Expression profile of serum LncRNAs MALAT-1 and CCAT-1 and their correlation with Mayo severity score in ulcerative colitis patients can diagnose and predict the prognosis of the disease.

Background: Ulcerative colitis (UC) has emerged as an accelerated-incidence chronic condition. UC has been identified as a precancerous lesion for colorectal cancer. Up-to-date genomic research revealed the value of many noncoding RNAs (ncRNAs) in UC pathogenesis, diagnosis, and prognosis. Aim: The present study was aimed at measuring both MALAT-1 and CCAT-1 in the sera of UC patients as diagnostic and prognostic biomarkers and correlating them with the Mayo score which is a novel predictive indicator of malignant transformation as well as with clinicopathological characteristics of the disease. Patients and methods: Sixty-six UC patients and 80 healthy individuals participated in this study, the serum fold changes of MALAT-1 and CCAT-1 were measured by using quantitative real-time PCR (qRT-PCR). Results: The current study findings include overexpressed lncRNAs MALAT-1 and CCAT-1 in the sera of ulcerative colitis patients [(median (IQR) = 2.290 (0.16-9.36), mean ± SD = 3.37 ± 3.904 for MALAT-1, and median (IQR) = 7.305 (0.57-16.96), mean ± SD = 6.81 ± 4.002 for CCAT-1 than controls, ROC curve analysis reported that these genes could predict UC. Both genes were positively correlated with each other which enforces their synergistic effects. Both genes are diagnostic for UC patients.We related studied genes to the severity of the disease. In addition to a significant positive correlation between each gene with ESR and Mayo score, we further classified the patients according to severity (according to Mayo score to remission, mild, moderate, and severe groups) with the following results; lower levels of MALAT-1 and CCAT-1 were significantly associated with mild disease and increased gradually with more severe forms of the disease (p < 0.05). Linear regression analysis with Mayo Score as a dependent variable revealed that only the predictive power of CCAT-1 and ESR are significant. Moreover, ROC curve analysis when compared to that of the Mayo score revealed that CCAT-1 reached 99 % accuracy. In summary, both genes are prognostic factors for UC patients. Conclusion: MALAT-1 and CCAT-1 are diagnostic and prognostic serum biomarkers of ulcerative colitis.

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.

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 relationship between hyperchloremia and acute kidney injury in pediatric diabetic ketoacidosis and its impact on clinical outcomes.

INTRODUCTION: Diabetic ketoacidosis (DKA) is characterized by hyperglycemia, ketogenesis, and increased anion gap metabolic acidosis. Such derangements are accompanied by volume depletion as well as electrolyte disturbances. Resuscitation using traditional saline in DKA patients can exacerbate electrolyte abnormalities, in particular the production of hyperchloremia. Severe hypovolemia can result in acute kidney injury (AKI). The link between hyperchloremia and AKI is controversial. This study aimed to assess the relationship between hyperchloremia and AKI in pediatric patients with DKA and its impacts on clinical outcomes. METHODS: This cross-sectional study was conducted on 70 children with DKA admitted to the pediatric intensive care unit in which all patients were subjected to detailed medical history taking and full clinical examination. Daily assessment of Na, K, urea, creatinine, chloride, arterial blood gases, and albumin/creatinine ratio (ACR) was done. AKI was defined as pRIFLE stage I and F. RESULTS: Hyperchloremia was detected in 65.7% of patients at admission and in 52.9% after 24 h (p = 0.17). AKI was documented in 28% of patients. At admission hyperchloremia was detected in 56% of patients without AKI versus 90% of patients with AKI (p = 0.007). After 24 h, hyperchloremia was detected in 48.4% patients without versus 100% of patients with AKI. Chloride was significantly positively correlated to duration of admission, creatinine, ACR, and negatively correlated to eGFR. CONCLUSION: The development of AKI in patients with DKA was accompanied by hyperchloremia, increased time to DKA resolution, and longer hospital stay. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical, laboratory, and radiological characteristics of COVID-19-infected children admitted to pediatric intensive care unit: a single-center experience.

