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.

Right Ventricular Strain Analysis By Tissue Tracking Cardiac Magnetic Resonance Imaging In Pediatric Patients With End-Stage Renal Disease.

PURPOSE: To investigate right ventricular (RV) volume and mass by cardiac magnetic resonance (CMR) and the added value of tissue tracking strain analysis as markers of RV dysfunction in pediatric patients with end-stage renal disease (ESRD) and preserved RV ejection fraction. MATERIALS AND METHODS: Twenty-five children with ESRD and preserved RVEF (>50%) and 10 healthy control children were enrolled. Tissue tracking CMR was used to assess Global Longitudinal, circumferential (GCS), and radial short and long axes (GRS SAX and GRS LAX) RV strains in the patients group compared with controls. Correlations between strain parameters and other CMR parameters and clinical biomarkers were assessed. Binary logistic regression was used to test the independence of cofounders and detect their significance. RESULTS: RV end-diastolic volume and mass (RVMi) were significantly higher in patients (97.2±19.3 mL/m 2 and 26.6±7gr/m 2 ) than control (71±7.8 mL/m 2 and 11.9±2 gr/m 2 , P values 0.000). All RV global strain parameters were significantly impaired in patients compared with control (all P values <0.05). RV Global Longitudinal was significantly correlated to LVEF (r=-0.416, P =0.039), LVEDVi (r=0.481, P =0.015), LVMi (r=0.562, P =0.004), and systolic blood pressure index (r=0.586, P =0.002). RV GRS (LAX) was significantly correlated to LV GCS (r=-0.462, P =0.020) and LV GRS (SAX) (r=0.454, P =0.023). GRS (SAX) and GCS demonstrated the highest diagnostic accuracy (area under curve: 0.82 and 0.81) to detect strain impairment. Univariate binary logistic regression with patients versus control as dependent variables identified LVMi, RV end-diastolic volume, RVMi, weight, body surface area, RV GCS, RV GRS (LAX), RV GRS (SAX), LV GCS, and LV GRS (SAX) as significantly correlated to patients with ESRD. When adjusted to other cofounders in the multivariable model, only RVMi remained as an independent significant cofounder (Odds ratio:0.395, P =0.046). CONCLUSION: RV global strain, volume, and mass by CMR are markers of RV dysfunction in ESRD pediatric patients with preserved RVEF.

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.

Trabecular Bone Score in Assessing Bone Mineralization Status in Children with End- Stage Renal Disease: A Promising Tool.

Areal-bone mineral density (aBMD) of lumbar-spine dual energy X-ray absorptiometry (DXA) scan is the most frequently used tool in evaluating BMD in pediatric patients, however its size dependency have significant impact on measurements accuracy in children with chronic kidney disease (CKD). This study aimed to evaluate the usefulness of trabecular bone score (TBS) computed during lumbar-spine DXA scan in assessing bone status in children on maintenance hemodialysis (HD). Ninety-three children on HD (aged 9-18 years) were subjected to lumbar-spine DXA-scan to obtain aBMD (g/cm2) and TBS.Z-scores of aBMD for chronological-age (aBMDZ-CA), height-age (aBMDZ-HA), and TBSZ-score were calculated using mean and SD values of 442 healthy controls. aBMD and TBS were significantly lower in short-for-age and normal height-for-age patients compared to the corresponding values of controls (p < 0.05 for all). Degraded vertebral microarchitecture (TBSZ-score < -2) was detected in 48% and 44% of male and female patients respectively. There were no significant differences in median TBSZ-score between short-for-age and normal height-for-age HD patients in male (p = 0.425) and in female (p = 0.316) patients. TBSZ-score correlated significantly with aBMDZ-CA (r = 0.234; p = 0.024) but not with aBMDZ-HA (r = 0.077; p = 0.462). Patients with history of fractures (5 patients only) had significantly lower TBS scores compared to those without fracture history (p = 0.016). CONCLUSION: TBS is significantly reduced in children on maintenance HD and is associated with increased fracture incidence. TBS has shown to be a promising tool in assessing bone quality (trabecular microarchitecture) in children with CKD being not size-dependent as is a-BMD, for further evaluation of its potential role in therapeutic and follow-up decisions. WHAT IS KNOWN: • In children with CKD, bone demineralization starts as early as CKD stage 2, so assessment of bone health is mandatory for follow up and therapeutic decisions. • aBMD of lumbar-spine DXA scan is the most used tool in evaluating BMD in pediatric patients, however its size dependency have significant impact on measurements made in children with CKD. WHAT IS NEW: • TBS is significantly reduced in children on maintenance HD and associated with increased fracture incidence. • TBS has shown to be a promising tool in assessing bone quality (trabecular microarchitecture) in children with CKD being not size-dependent as is a-BMD.

Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms.

BACKGROUND: Children with juvenile idiopathic arthritis (JIA) are at higher risk of decreased bone mineral density (BMD) compared with healthy children due to genetic, disease and medication-related causes. This study aims to investigate the possible effects of osteoprotegerin (OPG) gene polymorphisms and serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB-ligand (RANKL) and RANKL/OPG ratio on BMD in children with JIA. METHODS: OPG gene rs2073617, rs3134069, serum RANKL, OPG and RANKL/OPG ratio were evaluated in 60 JIA children and 100 matched healthy controls. BMD was evaluated by lumbar dual energy X-ray absorptiometry (DEXA) according to which patients were classified in 2 groups (DEXA z-score above and below - 2). Composite disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS) 27-joints. Articular damage was scored using the juvenile arthritis damage index (JADI). RESULTS: Patients aged 12.05 ± 3.2 years, included 38 females and 31% had BMD z-score below-2. Systemic-onset JIA was the most frequent phenotype (38%). Genotypes and alleles frequencies of the 2 studied polymorphisms did not differ between patients and controls (p > 0.05 for all) while serum RANKL and RANKL/OPG ratio were significantly higher in patients compared to controls (p = < 0.001 and 0.03 respectively). Patients with BMD < -2 had significantly greater frequencies of rs2073617 TT genotype and T allele (p < 0.001), higher serum RANKL, RANKL/OPG ratio (p = 0.01, 0.002), female predominance (p = 0.02), higher articular and extra-articular damage index (p = 0.008,0.009) and more frequent steroid usage (p = 0.02) compared to patients with BMD z-score >-2. Multivariate analysis showed rs2073617 TT genotype, RANKL/OPG ratio, long disease duration (above 36 months) and use of steroid to be associated with decreased BMD (p = 0.03,0.04,0.01,0.01 respectively) in JIA children. CONCLUSIONS: Egyptian children with JIA have decreased BMD. rs2073617 TT genotype and T allele, RANKL/OPG ratio are possible determinants of reduced BMD in JIA. Our results underline the importance of frequent monitoring of BMD in JIA children and trying to control disease activity to preserve long term bone health.

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.

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.

Role of detached podocytes in differentiating between minimal change disease and early focal segmental glomerulosclerosis, can we rely on routine light microscopy?

BACKGROUND: Detachment of podocytes represents a turning point in the development of glomerular sclerosis and consequently, of CKD progression. Furthermore, detachment may differentiate minimal change disease (MCD) cases-which have only podocyte effacement-from early focal segmental glomerulosclerosis (FSGS) in which effacement and detachment are observed by electron microscopy. Noteworthy, it is not uncommon for early FSGS to present with clinical presentation and light microscopy (LM) pictures identical to MCD. In our routine practice, we often find cells that lie freely in Bowman's space by LM. In this study, we try to determine whether these cells are detached podocytes that are worth reporting or just an artifact that can be ignored. METHODS: To the best of our knowledge, no study has discussed the accuracy of LM in detecting detached podocytes by the routinely used stains. We retrospectively selected 118 cases that were diagnosed as MCD by LM, and searched for detached cells in Bowman's space in their archived, routinely stained LM slides. After that, we tried to find any correlation between the clinical course, detached cells in LM picture and the EM reports. RESULTS: LM can significantly detect detached podocytes with a positive predictive value of 93%, specificity of 85%, and sensitivity of 46%. Significant correlations were found between detached cells and degree of proteinuria and late steroid resistance. CONCLUSION: Detecting detached podocytes by LM is a specific finding that must be reported whenever detected, as it predicts response to steroids and may be able to differentiate MCD from early FSGS by identifying patients who could have podocytopenia.

Inferior Vena Cava Collapsibility Index: A Precise, Noninvasive Tool for Evaluation of Edema in Children with Nephrotic Syndrome.

This study aimed to evaluate available volume status assessment tools in nephrotic syndrome (NS). Sixty children with INS were subdivided into hypovolemic and nonhypovolemic groups based on fractional excretion of sodium (FeNa%); all were studied for inferior vena cava collapsibility index (IVCCI), plasma atrial natriuretic peptide (ANP), and body composition monitor (BCM). Forty-four patients had nonhypovolemic and 16 had hypovolemic states. ANP did not differ between both groups. IVCCI was higher in hypovolemic group (p < 0.001) with sensitivity 87.5% and specificity 81.8% for hypovolemia detection, while BCM overhydration (BCM-OH) values were higher in nonhypovolemic group (p = 0.04) with sensitivity = 68.2% and specificity = 75% for detection of hypervolemia. FeNa% showed negative correlation with IVCCI (r = -0.578, p < 0.001) and positive correlation with BCM-OH (r = 0.33, p = 0.018), while FeNa% showed nonsignificant correlation to ANP concentration. IVCCI is a reliable tool for evaluating volume status in NS and is superior to BCM.

