Publications by authors named "Khalid Alhasan"

28 Publications

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Coronavirus disease in children: A multicentre study from the Kingdom of Saudi Arabia.

J Infect Public Health 2021 Apr 18;14(4):543-549. Epub 2021 Jan 18.

Paediatrics Department, King Saud University, Riyadh, Saudi Arabia.

Background: The COVID-19 global pandemic caused by severe acute respiratory syndrome coronavirus 2 infection, warranted attention for whether it has unique manifestations in children. Children tend to develop less severe disease with a small percentage present with clinical manifestations of paediatric multisystem inflammatory syndrome and have poor prognosis. We studied the characteristics of COVID-19 in children requiring hospitalisation in the Kingdom of Saudi Arabia and assessed the clinical presentation and the risk factors for mortality, morbidity, and paediatric intensive care (PICU) admission.

Methods: We conducted a retrospective analysis of COVID-19 patients under 15 years hospitalised at three tertiary academic hospitals between 1 March and 30 June 2020.

Results: Eighty-eight children were enrolled (>20% were infants). Seven (8%) were in critical condition and required PICU admission, and 4 (4.5%) died of which 3 met the full diagnostic criteria of multi-system inflammatory syndrome and had a high Paediatric Risk of Mortality (PRISM) score at the time of admission. The initial polymerase chain reaction (PCR) test result was positive for COVID-19 in most patients (97.7%), and the remaining two patients had positive result in the repeated confirmatory test. In a subset of patients (20 subjects), repeated PCR testing was performed until conversion to negative result, and the average duration for conversion was 8 (95% CI: 5.2-10.5) days Children requiring PICU admission presented with signs of respiratory distress, dehydration, and heart failure. Most had fever (71.4%) and tonsillitis; 61.4% were discharged within 7 days of hospitalisation. Risk factors for mortality included skin rash, hypotension, hypoxia, signs of heart failure, chest radiograph suggestive of acute respiratory distress syndrome, anaemia, leucocytosis, hypernatraemia, abnormal liver enzymes, and high troponin I, and risk factors for prolonged hospitalisation (>7 days) included the presence of comorbidities, leucopaenia, hyponatraemia, and elevated C-reactive protein.

Conclusions: The majority of hospitalised children had a brief febrile illness and made a full recovery, but a minority had severe disease.
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http://dx.doi.org/10.1016/j.jiph.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981189PMC
April 2021

Living well with kidney disease.

Pediatr Nephrol 2021 May 1;36(5):1035-1036. Epub 2021 Mar 1.

Department of Pediatrics, University of Puerto Rico, Medical Sciences Campus, PO Box 365067, San Juan, 00936-5067, Puerto Rico.

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http://dx.doi.org/10.1007/s00467-021-05011-0DOI Listing
May 2021

Diversity of Phenotype and Genetic Etiology of 23 Cystinuria Saudi Patients: A Retrospective Study.

Front Pediatr 2020 11;8:569389. Epub 2020 Nov 11.

King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia.

Cystinuria is an inborn error of metabolism that manifests with renal stones due to defective renal epithelial cell transport of cystine which resulted from pathogenic variants in the and/or genes. Among nephrolithiasis diseases, cystinuria is potentially treatable, and further stone formation may be preventable. We report 23 patients who were identified biochemically and genetically to have cystinuria showing the diversity of the phenotype of cystinuria and expanding the genotype by identifying a broad spectrum of mutations. This is a multicenter retrospective chart review, where clinical and biochemical data, genetic analysis and the progress of the disease were documented over five years at two centers from 2014 to 2019. Of 23 patients who were identified biochemically and/or genetically to have cystinuria, 14 (62%) were male. Thirteen patients were homozygous, and two were heterozygous for the gene. Seven were homozygous and one was compound heterozygous for the gene. We have detected 12 genetic variants including five novel variants. 1 gene variant c.1400 T > A (p.Met467Lys) is found in 38% of our cohort. Although 21 patients required surgical intervention, none developed ESRD. The number of stone episodes per year varied widely (median frequency of 0.45 stones/ per year, range between 0.06 and 78.2), with no significant difference in stone events per year between sexes ( = 0.73). Despite the high rate of consanguinity in Saudi Arabia, there was a broad spectrum of genetic variants. Most of our patients are homozygous recessive for genes with multiple generations affected which indicates early screening and prevention of disease in these families. Phenotypic heterogeneity is well documented in our cohort even with the same genotype and the first stone episode age was variable but most commonly seen in the first decade of life.
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http://dx.doi.org/10.3389/fped.2020.569389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686133PMC
November 2020

Long-stay patients in pediatric intensive care units. Five-years, 2-points, cross-sectional study.

Saudi Med J 2020 Nov;41(11):1187-1196

Pediatric Department, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.

Objectives: To explore the changing patterns of long-stay patients (LSP) to improve the utilization of pediatric intensive care units (PICUs) resources.

