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.

Efficacy of intradialytic amino acids on nutritional status in children with stage 5 chronic kidney disease.

BACKGROUND: Protein energy wasting (PEW) is a common cause of morbidity and mortality in patients with stage 5 chronic kidney disease (CKD 5). Intradialytic parenteral nutrition (IDPN) has been used as a therapy for preventing and treating PEW in children with CKD 5 when other conventional modalities fail. However, not enough data is available to define its effectiveness in treating malnutrition in children. This study aims to investigate potential benefits of IDPN in Egyptian children with CKD 5. METHODS: In this prospective, placebo-controlled, parallel-group single blinded study, we enrolled 50 CKD 5 patients; 25 patients (intervention group) received intravenous amino acids (KIDIMN), while 25 patients (control group) received normal saline as placebo, each given during regular dialysis 3 times a week for 9 months. Patients were subjected to nutritional assessment at baseline and 3-, 6-, and 9-month follow-up using height Z-score, hand grip strength (HGS) for muscle power assessment, body composition monitor (BCM) for assessing lean tissue mass (LTM) and adipose tissue mass (ATM), and biochemical measures including serum albumin, serum triglyceride, and serum cholesterol. RESULTS: When comparing baseline and 9-month follow-up values, significant improvement was recorded in height Z-score, LTM, and serum albumin in the intervention group unlike the control group where no significant changes were recorded. CONCLUSION: IDPN is proposed to be an effective method for preventing and treating malnutrition in children with CKD 5. However, further multi-centric studies with larger sample size and longer duration of follow-up are still recommended.

Effect of Everolimus versus Bone Marrow-Derived Stem Cells on Glomerular Injury in a Rat Model of Glomerulonephritis: A Preventive, Predictive and Personalized Implication.

Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6-8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (p < 0.05). Compared to BMDSCs, everolimus was significantly effective in attenuating glomerular injury, nephrinuria and podocalyxin excretion levels as well as in reducing inflammatory responses and apoptosis. Our findings suggest that bolus injection of BMDSCs fails to improve glomerular injury whereas everolimus slows the progression of glomerular injury in Anti-Thy-1 induced glomerulonephritis. Thus, everolimus could be used at the early stage of glomerulonephritis, suggesting potential implications of PPPM in the treatment of progressive renal injury.

CD40 and CD72 expression and prognostic values among children with systemic lupus erythematosus: a case-control study.

Systemic lupus erythematosus (SLE) is a chronic disease with proven interactions between immune system components, including both humoral- and cell-mediated immunity, as well as co-stimulatory and inhibitory molecules such as CD40 and CD72. Here, we investigated CD40 and CD72 expression on B cells of SLE children and assessed their prognostic values. We conducted a preliminary case-control study in Mansoura University Children's Hospital, Egypt from September 2018 to January 2020 including 27 SLE children and 27 healthy controls. We assessed cases during initial flare and after remission. Flow cytometry analysis was carried out for all participants for CD40 and CD72 expression of B cells. During flare, SLE cases had statistically significant higher CD40 and lower CD72 expression in comparison with controls (p < 0.001). After remission, the number of CD40+ B cells significantly decreased (p < 0.001), while the number of CD72+ B cells significantly increased (p < 0.001) in comparison with flare. We reported non-significant positive correlations between CD40 expression and SLE Disease Activity Index (SLEDAI; p = 0.347 during flare and p = 0.653 after remission) and negative correlations between CD72 expression and SLEDAI (p = 0.34 during flare and p = 0.044 after remission). No significant differences were detected between renal histopathology classes with regard to CDs expression on B cells (p = 0.45 for CD40 and p = 0.63 for CD72). In conclusion, CD40+ B cells and CD72+ B cells could be considered as markers of paediatric SLE flare and remission, respectively.

Changes of cardiac functions after hemodialysis session in pediatric patients with end-stage renal disease: conventional echocardiography and two-dimensional speckle tracking study.

