Reduced kidney function and hypertension in adolescents with low birth weight, NHANES 1999-2016.

BACKGROUND: Chronic kidney disease (CKD) is a major health problem, and the risk of CKD and hypertension in children born low birth weight (LBW) is under-recognized. We hypothesized that children born with LBW would have a higher prevalence of reduced kidney function and hypertension. METHODS: Using the National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study to evaluate whether LBW (< 2500 g), very low birth weight (VLBW < 1500 g), and large birth weight (BW) (> 4000 g) were associated with kidney disease using 4 different estimating equations. We used the Counahan-Barratt, updated Schwartz, CKiD-U25, and full age spectrum creatinine-based GFR estimating equations to evaluate associations between a history of LBW/VLBW/large BW and reduced kidney function (eGFR < 90 mL/min/1.73 m2) in children. We also assessed blood pressure (BP) using the old and new pediatric hypertension guidelines. RESULTS: Our analysis included 6336 children (age 12-15 years) in NHANES representing over 13 million US individuals. Using the updated Schwartz, the prevalence of reduced kidney function was 30.1% (25.2-35.6) for children born with LBW compared to 22.4% (20.5-24.3) in children with normal BW. Equations yielded different estimates of prevalence of reduced kidney function in LBW from 21.5% for Counahan-Barratt to 35.4% for CKiD-U25. Compared to those with normal BW, participants with LBW and VLBW had a 7.2 and 10.3% higher prevalence of elevated BP and a 2.4 and 14.6% higher prevalence of hypertension, respectively. CONCLUSIONS: Children born with LBW are at higher risk of reduced kidney function and hypertension than previously described. A higher resolution version of the Graphical abstract is available as Supplementary information.

Racial and Ethnic Disparities in Acute Care Utilization Among Patients With Glomerular Disease.

RATIONALE & OBJECTIVE: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort. EXPOSURE: Race and ethnicity as a participant-reported social factor. OUTCOME: Acute care utilization defined as hospitalizations or emergency department visits. ANALYTICAL APPROACH: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization. RESULTS: Black or Hispanic participants had lower SES and more severe glomerular disease than White or Asian participants. Acute care utilization rates were 45.6, 29.5, 25.8, and 19.2 per 100 person-years in Black, Hispanic, White, and Asian adults, respectively, and 55.8, 42.5, 40.8, and 13.0, respectively, for children. Compared with the White race (reference group), Black race was significantly associated with acute care utilization in adults (rate ratio [RR], 1.76 [95% CI, 1.37-2.27]), although this finding was attenuated after multivariable adjustment (RR, 1.31 [95% CI, 1.03-1.68]). Black race was not significantly associated with acute care utilization in children; Asian race was significantly associated with lower acute care utilization in children (RR, 0.32 [95% CI 0.14-0.70]); no significant associations between Hispanic ethnicity and acute care utilization were identified. LIMITATIONS: We used proxies for SES and lacked direct information on income, household unemployment, or disability. CONCLUSIONS: Significant differences in acute care utilization rates were observed across racial and ethnic groups in persons with prevalent glomerular disease, although many of these difference were explained by differences in SES and disease severity. Measures to combat socioeconomic disadvantage in Black patients and to more effectively prevent and treat glomerular disease are needed to reduce disparities in acute care utilization, improve patient wellbeing, and reduce health care costs.

Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations.

Background: Focal segmental glomerulosclerosis (FSGS) is a major cause of end stage kidney disease, with the collapsing form having the worst prognosis. Study of families with hereditary FSGS has provided insight into disease mechanisms. Methods: In this report, we describe a sibling pair with NUP93 mutations and collapsing FSGS (cFSGS). For each brother, we performed next generation sequencing and segregation analysis by direct sequencing. To determine if the variants found in the index family are a common cause of cFSGS, we screened 7 patients with cFSGS, gleaned from our cohort of 200 patients with FSGS, for variants in NUP93 as well as for APOL1 high-risk genotypes. Results: We identified segregating compound heterozygous NUP93 variants (1) c.1772G > T p.G591V, 2) c.2084T > C p.L695S) in the two brothers. We did not find any pathogenic variants in the seven patients with cFSGS from our cohort, and as expected five of these seven patients carried the APOL1 high-risk genotype. Conclusion: To the best of our knowledge, this is the first report of cFSGS in patients with NUP93 mutations, based on this report, mutations in NUP93 and other nucleoporin genes should be considered when evaluating a child with familial cFSGS. Determining the mechanisms by which these variants cause cFSGS may provide insight into the pathogenesis of the more common primary and virus-mediated forms of cFSGS.