BACKGROUND: During the second wave of COVID-19, there is an increasing incidence of reported cases in children compared to the early wave. Data on the clinical and laboratory characteristics of COVID-19 in children are evolving, and reports on the characteristics and outcomes of severe COVID-19 in children are still under evaluation. We aimed to describe the clinical, laboratory, and radiological characteristics and outcomes of children with COVID-19 infection admitted to the pediatric intensive care unit (PICU). RESULTS: The study included 27 children with COVID-19 infection. Fever, respiratory, and gastrointestinal (GIT) symptoms were predominant presenting symptoms in our patients. The median age of our patients was 9 months (2 m-12 years). Comorbidity was reported in 59.3%. The typical laboratory findings were leukocytosis, lymphopenia, elevated C-reactive proteins levels, and elevated d-dimer levels. The most frequent radiological findings were ground-glass opacities in 100% of patients and bilateral findings in 96%, while cardiomegaly was found in 44% of patients. The multisystem inflammatory syndrome was reported in 33% of patients with GIT symptoms were the most frequent presenting symptoms. Myocarditis was reported in 22% of patients. The mortality rate in this cohort was 14.8%. On multivariate analysis, the only predictor of mortality was the development of MIS-C. CONCLUSIONS: COVID-19 is more severe in children with comorbid conditions. Fever, respiratory and gastrointestinal (GIT) symptoms were predominant presenting symptoms. MIS-C is of increasing concern in children with high mortality rates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43088-021-00168-x.

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.

Tacrolimus can induce remission in cyclosporine and mycophenolate mofetil resistant pediatric onset nephrotic syndrome.

Nephrotic syndrome (NS) is one of the commonest pediatric renal disorders. Most of these patients are steroid responsive. About 10%-20% of children with new onset NS are resistant to steroid treatment. Patients who are resistant to steroids have limited treatment options such as calcineurin inhibitors (CNIs), mycophenolate mofetil (MMF) and rituximab. Despite several studies had documented that tacrolimus is superior to cyclosporine A (CsA) and MMF in treating SRNS but there are no studies on the efficacy of tacrolimus in treating CsA and MMF resistant NS in pediatric populations. Study objective was to evaluate the role of tacrolimus in treating refractory idiopathic nephrotic syndrome .One hundred-twenty patients with idiopathic nephrotic syndrome were included in the study. Patients with steroid resistant NS were given cyclosporine (CsA) (first step protocol). In patients with cyclosporine resistant NS a combination of CsA+ MMF was given as a second step protocol. Unresponsive patients received tacrolimus as a third step treatment protocol. Tacrolimus was given at a starting dose of 0.1mg/kg/day then the dose was modified according to serum trough levels and patients were followed up for 12 months to evaluate the outcome. Out of 120 patients, 15 were both cyclosporine and MMF resistant and received tacrolimus. Tacrolimus had induced remission in 11 (73.3%) patients during the 1st 6 months of therapy. Eight patients achieved complete remission and three patients had partial remission.Conclusions: Tacrolimus is effective in treating refractory multi-drug resistant NS with favorable outcomes in childhood onset NS.

High Serum Endothelin-1 Level is Associated with Poor Response to Steroid Therapy in Childhood-Onset Nephrotic Syndrome.

Nephrotic syndrome (NS) is one of the most common kidney diseases seen in children. It is a disorder characterized by severe proteinuria, hypoproteinemia, hyperlipidemia, and generalized edema resulting from alterations of permeability at the glomerular capillary wall. Endothelin-1 (ET1) has a central role in the pathogenesis of proteinuria and glomerulosclerosis and has a role in assessment of the clinical course of NS in children. This study aims to investigate the relationship between ET1 serum level and the response to steroid therapy in children with primary NS. Serum ET1 levels were evaluated in 55 children with NS. They were classified into two groups: 30 patients with steroid-sensitive NS (SSNS) and 25 patients with steroid-resistant NS (SRNS). The SSNS group was further divided into infrequent-relapsing NS (IFRNS) and steroid-dependent NS (SDNS), while the SRNS group was subdivided into two groups according to renal pathology. ET1 levels were significantly higher in the SRNS group (52.5 ± 45.8 pg/dL) compared to the SSNS group (18.3 ± 17 pg/dL) (P <0.001). Furthermore, ET1 levels were significantly higher in SDNS (54.3 ± 18.6) compared to IFRNS (11.9 ± 7.8, P = 0.001). There was no statistically significant difference in ET1 levels between minimal change disease group and focal segmental glomerulosclerosis group, (P = 0.28). Serum ET1 can be considered as a predictor for response to steroid therapy.

