Diffusion tensor magnetic resonance imaging in the grading of liver fibrosis associated with congenital ductal plate malformations.

Purpose: Liver biopsy is still the standard method for the diagnosis of ductal plate malformations (DPM). However, it is an invasive tool. Magnetic resonance imaging (MRI) has shown its accuracy in the diagnosis of this pathology. Herein, a study was conducted to elucidate the role of diffusion MRI parameters in predicting the degree of hepatic fibrosis. Material and methods: This prospective study included 29 patients with DPM and 20 healthy controls. Both groups underwent diffusion tensor magnetic resonance imaging (DT-MRI), and its parameters were compared between patients and controls, and then they were correlated with the degree of liver fibrosis in the patient group. Results: All patients with DPM, whatever its type, expressed a significantly lower hepatic apparent diffusion coefficient (ADC) compared to controls. However, fractional anisotropy (FA) showed no significant difference between them. The ADC value of 1.65 × 10-3 mm2/s had sensitivity and specificity of 82.1% and 90%, respectively, in differentiating DPM patients from healthy controls. It was evident that patients with higher fibrosis grades had significantly lower hepatic ADC, indicating a negative correlation between ADC and the grade of hepatic fibrosis; rs = -0.901, p < 0.001. Conclusions: DT-MRI showed good efficacy in the diagnosis of congenital DPM. Moreover, ADC could be applied to monitor the degree of liver fibrosis rather than the invasive liver biopsy. No significant correlation was noted between the FA and the grades of liver fibrosis.

Safety and Efficacy of Ledipasvir/Sofosbuvir in the Treatment of Chronic Hepatitis C Virus Infection in Treatment-Naïve Children without and with Comorbidities.

BACKGROUND: Chronic hepatitis C virus (HCV) infection represents a crucial health problem in children that greatly influences their quality of life. Many efforts have been directed toward investing in effective drugs with a high safety profile and oral administration for better compliance. OBJECTIVES: This study aims to assess the safety of a fixed-dose combination of ledipasvir/sofosbuvir plus drug efficacy and sustained virologic response (SVR) at 12 weeks after treatment discontinuation. METHOD: One tablet (90 mg ledipasvir, 400 mg sofosbuvir) was administered to treatment-naïve children aged 12-18 years weighing at least 35 kg with chronic HCV infection for 6 months, genotype 4. Patients were divided into 2 groups, (1) without comorbidities (24 patients) and (2) with comorbidities (26 patients). RESULTS: At the end of the therapy, all patients (100%) had SVR and a significant reduction of liver enzymes with mild tolerable side effects. CONCLUSION: Ledipasvir/sofosbuvir fixed-dose combination is a safe and highly effective therapeutic option in Egyptian children aged ≥ 12 years, with chronic HCV infection, genotype 4, either without or with comorbidities.

Role of magnetic resonance diffusion weighted imaging in diagnosis of diabetic nephropathy in children living with type 1 diabetes mellitus.

OBJECTIVES: Diabetic nephropathy is a serious and a common complication of diabetes that can lead to end stage renal disease among children living with type 1 diabetes, thus an early and accurate method of diagnosis that allows timely intervention is of high importance. This study aimed to evaluate the role of magnetic resonance diffusion weighted imaging in diagnosis of diabetic nephropathy in children with type 1 diabetes. METHODS: This prospective, observational, case control study included 30 children with type 1 diabetes and 30 matched healthy controls attending the outpatient clinics in Mansoura University Children's Hospital. All were subjected to magnetic resonance DWI of the renal parenchyma and their glomerular filtration rate (GFR) was estimated, along with micro albumin in 24 h urine collection and HbA1c in patients with diabetes. RESULTS: Children with diabetes who were positive for microalbuminuria had significantly lower apparent diffusion coefficient value compared to Children with diabetes who were negative for microalbuminuria (p = 0.034) as well as controls (p = 0.001). Among children with type 1 diabetes, apparent diffusion coefficient had significant positive correlation with estimated glomerular filtration rate (r = 0.491, p = 0.006) and negative correlation with microalbuminuria (r = -0.437, p = 0.016). CONCLUSION: Magnetic resonance DWI of the renal parenchyma is correlated with estimated glomerular filtration rate (eGFR) in children with type 1 diabetes and can detect GFR deterioration even in presence of normal albumin excretion.

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.

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.

Schimke immune-osseous dysplasia: A case report.

