Vascular access challenges in hemodialysis children.

BACKGROUND: Hemodialysis (HD) success is dependent mainly on vascular access (VA). The aim of this study is to share the experience of Pediatric Nephrology Unit (PNU), Cairo University Children's Hospital (CUCH), with VA-related obstacles in end stage kidney disease (ESKD) HD children. METHODS: This is a retrospective analysis of VA related data of 187 ESKD children received regular HD over 3 year duration (2019-2021). Kaplan-Meier curves were used to present arteriovenous fistula (AVF) and cuffed catheters survivals. RESULTS: Uncuffed central venous catheter (CVC) was the primary VA for HD in up to 97.3% with 2.7% of patients had AVF performed and attained maturation before initiation of regular HD. Fifty-six (29.9%) patients have inserted 120 tunneled CVCs. AVFs & AV grafts (AVF) were performed in 79 (42.2%) and 6 (3.2%) patients respectively. There were 112 uncuffed CVCs implanted beneath the screen in Rt internal jugular vein (IJV) (44%) Lt IJV (17%), right internal mammary vein (2.7%) while Trans hepatic (TH) technique was used to place 39 uncuffed CVCs (34%) in the inferior vena cava (IVC). Catheter-related bacteremia (CRB) was the most frequent complication in uncuffed and cuffed CVCs (2.58 / 100 catheters day and 10.1 /1000 catheter days respectively). AVFs achieved a high success rate (83%) after 757.71 ± 512.3 functioning days. CONCLUSION: Native AVF is the preferred VA for pediatric HD but its creation is limited by the small sized vessels where non-cuffed CVC could be a reasonable relatively long-term alternative. Challenging situations (occluded central veins) could benefit from TH technique of CVC insertion in IVC.

Next-generation sequencing in identification of pathogenic variants in primary hyperoxaluria among 21 Egyptian families: Identification of two novel AGXT gene mutations.

BACKGROUND: Primary hyperoxaluria (PH) is a rare heterogeneous, autosomal recessive disorder of glyoxylate metabolism. It is characterized by excessive hepatic production of oxalate resulting in a wide spectrum of clinical, imaging, and functional presentation. The characteristic features of PH comprise of recurrent urolithiasis, renal stones, and/or nephrocalcinosis. Three known types of PH have been identified PH1, PH2, and PH3. Pathogenic variants in AGXT, GRHPR, and HOGA1 cause the phenotypic expression of PH. METHODS: In this study, we describe the clinical and genetic findings of 22 patients from 21 unrelated Egyptian families with the distinctive clinical features of PH. A thorough clinical evaluation followed by an NGS custom panel of AGXT, GRHPR, and HOGA1 genes was done. RESULTS: Two novel mutations (p.Gly27Glu and p.Gln256Serfs*17) and six previously reported mutations (p.Lys12Glnfs*156, p.Lys12Argfs*34, p.Ile244Thr, p.Asn22Ser, p.Pro11Leu, and p.Ile340Met) were identified in AGXT gene. The NGS panel results were validated thereafter using Sanger sequencing. CONCLUSION: Our results extend the number of AGXT mutations identified so far and emphasize the important role of genetic testing in providing proper counseling and patients management.

Hearing assessment in Egyptian children with chronic renal failure on regular hemodialysis and renal transplantation children.

INTRODUCTION: Hearing impairment is frequent in patients with end-stage renal disease (ESRD). We aimed to assess the prevalence of hearing impairment in children on regular hemodialysis and renal transplantation. MATERIALS AND METHODS: Transient-evoked otoacoustic emissions (TEOAEs) has been done for 80 children on regular hemodialysis and 40 with renal transplant. RESULTS: In hemodialysis group, TEOAEs showed that 53.8% children had hearing affection, it was significantly related to dialysis duration, dialysis adequacy, vascular access infection, hepatitis C virus (HCV) infection, and ototoxic drugs (p = 0.001, 0.037, 0.011, 0.004, 0.030, 0.007, and 0.044, respectively). In renal transplant group hearing impairment was 25%. There was significant relation with period of dialysis before transplantation and biopsy proved rejection (p = 0.008, <0.001, respectively). CONCLUSION: Hearing impairment is a common finding in ESRD patients. Thus audiological assessment must be done in these patients.

Primary hyperoxaluria type 1 in children: Clinical classification, renal replacement therapy, and outcome in a single centre experience.

