Spectrum of NPHS1 and NPHS2 variants in egyptian children with focal segmental glomerular sclerosis: identification of six novel variants and founder effect.

The aim of this study is to screen for variants in NPHS1 and NPHS2, in a cohort of Egyptian children with steroid-resistant nephrotic syndrome (SRNS)/focal segmental glomerulosclerosis (FSGS) and compare the prevalence of such variants among other ethnic groups. The study included 25 patients: 21 children diagnosed clinically as steroid-resistant nephrotic syndrome and confirmed as FSGS by renal biopsy and four patients diagnosed as congenital nephrotic syndrome with FSGS. Mutational analysis revealed nine NPHS2 and NPHS1 variants in 13/25 patients with a pathogenic variant detection rate of 52%. NPHS2 variants were found in 8 patients (32%) while five patients from four unrelated families (20%) harbored variants in NPHS1 gene. Six variants were not described before including a likely founder NPHS2 variant in our population, c.596dupA (p.Asn199LysfsTer14). In conclusion, we reported the largest series of patients with SRNS/FSGS from Egypt and identified many novel NPHS1 and NPHS2 variants expanding their mutational spectrum. Further studies on a larger number of patients could provide new insights into the pathogenic mechanisms of SRNS/FSGS which might help in patient's management and prognosis.

Randomized controlled trial on immunomodulatory effects of azithromycin in children with steroid-dependent nephrotic syndrome.

BACKGROUND: Azithromycin (AZM) is a macrolide antibiotic with anti-inflammatory and immunomodulatory effects. Our aim was to compare the immunomodulatory effects of AZM combined with steroid therapy with that of steroid therapy alone in children with steroid-dependent nephrotic syndrome (SDNS). METHODS: We enrolled 57 patients with SDNS in a multicenter randomized control trial. Patients were classified into two groups: group A (intervention group, N = 29) and group B (control group, N = 28). After achievement of remission with full-dose daily prednisone, patients in group A received AZM in conjunction with steroids which was tapered gradually, while patients in group B received steroids alone. Urine protein creatinine ratio (uPCR) and TNF-α were measured at different points of follow-up throughout the study period (5 months after achieving remission). RESULTS: After achievement of remission by full-dose steroids, there were significant differences of TNF-α between the two groups after 1-, 3- and 5-month follow-up (p < 0.001, 0.003, and 0.001, respectively). Also, there was significant difference of TNF-α in both intervention and control groups after exclusion of the relapsed cases at 3- and 5-month follow-up (, p = 0.031 and p = 0.003, respectively). There was significant difference between both groups after 5-month follow-up as regards the number of relapsed patients (group A = 4, group B = 11, p = 0.015). CONCLUSION: AZM was capable of reducing serum TNF-α which is one of the inflammatory cytokines implicated in the pathogenesis of NS.

Transforming growth factor-ß1 in children with diabetic nephropathy.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine that has numerous biological processes. Earlier research indicates that protein and mRNA production of TGF-ß1 are enhanced in the renal tissues of patients with diabetic nephropathy (DN). Our aim was to evaluate the role of TGF-ß1 in early prediction of DN in children with type 1 diabetes mellitus (T1DM). METHODS: Fifty patients with T1DM were enrolled in an observational study. Patients were eligible to participate if at least 3 years had passed since T1DM diagnosis. Patients were classified into two groups (A and B) according to the presence or absence of microalbuminuria, respectively. Serum TGF-ß1 was measured by ELISA in the patients. RESULTS: Out of the 50 studied patients with T1DM, there were 23 (46%) patients with microalbuminuria. There was a significant difference between patients in group A and B as regards TGF-ß1 (p < 0.001). HbA1c had very little influence in controlling for the relationship between TGF-ß1 and disease duration. Diagnostic cutoff value of TGF-ß1 was 358.5 pg/ml with sensitivity and specificity of 100%. CONCLUSION: TGF-ß1 was significantly higher in children with DN in comparison with children without. It could be used as an early indicator of DN in children with T1DM with high sensitivity and specificity.

Double-blind, placebo-controlled trial on the effect of piracetam on breath-holding spells.

Breath-holding spells (BHS) are apparently frightening events occurring in otherwise healthy children.The aim of this study was to evaluate the efficacy of piracetam in the treatment of breath-holding spells. Forty patients with BHS (who were classified into two groups)were involved in a double-blinded placebo-controlled prospective study. Piracetam was given to group A while group B received placebo. Patients were followed monthly for a total period of 4 months. The numbers of attacks/month before and monthly after treatment were documented, and the overall number of attacks/month after treatment was calculated in both groups. The median number of attacks/month before treatment in the two groups was 5.5 and 5,respectively, while after the first month of treatment, it was 2 and 5, respectively. The median overall number of attacks/month after treatment in both groups was 1 and 5, respectively.There was a significant decline of number of attacks after piracetam treatment compared to placebo (p value<0.001). There were no reported side effects of the piracetam throughout the study period. In conclusion, piracetam is a safe and effective drug for the treatment of breath-holding spells in children.

The Association Between Plasma MicroRNA-451 Expression Levels and Chronic Kidney Disease in Children with ß-Thalassemia Major.