Methods: This is a 2-points cross-sectional study (5 years apart; 2014-2019) conducted among PICUs and SCICUs in Riyadh, Saudi Arabia. Children who have stayed in PICU for more than 21 days were included.

Results: Out of the 11 units approached, 10 (90%) agreed to participate. The prevalence of LSP in all these hospitals decreased from 32% (48/150) in 2014 to 23.4% (35/149) in 2019. The length of stay ranged from 22 days to 13.5 years. The majority of LSP had a neuromuscular or cardiac disease and were admitted with respiratory compromise. Ventilator-associated pneumonia was the most prevalent complication (37.5%). The most commonly used resources were mechanical ventilation (93.8%), antibiotics (60.4%), and blood-products transfusions (35.4%). The most common reason for the extended stay was medical reasons (51.1%), followed by a lack of family resources (26.5%) or lack of referral to long-term care facilities (22.4%).

Conclusion: A long-stay is associated with significant critical care bed occupancy, complications, and utilization of resources that could be otherwise utilized as surge capacity for critical care services. Decreasing occupancy in this multicenter study deserves further engagement of the healthcare leaders and families to maximize the utilization of resources.
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http://dx.doi.org/10.15537/smj.2020.11.25450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804226PMC
November 2020

Efficacy and safety of three times daily dosing of tacrolimus in pediatric kidney transplantation patients: A single-center comparative study.

Pediatr Transplant 2020 09 28;24(6):e13733. Epub 2020 May 28.

Biostatistics Epidemiology & Scientific Computing Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Background/aim: Several PK studies have shown that most pediatric patients may require higher doses on a mg/kg basis compared to adults to attain similar therapeutic trough concentrations. The aim of this study was to compare the efficacy and safety of three times daily to twice a day dosing of tacrolimus in pediatric kidney transplant recipients at a major tertiary care transplant center.

Methods And Materials: Retrospective, single-center, and comparative cohort study. All pediatric kidney transplant recipients received either tacrolimus BID (group 1) or tacrolimus TID (group 2).

Results: A total of 87 patients were included in this study; 48 patients received BID tacrolimus (group 1), and 39 patients received TID tacrolimus (group 2). The percentage of patients who achieved therapeutic trough concentrations in group 2 did not significantly differ from those in group 1 at day 7 (84.62% TID vs 83.33% BID; P = .42). The median time to reach therapeutic trough concentrations was three days in group 1 compared to four days in group 2.

Conclusion: No significant difference was observed between tacrolimus BID and TID dosing in the time to reach therapeutic trough concentration or in the proportion of patients achieving therapeutic trough concentrations at day 7.
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http://dx.doi.org/10.1111/petr.13733DOI Listing
September 2020

Cinacalcet use in pediatric chronic kidney disease. A survey study.

Saudi Med J 2020 May;41(5):479-484

Department of Pediatrics, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. E-mail.

Objectives: To evaluate the practice and attitude of pediatrics nephrologists about cinacalcet use in children.

Methods: An electronic structured questionnaire was answered by pediatric nephrologists practicing in the Kingdom of Saudi Arabia (KSA) and Gulf Council countries (GCC).

Results: A total of 42  pediatric nephrologists responded, of them, 42% used cinacalcet for young children ≤5 years of age and 79% used for children. There were wide variations in the method of administration (examples: crushed, divided, whole tablets), monitoring, doses and response definition, and follow-up. No serious complications after starting cinacalcet was observed in 50%, while 40% reported various complications, mainly hypocalcemia (70%). Cinacalcet was stopped without achieving the target parathyroid hormone in more than half (55%) of children because of intractable adverse effects (40%), poor response (30%), non-adherence (25%), or high cost (5%).

Conclusion: Cinacalcet is used by the majority of pediatric nephrologists in KSA and GCC. A standard clinical guideline is needed to be followed by all users.
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http://dx.doi.org/10.15537/smj.2020.5.25072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253826PMC
May 2020

Rituximab versus cyclophosphamide as first steroid-sparing agent in childhood frequently relapsing and steroid-dependent nephrotic syndrome.

Pediatr Nephrol 2020 08 27;35(8):1445-1453. Epub 2020 Apr 27.

Faculty of Medicine, King Abduaziz University, PO Box 80215, Jeddah, 21589, Kingdom of Saudi Arabia.

Background: Approximately 50% of children with steroid-sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications.

Methods: A prospective open-label non-randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia, or active infection. The recruited children were allocated either to the oral cyclophosphamide (3 mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months.

