Nephrology Commons^™

Fgf23 And Left Ventricular Hypertrophy In Children With Ckd., Mark M. Mitsnefes, Aisha Betoko, Michael F. Schneider, Isidro B. Salusky, Myles Selig Wolf, Harald Jüppner, Bradley A. Warady, Susan L. Furth, Anthony A. Portale

Manuscripts, Articles, Book Chapters and Other Papers

Background and objectives: High plasma concentration of fibroblast growth factor 23 (FGF23) is a risk factor for left ventricular hypertrophy (LVH) in adults with CKD, and induces myocardial hypertrophy in experimental CKD. We hypothesized that high FGF23 levels associate with a higher prevalence of LVH in children with CKD.

Design, setting, participants, & measurements: We performed echocardiograms and measured plasma C-terminal FGF23 concentrations in 587 children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. We used linear and logistic regression to analyze the association of plasma FGF23 with left ventricular mass index (LVMI) and LVH …

Mechanotransduction Signaling In Podocytes From Fluid Flow Shear Stress., Tarak Srivastava, Hongying Dai, Daniel P. Heruth, Uri S. Alon, Robert E. Garola, Jianping Zhou, R Scott Duncan, Ashraf El-Meanawy, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Recently, we and others have found that hyperfiltration-associated increase in biomechanical forces, namely, tensile stress and fluid flow shear stress (FFSS), can directly and distinctly alter podocyte structure and function. The ultrafiltrate flow over the major processes and cell body generates FFSS to podocytes. Our previous work suggests that the cyclooxygenase-2 (COX-2)-PGE2-PGE2 receptor 2 (EP2) axis plays an important role in mechanoperception of FFSS in podocytes. To address mechanotransduction of the perceived stimulus through EP2, cultured podocytes were exposed to FFSS (2 dyn/cm2) for 2 h. Total RNA from cells at the end of FFSS treatment, 2-h post-FFSS, and 24-h …

Therapeutic Considerations For Antihyperglycemic Agents In Diabetic Kidney Disease., Joshua J Neumiller, Radica Alicic, Katherine Tuttle

Articles, Abstracts, and Reports

Diabetic kidney disease is among the most frequent complications of diabetes, with approximately 50% of patients with ESRD attributed to diabetes in developed countries. Although intensive glycemic management has been shown to delay the onset and progression of increased urinary albumin excretion and reduced GFR in patients with diabetes, conservative dose selection and adjustment of antihyperglycemic medications are necessary to balance glycemic control with safety. A growing body of literature is providing valuable insight into the cardiovascular and renal safety and efficacy of newer antihyperglycemic medications in the dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, and sodium-glucose cotransporter 2 inhibitor …

Role Of Biomechanical Forces In Hyperfiltration-Mediated Glomerular Injury In Congenital Anomalies Of The Kidney And Urinary Tract., Tarak Srivastava, Ganesh Thiagarajan, Uri S. Alon, Ram Sharma, Ashraf El-Meanawy, Ellen T. Mccarthy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear. We re-examine the phenomenon of hyperfiltration in the context of biomechanical forces with special reference to glomerular podocytes. Capillary stretch exerts tensile …

Renin-Angiotensin Ii-Aldosterone System Blockers And Time To Renal Replacement Therapy In Children With Ckd., Alison G. Abraham, Aisha Betoko, Jeffrey J. Fadrowski, Christopher Pierce, Susan L. Furth, Bradley A. Warady, Alvaro Muñoz

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin-angiotensin II-aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD.

METHODS: A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m

RESULTS: There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more …

Assessment Of Dietary Intake Of Children With Chronic Kidney Disease., Wun Fung Hui, Aisha Betoko, Jonathan D. Savant, Alison G. Abraham, Larry A. Greenbaum, Bradley A. Warady, Marva M. Moxey-Mims, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Our aim was to characterize the nutrient intake of children with chronic kidney disease (CKD) relative to recommended intake levels.

METHODS: We conducted a cross-sectional study of dietary intake assessed by Food Frequency Questionnaire (FFQ) in The North American Chronic Kidney Disease in Children (CKiD) prospective cohort study. Nutrient intake was analyzed to estimate the daily consumption levels of various nutrients and compared with national guidelines for intake.

