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Sickle cell nephropathy:A review of novel biomarkers and their potential roles in early detection of renal involvement

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World Journal of Clinical Pediatrics 2022年第1期11卷 14-26页

作者： osama Y safdar Rana M Baghdadi Sereen A Alahmadi Bana E Fakieh Amaal M Algaydi of Pediatric King Abdulaziz UniversityJEDDAH 21414Saudi Arabia College of Medicine King Abdulaziz UniversityJEDDAH 21422Saudi Arabia

Whether the underlying mutations are homozygous,heterozygous,or coinherited with other hemoglobinopathies,sickle cell disease is known to afflict the kidneys,leading to the clinical entity known as sickle cell nephropathy(SCN).Although common,SCN remains diagnostically *** studies performed in the context of renal disorders often fail to detect early stage *** makes the quest for early diagnosis and treatment more challenging,and it increases the burden of chronic kidney disease-related morbidity among *** diagnostic tools have been employed to overcome this *** this study,we discuss various biomarkers of SCN,including those employed in clinical practice and others recently identified in experimental settings,such as markers of vascular injury,endothelial dysfunction,tubulo-glomerular damage,and oxidative *** include kidney injury molecule-1,monocyte chemoattractant protein-1,N-acetyl-B-D-glucosaminidase,ceruloplasmin,orosomucoid,nephrin,and cation channels,among ***,we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be *** highlight the importance of a collaborative approach to standardize the use of promising new ***,we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits,with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.

关键词： Sickle cell disease Sickle cell nephropathy Chronic kidney disease Kidney injury molecule-1 Monocyte chemoattractant protein-1 N-acetyl-B-D-glucosaminidase

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Rituximab for troublesome cases of childhood nephrotic syndrome

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World Journal of Clinical Pediatrics 2014年第4期3卷 69-75页

作者： osama Y safdar Adila Aboualhameael Jameela A Kari Department of Pediatrics King Abdulaziz University Hospital Pediatric Nephrology Unit King Abdulaziz University Hospital

Nephrotic syndrome(NS) is the most common glomerular disease of childhood. Steroid-dependent and steroid-resistant nephrotic syndrome present challenges in their pharmaceutical management; patients may need several immunosuppressive medication for optimum control, each of which medication has its own safety profile. Rituximab(RTX) is a monoclonal antibody that targets B cells and has been used successfully for management of lymphoma and rheumatoid arthritis. Recent clinical studies showed that rituximab may be an efficacious and safe alternative for the treatment of complicated nephrotic syndrome. In this review article, we aim to review the efficacy and safety of RTX therapy in nephrotic syndrome. We reviewed the literature pertaining to this topic by searching for relevant studies on Pub Med and Medline using specific keywords. The initial search yielded 452 articles. These articles were then examined to ensure their relevance to the topic of research. We focused on multicenter randomized controlled trials with relatively large numbers of patients. A total of 29 articles were finally identified and will be summarized in this review. The majority of clinical studies of RTX in complicated pediatric NS showed that rituximab is effective in approximately 80% of patients with steroid-dependent NS, as it decreases the number of relapses and steroid dosage. However, RTX is less effective at achieving remission in steroid-resistant NS. RTX use was generally safe, and most side effects were transient and infusion-related. More randomized, double-blinded clinical studies are needed to assess the role of RTX in children with nephrotic syndrome.

关键词： Rituximab Pediatric Nephrotic syndrome Efficacy Safety

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Genetics of congenital and infantile nephrotic syndrome

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World Journal of Pediatrics 2019年第2期15卷 198-203页

作者： Sara Nawfal Sharief Nada Abdullatif Hefni Walaa Ali Alzahrani Iman Ibrahim Nazer Marwa Abdullah Bayazeed Khalid A.Alhasan osama Y.safdar Sherif M.El-Desoky Jameela Abdulaziz Kari King Abdulaziz University JeddahKingdom of Saudi Arabia College of Medicine Pediatric DepartmentKing Saud UniversityRiyadhKingdom of Saudi Arabia Department of Pediatrics Faculty of MedicinePediatric Nephrology Center of ExcellenceKing Abdulaziz UniversityPO Box 80215Jeddah 21589Kingdom of Saudi Arabia

Background Congenital and infantile nephrotic syndrome (CNS and INS) are rare inherited defects in glomerular filtration involving a variety of gene *** study aimed to analyze all genetic mutations associated with congenital and infantile nephrotic syndrome treated at our *** also discussed our different approach secondary to culture and *** A retrospective single-center study of all children diagnosed as NS before the age of l year over a duration of over one *** Twenty-nine children (12 boys) were included in the *** median age (range) was 2.4 (0.1-12) months (20 CNS and 9 INS).Consanguinity was present in 90% of *** genetic analysis' results were only available for 20 *** 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 *** CNS cases were all managed with intermittent intravenous albumin infusion,ACEi,diuretics,and *** of the children were managed by nephrectomy followed by peritoneal dialysis (PD) because of limited *** one child achieved partial remission,while 15 children died at a median (range) age of 5.8 (1.25-29) *** remaining 14 children were followed up for an average of 36 (3.9-120) *** children progressed to end-stage kidney disease and PD was performed in only two *** NPHS1 is the main underlying cause of CNS and INS in our study *** and INS were associated with high morbidity and mortality.

关键词： Congenital nephrotic Infantile nephrotic Genetics Outcome

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

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World Journal of Pediatrics 2018年第2期14卷 134-142页

作者： Jameela Abdulaziz Kari Mohamed Ahmed Shalaby Kholoud Sofyani Ahmad Saleh Sanad Albaraa Fuad Ossra Rayan Smeer Halabi Maha Hassan Aljuhani Wael Mohammad Toffaha Feras Aymen Moria Samar Sabry Hanan AbdelAziz Ahmed Khalid Abdulaziz Alhasan Sara Sharief osama safdar Pediatric Nephrology Center of Excellence and Department of Pediatrics King Abdulaziz University80215Jeddah 21589Kingdom of Saudi Arabia Pediatric Intensive Care Unit Department of PediatricsKing Abdulaziz UniversityJeddahKingdom of Saudi Arabia Pediatric Department Cairo UniversityGizaEgypt Department of Pediatrics College of MedicineKing Khalid University HospitalKing Saud UniversityRiyadhKingdom of Saudi Arabia

Background Acute kidney injury(AKI)is common in critically ill children with significant mortality and *** creatinine is an insensitive and late biomarker compared to newly proposed AKI *** 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 *** Forty children were *** these 40 children,22 developed AKI according to pRIFLE *** 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 *** 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 1009μg/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.

关键词： Acute kidney injury Neutrophil gelatinase-associated lipocalin Serum cystatin C

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