Results: Forty-six subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR 0.36; 95% CI 0.09-1.45; p = 0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N = 10) and 6.3 months in the rituximab group (N = 3). Both treatments were associated with a significant (p < 0.001) reduction in prescribed dose of oral alternate-day steroid from 1.02 to 0.36 mg/kg (cyclophosphamide) and 0.86 to 0.08 mg/kg (rituximab). Importantly, a significantly (p = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group. Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity besides severe leucopenia and neutropenia in the 7th week of treatment with complete recovery with the withdrawal of cyclophosphamide and maintenance of remission. A minor infusion-related reaction in the form of a generalized macular skin rash was observed in one patient (5%) in the rituximab group.

Conclusions: Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide. Graphical abstract.
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http://dx.doi.org/10.1007/s00467-020-04570-yDOI Listing
August 2020

Correction to: Short-term outcome associated with disease severity and electrolyte abnormalities among critically ill children with acute kidney injury.

BMC Nephrol 2020 Apr 16;21(1):137. Epub 2020 Apr 16.

Pediatric Nephrology Center of Excellence, Pediatric Department, Faculty of Medicine, King Abdulaziz University, PO Box 80215, Jeddah, 21589, Kingdom of Saudi Arabia.

Following publication of the original article [1].
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http://dx.doi.org/10.1186/s12882-020-01790-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164215PMC
April 2020

Renal histopathology spectrum in children with kidney diseases in Saudi Arabia, 1998-2017.

Saudi Med J 2020 Apr;41(4):369-375

Department of Pediatric, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.

Objectives: To identify the trends in the diagnostic frequency of glomerular disease subtypes by renal biopsy in children in Saudi Arabia over the last 20 years.

Methods: In this retrospective observational study, we identified all patients aged less than 18 years for whom native kidney biopsy was performed between 1998 and 2017. The period during which biopsy was performed (1998-2004, 2005-2011, and 2012-2017) and the demographic information and their association with the prevalence of various glomerular disease subtypes were our primary outcomes. Results: A total of 326 cases with renal biopsy were analyzed; the mean age of participants being 11 years and 45.4% of them were girls. Unexpectedly, secondary glomerulonephritis accounted for 42.3% of the cases, and lupus nephritis was the most common cause noted in 20.7% of the cases. The minimal change and focal segmental glomerulosclerosis were the most common glomerulonephritis in 59% of the cases. The frequency of membranoproliferative glomerulonephritis and mesangioproliferative glomerulonephritis significantly decreased from 15% and 17% in the period prior to 2004 to 3.3% (p=0.003) and 1.7% in 2012-2017 (p less than 0.001).

Conclusions: We found a considerable shift in the frequency of many glomerular disease subtypes in 1998-2017, which make clinical predication of the underlying etiology challenging for clinician. Renal biopsy still remains a critical diagnostic procedure for managing a considerable proportion of renal diseases.
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http://dx.doi.org/10.15537/smj.2020.4.24999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841618PMC
April 2020

Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy.

Nat Rev Nephrol 2020 08 8;16(8):471-482. Epub 2020 Apr 8.

Division of Nephrology, University of Missouri-Kansas City School of Medicine, Children's Mercy, Kansas City, MO, USA.

Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations.
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http://dx.doi.org/10.1038/s41581-020-0267-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366888PMC
August 2020

Responsiveness of sphingosine phosphate lyase insufficiency syndrome to vitamin B6 cofactor supplementation.

J Inherit Metab Dis 2020 09 4;43(5):1131-1142. Epub 2020 May 4.

Department of Pediatrics, Division of Hematology/Oncology, University of California, San Francisco, California, USA.

Sphingosine-1-phosphate (S1P) lyase is a vitamin B6-dependent enzyme that degrades sphingosine-1-phosphate in the final step of sphingolipid metabolism. In 2017, a new inherited disorder was described caused by mutations in SGPL1, which encodes sphingosine phosphate lyase (SPL). This condition is referred to as SPL insufficiency syndrome (SPLIS) or alternatively as nephrotic syndrome type 14 (NPHS14). Patients with SPLIS exhibit lymphopenia, nephrosis, adrenal insufficiency, and/or neurological defects. No targeted therapy for SPLIS has been reported. Vitamin B6 supplementation has therapeutic activity in some genetic diseases involving B6-dependent enzymes, a finding ascribed largely to the vitamin's chaperone function. We investigated whether B6 supplementation might have activity in SPLIS patients. We retrospectively monitored responses of disease biomarkers in patients supplemented with B6 and measured SPL activity and sphingolipids in B6-treated patient-derived fibroblasts. In two patients, disease biomarkers responded to B6 supplementation. S1P abundance and activity levels increased and sphingolipids decreased in response to B6. One responsive patient is homozygous for an SPL R222Q variant present in almost 30% of SPLIS patients. Molecular modeling suggests the variant distorts the dimer interface which could be overcome by cofactor supplementation. We demonstrate the first potential targeted therapy for SPLIS and suggest that 30% of SPLIS patients might respond to cofactor supplementation.
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http://dx.doi.org/10.1002/jimd.12238DOI Listing
September 2020

Pediatric Continuous Renal Replacement Therapy (PCRRT) expert committee recommendation on prescribing prolonged intermittent renal replacement therapy (PIRRT) in critically ill children.

