Nephrology Commons^™

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

Manuscripts, Articles, Book Chapters and Other Papers

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

Manuscripts, Articles, Book Chapters and Other Papers

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

Manuscripts, Articles, Book Chapters and Other Papers

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

Manuscripts, Articles, Book Chapters and Other Papers

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

Manuscripts, Articles, Book Chapters and Other Papers

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

Manuscripts, Articles, Book Chapters and Other Papers

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

Manuscripts, Articles, Book Chapters and Other Papers

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

Manuscripts, Articles, Book Chapters and Other Papers

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 …

A New Paradigm: Ecmo Therapy In Pediatric Hematology/Oncology Patients, Igor Areinamo

Research Days

Background: The use of extracorporeal membrane oxygenation (ECMO) for support of pediatric patients has significantly increased in the past years. Patients with known oncologic diseases, immunodeficiencies, or bone marrow transplants (BMT) have traditionally not been considered candidates for Extracorporeal membrane oxygenation (ECMO) due to perceived high risk for mortality. Ongoing advances have continued to push the boundaries of ECMO use and we report our recent experience with this patient population

Objectives/Goal: To evaluate survival to discharge of pediatric patients who require ECMO support and who also have an underlying hematologic or oncologic disease process. To determine specific patient characteristics that …

Association Between Blood Pressure And Esa Dose In Pediatric Patients On Dialysis, Heather A. Morgans

Research Days

Background: Hypertension is a reported side effect of Erythropoiesis Stimulating Agents (ESAs), with a mechanism of action related to elevated hematocrit levels and direct vasopressor effects. Limited information exists on the relationship between ESA dosage and hypertension in children receiving maintenance dialysis.

Objectives/Goal: The primary aim of this study was to determine whether there is a significant association between ESA dose and blood pressure (BP) in pediatric patients on dialysis. The secondary aim was to determine covariates in relation to ESA dose.

Methods/Design: Data from the International Pediatric Dialysis Network (IPDN) database was used to retrospectively analyze the association between …

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

Manuscripts, Articles, Book Chapters and Other Papers

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 …

The Association Between Age And Unrecognized And Untreated Hypertension In Children With Chronic Kidney Disease, Chloe Douglas, J Roem, Joseph Flynn, Susan Furth, Bradley A. Warady, Susan Halbach

Presentations

Background: Younger age has been associated with unrecognized hypertension (HTN) in both the general pediatric population and in children on dialysis. An increased lifetime risk of cardiovascular disease and the association of HTN with chronic kidney disease (CKD) progression make optimal treatment of elevated blood pressure (BP) a key component of CKD management. However, the role of age in the recognition and treatment of HTN in non-dialysis pediatric CKD remains unknown.

Objective: Using data from the Chronic Kidney Disease in Children (CKiD) Cohort Study, we examined the relationship between age and recognized vs. unrecognized HTN, and the frequency with which …

Using Machine Learning To Identify Metabolomic Signatures Based On Pediatric Chronic Kidney Disease Etiology, Arthur Lee, Alison Abraham, Yunwen Xu, Jian Hu, Xia Or, Josef Coresh, Casey Rebholz, J Chen, Eugene Ree, Harold Feldman, Paul Kimmel, Bradley A. Warady, Susan Furth, Michelle Denburg

Presentations

Background: Untargeted plasma metabolomic profiling combined with novel machine learning (ML) tools may lead to the discovery of metabolic profiles that inform our understanding of pediatric chronic kidney disease (CKD) etiologies and identify potential therapeutic targets.

Objective: We sought to identify metabolomic signatures in pediatric CKD based on etiology: focal segmental glomerular sclerosis (FSGS), obstructive uropathy (OU), aplasia/dysplasia/hypoplasia (A/D/H), & reflux nephropathy (RN).

Design/Methods: Untargeted GC/MS2 and LC/MS2-based metabolomics quantification (Metabolon) was performed on baseline plasma samples from 702 Chronic Kidney Disease in Children (CKiD) participants. Participants per etiology were: FSGS (n=63), OU (n=122), A/D/H (n=109), & RN (n=86). Lasso …

Association Between Esa Dose And Blood Pressure In Pediatric Patients On Dialysis, Heather A. Morgans, Judith Sebestyen Vansickle, Franz Schaefer, Bradley A. Warady

Posters

Background: Hypertension is a reported side effect of Erythropoiesis Stimulating Agents (ESAs), with a mechanism of action related to elevated hematocrit levels and direct vasopressor effects. Limited information exists on the relationship between ESA dosage and hypertension in children receiving maintenance dialysis.


