Fatina I. Fadel

Plasma neutrophil gelatinase-associated lipocalin as an early biomarker for prediction of acute kidney injury after cardio-pulmonary bypass in pediatric cardiac surgery

Introduction Cardiopulmonary bypass (CPB) surgery is considered one of the most frequent surgical procedures in which acute kidney injury (AKI) represents a frequent and serious complication. The aim of the present study was to evaluate the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early AKI biomarker after CPB in pediatric cardiac surgery. Material and methods The study included forty children aged 2 to 78 months undergoing CPB. They were divided into group I: patients who suffered AKI grades II and III; and group II: patients who did not develop AKI or at risk. Peripheral venous blood was withdrawn pre- and post-operatively for serial measurements of NGAL and creatinine. Statistical analysis was performed using Statistical Package for Social Sciences version 14. Results Mean plasma NGAL levels showed highly significant elevations in group I patients at 2, 12, and 24 h after surgery (p < 0.0001) compared to group II. Significant correlations were found between NGAL and creatinine at different time intervals. Highly significant correlations (p < 0.0001) were found between plasma NGAL and AKI at 2, 12 and 24 h after surgery. A cut-off level of 100 ng/ml at 2 h, and 125 ng/ml at 12 h post-operatively both recorded the highest accuracy, being 95% accurate, with sensitivity of 100% and 89.5% respectively, and specificity of 90.5% and 100% respectively. Conclusions This study showed that plasma NGAL could be used as an early biomarker for detection of AKI following CPB. We recommend further studies on a wider scale to validate the current study results.

Passenger lymphocyte syndrome in ABO and Rhesus D minor mismatched liver and kidney transplantation: A prospective analysis

The increasing demand for solid organs has necessitated the use of ABO and Rhesus (Rh) D minor mismatched transplants. The passenger lymphocyte syndrome (PLS) occurs when donor lymphocytes produce antibodies that react with host red blood cell (RBC) antigens and result in hemolysis. Our aim was to evaluate prospectively the role of PLS in post transplant anemia and hemolysis in ABO and RhD minor mismatched recipients of liver and kidney grafts and to study the association of PLS with donor lymphocyte microchimerism. We examined 11 liver and 10 kidney recipients at Day +15 for anemia, markers of hemolysis, direct antiglobulin test and eluates, and serum RBC antibodies. Microchimerism was determined in peripheral blood lymphocytes by genotyping of simple sequence length polymorphisms encoding short tandem repeats. Immune hemolytic anemia and anti-recipient RBC antibodies were observed in 2 out of 11 liver (18.2%) and 2 out of 10 kidney (20%) transplants. RBC antibody specificity reflected the donor to recipient transplant, with anti-blood group B antibodies identified in 2 cases of O to B and 1 case of A to AB transplants while anti-D antibodies were detected in 1 case of RhD-negative to RhD-positive transplant. Donor microchimerism was found in only 1 patient. In conclusion, passenger lymphocyte mediated hemolysis is frequent in minor mismatched liver and kidney transplantation. Recognizing PLS as a potential cause of post transplant anemia may allow for early diagnosis and management to decrease the morbidity and mortality in some patients.

Surgical complications and graft function following live-donor extraperitoneal renal transplantation in children 20 kg or less

OBJECTIVES To evaluate the effect of patient, surgical, and medical factors on surgical complications and graft function following renal transplantation (Tx) in children weighing ≤ 20 kg, because the number of this challenging group of children is increasing. PATIENTS AND METHODS Between June 2009 and October 2013, 26 patients received living donor renal allotransplant using the extraperitoneal approach (EPA). The immunosuppression regimen was composed of prednisolone, mycophenolate mofetil, and ciclosporin or tacrolimus. RESULTS The mean weight was 16.46 ± 2.61 kg. Mean cold ischemia time was 53.85 ± 12.35 min. The graft survival rate (GSR) and patient survival rate (PSR) were 96% at 3 years. Acute rejection episodes (AREs) occurred in eight patients (30%). Postoperative surgical complications were ureteral leakage (3), vesicoureteric reflux (2), and renal vein thrombosis (2) (with one graft nephrectomy). Mean follow-up was 37.5 ± 7.4 months. CONCLUSION Excellent PSR and GSR can be achieved in low weight (<20 kg) recipients. Even in very low weight patients, the EPA was used. No cases were reported with primary graft non-function due to use of living donors, increasing pre-Tx body weight to at least 10 kg and maintaining adequate filling pressure before graft reperfusion. The presence of related donors and use of induction therapy and tacrolimus decreased the rate of ARE while the presence of pre-Tx lower urinary tract surgical interventions increased the rate of ureteric complications, but this was statistically insignificant.