Hemodial Int 2020 04 18;24(2):237-251. Epub 2020 Feb 18.

Pediatric Nephrology, Akron Children's Hospital, Akron, Ohio.

Introduction: Recently, prolonged intermittent renal replacement therapies (PIRRT) have emerged as cost-effective alternatives to conventional CRRT and their use in the pediatric population has started to become more prominent. However, there is a lack of consensus guidelines on the use of PIRRT in pediatric patients in an intensive care setting.

Methods: A literature search was performed on PubMed/Medline, Embase, and Google Scholar in conjunction with medical librarians from both India and the Cleveland Clinic hospital system to find relevant articles. The Pediatric Continuous Renal Replacement Therapy workgroup analyzed all articles for relevancy, proposed recommendations, and graded each recommendation for their strength of evidence.

Results: Of the 60 studies eligible for review, the workgroup considered data from 37 studies to formulate guidelines for the use of PIRRT in children. The guidelines focused on the definition, indications, machines, and prescription of PIRRT.

Conclusion: Although the literature on the use of PIRRT in children is limited, the current studies give credence to their benefits and these expert recommendations are a valuable first step in the continued study of PIRRT in the pediatric population.
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http://dx.doi.org/10.1111/hdi.12821DOI Listing
April 2020

Hypokalemic periodic paralysis due to CACNA1S gene mutation.

Neurosciences (Riyadh) 2019 Jul;24(3):225-230

Division of Pediatric Nephrology, Pediatric Department, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail:

Hypokalemic periodic paralysis (HypoPP) is a relatively rare but treatable disorder caused by mutations in the CACNA1S gene. HypoPP patients may experience paralytic episodes associated with hypokalemia and, infrequently, may develop late-onset proximal myopathy. The paralytic attacks are characterized by reversible flaccid paralysis and, in most cases, spare the respiratory muscles and heart. We report a case of CACNA1S periodic paralysis precipitated by vigorous exercise in a 14-year-old boy who presented with sudden-onset paralysis of both his upper and lower extremities. Laboratory evaluation revealed a markedly low serum potassium level. The patients symptoms resolved after correction of the potassium abnormality, and he was discharged with no neurological deficits. Although rare, HypoPP must be differentiated from other causes of weakness and paralysis so that proper treatment can be promptly initiated to ensure good outcomes.
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http://dx.doi.org/10.17712/nsj.2018.3.20180005DOI Listing
July 2019

Therapeutic plasma exchange for children with kidney disorders: Definitions, prescription, indications, and complications.

Authors:
Khalid A Alhasan

Saudi J Kidney Dis Transpl 2019 Mar-Apr;30(2):291-298

Department of Pediatrics, College of Medicine, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia.

Therapeutic plasma exchange (TPE) is a procedure that involves the removal of a large volume of plasma that is replaced with a replacement fluid, which is usually 5% albumin or fresh-frozen plasma. This therapeutic modality presents several technical challenges in children but has become increasingly used in pediatric nephrology. Owing to advances in technology, scientists have gained substantial knowledge of the molecular pathogenesis underlying many pediatric renal diseases, supporting the use of TPE in treating these disorders. This review presents a synopsis of the literature as it relates to the accepted indications for TPE in children, the technical aspects of the procedure, and the associated complications. Increased collaboration between pediatric nephrologists will hopefully allow scientists to obtain more data in children to assess the benefits of TPE in various renal disorders and improve the quality of care provided in children with renal disorders.
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http://dx.doi.org/10.4103/1319-2442.256835DOI Listing
December 2019

Preface.

Transplant Proc 2019 03;51(2):487

Consultant Nephrologist, College of Medicine, King Saud University; President of the Saudi Society of Nephrology and Transplantation. Electronic address:

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http://dx.doi.org/10.1016/j.transproceed.2019.01.003DOI Listing
March 2019

Short-term outcome associated with disease severity and electrolyte abnormalities among critically ill children with acute kidney injury.

BMC Nephrol 2019 03 12;20(1):89. Epub 2019 Mar 12.

Pediatric Nephrology Center of Excellence, Pediatric Department, Faculty of Medicine, King Abdulaziz University, PO Box 80215, Jeddah, 21589, Kingdom of Saudi Arabia.

Background: Acute kidney injury (AKI) in critically ill children is associated with increased mortality and morbidity. In this study we evaluated the effect of AKI severity on the incidence of short-term mortality and morbidity.

Methods: Multicenter prospective cohort study was conducted over two years period. We used the Kidney Disease Improving Global Outcomes (KDIGO) to diagnose and stage AKI.

