Nephrology Commons^™

Investigating The Use Of Finerenone In Children With Chronic Kidney Disease And Proteinuria: Design Of The Fiona And Open-Label Extension Studies., Franz Schaefer, Giovanni Montini, Hee Gyung Kang, Johan Vande Walle, Joshua Zaritsky, Michiel F. Schreuder, Mieczyslaw Litwin, Andrea Scalise, Helen Scott, James Potts, Pablo Iveli, Stefanie Breitenstein, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria.

OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that …

Real-World Evidence On The Dosing And Safety Of C.E.R.A. In Pediatric Dialysis Patients: Findings From The International Pediatric Dialysis Network Registries., Laura Kohlhas, Milena Studer, Loes Rutten-Jacobs, Sylvie Meyer Reigner, Anja Sander, Hui-Kim Yap, Karel Vondrak, Paula A. Coccia, Francisco Cano, Claus Peter Schmitt, Bradley A. Warady, Franz Schaefer, Ipdn Collaborators

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BACKGROUND: This retrospective real-world study used data from two registries, International Pediatric Peritoneal Dialysis Network (IPPN) and International Pediatric Hemodialysis Network (IPHN), to characterize the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) in pediatric patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) or hemodialysis (HD).

METHODS: IPPN and IPHN collect prospective data (baseline and every 6 months) from pediatric PD and HD centers worldwide. Demographics, clinical characteristics, dialysis information, treatment, laboratory parameters, number and causes of hospitalization events, and deaths were extracted for patients on C.E.R.A. treatment (IPPN: 2007-2021; IPHN: 2013-2021).

RESULTS: We analyzed 177 patients …

Associations Between Anemia And Fgf23 In The Ckid Study., Elizabeth Thomas, Alexandra M. Klomhaus, Marciana L. Laster, Susan L. Furth, Bradley A. Warady, Isidro B. Salusky, Mark R. Hanudel

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in chronic kidney disease-mineral bone disorder and is associated with CKD progression and cardiovascular morbidity. Factors related to CKD-associated anemia, including iron deficiency, can increase FGF23 production. This study aimed to assess whether anemia and/or iron deficiency are associated with increased circulating concentrations of FGF23 in the large, well-characterized Chronic Kidney Disease in Children (CKiD) study cohort.

METHODS: Hemoglobin concentrations, iron parameters, C-terminal (total) FGF23, intact FGF23, and relevant covariables were measured in cross-sectional analysis of CKiD study subjects.

RESULTS: In 493 pediatric patients with …

The Impact Of Pediatric Ckd On Educational And Employment Outcomes., Lyndsay A. Harshman, Ryan C. Ward, Matthew B. Matheson, Anne Dawson, Amy J. Kogon, Marc B. Lande, Stephen J. Molitor, Rebecca J. Johnson, Camille Wilson, Bradley A. Warady, Susan L. Furth, Stephen R. Hooper

Manuscripts, Articles, Book Chapters and Other Papers

KEY POINTS: This study evaluates educational and employment outcomes in patients with pediatric kidney disease and assesses predictors of educational attainment and employment in young adulthood. Despite high rates of high school graduation, nearly 20% of patients with CKD are unemployed or receiving disability at long-term follow-up.

BACKGROUND: Pediatric patients with CKD are at risk for neurocognitive deficits and academic underachievement. This population may be at risk for lower educational attainment and higher rates of unemployment; however, published data have focused on patients with advanced CKD and exist in isolation from assessment of neurocognition and kidney function.

METHODS: Data from …

Associations Of Biomarkers Of Kidney Tubule Health, Injury, And Inflammation With Left Ventricular Hypertrophy In Children With Ckd., Kuan Jiang, Jason H. Greenberg, Alison Abraham, Yunwen Xu, Jeffrey R. Schelling, Harold I. Feldman, Sarah J. Schrauben, Sushrut S. Waikar, Michael G. Shlipak, Nicholas Wettersten, Steven G. Coca, Ramachandran S. Vasan, Orlando M. Gutierrez, Joachim H. Ix, Bradley A. Warady, Paul L. Kimmel, Joseph V. Bonventre, Chirag R. Parikh, Mark M. Mitsnefes, Michelle R. Denburg, Susan Furth, Ckd Biomarkers Consortium

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KEY POINTS:

• Higher plasma and urine kidney injury molecule-1, urine monocyte chemoattractant protein-1, and lower urine alpha-1-microglobulin were associated with left ventricular hypertrophy, even after adjustment for confounders.
• Biomarkers of tubular injury, dysfunction, and inflammation may indicate the severity of kidney pathology and are associated with left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is common in children with CKD and is associated with an increased risk of cardiovascular disease and mortality. We have shown that several plasma and urine biomarkers are associated with increased risk of CKD progression. As CKD is associated with LVH, we sought to investigate the …

Persistent Increase In Serum Ferritin Levels Despite Converting To Permanent Vascular Access In Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study., Ali Mirza Onder, Md Abu Yusuf Ansari, Fang Deng, Matthew M. Grinsell, Larry Patterson, Jennifer Jetton, Sahar Fathallah-Shaykh, Daniel Ranch, Diego Aviles, Lawrence Copelovitch, Eileen Ellis, Vimal Chadha, Ayah Elmaghrabi, Jen-Jar Lin, Lavjay Butani, Maha Haddad, Olivera Marsenic, Paul Brakeman, Raymond Quigley, H Stella Shin, Rouba Garro, Rupesh Raina, Craig B. Langman

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Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). …

Trends In The Representation Of Women In The American Society Of Pediatric Nephrology Program At The Pediatric Academic Society Annual Meetings 2012-2021., Bahar Barani Najafabadi, David T. Selewski, Danielle E. Soranno, Darcy K. Weidemann

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INTRODUCTION: Women are under-represented in virtually all fields of academic medicine. Even in pediatrics, a field that historically attracts a workforce with a majority of women physicians, substantial gender disparities persist in leadership positions. However, previous studies of gender representation in various academic settings are limited to small studies or aggregate pediatric subspecialties, thereby omitting important granularity within each subspecialty. No prior studies have investigated potential gender disparities in pediatric nephrology. The aim of this study is to determine the representation of women physicians in leadership and speaking roles in the annual American Society of Pediatric Nephrology (ASPN) meeting.

METHODS: …

Tobacco Exposure In Adults And Children With Proteinuric Glomerulopathies: A Neptune Cohort Study., Linda Wang, Bayle Smith-Salzberg, Kevin Ec Meyers, Dorey A. Glenn, Katherine R. Tuttle, Vimal K. Derebail, Tammy M. Brady, Keisha Gibson, Abigail R. Smith, Michelle M. O'Shaughnessy, Tarak Srivastava, Gentzon Hall, Jarcy Zee, Markus Bitzer, Christine B. Sethna

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BACKGROUND: Tobacco exposure has been recognized as a risk factor for cardiovascular disease (CVD) and progression of kidney disease. Patients with proteinuric glomerulopathies are at increased risk for cardiovascular morbidity and mortality. Multiple studies have linked tobacco exposure to CVD and chronic kidney disease, but the relationships between smoking and proteinuric glomerulopathies in adults and children have not been previously explored.

METHODS: Data from the Nephrotic Syndrome Study Network (NEPTUNE), a multi-center prospective observational study of participants with proteinuric glomerulopathies, was analyzed. 371 adults and 192 children enrolled in NEPTUNE were included in the analysis. Self-reported tobacco exposure was classified …

Nutritional Management Of The Infant With Chronic Kidney Disease Stages 2-5 And On Dialysis., Vanessa Shaw, Caroline Anderson, An Desloovere, Larry A. Greenbaum, Dieter Haffner, Christina L. Nelms, Fabio Paglialonga, Nonnie Polderman, Leila Qizalbash, José Renken-Terhaerdt, Stella Stabouli, Jetta Tuokkola, Johan Vande Walle, Bradley A. Warady, Rukshana Shroff

Manuscripts, Articles, Book Chapters and Other Papers

The nutritional management of children with chronic kidney disease (CKD) is of prime importance in meeting the challenge of maintaining normal growth and development in this population. The objective of this review is to integrate the Pediatric Renal Nutrition Taskforce clinical practice recommendations for children with CKD stages 2-5 and on dialysis, as they relate to the infant from full term birth up to 1 year of age, for healthcare professionals, including dietitians, physicians, and nurses. It addresses nutritional assessment, energy and protein requirements, delivery of the nutritional prescription, and necessary dietary modifications in the case of abnormal serum levels …