INTRODUCTION: Patients with ß -thalassemia major (ß -TM) had a high rate of glomerular dysfunction due to chronic anemia, iron overload, and chelation therapy. There is also evidence of proximal tubular damage, as almost all patients have various amounts of proteinuria. MicroRNAs are non-coding RNA molecules that regulate gene expression. In diabetes, a relative increase in renal microRNA-451 appeared to protect against diabetic kidney injury. This study aimed to investigate the association between miRNA-451 and the development of chronic kidney disease (CKD) in children with ß-TM. METHODS: This study included 60 pediatric patients with ß-TM and 30 healthy children as controls. We categorized patients into two groups according to the presence of CKD. Complete blood and reticulocyte counts, serum levels of ferritin, creatinine and glucose, and urine albumin/creatinine ratio (ACR) were measured. Plasma miRNA-451 expression level was measured by real-time quantitative reversed transcription PCR in all included children. RESULTS: miRNA-451 levels were significantly higher in ß-TM (25.326 ± 12.191) as compared with controls (9.453 ± 5.753) (P < .001). Patients with ß-TM and CKD had significantly lower miRNA-451 levels (19.72 ± 13.023) than those without CKD (30.933 ± 8.23). MiRNA-451 levels had significantly positive correlated with eGFR (r = 0.385 P < .05) and reticulocyte counts (r = 0.27, P < .05). Linear logistic regression analysis showed that low plasma microRNA-451 was a significant independent predictor of CKD. CONCLUSION: miRNA-451 has a protective role against CKD development, and low plasma expression levels are associated with CKD in children with ß-TM  DOI: 10.52547/ijkd.6756.

Assessment of Carotid Intima Media Thickness and Left Ventricular Mass Index in Children with Idiopathic Nephrotic Syndrome.

BACKGROUND: Children with nephrotic syndrome (NS) are at a greater risk of atherosclerosis due to recurrent exposures to hyperlipidemia, hypertension, and immunosuppressive medications. CIMT (carotid intima media thickness) is a reliable marker for assessment of atherosclerosis of large and medium-sized blood vessels; endothelial dysfunction and increased CIMT usually precede the development of cardiovascular diseases. Some manifestations of NS, like proteinuria and hyperlipidemia, are associated with an increased risk of cardiac morbidity and mortality. The aim of the current study was to evaluate the carotid intima media thickness and LVM (left ventricular mass) thickness in children with nephrotic syndrome. SUBJECTS AND METHODS: Eighty-one children with nephrotic syndrome and 100 healthy children as controls were enrolled in the study. The inclusion criteria were: disease duration of minimum of 12 months, glomerular filtration rate >60mL/min/1.73m 2 and children aged two years or more at the time of study. CIMT and left ventricular mass index, lipid profile, protein/creatinine ratio in urine and kidney function tests were done for cases and controls after approval of internal ethical committee. RESULTS: The mean CIMT (mm) was significantly higher in NS (0.51± 0.12) compared to controls (0.42± 0.09) (P <0.001). LVM and LVM Index were significantly higher in NS than controls (p< 0.001, for both). Subsequently, CIMT was significantly correlated to duration of the disease (p< 0.001), LVM index was significantly correlated with duration of the disease, body mass index (BMI), blood pressures and triglycerides level (p< 0.05). CONCLUSION: Children with NS are at increasing risk to develop atherosclerosis as measured by CIMT. LVM was significantly higher in NS and positively correlated to BP, disease duration, triglyceride levels and BMI.

Assessment of Interleukin-27 and Chemokine RANTES as Biomarkers for Early Onset Neonatal Sepsis.

Early-onset neonatal sepsis (EONS) is a global health problem with high morbidity and mortality rates. Early diagnosis is a critical issue in determining treatment strategies. There is no single diagnostic test that can fulfill all requirements of the ideal biomarker yet. The current study enrolled 47 cases with EONS, admitted to the Neonatal Intensive Care Units at Beni-Suef University teaching Hospital from February 2017 to November 2017 and 37 apparently healthy controls. All were subjected to routine laboratory tests and serum concentration of IL-27 and regulation on activation normal T-cell expressed and secreted (RANTES) were measured. Significantly higher concentrations of IL-27 were observed in the septic group while RANTES were significantly lower in comparison to the controls. Moreover, there were no significant correlations between levels of IL-27 and RANTES either in the septic or the control group. Sensitivity, specificity, positive and negative predictive values for IL-27 were 93.6%, 81.1%, 86.3% and 90.9, respectively while for RANTES such values were 68.1%, 78.4%, 80% and 65.9%, respectively. A combination of both markers showed 97.3% specificity for sepsis. In conclusion, IL-27 is a useful and sensitive biomarker either individually or combined with other candidate biomarkers like RANTES.

Behavioral changes in Egyptian children with nephrotic syndrome.

INTRODUCTION: Chronic illnesses, including nephrotic syndrome (NS), are associated with psychosocial stress. Our study aimed to assess psychological problems in children with NS. MATERIALS AND METHODS: Sixty children with NS were assessed at the Children Hospital, in Cairo for behavioral changes. They responded to the Arabic version of the Strength and Difficulties Questionnaire. The results were compared between those with steroid-sensitive NS (SSNS), steroid-dependent NS (SDNS), and steroid-resistant NS (SRNS). RESULTS: Three groups of patients with SSNS, SDNS, and SRNS, each consisting of 20 children aged between 4 and 16 years, were included. The SRNS group was significantly different from the other two groups regarding age at the onset of disease, total serum protein, serum albumin, serum calcium, and estimated glomerular filtration rate (lowest in the SRNS group) as well as 24-hour urine protein, blood urea nitrogen, and serum total cholesterol (highest in the SRNS group). In the SRNS group, the scores for emotional symptoms, peer relationship problems, and the total score were higher and the prosocial score was lower than the other groups, but with no statistical significance. CONCLUSIONS: Emotional symptoms, conduct problems, peer relationship problems, hyperactivity, and the overall poor behavior scores might be more likely to be seen in children with SRNS group than other NS treatment status. We recommend that attention to behavioral problems of children with NS should be given early in the course of disease.