Childhood Idiopathic Nephrotic Syndrome as a Podocytopathy

Idiopathic nephrotic syndrome is the commonest manifestation of glomerular disease in children. The syndrome is characterized by massive proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia. Although genetic or congenital forms are now well recognized, nephrotic syndrome is largely acquired. The latter form can be idiopathic or primary (the causes are unknown) and secondary (the causes are known renal or non-renal diseases). Idiopathic nephrotic syndrome consists of the following glomerulonephritides: minimal change nephropathy (MCN), focal segmental glomerulosclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), mesangial proliferative glomerulonephritis (MesPGN), and membranous nephritis (MN). The etiopathogenesis of nephrotic syndrome has evolved through several hypotheses ranging from immune dysregulation theory and increased glomerular permeability theory to the current concept of podocytopathy. Podocyte injury is now thought to be the basic pathology in the syndrome. The book chapter aims to highlight the mechanisms underlying the pathogenesis of nephrotic syndrome as a podocytopathy

Childhood and Adult Asthma: Phenotype- and Endotype-Based Biomarkers

The concept of asthma has changed from that of a single disease entity to that of a heterogeneous disease comprising several phenotypes linked to specific endotypes. Recently, significant progress has been made in disease classification into phenotypes and biologically distinct variants (endotypes). Classification of patients into endotypes has led to precision medicine in which specific biomarkers and appropriate individualized treatments have now been identified. Despite the ongoing classification of disease endotypes, the presence or absence of a T-helper 2 (Th2) molecular signature has resulted in the association of asthma endotypes with phenotypes so as to establish responders and non-responders to inhaled corticosteroid therapy. More importantly, biologic therapies predicated on disease endotypes may in future constitute a paradigm shift from the traditional pharmacologic treatments and lead to better prognosis in moderate-to-severe forms of the disease (in which they are presently used). This book chapter aims to discuss the current concepts on asthma classification and biomarker-based diagnosis

Biomarkers of Common Childhood Renal Diseases

Novel biomarkers are now used in the diagnostic and prognostic evaluation of common kidney diseases in children. The increased scientific interest in these biomarkers is partly due to the remarkable progress in their discovery techniques, and their validation in clinical subjects. However, the wide variation in their sensitivity and specificity is still a major concern. In the identification of biomarkers of kidney injury, an ideal biomarker should be produced after organ injury in concentrations which directly correlates with the degree of injury; should be easily measured in body fluids; and should serve as a potential tool to monitor therapeutic response which is predicated upon a post-injury decrease in its concentration. This book chapter aims to highlight and discuss the novel biomarkers used in the diagnostic and prognostic evaluation of common acute diseases of the kidney in children, such as urinary tract infection (UTI) and acute kidney injury (AKI), as well as chronic kidney disease (CKD) secondary to idiopathic nephrotic syndrome (INS) and diabetic nephropathy (DN)

Diabetic Nephropathy in Childhood: Predictive Tools and Preventive Strategies

Diabetic nephropathy is the commonest microvascular complication in both types 1 and 2 diabetes mellitus. Disease pathogenesis is based on a multifactorial interaction between metabolic and hemodynamic factors. In response to hyperglycemia, which disrupts the body’s metabolic milieu, a cascade of complex molecular events occur leading to glomerular hypertrophy, tubular inflammation, mesangial expansion, oxidative stress, and renal fibrosis. Beyond the conventional microalbuminuria, which can predict disease onset, novel biomarkers are now proving more reliable as predictive tools. While several reports show that glomerular and tubular biomarkers are more sensitive than microalbuminuria, tubular markers specifically constitute earlier predictors of the disease. Similarly, biomarkers of inflammation and oxidative stress have been demonstrated as dependable diagnostic tools. As an important cause of mortality from end-stage renal disease (ESRD), diabetic nephropathy constitutes an important challenge in diabetic care. Interestingly, strict glycemic control assessed by glycated hemoglobin (Hb A1 c) estimates, and antihypertensive therapy with angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB) ± calcium-channel blockers form the main strategies for preventing its onset and slowing down its progression. Other strategies include uric acid antagonist, and renin and endothelin inhibitors. This book chapter discusses these predictive tools and possible preventive strategies

Nocturnal Enuresis in Children with Sickle Cell Anemia

Sickle cell anemia (SCA) is the commonest hemoglobin disorder among the black population worldwide. Children with SCA may eventually end up with end-organ complications: the kidneys being one of the most frequently affected organs. The renal complications arise from medullary ischemia and infarction leading to features of tubular dysfunction such as hyposthenuria and renal tubular acidosis. Early in life, children with SCA may present with hyposthenuria: one of the earliest renal defects in the disease which results in an obligatory urine output of more than 2 l in a day. The symptomatic manifestation as nocturnal polyuria is thought to be the reason for nocturnal enuresis observed in these children. In spite of the more prevalent occurrence of nocturnal enuresis in children with SCA than in their non-SCA colleagues, its precise underlying mechanisms still remain controversial, with divergent conclusions regarding its pathogenesis. However, the consensus is now tilting towards a multifactorial etiopathogenesis in affected children. This book chapter aims to discuss the epidemiologic perspectives of nocturnal enuresis in SCA, as well as the current hypotheses on the etiopathogenesis of this complication

