RhoA/ROCK inhibition attenuates endothelin-1-induced glomerulopathy in the rats.

Endothelin-1 (ET-1) contributes to the development of kidney diseases. However, the underlying molecular mechanism is largely undefined. Here we sought to investigate the potential role of ET-1 receptors, ETA and ETB in the regulation of increased glomerular permeability and underlying signaling pathways post-ET-1 infusion. Male Sprague-Dawley rats were infused with ET-1 (2 pmol/kg per minute, i.v.) for four weeks, and the effect on glomerular permeability to albumin (Palb) and albuminuria was measured. The selective ROCK-1/2 inhibitor, Y-27632, was administered to a separate group of rats to determine its effect on ET-1-induced Palb and albuminuria. The role of ETA and ETB receptors in regulating RhoA/ROCK activity was determined by incubating isolated glomeruli from normal rats with ET-1 and with selective ETA and ETB receptor antagonists. ET-1 infusion for four weeks significantly elevated Palb and albuminuria. Y-27632 significantly reduced the elevation of Palb and albuminuria. The activities of both RhoA and ROCK-1/2 were increased by ET-1 infusion. Selective ETB receptor antagonism had no effect on the elevated activity of both RhoA and ROCK-1/2 enzymes. Selective ETA receptor and combined ETA/ETB receptors blockade restored the activity of RhoA and ROCK-1/2 to normal levels. In addition, chronic ET-1 infusion increased the levels of glomerular inflammatory and fibrotic markers. These effects were all attenuated in rats following ROCK-1/2 inhibition. These observations suggest that ET-1 contributes to increased albuminuria, inflammation, and fibrosis by modulating the activity of the ETA-RhoA/ROCK-1/2 pathway. Selective ETA receptor blockade may represent a potential therapeutic strategy to limit glomerular injury and albuminuria in kidney disease.

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.

Myocardial function in Saudi adolescents with vitamin D deficiency: Tissue Doppler imaging study.

Vitamin D deficiency is a common health problem in Saudi Arabia especially in children and adolescents. Many studies have reported the relation between low 25-Hydroxyvitamin D (25(OH)D) levels with cardiovascular diseases risk factors as well as cardiovascular events, including stroke, myocardial infarction, and congestive heart failure. This study was conducted to evaluate the effect of 25(OH)D deficiency on the myocardial function and other echocardiographic variables in adolescent, using tissue Doppler imaging (TDI) and to correlate these parameters with 25(OH)D level. The study included 84 healthy adolescents, consecutively selected from adolescents attending the outpatient clinic of Saad Specialist Hospital, KSA between September 2013 and October 2014. The study population was classified into two groups; vitamin D deficient group with 25(OH)D level less than 20 ng/mL and normal vitamin D (control group) with 25(OH)D equal or more than 30 ng/mL. Both groups were subjected to measuring hemoglobin level, serum albumin, creatinine, total calcium, Phosphorous, intact parathyroid hormone (iPTH), B-type natriuretic peptide (BNP), and 25(OH)D levels. Both conventional and pulsed wave TDI were done for all participants. TDI measurements showed significant higher LV Tei Index and RV Tei index when compared to the control group (0.61 ± 0.11 Vs 0.32 ± 0.05 p < 0.0001), (0.54 ± 0.14 Vs 0.40 ± 0.06 p < 0.0001) respectively. Mitral and tricuspid annular systolic velocities were significantly lower in vitamin D deficient group (6.99 ± 1.92 Vs 10.69 ± 0.31 cm/sec p < 0.0001 and 12.30 ± 2.14 Vs 13.89 ± 0.29 p < 0.0001 respectively). The mitral and tricuspid E/Em ratio was significantly higher in vitamin D deficient group than control group (p < 0.0001, p 0.005) respectively. Left ventricular internal diameter at end-diastole (LVIDd) was significantly higher in vitamin D deficient group (44.72 ± 6.33 Vs 40.36 ± 6.21 p 0.003). Serum 25(OH)D level showed significant negative correlation with LV Tei index (r = -0.668, p < 0.0001), RV Tei index (r = -0.421, p < 0.0001). Vitamin D deficiency is associated with subtle systolic and diastolic myocardial dysfunction in Saudi adolescents. TDI is a useful tool for detecting early changes in the myocardium in this particular group.

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.

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.

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.