Pediatric Nephrology最新文献

Background: Adherence to cysteamine in nephropathic cystinosis (NC) remains challenging. A better adherence with delayed-release (DR) compared to immediate-release (IR) cysteamine at 1 year was previously shown. This study aimed to evaluate adherence to DR cysteamine at 2 years.

Methods: Treatment adherence was assessed using a medication event monitoring system; adherence ranged from 0 (poor) to 2 (good). Leukocyte cystine level was measured at each 3-month visit. Long-term follow-up data (7 years after the end of the study) on self-reported adherence and quality of life was also obtained in a sub-group of patients.

Results: Seventeen patients with NC under DR cysteamine from three French centers were included at a median age of 13.9 (5.4-33.0) years. The median adherence score was 1.62 (0.03-1.98) over the 2-year follow-up, with 65% of patients having good adherence and 75% having partial or good adherence. No significant difference in leukocyte cystine level between baseline and 2 years was found (0.8 nmol vs. 0.4 nmol, respectively; difference in median of - 1.0 nmol; 95% CI - 0.7, 0.4; P = 0.64). Long-term follow-up data highlighted that no patient wished to switch back to IR cysteamine, as taking the medication twice rather than four times a day was easier.

Conclusions: This study found a fairly good adherence to DR cysteamine over time. Decreasing the number of intakes per day may improve adherence and limit the side effects of the drug, representing an additional argument in favor of its use in patients with cystinosis.

The development of lymphatic-specific markers has enabled detailed visualization of the lymphatic vascular network that has greatly enhanced our ability to explore this often-overlooked system. Lymphatics remove fluid, solutes, macromolecules, and cells from the interstitium and return them to circulation. The kidneys have lymphatics. As in other organs, the kidney lymphatic vessels are highly sensitive to changes in the local microenvironment. The sensitivity to its milieu may be especially relevant in kidneys because they are central in regulating fluid homeostasis and clearance of metabolites delivered into and eliminated from the renal interstitial compartment. Numerous physiologic conditions and diseases modify the renal interstitial volume, pressure, and composition that can, in turn, influence the growth and function of the renal lymphatics. The impact of the renal microenvironment is further heightened by the fact that kidneys are encapsulated. This review considers the development, structure, and function of the renal lymphatic vessels and explores how factors within the kidney interstitial compartment modify their structure and functionality. Moreover, although currently there are no pharmaceutical agents that specifically target the lymphatic network, we highlight several medications currently used in children with kidney disease and hypertension that have significant but underappreciated effects on lymphatics.

Background: Caregiver burden in pediatric kidney disease is under-recognized and unquantified. The Pediatric Renal Caregiver Burden Scale (PR-CBS) is a validated tool that evaluates caregiver burden in this population. This study assesses caregiver burden at a tertiary center pediatric hospital in the following groups: dialysis, early post-kidney transplant (KT) (30 to 364 days), and late post-KT (> 1 year). Additionally, we aimed to demonstrate the feasibility of a translated PR-CBS among Spanish-speaking caregivers.

Methods: In this cross-sectional study, caregivers were approached at clinic visits to complete the PR-CBS. Total PR-CBS scores (ranging 51 to 255) and mean domain scores (ranging 1 to 5) were calculated. Descriptive statistics and t-tests were performed.

Results: Of the 30 caregivers approached, 26 consented: five of children receiving dialysis and 21 post-transplant. Survey completion was 100%. Total burden score was higher for caregivers of children on dialysis than post-KT, but not significantly (160 vs. 117, p = 0.09). The mean score for every domain was higher for caregivers of children on dialysis with significant differences in family life and caregiver identity (respectively, p = 0.04 and p = 0.03). PR-CBS scores did not differ across demographics. Four surveys were completed in Spanish; no significant difference was found.

Conclusions: Caregivers of children with kidney failure experience significant burden. While a small sample size limited this study, there was a trend for higher burden scores among caregivers of children on dialysis compared to post-KT. A larger, adequately powered study is needed to further assess the degree of burden in this population.