Results: A total of 511 out of 1367 included children (37.4%; 95% CI: 34.8-40.0) were diagnosed with AKI. They were categorized into three KDIGO stages: stage I (mild) in 47.5% (95% CI: 43.2-52.0), stage II (moderate) in 32.8% (95% CI: 28.8-37.1) and stage III (severe) in 19.7% (95% CI: 16.4-23.5). Stage II and III AKI had higher risk of mortality and longer length of stay (LOS) in hospital. Children with stage III AKI were more likely to require mechanical ventilation, referral to pediatric nephrology and discharge with abnormal creatinine level (above 100 uml\L). Hypervolemia, hypocalcemia, anemia, and acidosis were found to be independent risk factors of mortality.

Conclusion: The extent of severity of AKI is directly associated with increased mortality, LOS and short-term morbidity.
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http://dx.doi.org/10.1186/s12882-019-1278-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417256PMC
March 2019

Effect of new modalities of treatment on physicians management plan for patients with spinal muscular atrophy.

Neurosciences (Riyadh) 2019 01;24(1):16-21

Division of Neurology, Department of Pediatrics, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail:

Objective: To determine physicians` attitudes and stated practice in the management of patients with spinal muscular atrophy (SMA). We also aimed to explore their knowledge about consensus statement for standard of care in SMA and the role of new treatment modalities in changing the method of practice in the management of these cases.

Methods: This is a quantitative observational cross-sectional study, conducted from February to May 2017 among physicians who manage SMA patients in Kingdom of Saudi Arabia. The study cohort included pediatric neurologists, adult neurologists, and physicians of other sub-specialties who manage SMA patients. We used online and paper-based questionnaires.

Results: Half of the 169 participants were aware of the consensus guidelines for the care of SMA patients. With regard to the newly released Nursinersen treatment protocol for SMA-diagnosed patients, half of the participants were uncertain, and the other half were hesitant about its outcomes. Junior physicians tended to be significantly more inclined to reverse the do-not-resuscitate (DNR) status of an SMA-diagnosed child than more senior physicians.

Conclusion: Our results indicate the existence of wide differences in physician practice with children of SMA disease. Our data demonstrate a need for increased awareness of consensus guidelines and further awareness about the physician`s role in the variability of care for children with SMA.
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http://dx.doi.org/10.17712/nsj.2019.1.20180321DOI Listing
January 2019

Genetics of congenital and infantile nephrotic syndrome.

World J Pediatr 2019 Apr 5;15(2):198-203. Epub 2019 Feb 5.

King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.

Background: Congenital and infantile nephrotic syndrome (CNS and INS) are rare inherited defects in glomerular filtration involving a variety of gene mutations. This study aimed to analyze all genetic mutations associated with congenital and infantile nephrotic syndrome treated at our institution. We also discussed our different approach secondary to culture and resources.

Methods: A retrospective single-center study of all children diagnosed as NS before the age of 1 year over a duration of over one decade.

Results: Twenty-nine children (12 boys) were included in the study. Their median age (range) was 2.4 (0.1-12) months (20 CNS and 9 INS). Consanguinity was present in 90% of children. The genetic analysis' results were only available for 20 children. An underlying causative homozygous mutation was detected in 18 children (90%): NPHS1 (9), NPHS2(2), LAMB2(3), PLCE1(1), WT1(1), and ITSN1 novel mutation (2). One child had heterozygous mutation of NPHS2 and another child had heterozygous mutation of NPHS1 which could not explain the disease. All CNS cases were all managed with intermittent intravenous albumin infusion, ACEi, diuretics, and indomethacin. None of the children were managed by nephrectomy followed by peritoneal dialysis (PD) because of limited resources. Only one child achieved partial remission, while 15 children died at a median (range) age of 5.8 (1.25-29) months. The remaining 14 children were followed up for an average of 36 (3.9-120) months. Three children progressed to end-stage kidney disease and PD was performed in only two children.

Conclusions: NPHS1 is the main underlying cause of CNS and INS in our study population. CNS and INS were associated with high morbidity and mortality.
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http://dx.doi.org/10.1007/s12519-018-00224-0DOI Listing
April 2019

Recurrent hydrothorax in a child on peritoneal dialysis: A case report and review of the literature.

Authors:
Khalid A Alhasan

Clin Case Rep 2019 Jan 25;7(1):149-151. Epub 2018 Nov 25.

Pediatric Department King Saud University College of Medicine Riyadh Saudi Arabia.

Hydrothorax is a serious complication of peritoneal dialysis, and it may be resolved by deferring dialysis or decreasing dialysate volumes. Repeat thoracentesis is not well tolerated in children. Therefore, if conservative measures fail, thoracotomy or thoracoscopy with endoscopic repair of associated diaphragmatic eventration should be considered before reinstating peritoneal dialysis.
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http://dx.doi.org/10.1002/ccr3.1936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333082PMC
January 2019

Assessment of physicians knowledge and attitudes in the management of febrile seizures.