RESULTS: There were 658 FFQs available for analysis; 69.9 % of respondents were boys, with a median age [Interquartile range (IQR)] of 11 years (8-15). Median daily sodium, potassium, and phosphorus …

Cystatin C And Cardiac Measures In Children And Adolescents With Ckd., Tammy M. Brady, Kelly Townsend, Michael F. Schneider, Christopher Cox, Thomas Kimball, Peace Madueme, Bradley A. Warady, Susan Furth, Mark Mitsnefes

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent among children with chronic kidney disease (CKD). Cystatin C is an established marker of kidney function and an emerging biomarker for CVD events. We quantified the relationship between cystatin C level and cardiac structure and function over time among children with CKD and assessed whether cystatin C level and diastolic function retained an association after accounting for kidney function.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: 678 children and adolescents with mild to moderate CKD enrolled in the CKD in Children (CKiD) Study with 1,228 echocardiographically obtained cardiac structure and function measurements. …

Cardiovascular Disease Risk Factors And Left Ventricular Hypertrophy In Girls And Boys With Ckd., Rebecca L. Ruebner, Derek Ng, Mark Mitsnefes, Bethany J. Foster, Kevin Meyers, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

Background and objectives: Prior studies suggested that women with CKD have higher risk for cardiovascular disease (CVD) and mortality than men, although putative mechanisms for this higher risk have not been identified. We assessed sex differences in (1) CVD risk factors and left ventricular hypertrophy (LVH), and (2) the relationship of left ventricular mass (LVM) with different measures of body size in children with CKD.

Design, setting, participants, and measurements: The study population comprised 681 children with CKD from the Chronic Kidney Disease in Children cohort, contributing 1330 visits. CVD risk factors were compared cross-sectionally by sex. LVH was defined …

Association Of Blood Pressure Variability And Neurocognition In Children With Chronic Kidney Disease., Marc B. Lande, Susan R. Mendley, Matthew B. Matheson, Shlomo Shinnar, Arlene C. Gerson, Joshua A. Samuels, Bradley A. Warady, Susan L. Furth, Stephen R. Hooper

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Children with chronic kidney disease (CKD) and hypertension have increased blood pressure variability (BPV), which has been associated with lower neurocognitive test scores in adults. Children with CKD are at risk for decreased neurocognitive function. Our objective was to determine whether children with CKD and increased BPV had worse performance on neurocognitive testing compared with children with CKD and lower BPV.

METHODS: This was a cross-sectional and longitudinal analysis of the relation between BPV and neurocognitive test performance in children ≥6 years enrolled in the Chronic Kidney Disease in Children (CKiD) study. Visit-to-visit BPV was assessed by the standard …

Racial Differences In Renal Replacement Therapy Initiation Among Children With A Nonglomerular Cause Of Chronic Kidney Disease., Derek K. Ng, Marva Moxey-Mims, Bradley A. Warady, Susan L. Furth, Alvaro Muñoz

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: African American (AA) adults with chronic kidney disease (CKD) have a faster progression to end-stage renal disease and are less likely to receive a kidney transplant. It is unclear whether AA children experience renal replacement therapy (RRT) for end-stage renal disease sooner than non-AA children after accounting for socioeconomic status (SES).

METHODS: Among children with nonglomerular CKD in the Chronic Kidney Disease in Children study, we investigated time to RRT (i.e., first dialysis or transplant) after CKD onset using parametric survival models and accounted for SES differences by inverse probability weights.

RESULTS: Of 110 AA and 493 non-AA children …

Toxic Environmental Exposures And Kidney Health In Children., Darcy K. Weidemann, Virginia M. Weaver, Jeffrey J. Fadrowski

Manuscripts, Articles, Book Chapters and Other Papers

High-level exposures to a number of agents are known to have direct nephrotoxic effects in children. A growing body of literature supports the hypothesis that chronic, relatively low-level exposure to various nephrotoxicants may also increase the risk for chronic kidney disease (CKD) or accelerate its progression. In this review we highlight several environmental nephrotoxicants and their association with CKD in children and adolescents. We also discuss unique epidemiological challenges in the use of kidney biomarkers in environmental nephrotoxicology.