Analysis of Active and Passive Tobacco Exposures and Blood Pressure in US Children and Adolescents.

Importance: Hypertension is a leading cause of cardiovascular disease in adults; preclinical associations between hypertension and cardiovascular disease are seen in childhood. Nicotine is a known toxin, but its association with pediatric hypertension is unclear. Objective: To test the hypothesis that tobacco exposure is associated with the presence of elevated blood pressure in US children and adolescents and that this association is dose dependent. Design, Setting, and Participants: This cross-sectional study used data from the 2007 to 2016 National Health and Nutrition Examination Survey (NHANES), a population-based nationally representative sample of US children and adolescents. Children were eligible if they were aged 8 to 19 years at the time of participation in the main NHANES study. Exclusion criteria included those of the main NHANES study, inability to complete testing, or missing questionnaires. Of the 10 143 participants in NHANES aged 8 to 19 during the study years, 8520 were included in the analysis. Analysis was conducted from October 12, 2019, to July 9, 2020. Exposures: Tobacco exposure, defined as serum cotinine levels greater than 0.05 µg/L, or reporting living with a smoker or smoking themselves. Main Outcomes and Measures: Elevated blood pressure, classified as greater than 90% for a child's age, sex, and height according to the 2017 American Academy of Pediatrics Clinical Practice Guidelines. The a priori hypothesis that there is a positive association between tobacco exposure and elevated blood pressure in the study population was tested. Analysis included logistic regression with adjustment for possible confounders. Subgroup and sensitivity analyses were conducted. Results: A total of 8520 children were included in the analysis, representing 41 million US children. The mean (SD) age of the participants was 13.1 (0.05) years, 51% (95% CI, 49%-52%) were male, and 58% (95% CI, 54%-62%) were non-Hispanic White individuals. Participants with any tobacco smoke exposure were more likely than those without exposure to be older (mean [SD] age, 13.3 [0.07] years vs 12.8 [0.06] years), male (53% [95% CI, 51%-55%] vs 49% [95% CI, 47%-50%]), and non-Hispanic Black individuals (19% [95% CI, 16%-22%] vs 10% [95% CI, 8%-12%]). The odds of having elevated blood pressure was 1.31 (95% CI, 1.06-1.61) for any tobacco exposure after adjustment; odds were similar across subgroups and remained significant in multiple sensitivity analyses. Conclusions and Relevance: This study suggests that tobacco exposure is associated with elevated blood pressure in US children and adolescents. This modifiable risk factor represents a target for further research into reducing hypertension in children and adolescents.

COVID-19 in Children With Kidney Disease: A Report of 2 Cases.

The presentation of novel coronavirus disease 2019 (COVID-19) in children with kidney disease is largely unknown. We report on 2 children with kidney disease not receiving long-term immunosuppression who were hospitalized due to COVID-19. The first case is an infant with end-stage kidney disease secondary to bilateral cystic dysplastic kidneys and posterior urethral valves receiving peritoneal dialysis, with a history of prematurity previously requiring mechanical ventilation in the neonatal intensive care unit, who presented with fever, hypertension, and emesis. He had no respiratory symptoms and recovered with supportive care. His hypertension was managed well with amlodipine. The second case is a child with steroid-sensitive nephrotic syndrome who presented with a relapse of nephrotic syndrome with concurrent peritonitis and sepsis caused by Streptococcus agalactiae. He was treated with antibiotics and prophylactic anticoagulation therspy. Steroid therapy was initiated after 48 hours of antibiotic therapy. Neither child required mechanical ventilation or developed COVID-19-related multisystem inflammatory syndrome.