Neurosciences (Riyadh) 2018 Oct;23(4):314-319

Division of Neurology, Department of Pediatrics, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail:

Objective: To assess the knowledge and attitudes of physicians in different specialties who are involved in the care of children with FS.

Methods: We assessed knowledge and attitudes in the management of Febrile seizure (FS) among physicians working in different specialties in the Kingdom of Saudi Arabia using a questionnaire-based cross-sectional study conducted from September-December 2016.

Results: Of the 300 physicians who responded to the questionnaire, 178 (59.3%) were males, 119 (39.7%) were consultants, 92 (30.7%) were specialists, and 89 (29.7%) were residents. The majority were general pediatric consultants. Our study showed that the consultants were more aware of the definition of simple FS in comparison to other groups of physicians, and the difference was statistically significant. However, there was no difference between pediatric neurologists and general pediatricians. There was a statistically significant difference among various specialties in the perceived need to perform routine lumbar puncture, neuroimaging, and serum electrolyte determination in the evaluation of children with FS. On the other hand, there was no difference in the perceived need to perform an electroencephalogram among physicians in different specialties.

Conclusion: The study highlighted the wide variation in knowledge and attitudes of physicians in different specialties with different levels of experience toward the management of FS. The use of clinical practice guidelines will help minimize this diversity.
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http://dx.doi.org/10.17712/nsj.2018.4.20180097DOI Listing
October 2018

Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome.

J Clin Invest 2018 10 4;128(10):4313-4328. Epub 2018 Sep 4.

Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Steroid-resistant nephrotic syndrome (SRNS) almost invariably progresses to end-stage renal disease. Although more than 50 monogenic causes of SRNS have been described, a large proportion of SRNS remains unexplained. Recently, it was discovered that mutations of NUP93 and NUP205, encoding 2 proteins of the inner ring subunit of the nuclear pore complex (NPC), cause SRNS. Here, we describe mutations in genes encoding 4 components of the outer rings of the NPC, namely NUP107, NUP85, NUP133, and NUP160, in 13 families with SRNS. Using coimmunoprecipitation experiments, we showed that certain pathogenic alleles weakened the interaction between neighboring NPC subunits. We demonstrated that morpholino knockdown of nup107, nup85, or nup133 in Xenopus disrupted glomerulogenesis. Re-expression of WT mRNA, but not of mRNA reflecting mutations from SRNS patients, mitigated this phenotype. We furthermore found that CRISPR/Cas9 knockout of NUP107, NUP85, or NUP133 in podocytes activated Cdc42, an important effector of SRNS pathogenesis. CRISPR/Cas9 knockout of nup107 or nup85 in zebrafish caused developmental anomalies and early lethality. In contrast, an in-frame mutation of nup107 did not affect survival, thus mimicking the allelic effects seen in humans. In conclusion, we discovered here that mutations in 4 genes encoding components of the outer ring subunits of the NPC cause SRNS and thereby provide further evidence that specific hypomorphic mutations in these essential genes cause a distinct, organ-specific phenotype.
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http://dx.doi.org/10.1172/JCI98688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159964PMC
October 2018

Etiology, ethics, and outcomes of chronic kidney disease in neonates.

Saudi Med J 2018 Apr;39(4):361-367

Pediatric Nephrology Center of Excellence, Department of Pediatrics, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. E-mail.

Objectives: To report the epidemiology of chronic kidney disease (CKD)  in neonates at a single tertiary center and the outcomes of renal replacement therapy (RRT) in these patients and discuss ethical considerations regarding RRT in this population.

Methods: In this retrospective study, we reviewed clinical data from all neonates with evidence of CKD who were followed up at King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia between 2005 and 2015. Follow-up serum creatinine levels were recorded every 6 months. Results: A total of 181 neonates presented with CKD. Their mean age at the time of presentation was 11.1 days (95% confidence interval [CI]: 9.5-12.8) and the mean creatinine level was 106.5 µmol/ (95% CI: 91.3-121.7). Congenital anomalies of the kidneys and urinary tract (CAKUT) were the underlying causes of CKD in 84.5% of the neonates. Mortality was high, particularly in the first 6 months (10%), and reached 16% by 4 years of follow-up. At the time of the last follow-up, 42 (41%) neonates had hypertension and 27 (26.5%) had significant proteinuria. Five patients received dialysis in the neonatal period and another 6 were commenced on dialysis later.

Conclusion: Congenital anomalies of the kidneys and urinary tract is the most common etiology in neonates with CKD. Chronic kidney disease in neonates is associated with high morbidity and mortality rates.
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http://dx.doi.org/10.15537/smj.2018.4.21712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938649PMC
April 2018

Urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C measurements for early diagnosis of acute kidney injury in children admitted to PICU.

World J Pediatr 2018 04 20;14(2):134-142. Epub 2018 Feb 20.

