Pediatric Nephrology最新文献

Nephrotic syndrome is a common condition characterized by filtration of large amounts of protein, hypoalbuminemia, reduced plasma oncotic pressure, sodium retention, and edema. The mechanism responsible for sodium retention in this condition is still controversial. Two different pathophysiological pathways have been proposed to explain edema formation: activation of neurohumoral effector mechanisms, including the renin-angiotensin-aldosterone system, or abnormal intrinsic/primary renal sodium retention. A 5-year-old boy with X-linked adrenoleukodystrophy presented with bilateral leg swelling, massive proteinuria, and hypoalbuminemia. Minimal change disease was diagnosed. The patient was initially treated with corticosteroids and experienced several relapses. The progression of fractional excretion of sodium correlated with proteinuria and undetectable aldosterone levels. This unusual finding suggests that the mechanism of tubular sodium avidity in this child with mineralocorticoid insufficiency was independent of the renin-angiotensin-aldosterone system.

The finding of a simple kidney cyst in a child can pose a diagnostic and management challenge for pediatric nephrologists, urologists, and primary care providers. The reported prevalence varies from 0.22 to 1% in large ultrasonography-based series of more than 10,000 children each. The true prevalence, however, may be higher or lower, as factors such as variations in referral patterns, indications for ultrasonography, or technical considerations could impact prevalence rates. For many patients, simple kidney cysts may be found incidentally when imaging is performed for another indication. Although simple cysts can occur in children, they may also represent the first sign of autosomal dominant polycystic kidney disease (ADPKD) or other less common cystic kidney diseases. Definitive guidelines regarding the evaluation and monitoring of children with simple kidney cysts have not been established. The desire on the part of the practitioner and/or parents to establish a definitive diagnosis should be balanced with the cost and inconvenience of repeated imaging and visits with specialists. The goals of this review are to (1) outline the definition, epidemiology, clinical presentation, and natural history of simple kidney cysts in childhood; (2) describe clinical features that could suggest a diagnosis other than a simple kidney cyst; and (3) present a suggested framework for evaluating and monitoring of children with one or more simple kidney cysts.

Importance: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care.

Objective: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce.

Evidence review: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions.

Findings: A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology.

Conclusions and relevance: The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients.

Background: Pediatric blood pressure (BP) assessment and management is increasingly important. Uncontrolled systolic and combined hypertension leads to hypertension-mediated organ damage. The impact of isolated diastolic hypertension is less clearly understood.

Methods: We analyzed the prevalence of ambulatory isolated diastolic hypertension (IDH) in primary (PH) and secondary (SH) hypertension, and associations with BMI Z-score (BMIz) and left ventricular mass index adjusted to the 95th percentile (aLVMI) in a large, multicenter cohort of hypertensive children. Hypertensive children were divided and analyzed in three ambulatory hypertension subgroups: 24-h, daytime, and nighttime. Specifically, we sought to determine the prevalence of ambulatory 24-h, daytime, or nighttime IDH.

Results: Prevalence of IDH varied based on ambulatory phenotypes, ranging from 6 to 12%, and was highest in children with SH. Children with IDH tended to be more likely female and, in some cases, were leaner than those with isolated systolic hypertension (ISH). Despite previous pediatric studies suggesting no strong association between diastolic blood pressure and left ventricular hypertrophy (LVH), we observed that children with IDH were equally likely to have LVH and had comparable aLVMI to those with ISH and combined systolic-diastolic hypertension.

Conclusions: In summary, ambulatory IDH appears to be a unique phenotype with a female sex, and younger age predilection, but equal risk for LVH in children with either PH or SH.

Background: Children with established kidney failure may have additional medical conditions influencing kidney care and outcomes. This cross-sectional study aimed to examine the prevalence of co-existing diseases captured in the electronic hospital record compared to UK Renal Registry (UKRR) data and differences in coding.

Methods: The study population comprised children aged < 18 years receiving kidney replacement therapy (KRT) in England and Wales on 31/12/2016. Comorbidity data at KRT start was examined in the hospital record and compared to UKRR data. Agreement was assessed by the kappa statistic. Associations between patient and clinical factors and likelihood of coding were examined using multivariable logistic regression.

Results: A total of 869 children (62.5% male) had data linkage for inclusion. UKRR records generally reported a higher prevalence of co-existing disease than electronic health records; congenital, non-kidney disease was most commonly reported across both datasets. The highest sensitivity in the hospital record was seen for congenital heart disease (odds ratio (OR) 0.65, 95% confidence interval (CI) 0.51, 0.78) and malignancy (OR 0.63, 95% CI 0.41, 0.85). At best, moderate agreement (kappa ≥ 0.41) was seen between the datasets. Factors associated with higher odds of coding in hospital records included age, while kidney disease and a higher number of comorbidities were associated with lower odds of coding.

Conclusions: Health records generally under-reported co-existing disease compared to registry data with fair-moderate agreement between datasets. Electronic health records offer a non-selective overview of co-existing disease facilitating audit and research, but registry processes are still required to capture paediatric-specific variables pertinent to kidney disease.

Background: Cardiopulmonary bypass (CPB) is associated with hemolysis and acute kidney injury (AKI). The study aim was to determine if urine dipstick blood in infants after CPB was associated with AKI and urine neutrophil gelatinase-associated lipocalin (NGAL).