BACKGROUND: Although acute effects of hemodialysis (HD) on cardiac functions in end-stage renal disease (ESRD) have been studied frequently in adults, limited data are available in pediatric age. Therefore, this work elucidates the acute impact of HD on cardiac functions using conventional echocardiography and two-dimensional (2D) speckle tracking in ESRD pediatric patients. METHODS: Between June 2018 and April 2019, 40 ESRD pediatric subjects on chronic HD were prospectively recruited. All patients were subjected to history taking and baseline laboratory tests. Anthropometric measures, heart rate, blood pressure, and bioimpedance were assessed before and after HD session. Moreover, conventional echocardiography including M.mode and Doppler parameters for valves, as well as left ventricle (LV) 2D speckle tracking were performed pre- and post-dialysis session. RESULTS: The included patients mean age was 12.9 ± 2.9 years, and males were 24 (60%). Significant reductions in body weight and blood pressure were noted after sessions. Post-dialysis LV and left atrial diameters, as well as left atrium to aortic diameter ratio, were lower. Nevertheless, conventional echocardiography-derived LV ejection fraction (EF), and fractional shortening were not significantly changed. Doppler-derived E/A ratio of mitral and tricuspid valves were lower post-dialysis. Global longitudinal strain (GLS) for LV was significantly reduced after dialysis (- 20.31 ± 3.58%, - 17.17 ± 3.40% vs, P < 0.0001), and global circumferential strain (GCS) was lower post-dialysis in comparison to pre-dialysis (- 21.37 ± 6.46% vs - 17.74 ± 6.16%, P < 0.0001). The speckle tracking-derived EF was significantly lower post-dialysis (57.58 ± 6.94 vs 53.64 ± 10.72, P = 0.018). All myocardial segments longitudinal and circumferential strains decreased significantly after dialysis. CONCLUSIONS: Post-hemodialysis significant decline in left ventricular EF as well as global and segmental strains can be detected in ESRD pediatric patients using 2D speckle tracking, despite the nonsignificant changes in systolic functions derived from conventional echocardiography. This is considered additional evidence of HD deleterious effect on myocardial functions, particularly in the pediatric age.

Assessment of Nutritional Status in Children With Chronic Kidney Disease Using Hand Grip Strength Tool.

OBJECTIVE: Muscle status assessment is crucial for diagnosis of protein energy wasting PEW/cachexia in chronic kidney disease (CKD) population. Hand grip strength (HGS) has been used in muscle power assessment in adult CKD. However, no data is available about its usefulness in children with CKD. Hence, we aimed to study the reliability of HGS in reflecting the muscle power and thus, nutritional status in children with CKD. DESIGN AND METHODS: In this Observational cross sectional study we enrolled 73 CKD children; 45 had end stage kidney disease (ESKD) on hemodialysis (HD) and 28 had CKD but not on dialysis yet. Assessment of children's nutritional status was done through biochemical variables (serum albumin and serum cholesterol) and anthropometric measures (height and BMI). Body composition monitor (BCM) device was used for lean tissue mass (LTM) assessment whilst muscle power was tested by HGS tool. RESULTS: The study showed that 69.8% of CKD patients had HGS values below 10th percentile for age and sex. Moreover, HGS was observed to be more affected in CRI patients and those with non - glomerular causes. HGS was also found to be positively correlated to height but not to lean tissue mass or serum albumin. CONCLUSION: HGS tool can be used as a reliable bedside tool for nutritional assessment in children with CKD.

Low expression of glucocorticoid receptors in children with steroid-resistant nephrotic syndrome.

BACKGROUND: About 10-20 % of children with idiopathic nephrotic syndrome (NS) are steroid-resistant (SR). Low expression of glucocorticoid receptors (GRs) has been associated with poor response to steroids in a variety of autoimmune diseases. This study was done to assess the expression of cytoplasmic GRs for CD3 and CD14 in children with NS. METHODS: Expression of cytoplasmic GRs in lymphocytes (CD3(+)/GR) and monocytes (CD14(+)/GR) in the peripheral blood were assessed in 51 children with NS before the start of therapy by flow cytometry. Patients were divided into two groups: 30 children who were steroid-sensitive (SSNS) and 21 children who had initial steroid resistance (SRNS). Twenty age- and sex-matched healthy children served as controls. RESULTS: Expression of CD3(+)/GR was significantly lower in SRNS in comparison to SSNS patients and controls (p < 0.0001). Similarly, expression of CD14(+)/GR was significantly lower in SRNS in comparison to SSNS patients (p < 0.0001) and controls (p = 0.002). CD3(+)/GR and CD14(+)/GR expression were not significantly different in SSNS patients compared with controls (p = 0.06 and 0.07 respectively). CONCLUSIONS: Patients with initial SRNS showed decreased GR expression in peripheral blood mononuclear cells (PBMC) before starting therapy, and this low expression may be one of the pathophysiological mechanisms of steroid resistance in these children.