Objective: The primary aim of this study was to determine whether there is a significant correlation between ESA dose and blood pressure (BP) in pediatric patients on dialysis. The secondary aim was to determine confounding variables in relation to ESA dose and BP.


Design/Methods: Data from the International Pediatric Dialysis Network (IPDN) database was used to retrospectively evaluate …

Efficacy And Safety Of Bardoxolone Methyl In Pediatric Patients With Alport Syndrome In Cardinal Phase 3 Trial, Bradley A. Warady, Sharon Andreol, Vimal Chadha, Melanie Chin, Rasheed Gbadegesin, Keisha Gibson, Debbie Gipson, Angie Goldsberry, Kenneth Lieberman, Colin Meyer, Kevin Meyers, Nozu Kandai, Megan O'Grady, Michelle Rheault, Clifford Kashtan

Posters

Background: Alport syndrome accounts for an estimated 3% of children with end-stage kidney disease in the US (USRDS, 2014). Whereas current management recommendations include the use of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with proteinuria, no specific therapies have been approved for this disease.


Objective: A Phase 3 study (CARDINAL; NCT03019185) evaluated the safety and efficacy of bardoxolone methyl (Bard) in adult and adolescent patients with Alport syndrome.


Design/Methods: CARDINAL was an international, multicenter, double-blind, placebo-controlled, randomized trial conducted over two years in patients with confirmed diagnosis of Alport syndrome. Patients aged 12 to 70 years old with baseline eGFR …

Perinatal Exposure To Interleukin-6 (Il-6): A Model To Study Influence Of Developmental Insult On Susceptibility To Chronic Kidney Disease (Ckd), Tarak Srivastava, Robert E. Garola, Varun Chandra Boinpelly, Jianping Zhou, Daniel P. Heruth, Mohammad Rezaiekhaligh, M. Farhan Ali, Lakshmi Priya, Uri Alon, Trupti Joshi, Yuexu Jiang, Ellen T. Mccarthy, Ram Sharma, Madhulika Sharma, Gregory Vanden Heuvel, Virginia J. Savin, Pramod B. Mahajan, Mukut Sharma

Posters

Background: CKD and obesity are marked by elevated pro-inflammatory cytokines, including IL-6. Pregnant obese women are associated with 1.5- to 2-fold increase in serum IL-6, newborns with smaller kidney/body weight ratio, kidney anomalies and increased susceptibility to CKD. Maternal IL-6, but not TNFα or IL-1β, can cross the placental barrier and enter fetal compartment.


Objective: We examined the role of (a) maternal injection of IL-6 during mid-gestation, similar to levels observed in pregnant obese women, on kidney development as a specific molecular surrogate of gestational inflammation and (b) IL-6 on glomerular filtration barrier.


Design/Methods: Pregnant mice received IL-6 (10 pg/g …

Obesity Does Not Increase Risk For Kidney Replacement Therapy (Krt), But Weight Reduction Improves Kidney Function In Children With Chronic Kidney Disease (Ckd), Amy Kogon, J Roem, Mark Mitsnefes, Babette Zeme, Bradley A. Warady, Susan Furth, Nancy Rodig

Presentations

Background: Obesity is prevalent in pediatric CKD, but its impact on CKD progression is unclear.

Objective: To determine the relationship between obesity/weight changes with CKD progression among children and adolescents enrolled in the Chronic Kidney Disease in Children (CKiD) study.

Design/Methods: Participants were categorized based on body mass index (BMI) as normal, overweight (OW) or obese and those who were underweight were excluded. Kaplan-Meier survival curves and parametric failure time models determined the association of baseline BMI category on time to KRT stratified by non-glomerular (NG) and glomerular (G) etiology of CKD. The distribution of changes in BMI categories within …

A Smarter Way To Round, Charles Maloy, Adrienne G. Deporre, Erica Adams, Jessica Olson, Amber Hunley, Darcy K. Weidemann

Posters

Background: Communication is a key driver of health care outcomes. Poor communication practices contribute to sentinel safety events, poor family/patient experiences, and delays in care. Use of checklists in the healthcare setting is important to the development of high reliability and is increasingly common, however, the development and implementation of medical checklists for the standard patient floor are inadequately described.


Objective: To develop a sustainable rounding checklist for multidisciplinary discussion of patient safety measures and clinical plans.