Methods: Infants who underwent CPB at a single center were enrolled prospectively between October 2017 and June 2019. Urine samples prior to CPB and 6 h after CPB cessation were analyzed in batch for NGAL and dipstick blood. AKI was defined using creatinine-based KDIGO criteria within 72 h of CPB. Spearman correlation examined associations between urine dipstick blood and NGAL at each time point. Linear regression estimated the associations between urine dipstick blood and log-transformed NGAL 6 h after CPB. Logistic regression estimated associations and compared discrimination between urine dipstick blood and NGAL for predicting AKI.

Results: At baseline, 7/63 samples (11%) had > trace blood. Six hours after CPB, 62/98 samples (63%) had > trace blood and 26% had 3 + (large) blood. In total, 18/98 (18%) with a 6-h post-CPB sample had postoperative AKI. Urine dipstick blood values correlated with urine NGAL 6 h after CPB (r = 0.52, p < 0.01), but not at baseline (r = 0.06, p = 0.66). Those with 3 + (large) blood on urine dipstick had 6 times higher mean NGAL values compared to those with negative/trace blood (mean ratio 6.6, 95%CI 3.1-14.4, p < 0.01). Those with 3 + (large) blood had 8 times higher odds of AKI (OR 7.99, 95%CI 1.5-41.9, p = 0.01).

Conclusions: Urine dipstick blood post CPB may be a simple and inexpensive tool to help predict AKI in infants.

Background: There are proposed roles for inflammation in the development of congenital obstructive uropathy in the setting of posterior urethral valves (PUV). However, the value of inflammatory proteins as predictive markers of postnatal kidney function, key in the management of fetuses with PUV, has not been explored. We screened fetal urine of fetuses with PUV with a panel of inflammatory proteins to determine their predictive value of postnatal kidney function.

Methods: Twenty-five different chemokines and cytokines were measured using a multiplex immunoassay in fetal urine of 79 PUV patients from retrospective cohorts, separated in discovery (n = 52) and validation (n = 27). The candidate markers were also quantified in amniotic fluid samples obtained from 16 PUV and 25 other congenital anomalies of the kidney and the urinary tract pregnancies. The performance of validated candidate inflammatory proteins was compared to the previously published 12PUV fetal urine peptide signature.

Results: Fetal urine chemokines CCL2 (MCP-1), CXCL9 (MIG), and CCL4 (MIP-1β) were identified as predictive of postnatal kidney failure in fetuses with PUV from the discovery cohort. Their predictive potential was confirmed in the validation cohort (AUCs of 0.87, 0.81, and 0.86, respectively). The performance of these individual chemokines was lower than the previously published 12PUV fetal urine peptide signature. However, the combination of the three chemokines performed similarly to 12PUV. In contrast, these three chemokines were not predictive of outcome in amniotic fluid.

Conclusions: We identified chemokines in fetal urine of PUV pregnancies that, after external validation, could serve as predictive biomarkers of postnatal outcome and contribute to improve prenatal PUV management.

Background: Most infants with febrile urinary tract infection (UTI) do not have an underlying anatomical risk factor. Thus, other non-anatomical risk factors should be considered. Since the most common pathogens arise from the fecal microbiota, our aim was to investigate whether the gut microbiota composition differs between febrile infants younger than 2 months with or without UTI.

Methods: In this prospective, case-control, pilot study, we performed 16S ribosomal ribonucleic acid amplicon sequencing to characterize gut microbiota of febrile neonates with and without UTI admitted to the pediatric ward at Shamir Medical Center between February 2019 and May 2021.

Results: The study cohort included 42 febrile neonates: 17 with and 25 without febrile UTI. We found a significant difference in beta diversity (i.e. between-sample/study group similarity indices) between the UTI and non-UTI group (p = 0.016). There were also distinct differences in the relative abundance of the 20 most prevalent genera. Furthermore, several genera were significantly enriched in the UTI group, with others dominating the non-UTI group. Streptococci were underrepresented in the UTI group. There was no difference in alpha diversity (i.e. within-sample diversity/richness) between groups.

Conclusion: Febrile neonates with UTI have a different fecal microbiota composition (beta-diversity), but not alpha diversity, in comparison to febrile neonates without UTI. A larger study is warranted to confirm these findings and their potential applications.

Our review summarizes and evaluates the current state of knowledge on lipid metabolism in relation to the pathomechanisms of kidney disease with a focus on common pediatric kidney diseases. In addition, we discuss how nutrition in early childhood can alter kidney development and permanently shape kidney lipid and protein metabolism, which in turn affects kidney health and disease throughout life. Comprehensive integrated lipidomics and proteomics network analyses are becoming increasingly available and offer exciting new insights into metabolic signatures. Lipid accumulation, lipid peroxidation, oxidative stress, and dysregulated pro-inflammatory lipid mediator signaling have been identified as important mechanisms influencing the progression of minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diabetic kidney disease, and acute kidney injury. We outline key features of metabolic homeostasis and lipid metabolic physiology in renal cells and discuss pathophysiological aspects in the pediatric context. On the one hand, special vulnerabilities such as reduced antioxidant capacity in neonates must be considered. On the other hand, there is a unique window of opportunity during kidney development, as nutrition in early life influences the composition of cellular phospholipid membranes in the growing kidney and thus affects local signaling pathways far beyond the growth phase.