Schimke immune-osseous dysplasia (SIOD) is a rare autosomal recessive disorder characterized by spondylo-epiphyseal dysplasia (SED), progressive renal insufficiency beginning as steroid-resistant nephrotic syndrome (SRNS) and defective cellular immunity. This article reports a case from Egypt with a mild form of SIOD. A 14.5-year-old male patient presented with disproportionate short stature, SRNS (focal and segmental glomerulosclerosis), laboratory evidence of cellular immune deficiency and radiologic characteristics of SED. He died at the age of 16.5 years with bone marrow failure and severe pneumonia. To the best of our knowledge, this is the first case of SIOD to be reported from Egypt.

Lupus nephritis in Egyptian children: a 16-year experience.

We retrospectively evaluated the clinical features, histo-pathological patterns, treatment modalities, and outcome of children and adolescents with lupus nephritis (LN), followed-up in Lupus Clinic, Pediatric Nephrology Unit, Mansoura University Children's Hospital between January 1997 and December 2012. Out of 194 patients diagnosed with systemic lupus erythematosus (SLE), LN was reported in 136 (70 %) patient, they were 27 males (20 %) and 109 females (80 %). The mean age at presentation was 12.5 ± 2.9 years, the mean duration of follow up was 4.1 years (range 2 months-12 years). Hematuria was present in 79 patients (58 %), proteinuria in 126 (92.6 %), 38 of them were in nephrotic range, while renal impairment was documented in 20 patients (15 %). Renal biopsy was done in 132 patients; diagnosis of class II, III, IV, V were 23, 25, 39, and 2 % respectively. Second renal biopsy was indicated in 58 patients (insufficient first biopsy 2, follow up in 45, lupus flare in 8, no response to therapy in 3 patients), while the third one was needed in only eight patients. Steroids were the commonest initial medications; used in 128 patients (63 alone and 65 with others) and cyclophosphamide was used in 64 patients. At the last follow-up visit; 19 % of patients lost follow-up, 45 % had complete remission, 21 % still had active disease, 1 % had end-stage renal disease, and 11 % died. In conclusion, in Egypt, childhood SLE is associated with frequent and severe nephritis at presentation, and this may be attributed to genetic, ethnic, or environmental factors.

Fifteen years of kidney biopsies in children: a single center in Egypt.

This study retrospectively investigates the indications and results of renal biopsy in children to determine the patterns of childhood kidney disease in a single tertiary children's hospital in Egypt. We included all the patients who underwent ultrasound-guided renal biopsy from 1998 to 2012. All the kidney biopsies were studied under light microscopy, while immunofluorescence and electron microscopy were performed when indicated. A total of 1246 renal biopsies were performed over 15 years, on 1096 patients. The mean age of the patients at the time of biopsy was 9.2±3.7 years. The main indication for a biopsy was the steroid-resistant nephrotic syndrome (n=354, 28.4%), followed by the atypical nephrotic syndrome (n=250, 20.1%), and renal abnormalities in the systemic diseases (n=228, 18.3 %). In the 1226 pathologically diagnosed specimens, primary glomerulonephritis was the most common finding (n=826, 67.4%), followed by secondary glomerulonephritis (n=238, 19.4%). The most common causes of primary glomerulonephritis were Minimal Change Disease (MCD) (n=267, 21.8%), diffuse proliferative glomerulonephritis (n=188, 15. 3%), and focal proliferative glomerulonephritis (n=164, 13.3%). Lupus nephritis (n=209, 17%) was the most common cause of secondary glomerulonephritis. We conclude that the steroid-resistant nephrotic syndrome was the most frequent indication for biopsy and minimal change disease was the most common histopathological finding in our population.

Pathological profile of biopsied Egyptian children with primary nephrotic syndrome: 15-year single center experience.