Impaired aortic strain and distensibility by cardiac MRI in children with chronic kidney disease.

Renal disease is associated with increased arterial stiffness. The aim was to investigate the effect of renal disease on regional aortic strain and distensibility in children with chronic kidney disease (CKD) by cardiac magnetic resonance imaging (MRI). The study included 30 children with CKD on hemodialysis, and ten healthy control subjects. Using cardiac MRI, maximal and minimal aortic areas were measured in axial cine steady state free precision images at the ascending aorta, proximal descending, and aorta at diaphragm. Regional strain and distensibility were calculated using previously validated formulas. Second reader aortic areas measurements were used to assess inter-observer agreement. Ascending aorta strain was significantly reduced in patients (38.4 ± 17.4%) compared to the control group (56.1 ± 17%), p-value 0.011. Ascending Aorta distensibility was significantly reduced in patients (9.1 ± 4.4 [× 10-3 mm Hg-1]) compared to the control group (13.9 ± 4.9 [× 10-3 mm Hg-1]), p-value 0.006. Strain and distensibility were reduced in proximal descending aorta and aorta at diaphragm but did not reach statistical significance. Only ascending aorta strain and distensibility had significant correlations with clinical and cardiac MRI parameters. Inter-observer agreement for strain and distensibility was almost perfect or strong in the three aortic regions. Aortic strain and distensibility by cardiac MRI are important imaging biomarkers for initial clinical evaluation and follow up of children with CKD.

Diagnostic performance of chest computed tomography for COVID-19 in children: a systematic review and meta-analysis of clinical and computed tomography features in 987 patients.

Purpose: The outbreak of a new coronavirus is still spreading worldwide, affecting children and adults. However, COVID-19 in children shows distinctive characteristics in clinical and radiological presentation. We aimed to assess the diagnostic performance of chest CT and clarify the clinicoradiological CT features of COVID-19 among children with COVID-19. Material and methods: Adhering to PRISMA-DTA guidelines, we searched databases (PubMed, Google Scholar, and Web of Science) to identify relevant articles. The search keywords were: "Chest CT" AND "COVID-19" OR "coronavirus" OR "SARS-COV-2" AND "Children" OR "Pediatric". Published reports providing clinical and imaging findings of paediatric COVID-19 were included. Results: Twenty-eight studies were included, with 987 patients. Most of the patients were symptomatic (76.9%; 95% CI: 69.2-84.7%), with fever being the most frequent manifestation (64%; 95% CI: 58.0-71.2%). Only 2.3% of the cases were critical, and mortality was reported in one case. The proportion of COVID-19 detected by chest CT among children is relatively high (658/987), with ground-glass opacity (GGO) being the most prevalent feature (52.5%; 95% CI: 40.5-64.7%). The pooled sensitivity of chest CT in all patients was 67%; however, it was different between symptomatic and asymptomatic patients (71% and 33%, respectively). The pooled specificity was (67%), which was calculated after considering the symptomatic PCR-positive patients as the gold standard. Conclusions: Chest CT showed moderate pooled sensitivity and specificity among symptomatic children with COVID-19 and low sensitivity among asymptomatic children. This means that CT is not to be used as a screening tool or for confirmation of the diagnosis in children and should be reserved for specific clinical situations.

Edema in childhood nephrotic syndrome: possible genes-hormones interplay.

BACKGROUND: The role of atrial natriuretic peptide (ANP) in edema formation in idiopathic nephrotic syndrome (INS) was studied before with conflicting results reported; however, the possible contribution of genes regulating ANP expression and receptors was never explored. METHODS: One hundred children (60 with active INS and 40 in remission) were studied for plasma atrial natriuretic peptide (ANP), urinary sodium, ANP gene A2843G and ScaI polymorphisms, and natriuretic peptide receptor clearance C (-55) A polymorphism. For comparative purposes, 20 healthy controls were studied for ANP levels. RESULTS: ANP was higher in active compared to remission patients (p<0.001). ANP in the healthy control group was significantly lower than the ANP level of active INS (during edema) group (p=0.009) but did not show significant differences when compared to ANP levels of either active INS group after resolution of edema or remission group (p= 0.42 and 0.56, respectively). Urinary sodium levels in edematous patients were significantly lower while ANP levels were significantly higher during edema than after resolution (p< 0.001 for both). Genotypes' frequencies of studied polymorphisms did not differ between active and remission groups. Patients with the A1A1 genotype of ScaI polymorphism had higher ANP levels compared to other genotypes (p =0.01). CONCLUSIONS: During edema, ANP levels are elevated in INS children however this increment is not associated with natriuresis suggesting a blunted renal response to ANP. Polymorphisms of genes regulating ANP levels and receptors don't seem to be implicated in edema formation except for the A1A1 genotype of ScaI polymorphism however, its possible role needs further evaluation.