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.

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.

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.

Size-adjustment techniques of lumbar spine dual energy X-ray absorptiometry measurements in assessing bone mineralization in children on maintenance hemodialysis.

OBJECTIVES: Growing skeleton is uniquely vulnerable to impaired mineralization in chronic kidney disease (CKD). Continued debate exists about the optimal method to adjust for body size when interpreting dual energy X-ray absorptiometry (DXA) scans in children with CKD given the burden of poor growth. The study aimed to evaluate the clinical usefulness of size-adjustment techniques of lumber-spine DXA measurements in assessing bone mineralization in children with kidney failure on maintenance hemodialysis (HD). METHODS: Case-control study included 93 children on maintenance HD (9-18 years; 48 males). Participants were subjected to spinal-DXA-scan to obtain areal bone mineral density (aBMD; g/cm2). Volumetric-BMD (vBMD; g/cm3) was mathematically estimated. Z-scores of aBMD for chronological age (aBMDZ-CA), aBMD adjusted for height age (aBMDZ-HA), and vBMDZ-score were calculated using mean and SD values of age subgroups of 442 healthy controls (7-18 years). RESULTS: In short-for-age CKD patients, aBMDZ-CA was significantly lower than vBMDZ-score, while aBMDZ-HA was significantly higher than aBMDZ-CA and vBMDZ-score. In normal height-for-age CKD patients, no significant difference between aBMDZ-scores and vBMDZ-score was detected. aBMDZ-CA was significantly lower and aBMDZ-HA was significantly higher in short-for-age compared to normal height-for-age patients without significant differences in vBMDZ-score. We observed age-related decrements in the percentage of HD patients with normal densitometric Z-scores, the effect of age was less pronounced in aBMDZ-HA than vBMDZ-score. vBMDZ-score correlated negatively with age, but not with heightZ-score. CONCLUSIONS: Estimated vBMD seems to be a convenient size-adjustment approach of spinal-DXA measurements in assessing BMD especially in older short-for-age children with CKD. aBMDZ-CA underestimates, while aBMDZ-HA overestimates BMD in such patients.

Genetic Polymorphisms in Genes Involved in the Type I Interferon System (IFIH1/MDA-5, TNFAIP3/A20, and STAT4): Association with SLE Risk in Egyptian Children and Adolescents.

PURPOSE: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune inflammatory disease that is influenced by both genetic and environmental factors and associated with dysregulation of type I interferon (INF) response. This study aimed to investigate the effects of single nucleotide polymorphisms (SNPs) of the IFIH1, TNFAIP3, and STAT4 genes in the type I INF system on SLE risk in Egyptian children and adolescents. PATIENTS AND METHODS: We recruited 94 SLE individuals and 94 healthy subjects. SNPs of IFIH1 rs3747517 C/T, TNFAIP3 rs610604 G/T, and STAT4 rs7574865 G/T were evaluated using TaqMan™ SNP genotyping assay. RESULTS: Individuals with the TT, CT+TT genotypes, and T allele of rs3747517 in the IFIH1 gene were protective for SLE patients (OR = 0.429, 95% CI = 0.191-0.962, P = 0.040), (OR = 0.685, 95% CI = 0.477-0.984, P = 0.041), and (OR = 0.705, 95% CI = 0.527-0.944, P = 0.019), respectively. Also, individuals with the TT, GT+TT genotypes, and T allele of rs7574865 in the STAT4 gene were associated with SLE risk (OR = 3.945, 95% CI = 1.303-11.947, P = 0.015), (OR = 1.536, 95% CI = 1.058-2.231, P = 0.024), and (OR = 1.522, 95% CI = 1.113-2.082, P = 0.009), respectively. In the case of TNFAIP3 rs610604, no significant association of genotypes or alleles with SLE were detected, while the three SNPs did not show any significant association with the SLE clinical or laboratory features. CONCLUSION: Our findings indicated that rs3747517 in IFIH1 was protective for SLE in Egyptian children and adolescents. Moreover, rs7574865 in STAT4 not rs610604 in TNFAIP3 was associated with SLE risk.