A Review Of Ferric Citrate Clinical Studies, And The Rationale And Design Of The Ferric Citrate And Chronic Kidney Disease In Children (Fit4kid) Trial., Mark R. Hanudel, Marciana L. Laster, Anthony A. Portale, Aditi Dokras, Raymond P. Quigley, German A Lozano Guzman, Joshua J. Zaritsky, Nicole A. Hayde, Frederick J. Kaskel, Mark M. Mitsnefes, Jorge A. Ramirez, Peace D. Imani, Poyyapakkam R. Srivaths, Amy J. Kogon, Michelle R. Denburg, Tom D. Blydt-Hansen, Loretta Z. Reyes, Larry A. Greenbaum, Darcy K. Weidemann, Bradley A. Warady, David A. Elashoff, Susan R. Mendley, Tamara Isakova, Isidro B. Salusky

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production-dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use …

Comparing Kidney Health Outcomes In Children, Adolescents, And Adults With Focal Segmental Glomerulosclerosis., Debbie S. Gipson, Jonathan P. Troost, Cathie Spino, Samara Attalla, Joshua Tarnoff, Susan Massengill, Richard Lafayette, Virginia Vega-Warner, Sharon Adler, Patrick Gipson, Matthew Elliott, Frederick Kaskel, Damian Fermin, Marva Moxey-Mims, Richard N. Fine, Elizabeth J. Brown, Kimberly Reidy, Katherine Tuttle, Keisha Gibson, Kevin V. Lemley, Larry A. Greenbaum, Meredith A. Atkinson, Sangeeta Hingorani, Tarak Srivastava, Christine B. Sethna, Kevin Meyers, Cheryl Tran, Katherine M. Dell, Chia-Shi Wang, Jennifer Lai Yee, Matthew G. Sampson, Rasheed Gbadegesin, J J Lin, Tammy Brady, Michelle Rheault, Howard Trachtman

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Importance: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials.

Objective: To examine whether there are differences in the kidney health outcomes among children, adolescents, and adults with FSGS.

Design, Setting, and Participants: This cohort study used pooled and parallel analyses, completed July 5, 2022, from 3 complimentary data sources: (1) …

Gluten-Free Diet In Childhood Difficult-To-Treat Nephrotic Syndrome: A Pilot Feasibility Study., Tarak Srivastava, Katherine M. Dell, Kevin V. Lemley, Debbie S. Gipson, Frederick J. Kaskel, Kevin Edward Meyers, Christian Faul, Ayelet Goldhaber, Laurajane Pehrson, Howard Trachtman

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Minimal change disease in childhood can follow a frequently relapsing or steroid-dependent course in up to 40% of cases. Second-line immunosuppressive medications that are used to manage these patients are associated with significant adverse effects. There is a need for safer alternative treatments for difficult-to-treat nephrotic syndrome. Therefore, we conducted an open-label feasibility study to assess the safety and efficacy of a gluten-free diet as treatment for pediatric patients with difficult-to-treat nephrotic syndrome. As a second aim, we sought to determine if the plasma zonulin concentration can identify those who are more likely to respond to this intervention.

METHODS: …

Burnout In Pediatric Nephrology Fellows And Faculty: Lessons From The Sustainable Pediatric Nephrology Workforce Project (Superpower)., Susan M. Halbach, Kartik Pillutla, Patricia Seo-Mayer, Alan Schwartz, Darcy K. Weidemann, John D. Mahan

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Physician well-being is an important contributor to both job satisfaction and patient outcomes. Rates of burnout among physicians vary by specialty, ranging from 35 to 70%. Among pediatric residents, longitudinal data demonstrates consistent rates of burnout around 50-60%, although little is known about burnout among pediatric subspecialty fellows. Specifically, the degree of burnout among pediatric nephrologists remains unknown, as does the impact faculty burnout may have on trainee burnout. We sought to evaluate prevalence and predictors of burnout among US pediatric nephrology fellows and faculty, and assess for interactions between groups. In this multi-center pilot survey of all United States …

The Burden Of Mental Health Conditions In Children With Ckd., Katherine L. Kurzinski, Darcy K. Weidemann

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No abstract provided.