BACKGROUND: Primary nephrotic syndrome (PNS) in children is a common problem worldwide. The pathological pattern of PNS differs between countries. However, data on the pathological pattern of PNS in Egyptian children are scant. This study was conducted to determine indications and results of renal biopsy in Egyptian children with PNS from a single tertiary children's hospital. METHODS: Medical records of all children with PNS aged 3 months-18 years who underwent renal biopsy from 1998 to 2012 at Mansoura University Children's Hospital were retrospectively reviewed. RESULTS: A total of 741 patients (441 males, 300 females) underwent 798 biopsies of which only four specimens were insufficient. Mean age at time of biopsy was 7.4 ± 3.6 years. The main indication for biopsy was steroid resistance (n = 354, 44.4%) followed by atypical PNS (n = 234, 29.3%) of which gross hematuria was the most common cause. Minimal change disease (MCD) and its variants were the most frequent pathology (n = 431, 54.3%) irrespective of biopsy indication, and incidence of focal segmental glomerulosclerosis was observed to be increasing over the years. CONCLUSION: This is the first large study on the pathological pattern of PNS in children from Egypt, and it shows that MCD is the most frequent underlying pathology and steroid resistance is the most frequent indication for biopsy.

Sleep quality assessment using polysomnography in children on regular hemodialysis.

Studies examining sleep patterns in children on hemodialysis (HD) are lacking. This cross-sectional, control-matched group study was performed to assess the sleep quality in children on HD. The assessment was made using a subjective sleep assessment and sleep questionnaire and objective analysis was made using full night polysomnography. A total of 25 children with end-stage renal disease (ESRD) on HD were compared with 15 age- and sex-matched controls. The average age of the cases was 14 ± 4 years, 52% were males and the mean body mass index was 20 ± 3.8 kg/m². The average duration on dialysis was 2.6 ± 2 years. Analysis of subjective data revealed markedly affected sleep quality in HD patients, as evidenced by excessive day time sleepiness (P <0.005), night awakening (P <0.005), difficult morning arousal (P <0.005) and limb pains (P <0.005). Objective analysis showed differences in sleep architecture, less slow wave sleep in HD children, similar rapid eye movement and non-rapid eye movement, more sleep disordered breathing (P <0.0001) and more periodic limb movement disorders (P <0.0001). Our study suggests that children on regular HD have markedly affected objective as well as subjective quality of sleep.

Sister Mary Joseph's nodule: a case of umbilical cutaneous metastasis with signet ring cell histology.

The metastasis of a visceral malignancy to the umbilicus is known as "Sister Mary Joseph's nodule". It is a rare clinical sign indicating advanced, metastasizing intraabdominal cancer. We report a 50-year-old man who developed metastatic skin cancer in the form of semicircular indurated plaque on top of which was a firm mobile rounded nodule at the umbilical area. Histopathological examination demonstrated diastase-resistant periodic acid-Schiff and mucicarmine positive signet ring cells, suggesting gastric carcinoma. Immunohistochemical staining showed that these cells were positive for cytokeratins and epithelial membrane antigen, suggesting epithelial origin.

NPHS2 mutations.

OBJECTIVE: To uncover the frequency and the spectrum of NPHS2 mutations in Egyptian children with non familial steroid-resistant nephrotic syndrome (SRNS). METHODS: Sixteen patients were screened by PCR-single-strand conformation polymorphism analysis of NPHS2 gene followed by direct sequencing. RESULTS: NPHS2 mutations were evident in four patients (25%) who were bearing four novel mutations including two frame shift mutations (R238fs and P45fs) and two missense mutations (I136L and F216Y). There were no phenotypic or histological characteristics of patients bearing NPHS2 mutations, apart from the earlier onset of the disease, compared to those who were not bearing mutations. CONCLUSION: NPHS2 mutations are prevalent in Egyptian children with non-familial SRNS and this may in part explain the less favorable prognosis reported in these patients.

Psychiatric disorders in children with chronic renal failure.

Psychiatric assessment was done according to the DSM-IV TR criteria in 19 children with predialysis chronic renal failure (CRF) and 19 children with end-stage renal disease on regular hemodialysis. The prevalence rate of psychiatric disorders in all the studied patients was 52.6%. Adjustment disorders were the most common disorders (18.4%), followed by depression (10.3%) and neurocognitive disorders (7.7%). Anxiety and elimination disorders were reported in 5.1 and 2.6%, respectively. The disorders were more prevalent (P=0.05) in dialysis (68.4%) than in predialysis patients (36.8%). The presence of psychiatric disorders was not significantly correlated with sex, severity of anemia, duration of CRF or the efficiency or the duration of hemodialysis. In conclusion, psychiatric disorders were prevalent in our patients, especially in those on hemodialysis. Both adjustments with depression and depressive disorders were the most common psychiatric disorders. This array of disorders was more likely explained by the difficulties encountered in living with CRF rather than by demographic or physical factors.