Clinicopathological Impact of Gene Polymorphism of Nephrin and Glucocorticoid Receptor Genes in Egyptian Children with Nonfamilial Nephrotic Syndrome.

Idiopathic nephrotic syndrome (NS) is one of the most common primary glomerular diseases in children. In this study, we investigate the association of single-nucleotide polymorphisms of nephrin gene and glucocorticoid receptor gene (NR3C1) and susceptibility to develop NS and the response to steroid therapy in 100 Egyptian children with NS using polymerase chain reaction-restriction fragment length polymorphism. We also analyzed the correlation between the genotypes and clinicopathologic features of the patients. Thirty-four patients (34%) were initial steroid nonresponders, renal biopsy findings of those patients were available, of which 22 (64.7%) showed minimal change NS and 12 (35.3%) had focal segmental glomerulosclerosis. The distribution of the genotypes was comparable between the patient and control groups, allele frequencies showed no significant difference between the patient's group and the control group. The genotypes showed no correlation with the age of onset of NS, initial steroid responsiveness, renal pathologic findings, estimated glomerular filtration rate (eGFR), and serum albumin. However, 24-h protein in urine showed a significant association with the NR3C1 gene. These data suggested that the nephrin gene and NR3C1 gene SNPs do not affect the development of NS, initial steroid responsiveness, renal pathological lesion, eGFR, and serum albumin. However, 24-h protein in urine showed a significant association with the NR3C1 gene in Egyptian children with NS.

Primary focal segmental glomerulosclerosis in Egyptian children: a 10-year single-centre experience.

Primary focal segmental glomerulosclerosis (FSGS) in children accounts for 7-20% of all cases of idiopathic nephrotic syndrome (NS). To evaluate the clinical course of children with primary FSGS, the records of 72 patients with biopsy-proven FSGS admitted between 1995 and 2008 were retrospectively analysed. Forty-eight patients were male (66.7%). The mean age at presentation was 76.5 +/- 54 (range 12-192) months. The mean duration of follow-up was 76.3 +/- 42 (range 9-156) months. Seventeen patients (23.6%) presented with gross haematuria at initial presentation, 15 (20.8%) presented with hypertension and 10 patients (14%) presented with chronic renal insufficiency (CRI). The initial response to oral prednisolone was steroid resistance in 63 patients (87.5%) and steroid dependence in 4 patients (5%), while 5 patients (6.9%) were biopsied from the start because of atypical presentation. According to pathological classification, there were the tip variant (2%), collapsing variant (6%), perihilar variant (7%) and NOS (not otherwise specified; 85%). At the last clinical visit, 12 patients (16.7%) were in complete remission and 11 (15.3%) had progressed to CRI. Renal survival rates at 5 and 10 years were 93% and 68%, respectively. In conclusion, in this study we had a low percentage of FSGS, and fewer patients presenting with gross haematuria and hypertension compared with previous reports. In addition, the short-term overall renal survival seems to be better in our cohort.

Prevalence of Helicobacter pylori infection among children with primary nephrotic syndrome: a cross-sectional study.

BACKGROUND: Limited data are available about the prevalence of helicobacter pylori (H.pylori) infection among primary NS children. OBJECTIVES: To assess the frequency and risk factors of H.pylori infection among children with primary NS. METHODS: A cross-sectional study was carried out in Mansoura University Children's Hospital, Egypt during the period from 2017 to 2019 including 100 NS children (NS group) and 100 healthy controls. NS group included 88 steroid sensitive (SSNS) and 12 steroid resistant (SRNS) cases. All patients were assessed for H.pylori infection using H.pylori stool antigen (HpSA) test. Statistical analysis was done using chi-square, fisher exact and Mann-Whitney tests. RESULTS: With regard to HpSA test results, no significant differences were detected between control and NS groups (p = 0.193) and between SSNS and SRNS groups (p = 0.286). Concerning total biopsied cases and MCD (proven plus presumed) cases, no significant differences were found between those with positive and negative HpSA test (p = 0.648 and 0.126, respectively). The high dose of steroid therapy was associated with a higher risk of H.pylori infection among NS group (Odds ratio = 3.8; 95% confidence interval = 1.3-11.3). CONCLUSION: The current study negates the increased risk of H.pylori infection in children with primary 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 DEEP LEARNING-BASED CAD SYSTEM FOR RENAL ALLOGRAFT ASSESSMENT: DIFFUSION, BOLD, AND CLINICAL BIOMARKERS.

