol levels based on the genotype. CONCLUSIONS: The GG genotype at the rs5370 locus of the EDN1 gene may be associated with an increased risk of primary NS and a better response to steroid therapy.

Postdiarrheal hemolytic uremic syndrome in Egyptian children: An 11-year single-center experience.

Hemolytic-uremic syndrome (HUS) is a leading cause of childhood acute kidney injury (AKI) worldwide, with its postdiarrheal (D+HUS) form being the most common. Scarce data are available regarding D+HUS epidemiology from developing countries. This study aims to reveal the characterization of D+ HUS in Egyptian children. This is a retrospective study of all children with D+HUS admitted to a tertiary pediatric hospital in Egypt between 2007 and 2017. The study included epidemiological, clinical and laboratory data; management details; and outcomes. A cohort of 132 children aged 4months to 12 years was analyzed. Yearly incidence peaked in 2017, and spring showed the highest peak. All cases had a diarrheal prodrome that was bloody in 83% of the cases. Edema and decreased urine output were the most frequent presentations (50.3% and 42.4%, respectively). Escherichia coli was detected in 56 cases. Dialysis was performed in 102 cases. Eight patients died during acute illness, while five patients experienced long-term sequels. Lactate dehydrogenase (LDH) positively correlated with serum creatinine and negatively correlated with reticulocytic count. Univariate analysis showed that longer anuria duration, short duration between diarrheal illness and development of AKI (P = 0.001), leukocyte count above 20 × 109 cells/L (P ≤ 0.001), platelet count below 30 × 109 cells/L (P = 0.02), high LDH levels (P = 0.02) and hematocrit above 30% (P = 0.0001), need for dialysis (P = 0.03), and neurological involvement (P ≤ 0.001) were associated with unfavorable outcomes. This is the first report with a detailed insight into the epidemiology of D+HUS in Egyptian children. The incidence of D+HUS is increasing in our country due to increased awareness of the disease and the poor public health measures. Anuria duration, leukocyte count, and neurological involvement are predictors of poor outcome in the current work, and LDH is introduced as a marker of disease severity.

Oxidative stress and vitamin D receptor BsmI gene polymorphism in Egyptian children with systemic lupus erythematosus: a single center study.

Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown exact etiology. Vitamin D receptor gene ( VDR) and oxidative stress play important roles in the pathogenesis of SLE. Here we investigated the genotypes and allelic frequencies of VDR BsmI polymorphism as well as their relationship with oxidative stress markers in Egyptian SLE children. We conducted a cross-sectional comparative study at Mansoura University Children's Hospital, Egypt from 2014 to 2018 including 100 SLE children and 100 controls. We investigated both groups for VDR BsmI polymorphism using polymerase chain reaction. Oxidative stress was assessed using malondialdehyde, glutathione S-transferase, superoxide dismutase, catalase and total antioxidant capacity. BB genotype frequency was found to be significantly higher in the SLE group ( p = 0.04, odds ratio (95% confidence interval) = 2.5 (1.01-5.9)). However, VDR B allele and b allele showed insignificant differences between SLE patients and controls ( p = 0.36, odds ratio (95% confidence interval) = 1.2 (0.8-1.8)). Lower levels of glutathione S-transferase, superoxide dismutase and total antioxidant capacity were found in the SLE group with statistically significant differences as regards glutathione S-transferase and superoxide dismutase ( p < 0.001). Serum malondialdehyde and catalase levels were significantly higher in the SLE group ( p < 0.001). No significant differences were found between VDR BsmI polymorphism (genotypes and alleles) and oxidative stress markers in the SLE group. In conclusion, BB genotype of VDR BsmI polymorphism is associated with an increased risk of SLE among Egyptian children. Oxidative stress may contribute in pathogenesis of SLE but is not associated with VDR BsmI polymorphism.

Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus.

Angiotensin II, the major effective molecule of the renin-angiotensin system, plays a vital role in the development of systemic lupus erythematosus (SLE). To study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in Egyptian children with SLE and its correlation with serum ACE level and SLE manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE in comparison to 100 healthy controls using polymerase chain reaction-based restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) to confirm the results of the genotyping. Serum ACE level measurement was done using ELISA technique. The frequencies of C-containing genotypes (AC + CC) and C-allele of AT1R (A1166C) were significantly higher in SLE patients compared to controls (p < 0.0001, OR = 4.9, 95% CI = 2.7-8.8; p Ë‚ 0.0001, OR = 3.6, 95% CI = 2.2-5.9, respectively). Lupus nephritis (LN) patients had significantly higher frequency of (AC + CC) genotypes and C-allele compared with controls (p Ë‚ 0.0001, OR = 5.1, 95% CI = 2.7-9.7; p Ë‚ 0.0001, OR = 3.5, 95% CI = 2.1-6.02, respectively). Mean serum ACE levels were significantly higher in SLE patients compared to controls (p Ë‚ 0.0001). There were no associations between AT1R gene polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R gene polymorphism can be considered a risk factor for the development of SLE in Egyptian children.

A novel fibrillin-1 mutation in an egyptian marfan family: A proband showing nephrotic syndrome due to focal segmental glomerulosclerosis.

Marfan syndrome (MFS), the founding member of connective tissue disorder, is an autosomal dominant disease; it is caused by a deficiency of the microfibrillar protein fibrillin-1 (FBN1) and characterized by involvement of three main systems; skeletal, ocular, and cardiovascular. More than one thousand mutations in FBN1 gene on chromosome 15 were found to cause MFS. Nephrotic syndrome (NS) had been described in very few patients with MFS being attributed to membranoproliferative glomerulonephritis secondary to infective endocarditis. Focal segmental glomerulosclerosis (FSGS) had been reported in NS in conjunction with MFS without confirming the diagnosis by mutational analysis of FBN1. We hereby present an Egyptian family with MFS documented at the molecular level; it showed a male proband with NS secondary to FSGS, unfortunately, we failed to make any causal link between FBN dysfunction and FSGS. In this context, we review the spectrum of renal involvements occurring in MFS patients.