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.

Acute Kidney Injury Following Usage of Formaldehyde-Free Hair Straightening Products.

Acute kidney injury is manifested by sudden deterioration of kidney functions, with or without reduction of urine output. The spectrum of injury ranges from mild to severe, sometimes requires renal replacement therapy. The initial workup includes a patient history to identify the use of nephrotoxic medications or systemic illnesses that may cause poor renal perfusion or directly impair renal function. Formaldehyde which present in cosmetic products; is toxic to many parts including respiratory, renal, and neurologic systems. Here, we have reported 2 cases of acute kidney injury (AKI) after using formaldehyde free hair straightening protein presented with acute tubular injury, responded to corticosteroid therapy.

The relation between serum levels of epidermal growth factor and necrotizing enterocolitis in preterm neonates.

PURPOSE: Necrotizing enterocolitis (NEC) is one of the most serious complications of prematurity. Many risk factors can contribute to the development of NEC. The epidermal growth factor (EGF) plays a major role in intestinal barrier function, increases intestinal enzyme activity, and improves nutrient transport. The aim of this study was to assess the role of epidermal growth factor in the development of NEC in preterm neonates. METHODS: In this study, 130 preterm neonates were included and divided into 3 groups, as follows: group 1, 40 preterm neonates with NEC; group 2, 50 preterm neonates with sepsis; and group 3, 40 healthy preterm neonates as controls. The NEC group was then subdivided into medical and surgical NEC subgroups. The serum EGF level was measured using enzyme-linked immunosorbent assay. RESULTS: Serum EGF levels (pg/dL) were significantly lower in the NEC group (median [interquartile range, IQR], 9.6 [2-14]) than in the sepsis (10.1 [8-14]) and control groups (11.2 [8-14], P<0.001), with no significant difference between the sepsis and control groups, and were positively correlated with gestational age (r=0.7, P<0.001). A binary logistic regression test revealed that low EGF levels and gestational ages could significantly predict the development of NEC. The receiver-operating characteristic curve for EGF showed an optimal cutoff value of 8 pg/mL, with 73.3% sensitivity, 98% specificity, and an area under the curve of 0.92. CONCLUSION: The patients with NEC in this study had significantly lower serum EGF levels (P<0.001), which indicated that EGF could be a reliable marker of NEC in preterm neonates.

Urinary CD80 as a Replacement for Renal Biopsy for Diagnosis of Pediatric Minimal Change Disease.

INTRODUCTION: Early diagnosis of minimal change disease (MCD) is challenging in nephrotic children. CD80 is a protein expressed on the surface of podocytes associated with nephrotic syndrome and it is implicated in the induction of proteinuria. This study aimed to investigate the use of urinary CD80 for the diagnosis of MCD. MATERIALS AND METHODS: Urinary CD80 levels were evaluated in 36 children with nephrotic syndrome and normal glomerular filtration rate. They were divided into three groups of MCD (n = 21), focal segmental glomerulosclerosis (n = 9), and other glomerulopathies (n = 6). The MCD group was subdivided into 2 of those with remission (n = 11) and those in the active stage (n = 10). Forty healthy children were included as controls. RESULTS: The urinary CD80 level was significantly higher in the MCD group (3.5 ± 2.1 ng/mg creatinine) than in the focal segmental glomerulosclerosis group (1.2 ± 0.5 ng/mg creatinine, P < .001), the other glomerulopathies group (1.4 ± 0.7 ng/mg creatinine, P < .001), and the control group (0.7 ± 0.2 ng/mg creatinine, P < .001), while it showed no significant difference among the non-MCD groups. There was no significant difference between MCD in remission and MCD in relapse, either. A urinary CD80 cutoff value of 1.5 ng/gm creatinine showed a sensitivity of 100% and a specificity of 86% for diagnosis of MCD. CONCLUSIONS: Urinary CD80 levels were significantly higher in the children with MCD than in the controls and patients with other causes of nephrotic syndrome.