Health And Dental Insurance And Health Care Utilization Among Children, Adolescents, And Young Adults With Ckd: Findings From The Ckid Cohort Study., Andrea R. Molino, Maria Lourdes G. Minnick, Judith Jerry-Fluker, Jacqueline Karita Muiru, Sara A. Boynton, Susan L. Furth, Bradley A. Warady, Derek K. Ng, Chronic Kidney Disease In Children Study

Manuscripts, Articles, Book Chapters and Other Papers

Rationale & Objective: To understand the association between health and dental insurance status and health and dental care utilization, and their relationship with disease severity in a population with childhood-onset chronic kidney disease (CKD).

Study Design: Observational cohort study.

Settings & Participants: Nine hundred fifty-three participants contributing 4,369 person-visits (unit of analysis) in the United States enrolled in the Chronic Kidney Disease in Children (CKiD) Study from 2005 to 2019.

Exposures: Health insurance (private vs public vs none) and dental insurance (presence vs absence) self-reported at annual visits.

Outcomes: Self-reported suboptimal health care utilization in the past year, defined separately …

Moving The Needle Toward Fair Compensation In Pediatric Nephrology., Darcy K. Weidemann, I A Ashoor, D E Soranno, R Sheth, C Carter, P D Brophy

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Remuneration issues are a substantial threat to the long-term stability of the pediatric nephrology workforce. It is uncertain whether the pediatric nephrology workforce will meet the growing needs of children with kidney disease without a substantial overhaul of the current reimbursement policies. In contrast to adult nephrology, the majority of pediatric nephrologists practice in an academic setting affiliated with a university and/or children's hospital. The pediatric nephrology service line is crucial to maintaining the financial health and wellness of a comprehensive children's hospital. However, in the current fee-for-service system, the clinical care for children with kidney disease is neither sufficiently …

Glomerular Biomechanical Stress And Lipid Mediators During Cellular Changes Leading To Chronic Kidney Disease., Mukut Sharma, Vikas Singh, Ram Sharma, Arnav Koul, Ellen T. Mccarthy, Virginia J. Savin, Trupti Joshi, Tarak Srivastava

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Hyperfiltration is an important underlying cause of glomerular dysfunction associated with several systemic and intrinsic glomerular conditions leading to chronic kidney disease (CKD). These include obesity, diabetes, hypertension, focal segmental glomerulosclerosis (FSGS), congenital abnormalities and reduced renal mass (low nephron number). Hyperfiltration-associated biomechanical forces directly impact the cell membrane, generating tensile and fluid flow shear stresses in multiple segments of the nephron. Ongoing research suggests these biomechanical forces as the initial mediators of hyperfiltration-induced deterioration of podocyte structure and function leading to their detachment and irreplaceable loss from the glomerular filtration barrier. Membrane lipid-derived polyunsaturated fatty acids (PUFA) and their …

The Similarities And Differences Between Glomerular Vs. Non-Glomerular Diagnoses On Intelligence And Executive Functions In Pediatric Chronic Kidney Disease: A Brief Report., Stephen R. Hooper, Rebecca J. Johnson, Marc Lande, Matthew Matheson, Shlomo Shinnar, Amy J. Kogon, Lyndsay Harshman, Joann Spinale, Arlene C. Gerson, Bradley A. Warady, Susan L. Furth

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Pediatric chronic kidney disease (CKD) appears to be a heterogeneous group of conditions, but this heterogeneity has not been explored with respect to its impact on neurocognitive functioning. This study investigated the neurocognitive functioning of those with glomerular (G) vs. non-glomerular (NG) diagnoses. Data from the North American CKiD Study were employed and the current study included 1,003 children and adolescents with mild to moderate CKD. The G Group included 260 participants (median age = 14.7 years) and the NG Group included 743 individuals (median age = 9.0 years). Neurocognitive measures assessed IQ, inhibitory control, attention regulation, problem solving, working …

Organophosphate Pesticides And Progression Of Chronic Kidney Disease Among Children: A Prospective Cohort Study., Melanie H. Jacobson, Yinxiang Wu, Mengling Liu, Kurunthachalam Kannan, Adela Jing Li, Morgan Robinson, Bradley A. Warady, Susan Furth, Howard Trachtman, Leonardo Trasande

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Background: Growing evidence suggests that exposure to environmental chemicals, such as pesticides, impacts renal function and chronic kidney disease (CKD). However, it is not clear if pesticides may affect CKD progression and no studies exist in children.

