Perspectives: Neonatal acute kidney injury (AKI) in low and middle income countries (LMIC).

Neonatal AKI (NAKI) remains a challenge in low- and middle-income countries (LMICs). In this perspective, we address issues of diagnosis and risk factors particular to less well-resourced regions. The conservative management pre-kidney replacement therapy (pre-KRT) is prioritized and challenges of KRT are described with improvised dialysis techniques also included. Special emphasis is placed on ethical and palliation principles.

Long-term outcome among females with Alport syndrome from a single pediatric center.

BACKGROUND: Alport syndrome (AS) is a multisystem condition which can result in progressive kidney disease, hearing loss, and ocular changes. X-linked inheritance is observed in 85% of affected individuals. As a result, most prior studies have focused on males. Girls with AS can also be symptomatic although historically thought to have few clinical manifestations in childhood. The objective of the study was to describe the clinical presentation and course of females with AS. METHODS: A single-center retrospective study of all young females with AS between January 1, 1987, and May 20, 2019. Subjects were identified using ICD-9/10 diagnosis codes for AS, familial hematuria, or nephritis. Clinical data were extracted by retrospective chart review. RESULTS: Thirty-six female patients were included in the analysis. Mean age at presentation was 5.58 ± 3.0 years, and mean follow-up was 5.9 ± 3.9 years. Twenty-nine patients (80%) had a family history of AS. At end of the follow-up period, gross hematuria was observed in 15 patients (42%), 20 (56%) developed proteinuria, and 2 (6.7%) had an estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m2 with one patient developing stage 5 chronic kidney disease. Four of the twenty-seven (14.8%) who underwent audiologic testing had an abnormal exam. CONCLUSIONS: Known family histories of AS or gross hematuria were the most common reasons for the initial presentation in our cohort. Development of proteinuria, eGFR < 90 ml/min/1.73m2, and abnormal audiology exam are not exceptional findings, suggesting that close monitoring of young females into adulthood is warranted.

Medical Expulsive Therapy for Urinary Stone Disease in Children.

The rising incidence of urinary stone disease in children requires pediatric practitioners to keep abreast of management recommendations which are generally geared towards adults. Medical expulsive therapy (MET) is a non-surgical therapeutic option that can be trialed in patients who present with uncomplicated symptomatic ureteral stones. Seminal articles published and indexed in Medline on the topic of MET were extracted and reviewed. Studies suggest a potential benefit of alpha-blockade for the expulsion of distal ureteral stones that are >5 mm but ≤10 mm in adults and possibly >4 mm in children. Conversely, there does not seem to be any added benefit for MET in smaller stones (<5 mm) in which the spontaneous passage rate is high. Conclusions: The off-label use of these medications is one of the several barriers which contribute to the underutilization of MET in children. However, these may be a reasonable option in particular for older children and adolescents with the appropriate-sized stones.

Prevention of recurrent urinary stone disease.

PURPOSE OF REVIEW: Urinary stone disease (USD) is increasing in prevalence and recurrence is common. In pediatrics, most stones are composed primarily of calcium with the highest incidence observed in adolescents. Given the morbidity associated with USD, an in depth review of current management strategies is of paramount importance to highlight the data supporting the recommended treatments and the knowledge gaps which still exist. RECENT FINDINGS: Several interventions for the management of recurrent calcium USD in children have been recommended based on primarily adult studies. These interventions include modification of diet and fluid intake in addition to the utilization of medications such as thiazide diuretics and citrates when supportive care is inadequate. Overall there is conflicting data in the adult literature which is further complicated by our attempts to extrapolate these data to children. SUMMARY: Based on the currently available literature the management of USD in pediatrics should be individualized to each patient and focused on the particular metabolic risk factors that are identified during the course of their evaluation. Several interventions may be required or trialed in a particular patient to show an effect. Well designed trials to assess the efficacy of each intervention in the pediatric population are needed.

Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry.

Structural characterization of epitope-paratope pairs has contributed to the understanding of antigenicity. By contrast, few structural studies relate to immunogenicity, the process of antigen-induced immune responses in vivo. Using a lipid-arrayed membrane-proximal external region (MPER) of HIV-1 glycoprotein 41 as a model antigen, we investigated the influence of physicochemical properties on immunogenicity in relation to structural modifications of MPER/liposome vaccines. Anchoring the MPER to the membrane via an alkyl tail or transmembrane domain retained the MPER on liposomes in vivo, while preserving MPER secondary structure. However, structural modifications that affected MPER membrane orientation and antigenic residue accessibility strongly impacted induced antibody responses. The solvent-exposed MPER tryptophan residue (Trp-680) was immunodominant, focusing immune responses, despite sequence variability elsewhere. Nonetheless, immunogenicity could be readily manipulated using site-directed mutagenesis or structural constraints to modulate amino acid surface display. These studies provide fundamental insights for immunogen design aimed at targeting B cell antibody responses.