Fracture Burden And Risk Factors In Childhood Ckd: Results From The Ckid Cohort Study., Michelle R. Denburg, Juhi Kumar, Thomas Jemielita, Ellen R. Brooks, Amy Skversky, Anthony A. Portale, Isidro B. Salusky, Bradley A. Warady, Susan L. Furth, Mary B. Leonard

Manuscripts, Articles, Book Chapters and Other Papers

Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence …

Genetic Loci Associated With Renal Function Measures And Chronic Kidney Disease In Children: The Pediatric Investigation For Genetic Factors Linked With Renal Progression Consortium., Matthias Wuttke, Craig S. Wong, Elke Wühl, Daniel Epting, Li Luo, Anselm Hoppmann, Anke Doyon, Yong Li, Gkdgen Consortium, Betül Sözeri, Daniela Thurn, Martin Helmstädter, Tobias B. Huber, Tom D. Blydt-Hansen, Albrecht Kramer-Zucker, Otto Mehls, Anette Melk, Uwe Querfeld, Susan L. Furth, Bradley A. Warady, Franz Schaefer, Anna Köttgen

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown.

METHODS: The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular …

Can Office Blood Pressure Readings Predict Masked Hypertension?, Mark M. Mitsnefes, Chris Pierce, Joseph Flynn, Joshua Samuels, Janis Dionne, Susan Furth, Bradley A. Warady, Ckid Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Studies in children with chronic kidney disease indicate a high prevalence of masked hypertension detected by ambulatory blood pressure monitoring (ABPM). However, it is not well known if the frequency of masked hypertension is related to the level of normal casual blood pressure (BP).

METHODS/RESULTS: We hypothesized that lower levels of normal casual BP are associated with a lower prevalence of masked hypertension. Data from the chronic kidney disease (CKiD) cohort were analyzed cross-sectionally across multiple visits. The majority of children with normal casual BP also had normal wake and sleep ABP (60 %), even at the highest percentiles …

Depressive Symptoms In Children With Chronic Kidney Disease., Amy J. Kogon, Matthew B. Matheson, Joseph T. Flynn, Arlene C. Gerson, Bradley A. Warady, Susan L. Furth, Stephen R. Hooper, Chronic Kidney Disease In Children (Ckid) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To assess depression in children with chronic kidney disease and to determine associations with patient characteristics, intellectual and educational levels, and health-related quality of life (HRQoL).

STUDY DESIGN: Subjects aged 6-17 years from the Chronic Kidney Disease in Children cohort study completed the Children's Depression Inventory (CDI), Wechsler Abbreviated Scales of Intelligence, Wechsler Individual Achievement Test-II-Abbreviated, and the Pediatric Inventory of Quality of Life Core Scales 4.0. Regression analyses determined associations of CDI score and depression status with subject characteristics, intellectual and educational levels, and HRQoL. A joint linear mixed model and Weibull model were used to determine the …

Renal And Cardiovascular Morbidities Associated With Apol1 Status Among African-American And Non-African-American Children With Focal Segmental Glomerulosclerosis., Robert P. Woroniecki, Derek K. Ng, Sophie Limou, Cheryl A. Winkler, Kimberly J. Reidy, Mark Mitsnefes, Matthew G. Sampson, Craig S. Wong, Bradley A. Warady, Susan L. Furth, Jeffrey B. Kopp, Frederick J. Kaskel

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children.

DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease.

RESULTS: A total of 140 AA children in the CKiD study were genotyped. High …

Cyclooxygenase-2, Prostaglandin E2, And Prostanoid Receptor Ep2 In Fluid Flow Shear Stress-Mediated Injury In The Solitary Kidney., Tarak Srivastava, Uri S. Alon, Patricia A. Cudmore, Belal Tarakji, Alexander Kats, Robert E. Garola, R Scott Duncan, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Lynda F. Bonewald, Ashraf El-Meanawy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Hyperfiltration subjects podocytes to increased tensile stress and fluid flow shear stress (FFSS). We showed a 1.5- to 2.0-fold increase in FFSS in uninephrectomized animals and altered podocyte actin cytoskeleton and increased synthesis of prostaglandin E2 (PGE2) following in vitro application of FFSS. We hypothesized that increased FFSS mediates cellular changes through specific receptors of PGE2. Presently, we studied the effect of FFSS on cultured podocytes and decapsulated isolated glomeruli in vitro, and on solitary kidney in uninephrectomized sv129 mice. In cultured podocytes, FFSS resulted in increased gene and protein expression of cyclooxygenase (COX)-2 but not COX-1, prostanoid receptor EP2 …