Objectives: The objective of this study was to examine associations between serially measured urinary OP pesticide metabolites and clinical and laboratory measures of kidney function over time among children with CKD.

Methods: This study used data on 618 participants enrolled in the CKD in Children study (CKiD), a cohort study of pediatric CKD patients from the US and Canada. Children were followed over …

Mortality In Children Treated With Maintenance Peritoneal Dialysis: Findings From The International Pediatric Peritoneal Dialysis Network Registry., Sophie Ploos Van Amstel, Marlies Noordzij, Dagmara Borzych-Duzalka, Nicholas C. Chesnaye, Hong Xu, Lesley Rees, Il-Soo Ha, Zenaida L. Antonio, Nakysa Hooman, William Wong, Karel Vondrak, Yok Chin Yap, Hiren Patel, Maria Szczepanska, Sara Testa, Monica Galanti, Jameela A. Kari, Charlotte Samaille, Sevcan A. Bakkaloglu, Wai-Ming Lai, Luisa Fernanda Rojas, Mabel Sandoval Diaz, Biswanath Basu, Alicia Neu, Bradley A. Warady, Kitty J. Jager, Franz Schaefer

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RATIONALE & OBJECTIVE: Research on pediatric kidney replacement therapy (KRT) has primarily focused on Europe and North America. In this study, we describe the mortality risk of children treated with maintenance peritoneal dialysis (MPD) in different parts of the world and characterize the associated demographic and macroeconomic factors.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: Patients younger than 19 years at inclusion into the International Pediatric Peritoneal Dialysis Network registry, who initiated MPD between 1996 and 2017.

EXPOSURE: Region as primary exposure (Asia, Western Europe, Eastern Europe, Latin America, North America, and Oceania). Other demographic, clinical, and macroeconomic (4 …

Survey Of Telemedicine By Pediatric Nephrologists During The Covid-19 Pandemic., Rupesh Raina, Nikhil Nair, Hui Kim Yap, Guido Filler, Sidharth K. Sethi, Arvind Bagga, Pankaj Hari, Timothy Bunchman, Sharon Bartosh, Katherine Twombley, Gaurav Kapur, Mignon Mcculloch, Bradley A. Warady, Maria Díaz-González De Ferris, Sarah Rush

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Introduction: The slow increase in use of telemedicine began to expand rapidly, along with reimbursement changes, during the coronavirus disease-2019 (COVID-19) pandemic. Standardized protocols for these services are lacking but are needed for effective and equitable health care. In this study, we queried pediatric nephrologists and their patients about their telemedicine experiences during the pandemic.

Methods: Surveys that were in compliance with the Health Insurance Portability and Accountability Act were deployed online to patients and physicians.

Results: We collected survey responses from 400 patients and 197 pediatric nephrologists. Patients reported positive experiences with telemedicine visits as it was logistically easier …

A Mouse Model Of Prenatal Exposure To Interleukin-6 To Study The Developmental Origin Of Health And Disease., Tarak Srivastava, Trupti Joshi, Daniel P. Heruth, Mohammad Rezaiekhaligh, Robert E. Garola, Jianping Zhou, Varun C. Boinpelly, M. Farhan Ali, Uri S. Alon, Madhulika Sharma, Gregory B. Vanden Heuvel, Pramod Mahajan, Lakshmi Priya, Yuexu Jiang, Ellen T. Mccarthy, Virginia J. Savin, Ram Sharma, Mukut Sharma

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Systemic inflammation in pregnant obese women is associated with 1.5- to 2-fold increase in serum Interleukin-6 (IL-6) and newborns with lower kidney/body weight ratio but the role of IL-6 in increased susceptibility to chronic kidney (CKD) in adult progeny is not known. Since IL-6 crosses the placental barrier, we administered recombinant IL-6 (10 pg/g) to pregnant mice starting at mid-gestation yielded newborns with lower body (p < 0.001) and kidney (p < 0.001) weights. Histomorphometry indicated decreased nephrogenic zone width (p = 0.039) with increased numbers of mature glomeruli (p = 0.002) and pre-tubular aggregates (p = 0.041). Accelerated maturation in IL-6 newborns was suggested by early expression of podocyte-specific protein podocin in glomeruli, increased 5-methyl-cytosine (LC-MS analysis for CpG DNA methylation) and altered expression of certain genes of cell-cycle and apoptosis (RT-qPCR array-analysis). Western blotting showed upregulated pJAK2/pSTAT3. Thus, treating dams with IL-6 as a surrogate provides newborns to study effects of maternal systemic inflammation on future susceptibility to CKD in adulthood.