Primary hyperoxaluria type 1 (PH1) is a rare disease that is challenged by the overproduced oxalate and commonly presented with radiopaque renal stones or obstructive uropathy. This study aimed to report clinical presentations, renal replacement therapy (RRT), and outcome of PH1 in end stage kidney disease (ESKD) children. This is an observational cohort study. Data of 22 patients with ESKD due to PH1 were analyzed at Pediatric Nephrology Unit, Faculty of Medicine Cairo University. Infantile onset patients (n = 10) had worst renal outcome (80% with ESRD at presentation, p = 0.019) and worse patient outcome (mortality 40%, p = 0.016) than juvenile (n = 9) and late onset (PH1 n = 3) patients. RRT modalities include peritoneal dialysis (PD) in 7 (31.8%), hemodialysis (HD) in 11 (50%), and combined liver kidney transplantation (CLKT) in 4 (18.2%) patients. Infectious complications were encountered in 42.8% of PD patients. Better HD adequacy was observed with frequent HD (n = 6) and/or HD via arteriovenous fistula (AVF) than with infrequent dialysis (n = 5) and/or via central venous line (CVL) (p = 0.0001 and 0.0047, respectively). Morbidity and mortality (infection related) rates of the whole cohort were 63.6% and 31.8%, respectively. Clinical presentation of PH1 varies according to the age of onset (infantile onset being the most aggressive form). Aggressive HD (better through AVF) is needed to achieve acceptable HD adequacy, PD was challenged by infection. Infection found to be the main cause of mortality even after successful CLKT.

Pediatric focal segmental glomerulosclerosis: favorable transplantation outcome with plasma exchange.

BACKGROUND: Although kidney transplantation (KTX) is the treatment of choice for pediatric end stage kidney disease (ESKD); concerns for recurrence in cases of focal segmental glomerulosclerosis (FSGS) are still present. This study aimed to investigate the outcome of KTX in children with ESKD secondary to FSGS, with implementation of preemptive perioperative plasma exchange (PE) for non-genetically proven patients. METHODS: Forty FSGS pediatric kidney transplant recipients were studied. Of them: 12 patients (30%) had genetically proven NPHS2 mutations/familial and 28 (70%) were sporadic FSGS patients. All sporadic patients electively received 6 perioperative PE sessions. Patients with recurrence of proteinuria (n = 13; including 3 patients with genetic/familial and 10 patients with sporadic FSGS) were managed with PE and Rituximab (RTX). Kaplan-Meier curves were used to analyze graft and recurrence free survival data. RESULTS: The mean follow-up duration after KTX was 3.8 ± 2.86 years. Recurrence of proteinuria was encountered early postoperative in 11 patients (27.5%) and late (1.6 and 2.9 years after KTX) in 2 patients (5%). All patients with early recurrence achieved complete remission, while patients with late recurrence developed graft failure. Current serum creatinine and proteinuria levels were not different in patients received PE (n = 31) and patients did not PE (n = 9) (p = 0.308 and 0.287 respectively). Current serum creatinine and proteinuria levels in sporadic patients (n = 28) after prophylactic perioperative PE were not different from those of genetic/ familial patients (n = 12) (p = 0.303 and 0.144 respectively). Proteinuria was less in patients underwent native nephrectomy than others immediately postoperative and at assessment (p = 0.002 & 0.0031 respectively). One-year graft and patient survival was 93.8% with a mean 1-year serum creatinine of 0.67 ± 0.25 mg/dl. Three graft losses (7.5%) were due to chronic rejection 3.3, 3.75 and 4.17 years after KTX and 2 patients' mortality (5%) occurred early postoperative (first 2 weeks). CONCLUSION: FSGS transplanted children have favorable outcomes with perioperative PE for non-genetically proven cases. Early recurrence after KTX can be successfully managed with PE and RTX.

Accelerating Hepatitis C virus elimination in Egypt by 2030: A national survey of communication for behavioral development as a modelling study.