Recently, studies for non-invasive renal transplant evaluation have been explored to control allograft rejection. In this paper, a computer-aided diagnostic system has been developed to accommodate with an early-stage renal transplant status assessment, called RT-CAD. Our model of this system integrated multiple sources for a more accurate diagnosis: two image-based sources and two clinical-based sources. The image-based sources included apparent diffusion coefficients (ADCs) and the amount of deoxygenated hemoglobin (R2*). More specifically, these ADCs were extracted from 47 diffusion weighted magnetic resonance imaging (DW-MRI) scans at 11 different b-values (b0, b50, b100, …, b1000 s/mm2), while the R2* values were extracted from 30 blood oxygen level-dependent MRI (BOLD-MRI) scans at 5 different echo times (2ms, 7ms, 12ms, 17ms, and 22ms). The clinical sources included serum creatinine (SCr) and creatinine clearance (CrCl). First, the kidney was segmented through the RT-CAD system using a geometric deformable model called a level-set method. Second, both ADCs and R2* were estimated for common patients (N = 30) and then were integrated with the corresponding SCr and CrCl. Last, these integrated biomarkers were considered the discriminatory features to be used as trainers and testers for future deep learning-based classifiers such as stacked auto-encoders (SAEs). We used a k-fold cross-validation criteria to evaluate the RT-CAD system diagnostic performance, which achieved the following scores: 93.3%, 90.0%, and 95.0% in terms of accuracy, sensitivity, and specificity in differentiating between acute renal rejection (AR) and non-rejection (NR). The reliability and completeness of the RT-CAD system was further accepted by the area under the curve score of 0.92. The conclusions ensured that the presented RT-CAD system has a high reliability to diagnose the status of the renal transplant in a non-invasive way.

A multimodal computer-aided diagnostic system for precise identification of renal allograft rejection: Preliminary results.

PURPOSE: Early assessment of renal allograft function post-transplantation is crucial to minimize and control allograft rejection. Biopsy - the gold standard - is used only as a last resort due to its invasiveness, high cost, adverse events (e.g., bleeding, infection, etc.), and the time for reporting. To overcome these limitations, a renal computer-assisted diagnostic (Renal-CAD) system was developed to assess kidney transplant function. METHODS: The developed Renal-CAD system integrates data collected from two image-based sources and two clinical-based sources to assess renal transplant function. The imaging sources were the apparent diffusion coefficients (ADCs) extracted from 47 diffusion-weighted magnetic resonance imaging (DW-MRI) scans at 11 different b-values (b0, b50, b100, ..., b1000 s/mm 2 ), and the transverse relaxation rate (R2*) extracted from 30 blood oxygen level-dependent MRI (BOLD-MRI) scans at 5 different echo times (TEs = 2, 7, 12, 17, and 22 ms). Serum creatinine (SCr) and creatinine clearance (CrCl) were the clinical sources for kidney function evaluation. The Renal-CAD system initially performed kidney segmentation using the level-set method, followed by estimation of the ADCs from DW-MRIs and the R2* from BOLD-MRIs. ADCs and R2* estimates from 30 subjects that have both types of scans were integrated with their associated SCr and CrCl. The integrated biomarkers were then used as our discriminatory features to train and test a deep learning-based classifier, namely stacked autoencoders (SAEs) to differentiate non-rejection (NR) from acute rejection (AR) renal transplants. RESULTS: Using a leave-one-subject-out cross-validation approach along with SAEs, the Renal-CAD system demonstrated 93.3% accuracy, 90.0% sensitivity, and 95.0% specificity in differentiating AR from NR. Robustness of the Renal-CAD system was also confirmed by the area under the curve value of 0.92. Using a stratified tenfold cross-validation approach, the Renal-CAD system demonstrated its reproducibility and robustness by a diagnostic accuracy of 86.7%, sensitivity of 80.0%, specificity of 90.0%, and AUC of 0.88. CONCLUSION: The obtained results demonstrate the feasibility and efficacy of accurate, noninvasive identification of AR at an early stage using the Renal-CAD system.