Pediatric Nephrology Center of Excellence and Department of Pediatrics, King Abdulaziz University, 80215, Jeddah, 21589, Kingdom of Saudi Arabia.

Background: Acute kidney injury (AKI) is common in critically ill children with significant mortality and morbidity. Serum creatinine is an insensitive and late biomarker compared to newly proposed AKI biomarkers.

Methods: Prospective study in pediatric intensive care unit (PICU) over three months to compare between serum cystatin-C (s-Cys-C) and urinary neutrophil gelatinase-associated lipocalin (uNGAL) as AKI biomarkers at multiple time points with pediatric risk, injury, failure, loss, end-stage renal disease (pRIFLE) classification in diagnosing AKI.

Results: Forty children were recruited. Of these 40 children, 22 developed AKI according to pRIFLE criteria. There was no significant difference between AKI and non-AKI in age (P = 0.29). Post cardiac surgery, renal insult was the main cause of AKI (27.3%). There was a twofold increased risk of incident AKI in those patients with high baseline uNGAL at PICU admission and almost a fourfold increased risk in patients with high baseline s-Cys-C at PICU admission. uNGAL levels were highly predictive of AKI during the follow-up period [area under the curve (AUC) = 0.76, 95% confidence interval (CI) 0.61-0.92]. The cutoff point with the highest correctly classified proportion was 223 ng/mL (≥ 12 centiles) which correctly predict 80.0% patients with AKI, with a corresponding sensitivity of 72.7% and a specificity of 89.9%. AUC for s-Cys-C was 0.86 (95% CI 0.75-0.97), and the highest correctly classified proportion was 1009 µg/L (≥ 13 centiles); 75% of patients with AKI, with a corresponding sensitivity of 63.6% and a specificity of 88.9%.

Conclusion: uNGAL and s-Cys-C predicts AKI early in critically ill children.
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http://dx.doi.org/10.1007/s12519-017-0110-xDOI Listing
April 2018

Association of IL-13 rs20541 and rs1295686 variants with symptomatic asthma in a Saudi Arabian population.

J Asthma 2018 11 6;55(11):1157-1165. Epub 2017 Dec 6.

a Immunology Research Laboratory and Asthma Research Chair, College of Medicine , King Saud University , Riyadh , Saudi Arabia.

Objective: Interleukin 13 (IL-13) plays a critical pro-inflammatory role in asthma. Several single nucleotide polymorphisms (SNPs) are associated with asthma susceptibility in specific populations; however, further replicative studies in other ethnic groups are mandatory.

Methods: The association between IL-13 SNPs rs762534, rs20541, rs1295686, and rs1800925 (risk alleles A, A, T, and A, respectively) and asthma predisposition in a Saudi Arabian cohort was examined via a case-control cross-sectional study.

Results: The frequencies of alleles between asthmatics and control populations were significantly different for rs20541 and rs1295686 SNPs (p < 0.001), whereas the frequencies of genotypes between asthmatics and controls were significantly different only for rs20541. The association of the risk (minor) alleles with asthma was examined using the dominant genetic model. Individuals with at least one copy of the risk alleles A (for rs20541) and T (for rs1295686) had significantly greater odds of being asthmatic (OR = 2.13, 95% CI = 1.39-3.26, p < 0.0001; OR = 1.69, 95% CI = 1.12-2.54, p = 0.008) relative to their most common homozygous genotypes. On the other hand, the minor A alleles for rs762534 and rs1800925 were not significantly associated with asthma risk. Regarding haplotype association analysis, individuals with at least one copy of the minor "risk" allele for both rs20541 and rs1295686 (CATG and CATA, respectively) had greater odds of being asthmatic relative to CGCG haplotype; however, this trend was not statistically significant (p > 0.3).

Conclusions: IL-13 minor T and A alleles for rs1295686 and rs20541, respectively, were associated with significantly higher risk of asthma in the Saudi Arabian population.
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http://dx.doi.org/10.1080/02770903.2017.1400047DOI Listing
November 2018

Outcome of pediatric acute kidney injury: a multicenter prospective cohort study.

Pediatr Nephrol 2018 02 15;33(2):335-340. Epub 2017 Sep 15.

King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia.

Background: Acute kidney injury (AKI) is a common problem encountered in critically ill children with an increasing incidence and evolving epidemiology. AKI carries a serious morbidity and mortality in patients requiring admission to a pediatric intensive care unit (PICU).

Methods: We undertook a prospective cohort study of PICU admissions at three tertiary care hospitals in the Kingdom of Saudi Arabia over 2 years. The Kidney Disease Improving Global Outcomes (KDIGO) definition was used to diagnose AKI.

