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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 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 m.sup.2) 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. Graphical Abstract, Author(s): Kaye E. Brathwaite [sup.1] , Rebecca V. Levy [sup.2] [sup.3] , Harini Sarathy [sup.4] , Ilir Agalliu [sup.5] , Tanya S. Johns [sup.6] , Kimberly J. Reidy [sup.7] , [...]

Background Longitudinal changes in body mass index (BMI) among overweight and obese children with chronic kidney disease (CKD) are not well characterized. We studied longitudinal trajectories and correlates of these trajectories, as results may identify opportunities to optimize health outcomes. Methods Longitudinal changes in age-sex-specific BMI z-scores over 1851 person-years of follow-up were assessed in 524 participants of the Chronic Kidney Disease in Children Study. A total of 353 participants were categorized as normal (BMI > 5th to < 85th percentile), 56 overweight (BMI [greater than or equal to] 85th to 95th percentile) and 115 obese (BMI [greater than or equal to] 95th percentile) based on the average of three BMI measurements during the first year of follow-up. Studied covariates included age, sex, race, CKD etiology, corticosteroid usage, household income, and maternal education. Results In unadjusted analysis, BMI z-scores decreased over time in elevated BMI groups (overweight: mean = - 0.06 standard deviations (SD) per year, 95% CI: - 0.11, - 0.01; obese: mean = - 0.04 SD per year, 95% CI: - 0.07, - 0.01). Among obese children, only age was associated with change in BMI z-score; children < 6 years had a mean decrease of 0.19 SD during follow-up (95% CI: - 0.30, - 0.09). Socioeconomic factors were not associated with change in BMI. Conclusion Overweight and obese children with CKD demonstrated a significant annual decline in BMI, though the absolute change was modest. Among obese children, only age < 6 years was associated with significant decline in BMI. Persistence of elevated BMI in older children and adolescents with CKD underscores the need for early prevention and effective intervention., Author(s): Nancy M. Rodig [sup.1] , Jennifer Roem [sup.2] , Michael F. Schneider [sup.2] , Patricia W. Seo-Mayer [sup.3] , Kimberly J. Reidy [sup.4] , Frederick J. Kaskel [sup.4] , [...]

In the past 20 years, multiple genetic mutations have been identified in patients with congenital nephrotic syndrome (CNS) and both familial and sporadic focal segmental glomerulosclerosis (FSGS). Characterization of the genetic basis of CNS and FSGS has led to the recognition of the importance of podocyte injury to the development of glomerulosclerosis. Genetic mutations induce injury due to effects on the podocyte's structure, actin cytoskeleton, calcium signaling, and lysosomal and mitochondrial function. Transgenic animal studies have contributed to our understanding of podocyte pathobiology. Podocyte endoplasmic reticulum stress response, cell polarity, and autophagy play a role in maintenance of podocyte health. Further investigations related to the effects of genetic mutations on podocytes may identify new pathways for targeting therapeutics for nephrotic syndrome. Keywords Focal segmental glomerulosclerosis * Nephrotic syndrome * Steroid resistantnephrotic syndrome * Genetic mutation * Podocyte signaling, Introduction Podocytes are highly differentiated and specialized pericyte-like cells with a complex cyto-architecture that form a major component of the glomerular filtration barrier. The podocyte consists of a cell body [...]

Background Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS). Methods FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied. Results There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (−7.6 points, P = 0.02) and mobility (−4.2, P = 0.02), the number of reported symptoms was associated with worse depression (−2.7 per symptom, P = 0.009) and anxiety (−2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (−2.8 per visit, P < 0.001) and fatigue (−2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P  =  0.03). Conclusions PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) in preterm neonates is becoming an increasingly recognized morbidity in the neonatal intensive care unit neonatal intensive care unit (NICU), yet its epidemiology, delineation and relation to numerous toxic exposures and common morbidities such as systemic hypertension is just evolving. With a frequency of the patent ductus arteriosus (PDA) as high as 70% in preterm infants born before 28-week gestation, the role of the hemodynamically significant PDA (hs-PDA) remains unclear. Objective: To determine if AKI and systemic hypertension is more common in extremely low gestational age newborns (ELGAN) with hs PDA compared to ELGAN with no or non-hs PDA using modified AKIN and Neonatal Risk, Injury, Failure, Loss of Kidney Function, and End-stage (N-RIFLE) scoring systems. Methods: This was a retrospective cohort study of infants ≤28 weeks gestational age born between 2010 and 2016 who had echocardiographic PDA evaluation completed for hemodynamical significance as well as serial serum creatinine and urine output measurement documented, needed for the two AKI scoring systems: modified AKIN (based on serial serum creatinine) and N-RIFLE (using urine output data). Blood pressure measurements and therapy were evaluated during the hospitalization and on the day of NICU discharge. Baseline characteristics and outcome variables were compared between the hs-PDA and no or non-hs PDA using unpaired t-tests for continuous variables and chi square tests for categorical data. Results: One hundred fifty-one infants were eligible of which 110 had hs-PDA. Infants with hs-PDA were smaller (777 versus 867 g, p = .026), less mature (25.8 versus 26.4 weeks, p = .023) and had greater exposure to nephrotoxic drugs (14 versus 9.4 days, p = .001). Other clinical and demographic variables were similar between the two groups. The overall incidence of AKI was not different between the hs-PDA and no PDA or non-hs PDA groups when evaluated by the acute kidney injury network (AKIN) or N-RIFLE staging; however, preterm newborns with hs-PDA demonstrated a trend towards increased risk of AKI injury (12.7 versus 0.02%, p = .06). The N-RIFLE and AKIN scoring systems demonstrated very poor degree of agreement (kappa = 0.00853) in our study. There was no difference in the rates of hypertension during the hospitalization as well as on the day of NICU discharge. Conclusion: Preterm neonates with hs-PDA had similar rates of AKI and hypertension as neonates with no or non-hs PDA. [ABSTRACT FROM AUTHOR]