Maternal Diet during Exclusive Breastfeeding can Predict Food Preference in Preschoolers: A Cross-Sectional Study of Mother- Child Dyads in Enugu, South-East Nigeria

Background: The relationship between food preference in early childhood and prenatal exposure to flavor in the amniotic fluid is well documented. Although its association with flavor transmission in the breast milk has also been noted, it is poorly reported in this country. Objective: The present study aims to determine the relationship between mothers’ dietary exposure during exclusive breastfeeding and food preference in their preschool-aged children. Methods: Two hundred and twenty (220) mother-child dyads who met the study criteria were enrolled. A pre-tested, structured questionnaire was administered to the mothers. The relationship between maternal consumption of flour-based snacks and staple foods during exclusive breastfeeding and the child’s preference for these foods was determined using risk estimates. After controlling for potential confounders, logistic regression was used for multivariate analysis. Statistical significance was determined at p < 0.05 and all the risk estimates were presented as odds ratios (OR) at 95% confidence intervals (CI). Results: The relationship between daily maternal exposure to staple foods during exclusive breastfeeding and the children’s preference for this variety of food was not statistically significant (p = 0.847, OR= 1.083, 95% CI = 0.481-2.437). However, the children’s preference for flour-based snacks was significantly related to weekly or fourth-nightly maternal exposure to similar diet during exclusive breast feeding (p = 0.035, OR = 2.405, 95% C.I = 1.064 - 5.435). Conclusion: Transmission of flavor in the breast milk may contribute in shaping children’s feeding behavior early in life

The prevalence and risk of urinary tract infection in malnourished children : a systematic review and meta-analysis

There are vast differences in prevalence rates of urinary tract infection (UTI) reported among malnourished children globally. We conducted a systematic review and meta-analysis to provide estimates of pooled prevalence of UTI among these children and combined UTI risk in comparison with their well-nourished counterparts.; We systematically searched electronic databases (MEDLINE, EMBASE, ISI Web of Science and African Journals Online; date of the last search: 22 December 2018) for studies reporting either the prevalence of UTI in malnourished children or parallel healthy controls. Eligible primary studies were observational studies of children in English Language reporting UTI prevalence with background malnutrition or with enough data to compute these estimates, as well as studies which reported at the same time UTI prevalence in healthy controls. We synthesized published prevalence rates or associations (odds ratios [OR]) between malnutrition and UTI and their 95% confidence intervals (CI) using random effects meta-regression and explored potential heterogeneity determinants using meta-regression analysis. This review is registered with PROSPERO, number- CRD42018084765.; We included 26 cross-sectional and 8 case-control studies reporting on UTI prevalence in malnourished children, and in malnourished children vs. healthy controls, respectively. The pooled prevalence of UTI in 3294 malnourished children was 17% (95% CI, 13, 21%). Heterogeneity was high (I; 2; = 87.6%; Tau; 2; = 0.06) as studies varied in their sample size, degree of malnutrition, and study period. Multivariate meta-regression model, including these factors, explained 34.6% of the between-study variance. Pooled OR of UTI in association with malnutrition in 2051 children (1052 malnourished children vs. 999 controls) was 2.34 (95% CI, 1.15, 3.34), with lower between-study heterogeneity (I; 2; = 53.6%; Tau; 2; = 0.47).; UTI is more prevalent in malnourished children than in their well-nourished counterparts. Screening and treatment for UTI should be incorporated in the management protocol of malnourished children to improve disease outcomes

The effectiveness of locally-prepared peritoneal dialysate in the management of children with acute kidney injury in a south-east Nigerian tertiary hospital

Background: Peritoneal dialysis (PD) is the preferred mode of renal replacement therapy (RRT) in children with acute kidney injury (AKI). The gold standard remains the use of commercially-prepared PD fluid. In resource-poor nations, its availability and affordability remain a challenge.Aim: This study aims to report the effectiveness of locally-prepared PD fluid in the management of AKI in a south-east Nigerian tertiary hospital.Subjects and Methods: This was a retrospective study conducted at the paediatric ward of the University of Nigeria Teaching hospital, Enugu. The case records of 36 children seen over three years, diagnosed with AKI and requiring PD were reviewed. The retrieved information comprised biodata, aetiology of AKI, indications for PD, pre-and post-dialysis estimated glomerular filtration rate (eGFR) and patient outcomes.Results: The children (20 males and 16 females) were aged 3 to 36 months with a mean age of 9.92 ± 6.29 months. The common aetiologies of AKI were septicemia (30.6%), hemolytic uremic syndrome (19.4%), and toxic nephropathy (16.7%). The frequent indications for PD were uremic encephalopathy (58.3%) and severe metabolic acidosis (38.8%). The pre-and post-dialysis mean urine flow rate was 0.16 + 0.13 and 2.77 + 0.56 ml/kg/hour respectively. The eGFR before PD, at discontinuation, and a week later was 6.06 + 2.87, 24.44 + 15.71 and 59.07 + 22.22 mls/min/1.73m2 respectively.Conclusion: PD with locally-prepared dialysate is safe, effective and a life-saving alternative in the management of AKI in childrenKeywords: Peritoneal dialysis; renal replacement therapy; acute kidney injury; children; dialysate; developing country