AIM OF THE WORK: This study aimed at assessing the dominance of risk practices associated with HCV endemicity in Egypt and detecting the behavioral development level concerning different aspects of HCV risk behaviors with respect to age and gender. The survey highlights the most cost-effective strategies that could accelerate HCV elimination in Egypt. SUBJECTS AND METHODS: A national household survey targeted 3780 individuals (age range: 10-85 years). The sample was a systematic probability proportionate to size from 6 governorates representing the six major subdivisions of Egypt. The indicators used for assessing the behavioral development level towards HCV included six domains: awareness (7 indicators), perceived risk (5 indicators), motivation with the intention to change (4 and 5 indicators for males and females respectively), trial, rejection or adoption (6 and 5 indicators for males and females respectively). RESULTS: The study revealed that along the continuum of behavior development, the percentage of the participants who acquired half of the scores was as follows: 73.1% aware, 69.8% developed perceived risk, 80.6% motivated with only 28.9% adopting the recommended behaviors, 32% rejected them, 2.3% were in the trial stage versus 35.8% who did not try any. Adolescents had significantly lower levels of development for almost all domains when compared to adults. Statistical higher significance was detected in favor of adults, employees, married, Lower Egypt governorates, and university-educated participants (p<0.001) regarding awareness, perceived risk, and motivation scores. More than half of the participants incorrectly believed that contaminated food, sharing food utilities, contaminated water, mosquitoes, and schistosomiasis would lead to HCV transmission. CONCLUSION: Egypt would be closer to HCV elimination when cost-effective strategies are directed not towards creating awareness, perceived risk or motivation to change- (at an acceptable level)- but towards motivating adopting risk-reduction behaviors for HCV, tackling misconceptions and reinforcement of social support.

Pediatric kidney transplantation in Egypt: Results of 10-year single-center experience.

Pediatric kidney transplantation is a multidisciplinary therapy that needs special consideration and experience. In this study, we aimed to present CUCH experience; over a 10-year period, as a specialized center of kidney transplantation in children. We studied 148 transplantations performed at a single center from 2009 to 2018. Pretransplant and follow-up data were collected and graft/patient survival rates were evaluated. A total of 48 patients developed at least one rejection episode during 688 patient-years of follow-up. Infections, recurrence of original disease, and malignancy were the most important encountered medical complications (20%, 2%, and 1.4%, respectively). One-year patient survival was 94.1%, while graft and patient survival was 91.9%. Graft/patient survival at 5, 7, and 9 years was 90%, 77%, and 58%, respectively. Infections were the main cause (69%) of mortality. Death with a functioning graft and CR were the main causes of graft loss (48% and 33%, respectively). Pediatric kidney transplantation in Egypt is still a challenging yet successful experience. Rejections and infections are the most frequent complications. Short-term outcomes surpass long-term ones and graft survival rates are similar to the international standard.

Safety and Efficacy of Pegylated Interferon Alpha-2b Monotherapy in Hepatitis C Virus-Infected Children with End-Stage Renal Disease on Hemodialysis.

Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-α 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 µg/m2 of PEG IFN-α 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects.

MEFV mutations in Egyptian children with systemic-onset juvenile idiopathic arthritis.

BACKGROUND AND OBJECTIVES: Systemic-onset juvenile idiopathic arthritis (SoJIA) is a chronic auto-inflammatory disease of childhood, with a complex genetic trait, which is characterized by arthritis associated with systemic manifestations. Familial Mediterranean fever (FMF) is another auto-inflammatory disorder that is monogenic. There are speculations as to whether Mediterranean fever (MEFV) mutations are among the genetic determinants of SoJIA. Our aim was to explore the frequency and clinical significance of MEFV mutations in Egyptian SoJIA patients. A group of healthy children were assigned to the control group in an attempt to estimate the carrier rate of MEFV mutations in Egypt. METHODS: Eighty-four children were recruited in this study; 54 children, age (mean ± standard deviation; 8.31 ± 2.85 years), diagnosed as having SoJIA with no typical symptoms of FMF; 30 healthy age- and gender-matched children served as the control group. All recruited children were screened for 12 common MEFV mutations using a reverse hybridization assay of biotinylated PCR products. RESULTS: SoJIA patients had a significantly higher frequency of MEFV mutations (66.7 %) than in the healthy control population (16.7 %). V726A was the leading mutation in SoJIA patients, with an allelic frequency of 15.74 %, followed by E148Q, with an allelic frequency of 7.4 %. Children who were carriers of MEFV mutations had an 18 times higher risk of developing SoJIA than wild-type carriers [odds ratio 18.0 (95 % CI 5-69), P < 0.01]. E148Q was the leading mutation, present in 13.3 % of healthy controls. CONCLUSION: These findings suggest that MEFV mutations may be responsible for auto-inflammatory diseases other than FMF, and patients with SoJIA, especially those with a positive family history of FMF or SoJIA, should be screened for MEFV mutations in countries where FMF is frequent.