Causes of chronic kidney disease in Egyptian children

There are very few published reports on the causes of chronic kidney disease (CKD) in Egyptian children. We reviewed the records of 1018 (males 56.7%, age ranged from 1 to 19 years) Egyptian patients suffering from CKD and followed-up at the pediatric nephrology units (outpatient clinics and dialysis units) of 11 universities over a period of two years. The mean of the estimated glomerular filtration rate was 12.5 mL/min/1.73 m 2 . Children with CKD stage I and stage II comprised 4.4% of the studied group, while those with stage III, IV and V comprised 19.7%, 18.3% and 57.6%, respectively. The most common single cause of CKD was obstructive uropathy (21.7%), followed by primary glomerulonephritis (15.3%), reflux/urinary tract infection (14.6%), aplasia/hypoplasia (9.8%) and familial/metabolic diseases (6.8%); unknown causes accounted for 20.6% of the cases. Of the 587 patients who had reached end-stage renal disease, 93.5% was treated with hemodialysis and only 6.5% were treated with peritoneal dialysis.

Advanced glycation end products and soluble receptor as markers of oxidative stress in children on hemodialysis

Abstract Background: Advanced glycation end products (AGEs) have biological properties that may contribute to the mortality of children on hemodialysis (HD). This study examines the relationship of LMW fluorescence AGEs, oxidized LDL (ox-LDL), soluble receptor AGE (sRAGE) as markers of oxidative stress in children with end stage renal disease (ESRD) undergoing HD. Method: Thirty children with ESRD undergoing HD, and 30 healthy, age- and sex-matched children were included. Serum levels of LMW fluorescence AGEs, sRAGE, oxidized LDL (ox-LDL), pre- and post-dialysis urea, high-sensitivity C-reactive protein (hs-CRP), hemoglobin (Hb) and serum albumin (ALB), were measured. Results: Abnormal serum inflammatory changes: elevated levels of LMW AGEs, sRAGE, oxLDL, CRP and urea were exhibited in HD children compared with healthy controls; more so in anemic when compared to non-anemic patients. Significant positive correlation was found between serum levels of AGEs and sRAGE. Conclusion: The low molecular weight form of AGEs is associated with oxidative stress in children receiving chronic HD, and may be important in the mechanisms leading to atherosclerosis and inflammation in such patients. LMW AGEs levels showed a negative correlation with sRAGE and both exhibit a significant negative relation to seum urea.

Outcomes of living donor renal transplantation in children with lower urinary tract dysfunction: a comparative retrospective study.

To compare outcomes of renal transplantation (RTx) in children with end‐stage renal disease (ESRD) resulting from lower urinary tract dysfunction (LUTD) vs other causes.

Risk factors for urological complications following living donor renal transplantation in children

The aim of this study was to detect possible risk factors for UC and UTI following pediatric renal Tx and effect of these complications on outcome. One hundred and eight children who underwent living donor Tx between 2009 and 2015 were retrospectively included. Extraperitoneal approach was used with stented tunneled extravesical procedure. Mean recipient age was 9.89 ± 3.46 years while mean weight was 25.22 ± 10.43 kg. Seventy‐three (67.6%) recipients were boys while 92 (85.2%) were related to donors. Urological causes of ESRD were present in 33 (30.6%) recipients (14 [13%] posterior urethral valve, 16 [14.8%] VUR, and 3 [2.8%] neurogenic bladder). Augmentation ileocystoplasty was performed in 9 (8.3%) patients. Mean follow‐up was 39.3 ± 17.33 months. UC were detected in 10 (9.3%) children (leakage 4 [3.7%], obstruction 3 [2.8%], and VUR 3 [2.8%]) while UTIs were reported in 40 (37%) children. After logistic regression analysis, UC were significantly higher in children with cystoplasty (44.4% vs 6.1%; P = .001). UTIs were significantly higher in girls (51.4% vs 30.1%; P = .001) and in children with urological causes of ESRD (51.5% vs 30.7%; P = .049). UC and UTI were not significantly associated with increased graft loss or mortality. UC were significantly higher in children with cystoplasty while UTIs were significantly higher in girls and children with urological causes of ESRD. Presence of UC did not affect the rate of graft loss or mortality due to its early detection and proper management.