Variability In Ckd Biomarker Studies: Soluble Urokinase Plasminogen Activator Receptor (Supar) And Kidney Disease Progression In The Chronic Kidney Disease In Children (Ckid) Study., Alison G. Abraham, Yunwen Xu, Jennifer L. Roem, Jason H. Greenberg, Darcy K. Weidemann, Venkata S. Sabbisetti, Joseph V. Bonventre, Michelle Denburg, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

Rationale & Objective: Biomarker studies are important for generating mechanistic insight and providing clinically useful predictors of chronic kidney disease (CKD) progression. However, variability across studies can often muddy the evidence waters. Here we evaluated real-world variability in biomarker studies using two published studies, independently conducted, of the novel plasma marker soluble urokinase-type plasminogen activator receptor (suPAR) for predicting CKD progression in children with CKD.

Study Design: A comparison of 2 prospective cohort studies.

Setting & Participants: 541 children from the Chronic Kidney Disease in Children (CKiD) study, median age 12 years, median glomerular filtration rate (GFR) of 54 mL/min/1.73m …

The Dietary Management Of Potassium In Children With Ckd Stages 2-5 And On Dialysis-Clinical Practice Recommendations From The Pediatric Renal Nutrition Taskforce., An Desloovere, José Renken-Terhaerdt, Jetta Tuokkola, Vanessa Shaw, Larry A. Greenbaum, Dieter Haffner, Caroline Anderson, Christina L. Nelms, Michiel J S Oosterveld, Fabio Paglialonga, Nonnie Polderman, Leila Qizalbash, Bradley A. Warady, Rukshana Shroff, Johan Vande Walle

Manuscripts, Articles, Book Chapters and Other Papers

Dyskalemias are often seen in children with chronic kidney disease (CKD). While hyperkalemia is common, with an increasing prevalence as glomerular filtration rate declines, hypokalemia may also occur, particularly in children with renal tubular disorders and those on intensive dialysis regimens. Dietary assessment and adjustment of potassium intake is critically important in children with CKD as hyperkalemia can be life-threatening. Manipulation of dietary potassium can be challenging as it may affect the intake of other nutrients and reduce palatability. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, has developed clinical practice recommendations …

Transcription Factor Β-Catenin Plays A Key Role In Fluid Flow Shear Stress-Mediated Glomerular Injury In Solitary Kidney., Tarak Srivastava, Daniel P. Heruth, R Scott Duncan, Mohammad H. Rezaiekhaligh, Robert E. Garola, Lakshmi Priya, Jianping Zhou, Varun C. Boinpelly, Jan Novak, Mohammed Farhan Ali, Trupti Joshi, Uri S. Alon, Yuexu Jiang, Ellen T. Mccarthy, Virginia J. Savin, Ram Sharma, Mark L. Johnson, Mukut Sharma

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Increased fluid flow shear stress (FFSS) in solitary kidney alters podocyte function in vivo. FFSS-treated cultured podocytes show upregulated AKT-GSK3β-β-catenin signaling. The present study was undertaken to confirm (i) the activation of β-catenin signaling in podocytes in vivo using unilaterally nephrectomized (UNX) TOPGAL mice with the β-galactosidase reporter gene for β-catenin activation, (ii) β-catenin translocation in FFSS-treated mouse podocytes, and (iii) β-catenin signaling using publicly available data from UNX mice. The UNX of TOPGAL mice resulted in glomerular hypertrophy and increased the mesangial matrix consistent with hemodynamic adaptation. Uninephrectomized TOPGAL mice showed an increased β-galactosidase expression at 4 weeks …

Chronic Inflammation In Chronic Kidney Disease Progression: Role Of Nrf2., Peter Stenvinkel, Glenn M. Chertow, Prasad Devarajan, Adeera Levin, Sharon P. Andreoli, Sripal Bangalore, Bradley A. Warady

