Is Preoperative Preparation Time a Barrier to Small Children Being Ready for Kidney Transplantation?

BACKGROUND: Small children are less frequently transplanted when compared with older. The objective of the present study was to compare the preparation time for transplantation in children of different weights and to identify factors associated with a delay in the workup of small children. METHODS: We report on a retrospective cohort comprising all children referred for renal transplantation (RTx) workup between 2009 and 2017. The main outcome was transplantation workup time, defined as the time elapsed between the first consultation and when the child became ready for the surgery. RESULTS: A total of 389 children (63.5% males) were selected, with a median weight of 18 kg (interquartile range, 11-32). Patients were categorized into 2 groups: group A (study group): ≤15 kg (n = 165) and group B (control group): >15 kg (n = 224). The probability of being ready for RTx was comparable between groups A and B. The cumulative incidence rate difference between groups is -0.05 (95% confidence interval, -0.03 to 0.02). The median time for RTx workup was 5.4 (2.4-9.4) in group A and 4.3 (2.2-9.0) months in group B (P = 0.451). Moreover, the presence of urinary tract malformation was associated with the need for longer transplantation workup time (P < 0.001). CONCLUSIONS: In children >7 kg, the workup time for transplantation is not related to body weight. In a specialized center, children weighing 7-15 kg became ready within the same timeframe as children weighing >15 kg, despite the smaller children had greater difficulty being nourished, dialyzed, and a greater need for surgical correction of the urinary tract pretransplant.

Genetics of Nephrotic Syndrome Presenting in Childhood: Core Curriculum 2019.

Nephrotic syndrome (NS) is one of the most challenging conditions to manage and treat, partly because we lack a specific molecular understanding of its pathogenesis and progression. This limits our ability to provide targeted therapy or precise prognostications. Fortunately, genomic discovery in NS and its translation to genomic-informed medicine is allowing us to improve our understanding of the molecular anatomy of NS and our ability to care for patients with NS. In this Core Curriculum, we review the specific genes and loci discovered in childhood NS, specifically NS of Mendelian origin, APOL1-associated NS in black patients, HLA region variants associated with steroid-sensitive NS, their biological impacts, prevalence across populations, and clinical correlates. We also review the fundamentals of genetic architecture of human disease, technologies, and analytic strategies that currently exist to discover disease-related genetic variations. A facility with the concepts and vocabulary of modern genomics and ability to interpret results of genetic studies are essential skills for nephrologists caring for children with NS. As such, we hope to empower them to understand the literature in this area, appropriately order genetic tests and accurately interpret the results, and consider how they may participate in or drive the next wave of genomic discoveries in NS.

Targeted Next-Generation Sequencing in Brazilian Children With Nephrotic Syndrome Submitted to Renal Transplant.

BACKGROUND: The aims of this study were to identify the genetic mutations profile in Brazilian children with nephrotic syndrome (NS) and to determine a genotype-phenotype correlation in this disease. METHODS: Next-generation sequencing and mutation analysis were performed on 24 genes related to NS in a cross-sectional study involving 95 children who underwent kidney transplantation due to NS, excluding congenital cases. RESULTS: A total of 149 variants were identified in 22 of 24 sequenced genes. The mutations were classified as pathogenic, likely pathogenic, likely benign and benign per the chance of causing the disease. NPHS2 was the most common mutated gene. We identified 8 (8.4%) patients with hereditary NS and 5 (5%) patients with probably genetically caused NS. COL4A3-5 variants were found as well, but it is not clear whether they should be considered isolated FSGS or simply a misdiagnosed type of the Alport spectrum. Considering the clinical results, hereditary NS patients presented a tendency to early disease onset when compared with the other groups (P = 0.06) and time to end stage renal disease (ESRD) was longer in this group (P = 0.03). No patients from hereditary NS group had NS recurrence after transplantation. CONCLUSIONS: This is the first study in children with steroid-resistant NS who underwent kidney transplantation using next-generation sequencing. Considering our results, we believe this study has shed some light to the uncertainties of genotype-phenotype correlation in NS, where several genes cooperate to produce or even to modify the course of the disease.