Design/Methods: Key stakeholders in the rounding process (subspecialty and general pediatrics physicians, resident physician, bedside nurses, and nursing leadership) created a rounding checklist …

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 …

Ispd Guidelines For Peritoneal Dialysis In Acute Kidney Injury: 2020 Update (Paediatrics)., Peter Nourse, Brett Cullis, Fredrick Finkelstein, Alp Numanoglu, Bradley A. Warady, Sampson Antwi, Mignon Mcculloch

Manuscripts, Articles, Book Chapters and Other Papers

1.1 Peritoneal dialysis is a suitable renal replacement therapy modality for treatment of acute kidney injury in children. (1C)2. Access and fluid delivery for acute PD in children.2.1 We recommend a Tenckhoff catheter inserted by a surgeon in the operating theatre as the optimal choice for PD access. (1B) (optimal)2.2 Insertion of a PD catheter with an insertion kit and using Seldinger technique is an acceptable alternative. (1C) (optimal)2.3 Interventional radiological placement of PD catheters combining ultrasound and fluoroscopy is an acceptable alternative. (1D) (optimal)2.4 Rigid …

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

Manuscripts, Articles, Book Chapters and Other Papers

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

Manuscripts, Articles, Book Chapters and Other Papers

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, …

Serially Assessed Bisphenol A And Phthalate Exposure And Association With Kidney Function In Children With Chronic Kidney Disease In The Us And Canada: A Longitudinal Cohort Study., Melanie H. Jacobson, Yinxiang Wu, Mengling Liu, Teresa M. Attina, Mrudula Naidu, Rajendiran Karthikraj, Kurunthachalam Kannan, Bradley A. Warady, Susan Furth, Suzanne Vento, Howard Trachtman, Leonardo Trasande

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD.

METHODS AND FINDINGS: Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) …

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

Manuscripts, Articles, Book Chapters and Other Papers

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 …

Alport Syndrome Classification And Management., Bradley A. Warady, Rajiv Agarwal, Sripal Bangalore, Arlene Chapman, Adeera Levin, Peter Stenvinkel, Robert D. Toto, Glenn M. Chertow

Manuscripts, Articles, Book Chapters and Other Papers

Alport syndrome affects up to 60,000 people in the United States. The proposed reclassification of thin basement membrane nephropathy and some cases of focal segmental glomerulosclerosis as Alport syndrome could substantially increase the affected population. The reclassification scheme categorizes Alport syndrome as 3 distinct diseases of type IV collagen α3/4/5 based on a genetic evaluation: X-linked, autosomal, and digenic. This approach has the advantage of identifying patients at risk for progressive loss of kidney function. Furthermore, the shared molecular cause of Alport syndrome and thin basement membrane nephropathy arises from mutations in the COL4A3, COL4A4, and COL4A5 genes, …

Consensus Guidelines For Management Of Hyperammonaemia In Paediatric Patients Receiving Continuous Kidney Replacement Therapy., Rupesh Raina, Jirair K. Bedoyan, Uta Lichter-Konecki, Philippe Jouvet, Stefano Picca, Nicholas Ah Mew, Marcel C. Machado, Ronith Chakraborty, Meghana Vemuganti, Manpreet K. Grewal, Timothy Bunchman, Sidharth Kumar Sethi, Vinod Krishnappa, Mignon Mcculloch, Khalid Alhasan, Arvind Bagga, Rajit K. Basu, Franz Schaefer, Guido Filler, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the …

Association Between Chronic Kidney Disease-Mineral Bone Disease (Ckd-Mbd) And Cognition In Children: Chronic Kidney Disease In Children (Ckid) Study., Jennifer S. Yokoyama, Mina Matsuda-Abedini, Michelle R. Denburg, Juhi Kumar, Bradley A. Warady, Susan L. Furth, Stephen R. Hooper, Anthony A. Portale, Farzana Perwad

Manuscripts, Articles, Book Chapters and Other Papers

Rationale & objective: Chronic kidney disease (CKD) in children is associated with cognitive dysfunction that affects school performance and quality of life. The relationship between CKD-mineral and bone disorder and cognitive function in children is unknown.

Study design: Observational study.

Participants: 702 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study.

Predictors: Plasma fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphorus, 25 hydroxyvitamin D (25[OH]D), and 1,25 dihydroxyvitamin D (1,25[OH]2D).

Outcomes: Neurocognitive tests of intelligence, academic achievement, and executive functions.

Analytical approach: Linear regression models to analyze the cross-sectional associations between log2FGF-23, 25(OH)D, 1,25(OH)2D, PTH, calcium, …

International Society For Peritoneal Dialysis Practice Recommendations: Prescribing High-Quality Goal-Directed Peritoneal Dialysis., Edwina A. Brown, Peter G. Blake, Neil Boudville, Simon Davies, Javier De Arteaga, Jie Dong, Fred Finkelstein, Marjorie Foo, Helen Hurst, David W. Johnson, Mark Johnson, Adrian Liew, Thyago Moraes, Jeff Perl, Rukshana Shroff, Isaac Teitelbaum, Angela Yee-Moon Wang, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.