Background: Shiga toxin-producing Escherichia coli hemolytic-uremic syndrome (STEC-HUS) is a severe illness predominantly affecting young children, with limited treatment options beyond supportive care. Eliglustat, approved for Gaucher disease, shows potential in reducing Shiga toxin binding to target glomerular endothelial cells in vitro, prompting interest as a treatment for STEC-HUS. However, it remains unknown what dose is likely to be effective and safe for treatment of STEC-HUS in the pediatric population. We hypothesize that effective and safe levels of eliglustat can be reached in children.

Methods: We identified pharmacokinetic targets of efficacy for treatment and prophylaxis of STEC-HUS based on a preclinical model and human cardiac safety data. Then, we developed oral and intravenous dosing regimens using population pharmacokinetic (popPK) simulations based on an existing model enriched to allow extrapolation to a simulated virtual pediatric population. These dosing regimens were then confirmed using a verified physiologically based pharmacokinetic (PBPK) model.

Results: We simulated, using popPK data, oral and intravenous dosing regimens resulting in adequate target exposure in > 90% of all patients, with minimal expected risk for cardiotoxicity. Confirmation of these dosing regimens with PBPK modeling resulted in very similar exposure, with lower interindividual variability and minimal toxicity potential.

Conclusions: Based on pharmacokinetic modeling, we developed oral and intravenous eliglustat dosing regimens that are likely safe and effective for treatment of STEC-HUS and prophylaxis in case of outbreaks of STEC infections. Clinical evaluation of these dosing regimens in children suspected of or diagnosed with STEC-HUS is required and should include assessment of pharmacokinetics, efficacy, and safety (e.g., ECG monitoring).

Background: Acute kidney injury (AKI) in neonates is associated with increased morbidity and mortality, longer hospitalization, and a higher risk for future kidney damage. Caffeine treatment has reportedly been associated with a decreased AKI occurrence. However, previous studies lack uniformity regarding dosage and timing of administration. This study aimed to assess AKI incidence in very-low-birth-weight (VLBW) preterm infants (< 1500 g) treated with early high-dose caffeine and to identify risk factors associated with AKI.

Methods: A retrospective cohort study of VLBW preterm infants admitted to the Neonatal Intensive Care Unit at the Shaare Zedek Medical Center between January 1, 2017, and December 31, 2019. All VLBW infants born < 32 weeks of gestation were treated with a standardized caffeine regimen (20 mg/kg bolus; in the first hour of life, maintenance 10 mg/kg/day). Maternal and infant data including clinical, demographic, and laboratory measurements were retrieved from electronic medical records.

Results: Of 311 VLBW infants admitted, all had adequate serum creatinine and urine output data. Of 301 patients included for analysis, 41 (14%) were diagnosed with AKI, while only 12/301 (4%) were diagnosed during the first week of life. Sixteen infants (5%) had > 1 AKI episode. Seven (7/41, 17%) had AKI stage 1 and seventeen infants (17/41, 42%) had stages 2 and 3. In univariate analysis, sepsis, patent ductus arteriosus, necrotizing enterocolitis (NEC), and hemodynamic instability during the first week of life were more prevalent in the AKI group. Infants with AKI were born with lower birth weights, at earlier gestational weeks, and had lower APGAR and higher CRIB II scores. NEC was the only significant risk factor associated with AKI in multivariate analysis. They also had a higher risk for bronchopulmonary dysplasia (BPD), longer hospitalization, and higher mortality rate.

Conclusions: The incidence of AKI in a cohort of VLBW infants universally treated early with caffeine was 14%, while only 4% had AKI during the first week. Infants with AKI had worse outcomes (BPD and mortality) and longer hospitalization.

Introduction: Amyloidosis of the kidney is a rare complication in children with juvenile idiopathic arthritis (JIA), more commonly seen with systemic onset juvenile idiopathic arthritis (SOJIA). It usually presents with asymptomatic proteinuria.

Case report: An 11.5-year-old boy with onset of SOJIA at 6 years of age came to our clinic with anasarca. Urinalysis and serum albumin suggested a diagnosis of nephrotic syndrome (NS) and kidney biopsy confirmed amyloidosis deposits. Treatment with injection tocilizumab was initiated. The proteinuria has decreased, and kidney functions are normal.

Conclusion: Children with SOJIA should be monitored for proteinuria so that they can be offered timely appropriate therapy.