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.

Assessment of health-related quality of life in Sudanese children with nephrotic syndrome: a questionnaire-based study.

Introduction: nephrotic syndrome (NS) is a common glomerular disease in children. The long relapsing nature of the disease along with medication-related complications can affect all aspects of the life of the affected children. This study points to estimate the health-related quality of life (HRQOL) in Sudanese children with NS. Methods: this case-control questionnaire-based descriptive study included 100 children with NS aged 2-18 years and 100 healthy children. HRQOL was assessed using the Arabic copy of the Pediatric Quality of Life Inventory Generic Core Scales (PedsQL™ 4.0 GCS). Results: most of the patients were males (64%) and 17% were steroid resistant. Mean PedsQL™ 4.0 summary and domains´ scores in NS were significantly lower than controls (p≤ 0.05 for all) except for the social domain (p=0.266) with the lowest patients´ scores being for school functioning (mean ± SD, 74.4 ± 26.4). The QOL scores considerably differed between the various clinical phenotypes of NS with patients in the initial episode (N=25) having considerably lower total, school, and social domains scores compared to other clinical types (p=0.027, 0.017, 0.006 respectively). Conclusion: this study assesses for the first time the QOL in Sudanese children with NS. Sudanese children with NS had lower life quality scores in comparison to healthy children and need tireless efforts to improve their lives. PedsQL™ 4.0 scale is simple and can be used in everyday clinical practice to evaluate QOL in children with NS.

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.

Pediatric glomerular hematuria: a clinicopathological study.

BACKGROUND: Hematuria is a common problem in pediatric practice and necessitates exhausting studies to detect etiology and establish proper management and counselling. SUBJECTS AND METHODS: We reviewed the clinical and pathological findings in 95 children presented between 2013 and 2019 with gross or microscopic hematuria with or without proteinuria in whom non-glomerular causes were excluded. In addition, a reference range for normal glomerular basement membrane thickness (GBMT) is introduced based on the assessment of biopsies of 20 steroid-resistant nephrotic syndrome cases aged 3-15 years, and with minimal change pathology. RESULTS: Fifty-seven males and 38 females with a mean age of 7.72 ± 3.27 years were included. Recurrent gross hematuria was the most frequent presentation (42%) while accidentally discovered hematuria was reported in 34.7% of patients. Alport syndrome (AS) was the most frequent diagnosis (66.3%) followed by thin basement membrane disease (TBMD) (29.5%) and Immunoglobulin A nephropathy (IgAN) (4%). A reference for normal GBMT was 360.3 ± 87.5 nm which is comparable to published references. Males with AS had a higher incidence of progression to renal failure and requirement for dialysis (p = 0.006 and 0.03, respectively) compared to females. Persistent proteinuria and lower glomerular filtration rate at diagnosis were associated with poor outcomes (p < 0.001 each). CONCLUSION: Alport Syndrome is the most common cause of glomerular hematuria in Egyptian children. Persistence of proteinuria and lower GFR at initial presentation were the main predictors of poor outcomes. The establishment of GBMT reference range for each locality is mandatory for the proper diagnosis of such cases.

Health-related quality of life in Egyptian children with nephrotic syndrome.

PURPOSE: This research aimed to evaluate Quality of life (QoL) in Egyptian children with idiopathic Nephrotic syndrome (INS) in comparison to healthy children and children with chronic non-renal illnesses. METHODS: In this questionnaire-based study, 300 children were included, 100 with INS and 2 matched control groups: healthy group, and chronic non-renal illness group. QoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™ 4.0 Generic Core Scales) and the Generic Children's QoL Measure (GCQ). RESULTS: All mean scores of PedsQL domains in INS group were significantly higher than chronic non-renal illness group and significantly lower than the healthy control group (p = < 0.001) for all and similar results reported also regarding GCQ scores in INS compared to diseased (p = 0.02) and healthy controls (p = 0.006). Steroid-resistant NS group had lowest scores in all domains (p = < 0.001) compared to other clinical phenotypes of NS group. The long duration of illness, higher number of relapses, high cumulative steroid dose, and high number of medications used were associated with lower PedsQL and GCQ scores (p < 0.001 for all) CONCLUSION: This is the first study to asses QoL in Egyptian children with INS and correlates QoL scores to clinical phenotypes and complications of the disease. Egyptian children with INS need strenuous efforts from pediatricians and psychiatrists to improve QoL. Both PedsQL™ 4.0 scale and GCQ are simple, convenient, and can be used in daily clinical practice to asses QoL in children with NS.

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.

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.