Klotho G-395A gene polymorphism: impact on progression of end-stage renal disease and development of cardiovascular complications in children on dialysis

BackgroundKlotho G-395-A gene polymorphism may impact children with end-stage renal disease (ESRD). We investigated the relevance of Klotho G-395-A on ESRD development and progression, and its relationship with evolution of cardiovascular complications in pediatric dialysis patients.MethodsFifty-five children with chronic kidney disease (CKD) and seventy healthy children were genotyped for Klotho G-395A.ResultsIncidence of GA/AA genotypes and A allele were higher in ESRD patients compared with controls (54.5 vs. 7.1%, P < 0.001; 30.9 vs. 13.6%, P = 0.001, respectively). Also, children with GA/AA genotypes were 15.6 times more likely to develop ESRD than with GG genotype (95% CI 5.4–44.7, P < 0.001). A allele carriers have 2.8 times higher risk of developing ESRD than those with G allele (95% CI 1.5–5.35, P = 0.001). Also, the A allele could be considered a predictor of cardiovascular disease (CVD), as carriers have 161 times higher risk of cardiovascular complications than non-carriers (95% CI 21–1233, P < 0.001). All ESRD patients with CVD presented with left ventricular hypertrophy (LVH) and the frequency of A allele was significantly higher among ESRD children with LVH, whereas G allele frequency was significantly higher among ESRD children without LVH.ConclusionsThe A allele of the G-395A Klotho gene polymorphism shows a significantly higher frequency among children with CKD and those with CVD and LVH. This mutant allele could be used as a risk marker for the development of ESRD as well as a predictor of CVD in these children.

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

BACKGROUND An essential milestone in pediatric transplantation is to find noninvasive biomarkers to monitor acute rejection (AR). In this retrospective (Case-control) study, we examined the role of Fas -670A/G and Fas Ligand (FasL) -843C/T gene polymorphisms in allograft nephropathy in pediatric renal transplant recipients. METHODS In 47 pediatric kidney transplant recipients and 20 healthy controls, Fas -670A/G and FasL -843C/T gene polymorphisms as well as serum soluble Fas Ligand level (sFasL) were measured. RESULTS Serum sFasL levels were significantly higher in transplant recipients children than that in controls (548.25±298.64pg/ml vs 143.17±44.55pg/ml, p=0.0001). There was no significant difference between patients with AR and those without AR in regards to serum sFasL levels (567.70±279.87pg/ml vs 507.85±342.80pg/ml, p=0.56). Fas -670A/G genotypes or alleles were not significantly different between controls and transplant recipients and among transplant recipients with and without AR. (P>0.05 for all). FasL -843C/T genotypes were not different between transplant recipients and controls and among transplant recipients with and without AR (P>0.05 for all). However, Frequency of C allele in transplant patients was significantly higher than that in the control group (44.68% vs 25%, P=0.03). FasL -843C/T alleles were significantly different between patients with and without AR (P=0.03). The percentages of C allele were higher in children with AR (58.82% vs 36.67%). We found that serum FasL and serum creatinine were variables that were independently associated with AR. CONCLUSION This study suggests that FasL gene polymorphisms in peripheral blood might be accurate in detecting cellular AR.

The effect of on-line hemodiafiltration on improving the cardiovascular function parameters in children on regular dialysis.

The cardiovascular disease is an important cause of morbidity and accounts for almost 50% of deaths in patients undergoing maintenance dialysis. Many harmful molecules of the uremic milieu, such as the middle molecules, are difficult to remove by conventional hemodialysis (HD). On-line hemodiafiltration (OL-HDF) can achieve a considerable clearance of middle molecules and, together with its sterile ultrapure infusate, may have favorable effects on inflammation and cardiovascular complications. We aimed in this study to assess the effect of OL-HDF on improving the chronic inflammatory state associated with chronic kidney disease and the possible impact of these changes on myocardial function in chronic HD children. Thirty pediatric patients [12 (40%) males and 18 (60%) females with a mean age of 11.3 ± 3.2 years] on conventional HD for at least six months were switched to OL-HDF for six months. Variables for comparison at the end of each period included the levels of serum C-reactive protein and Kt/V as well as electrocardiography and echocardiographic measurements, including left ventricular mass index (LVMI). On changing from HD to OL-HDF, there was a significant decrease in hs-CRP (from 7.9 ± 8.9 to 3.4 ± 3 μ g/mL) (P = 0.01) and frequency of diastolic dysfunction (P = 0.04), while systolic function (FS and EF) improved significantly (P = 0.007 and 0.05, respectively), while LVMI did not change. We conclude that OL-HDF was well tolerated in children with improvement of the systolic function of the myocardium and the overall frequency of diastolic dysfunction.