Results: A total of 1367 pediatrics PICU admissions were included in the study. AKI affected 511 children (37.4%), with 243 children (17.8%) classified as stage I (mild), 168 patients (12.3%) stage II (moderate), and 100 children (7.3%) were classified as stage III (severe). After adjustment for age, sex, and underlying diagnosis, in-hospital mortality was six times more likely among patients with AKI as compared to patients with normal renal function (adjusted OR: 6.5, 95% CI: 4.2-10). AKI was also a risk factor for hypertension (adjusted OR: 4.1, 95% CI: 2.8-5.9) and prolonged stay in the PICU and hospital, as it increased the average number of admission days by 10 (95% CI: 8.6-11) days in the PICU and 12 (95% CI: 10-14) days in the hospital.

Conclusions: One-third of PICU admissions were complicated with AKI. AKI was associated with increased hospital mortality and the length of stay in both PICU and hospital.
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http://dx.doi.org/10.1007/s00467-017-3786-1DOI Listing
February 2018

Impact of acute kidney injury on long-term mortality and progression to chronic kidney disease among critically ill children.

Saudi Med J 2017 Feb;38(2):138-142

Pediatric Nephrology Center of Excellence, Department of Pediatrics, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. E-mail.

Objectives: To determine the 2-year outcome of acute kidney injury (AKI) following admission to pediatric critical care units (PICU). Methods: A retrospective cohort study was conducted between January 2012 and December 2013. We followed 131 children admitted to PICU, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia with a diagnosis of AKI, based on pRIFLE (pediatric risk, injury, failure, loss, and end-stage renal disease), for 2 years. During the study period, 46 children died and 38 of survivors completed the follow-up. Factors affecting long-term progression to chronic kidney disease were also evaluated. Results: The 2-year mortality was more than 40%. The main determinant of the 2-year mortality was the pediatric risk of mortality (PRISM) score, which increased the risk of mortality by 6% per each one score (adjusted odds ratio, 1.06: 95% confidence interval: 1.00-1.11). By the end of the 2 years, 33% of survivors had reduction in the glomerular filtration rate and proteinuria, and 73% were hypertensive. Patients with more severe renal impairment at admission, based on the pRIFLE criteria, had higher mortality rate. This association, however, was not independent since it was influenced by baseline disease severity (PRISM score).  Conclusion: Large proportion of patients admitted to PICU with AKI either died during the first 2 months of follow-up or developed long-term complications. The severity of AKI, however, was not an independent risk factor for mortality.
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http://dx.doi.org/10.15537/smj.2017.2.16012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329624PMC
February 2017

A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families.

J Hum Genet 2013 Jul 18;58(7):480-9. Epub 2013 Apr 18.

Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Nephrotic syndrome (NS) is a renal disease characterized by heavy proteinuria, hypoalbuminemia, edema and hyperlipidemia. Its presentation within the first 3 months of life or in multiple family members suggests an underlying inherited cause. To determine the frequency of inherited NS, 62 cases (representing 49 families with NS) from Saudi Arabia were screened for mutations in NPHS1, NPHS2, LAMB2, PLCE1, CD2AP, MYO1E, WT1, PTPRO and Nei endonuclease VIII-like 1 (NEIL1). We detected likely causative mutations in 25 out of 49 families studied (51%). We found that the most common genetic cause of NS in our cohort was a homozygous mutation in the NPHS2 gene, found in 11 of the 49 families (22%). Mutations in the NPHS1 and PLCE1 genes allowed a molecular genetic diagnosis in 12% and 8% of families, respectively. We detected novel MYO1E mutations in three families (6%). No mutations were found in WT1, PTPRO or NEIL1. The pathogenicity of novel variants was analyzed by in silico tests and by genetic screening of ethnically matched control populations. This is the first report describing the molecular genetics of NS in the Arabian Peninsula.
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http://dx.doi.org/10.1038/jhg.2013.27DOI Listing
July 2013

Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1.

Ther Clin Risk Manag 2012 28;8:373-6. Epub 2012 Aug 28.

Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Background: Primary hyperoxaluria type 1 (PH1) is characterized by progressive renal insufficiency culminating in end-stage renal disease, and a wide range of clinical features related to systemic oxalosis in different organs. It is caused by autosomal recessive deficiency of alanine:glyoxylate aminotransferase due to a defect in AGXT gene.

Case Report: Two brothers (one 6 months old; the other 2 years old) presented with acute renal failure and urinary tract infection respectively. PH1 was confirmed by high urinary oxalate level, demonstration of oxalate crystals in bone biopsy, and pathogenic homozygous known AGXT gene mutation. Despite the same genetic background, same sex, and shared environment, the outcome of the two siblings differs widely. While one of them died earlier with end-stage renal disease and multiorgan failure caused by systemic oxalosis, the older brother is pyridoxine responsive with normal development and renal function.

Conclusion: Clinicians should be aware of extreme intrafamilial variability of PH1 and international registries are needed to characterize the genotype-phenotype correlation in such disorder.
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http://dx.doi.org/10.2147/TCRM.S34954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431957PMC
September 2012