Antimicrobial Stewardship Implementation in Nigerian Hospitals: Gaps and Challenges

Background: Antimicrobial resistance (AMR) is a major clinical challenge globally. It is mainly a consequence of inappropriate prescribing and use of antibiotics. Antimicrobial stewardship (AMS) ensures that antibiotics are prescribed and used appropriately. This study assessed AMS practice in selected Nigerian hospitals.Methodology: This was a cross sectional survey of 20 Federal, State and Private tertiary hospitals randomly selected from the six geopolitical zones of Nigeria. Using an adapted WHO tool on AMS, data were collected from each hospital as regard the existence of AMS committee, Accountability and Responsibility, AMS actions, Education and Training, Monitoring and Evaluation, Infection Prevention and Control (IPC) practice, facilities to support AMS, and challenges to AMS implementation. Gaps and challenges to the implementation of the AMS among the hospitals were identified.Results: Only 6 (30%) of the 20 hospitals had AMS committees while 2 (10%) had any evidence of leadership commitment to AMS. All the hospitals had laboratory facilities to support culture and sensitivity testing. There were no regular AMS-related education or training, monitoring, evaluation or reporting activities in the hospitals, except in 7 (25%) that had participated in the global point prevalence survey (Global-PPS) of antimicrobial use and resistance being hosted by the University of Antwerp, Belgium. Challenges impeding AMS activities included lack of human and financial resources, prescribers’ opposition, lack of awareness and absence of AMS committees. Most of the gaps and challenges bordered on seeming lack of knowledge and inadequate communication among prescribers and other stakeholders.Conclusion: There is need for intense education and training activities for prescribers and other stakeholders, including but not limited to hospital administrators. Keywords: Survey, Antimicrobial Stewardship, Antimicrobial Resistance; Nigeria   French title: Mise en œuvre de la gestion des antimicrobiens dans les hôpitaux Nigérians: lacunes et défis Contexte: La résistance aux antimicrobiens (RAM) est un défi clinique majeur à l'échelle mondiale. C'estprincipalement une conséquence d'une prescription et d'une utilisation inappropriées d'antibiotiques. La gestion des antimicrobiens (AMS) garantit que les antibiotiques sont prescrits et utilisés de manière appropriée. Cette étude a évalué la pratique de l'AMS dans certains hôpitaux Nigérians. Méthodologie: Il s'agissait d'une enquête transversale de 20 hôpitaux tertiaires fédéraux, d'État et privéssélectionnés au hasard dans les six zones géopolitiques du Nigéria. À l'aide d'un outil OMS adapté sur l'AMS, des données ont été collectées auprès de chaque hôpital en ce qui concerne l'existence d'un comité AMS, la responsabilité et la responsabilité, les actions AMS, l'éducation et la formation, le suivi et l'évaluation, la  pratique de prévention et de contrôle des infections (IPC), les installations pour soutenir l'AMS. et les défis de la mise en œuvre de l'AMS. Les lacunes et les défis liés à la mise en œuvre de l'AMS parmi les hôpitaux ont été identifiés. Résultats: Seuls 6 (30%) des 20 hôpitaux avaient des comités AMS tandis que 2 (10%) avaient des preuves d'engagement du leadership envers l'AMS. Tous les hôpitaux disposaient d'installations de laboratoire pour soutenir la culture et les tests de sensibilité. Il n'y avait pas d'activités régulières d'éducation ou de formation, de suivi, d'évaluation ou de rapportage liées à la MGS dans les hôpitaux, sauf dans 7 (25%) qui avaient participé à l'enquête mondiale sur la prévalence ponctuelle (Global-PPS) de l'utilisation et de la résistance aux  antimicrobiens organisée par l'Université d'Anvers, Belgique. Les défis entravant les activités de l'AMS  comprenaient le manque de ressources humaines et financières, l'opposition des prescripteurs, le manque de sensibilisation et l'absence de comités AMS. La plupart des lacunes et des défis se limitaient à un manque apparent de connaissances et à une communication inadéquate entre les prescripteurs et les autres intervenants.Conclusion: Des activités d'éducation et de formation intensives sont nécessaires pour les prescripteurs et autres intervenants, y compris, mais sans s'y limiter, les administrateurs d'hôpitaux. Mots clés: enquête, gestion des antimicrobiens, résistance aux antimicrobiens; Nigeria   &nbsp

Corrigendum: Antimicrobial Stewardship Implementation in Nigerian Hospitals: Gaps and Challenges

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