Oxidant stress in primary nephrotic syndrome: does it modulate the response to corticosteroids?

In order to assess the oxidative stress in newly diagnosed children with primary nephrotic syndrome (PNS), we serially measured serum total antioxidant capacity (TAC) and malondialdehyde (MDA) in 33 children with PNS and ten healthy matched controls. Patients were classified into two groups: those who had steroid-sensitive nephrotic syndrome (SSNS; n = 26) and those who had steroid-resistant nephrotic syndrome (SRNS; n = 7). Of the patients with SSNS, 15 were non-relapsers and 11 were relapsers. At the proteinuric phase, all patients had significantly higher MDA levels and lower TAC than the controls. These changes were more marked in patients with SRNS than in those with SSNS. During remission and still on corticosteroids, patients had higher TAC and similar MDA levels as in the proteinuric phase, but the TAC and MDA levels still significantly differed from those of the controls. More improvement in TAC and MDA levels occurred in patients following the weaning of corticosteroids, but TAC was still lower in the patients than in the controls. Moreover, TAC was higher in non-relapsers than in relapsers. Using a receiver operating characteristic curve, the initial response to corticosteroids could be predicted at serum TAC level > or =0.73 mM/L (sensitivity 89%, specificity 86%), while serum TAC levels < or = 1.14 mM/L after the weaning of corticosteroids could predict that the patient would not relapse (sensitivity 91%, specificity 80%). In conclusion, based on our results, PNS can be considered to be associated with oxidative stress even during remission. This stress may modulate the response to corticosteroids. Further prospective studies using larger numbers of patients are needed to validate these results.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: unusual clinical associations and novel claudin16 mutation in an Egyptian family.

BACKGROUND: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder that eventually progresses to renal failure, depending upon the extent of nephrocalcinosis. Its basic pathogenesis is impaired tubular resorption of magnesium and calcium in the thick ascending limb of the loop of Henle (TAL) due to a genetic defect in paracellin-1 (a tight junction protein expressed in TAL). Mutations of the claudin16 gene (CLDN16), formerly called paracellin-1 gene (PCLN-1), have been linked to FHHNC. METHODS: An extended Egyptian family with more than one member affection by nephrocalcionsis was included and thoroughly investigated in the current study after giving informed consent. Thorough history was taken for polyuria, polydipsia and hypocalcemia symptoms, as well as clinical examination with stress on anthropometric measurements and radiological evaluation for kidneys and bones. Laboratory workup for the differential diagnosis of nephrocalcinosis was done: complete urinalysis, including urinary calcium excretion, urine pH and electrolytes, arterial blood gas (ABG), serum electrolytes (sodium, potassium, calcium, magnesium and phosphorous), renal function tests as well as parathyroid and gonadotropin-sex hormone assay. DNA extraction from peripheral blood leukocytes was done followed by amplification using primers previously described, purification and finally sequencing to analyze each exon of the CLDN16 gene. RESULTS: Two sibs for a consanguineous couple were affected by nephrocalcinosis and showed persistent hypocalcemia, hypercalciuria, nephrocalcinosis with persistently alkaline urine and ocular manifestations in the form of congenital cataracts, high myopia and retinal abnormalities. The elder sib showed genitourinary abnormalities in the form of hypospadias and cryptorchidism. These two sibs had a homozygous two-base deletion in exon 1 of the CLDN16 gene (C. 233_234 del GG; Ins C), causing a frame shift mutation (Arg55 fs); however, their parents were heterozygote carriers for that mutation. CONCLUSION: The above-mentioned clinical data in the two affected sibs together with the family history of end-stage renal disease associated with nephrocalcinosis and high myopia suggested a diagnosis of FHHNC, which was confirmed for the first time in an Egyptian family by a novel mutation in exon 1 of the CLDN16 gene. Genitourinary associations with FHHNC have not yet been reported in the literature. Here, we will try to highlight the principles of mutation detection based on sequencing with the use of the online NCBI databases, statistics and other search tools.