Background: Food insecurity (FI) is prevalent among children with chronic kidney disease (CKD), but its impact on health outcomes, and feasibility of prescribed diet restrictions is unknown. Accordingly, this study aims to explore associations of FI and CKD outcomes, and understand its role in following prescribed kidney diet recommendations.

Methods: We performed a mixed-methods single-center cohort study of children with advanced CKD or kidney failure. Demographics, socioeconomic status, and health outcomes were compared across FI status; associations between FI and CKD outcomes were explored using multivariable regression. A qualitative sub-analysis of de-identified caregiver interview transcripts was analyzed for themes around diet restrictions.

Results: There was a trend that FI patients were more likely to be of Black race (33% vs. 20%); have public insurance (67% vs. 48%); need more blood pressure medications (2 [0.75,3] vs. 1 [0,3]); and have a higher likelihood of emergency department (42% vs. 25%) or intensive care unit encounters (25% vs. 14%). There were no associations of FI and outcomes of interest. Major themes that emerged from caregiver interviews include (1) understanding of the kidney diet focuses on foods to avoid; (2) adapting to suggested dietary restrictions requires changes in meal preparation; and (3) challenges to adherence include social stigma, growth, budget, and time.

Conclusions: The impact of FI on children's medical needs with CKD remains inconclusive but trends suggest a higher risk. Regardless of FI status, adhering to prescribed diet restrictions in kidney disease involves significant dedication. Challenges involve food availability, a child's response to restrictions, and social stigma.

Background: Protein energy wasting (PEW) and undernutrition are highly prevalent in children with chronic kidney disease (CKD), but their impact on clinical outcomes is not well described. This prospective longitudinal study in children with CKD assessed the association of nutritional parameters with infection-related hospital admissions (IRHA).

Methods: Children with CKD2-5D aged 2-18 years and infection-free for 1 month were recruited over 5 years. Evaluation for undernutrition by subjective global nutritional assessment and for PEW using paediatric criteria was undertaken and categorized as mild (>2 criteria), standard (>3 criteria) and modified PEW (>3 criteria with short stature). The IRHA (severe viral, bacterial or fungal infections) were recorded.

Results: Among 137 children (45 on dialysis; age 123 ± 46 months; 70% males), undernutrition was seen in 60% and PEW in 52%. In over 38 ± 21 months follow-up, 107 (78%) required hospital admissions (67% IRHA). The incidence rate of IRHA in days per patient-year was higher in those with undernutrition compared to well-nourished children [1.74 (1.27, 2.31) vs. 0.65 (0.44, 0.92) p < 0.0001] and higher in those with PEW compared to no PEW [1.74 (1.30, 2.28) vs. 0.56 (0.36, 0.82) p < 0.0001] respectively. On adjusted analysis, independent risk factors for IRHA were undernutrition, low BMI, hypoalbuminemia and dialysis status with modified PEW [OR 5.34 (2.16, 13.1) p < 0.001] and raised CRP [OR 4.66 (1.56, 13.9) p = 0.006] having the highest risk. Additionally, modified PEW and BMI were noted to have a twofold risk for recurrent infections.

Conclusion: In children with CKD2-5D, incidence rate of IRHA was significantly higher in those with undernutrition and PEW. While dialysis, poor nutritional status and inflammation were risk factors for IRHA, modified PEW and BMI were associated with recurrent infections.

The gut microbiome is made up of trillions of bacteria, viruses, archaea, and microbes that play a significant role in the maintenance of normal physiology in humans. Recent research has highlighted the effects of the microbiome and its dysbiosis in the pathogenesis and maintenance of kidney disease, especially chronic kidney disease (CKD) and its associated cardiovascular disease. While studies have addressed the kidney-microbiome axis in adults, how dysbiosis may uniquely impact pediatric kidney disease patients is not well-established. This narrative review highlights all relevant studies focusing on the microbiome and pediatric kidney disease that were published between 7/2015 and 7/2023. This review highlights pediatric-specific considerations including growth and bone health as well as emphasizing the need for increased pediatric research. Understanding microbiome-kidney interactions may allow for novel, less invasive interventions such as dietary changes and the use of probiotics to improve preventive care and ameliorate long-term morbidity and mortality in this vulnerable population.