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Despite recent advances in the management of chronic kidney disease (CKD), morbidity and mortality rates in these patients remain high. Although pressure-mediated injury is a well-recognized mechanism of disease progression in CKD, emerging data indicate that an intermediate phenotype involving chronic inflammation, oxidative stress, hypoxia, senescence, and mitochondrial dysfunction plays a key role in the etiology, progression, and pathophysiology of CKD. A variety of factors promote chronic inflammation in CKD, including oxidative stress and the adoption of a proinflammatory phenotype by resident kidney cells. Regulation of proinflammatory and anti-inflammatory factors through NF-κB- and nuclear factor, erythroid 2 like 2 (Nrf2)-mediated …

Assessment Of Nutritional Status In Children With Kidney Diseases-Clinical Practice Recommendations From The Pediatric Renal Nutrition Taskforce., Christina L. Nelms, Vanessa Shaw, Larry A. Greenbaum, Caroline Anderson, An Desloovere, Dieter Haffner, Michiel J S Oosterveld, Fabio Paglialonga, Nonnie Polderman, Leila Qizalbash, Lesley Rees, José Renken-Terhaerdt, Jetta Tuokkola, Johan Vande Walle, Rukshana Shroff, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

In children with kidney diseases, an assessment of the child's growth and nutritional status is important to guide the dietary prescription. No single metric can comprehensively describe the nutrition status; therefore, a series of indices and tools are required for evaluation. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists who develop clinical practice recommendations (CPRs) for the nutritional management of children with kidney diseases. Herein, we present CPRs for nutritional assessment, including measurement of anthropometric and biochemical parameters and evaluation of dietary intake. The statements have been graded using the American …

Unilateral Nephrectomy Stimulates Erk And Is Associated With Enhanced Na Transport., Robert Repetti, Nomrota Majumder, Karin Carneiro De Oliveira, Jennifer Meth, Tenzin Yangchen, Mukut Sharma, Tarak Srivastava, Rajeev Rohatgi

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Nephron loss initiates compensatory hemodynamic and cellular effects on the remaining nephrons. Increases in single nephron glomerular filtration rate and tubular flow rate exert higher fluid shear stress (FSS) on tubules. In principal cell (PC) culture models FSS induces ERK, and ERK is implicated in the regulation of transepithelial sodium (Na) transport, as well as, proliferation. Thus, we hypothesize that high tubular flow and FSS mediate ERK activation in the cortical collecting duct (CCD) of solitary kidney which regulates amiloride sensitive Na transport and affects CCD cell number. Immunoblotting of whole kidney protein lysate was performed to determine phospho-ERK (pERK) …

Study Design And Baseline Characteristics Of The Cardinal Trial: A Phase 3 Study Of Bardoxolone Methyl In Patients With Alport Syndrome., Glenn M. Chertow, Gerald B. Appel, Sharon Andreoli, Sripal Bangalore, Geoffrey A. Block, Arlene B. Chapman, Melanie P. Chin, Keisha L. Gibson, Angie Goldsberry, Kazumoto Iijima, Lesley A. Inker, Bertrand Knebelmann, Laura H. Mariani, Colin J. Meyer, Kandai Nozu, Megan O'Grady, Arnold L. Silva, Peter Stenvinkel, Roser Torra, Bradley A. Warady, Pablo E. Pergola

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INTRODUCTION: Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome.

METHODS: The CARDINAL phase 3 study is an international, …

Cinacalcet Studies In Pediatric Subjects With Secondary Hyperparathyroidism Receiving Dialysis., Bradley A. Warady, Eric Ng, Laura Bloss, May Mo, Franz Schaefer, Justine Bacchetta

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BACKGROUND: Secondary hyperparathyroidism (sHPT), a complication of chronic kidney disease (CKD) characterized by persistently elevated parathyroid hormone (PTH), alterations in calcium-phosphorus homeostasis, and vitamin D metabolism, affects 50% of children receiving dialysis. A significant proportion of these children develop CKD-mineral and bone disorder (CKD-MBD), associated with an increased risk of fractures and vascular calcification. The standard of care for sHPT in children includes vitamin D sterols, calcium supplementation, and phosphate binders. Several agents are approved for sHPT treatment in adults undergoing dialysis, including vitamin D analogs and calcimimetics, with limited information on their safety and efficacy in children. The calcimimetic …