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.

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.