Nephrology Commons^™

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 …

Acute Renal Failure And An Acid-Base Dilemma, Kamil Sardarli, Russell Leong, Matthew Weatherhead, Bhavinkumar Dalal

Conference Presentation Abstracts

Introduction: Acute renal failure (ARF) is well-recognized to result in metabolic acidosis. The acidosis of ARF is associated with decreased ammoniagenesis and anion excretion. Alkalosis in the presence of ARF presents diagnostic uncertainty and therapeutic challenges. This vignette describes a case of ARF resulting in several electrolyte imbalances and metabolic alkalosis. Case Description: A 54-year-old female with past medical history of small bowel resection with colostomy presented for nausea and vomiting for two weeks. On presentation, she was noted to be tachycardic and lethargic. Her workup revealed a serum creatinine of 6.8 mg/dL, blood urea nitrogen of 147 mg/dL, bicarbonate …

Retrospective Analysis Of Post-Operative Sepsis Rates, Stone Composition, And Ureteral Stent Duration After Ureteroscopy And Laser Lithotripsy During Covid-19, Young Son, Julia T. Scali, Ian Madison, Paul Chialastri, Thomas Mueller

Stratford Campus Research Day

Ureteroscopy with laser lithotripsy is routinely used to remove stones but results in manipulation of the genitourinary mucosa and has a well-established relationship with post-operative sepsis under certain conditions. Postoperative sepsis represents a significant morbidity and mortality cost to patients and the healthcare system. Several studies to determine risk factors for sepsis after ureteroscopy have been completed. Such risk factors include positive preoperative urine cultures, female gender, prolonged preoperative stent time > 1 month, and patients with sepsis at the time of initial stenting. To improve sepsis rates, procedural alterations such as the use of disposable ureteroscopes have been introduced, as …

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 …

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 …

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 …

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 …

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 …

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 …

Infective Endocarditis-Associated Glomerulonephritis Versus Cryoglobulinemic Glomerulonephritis: An Unfortunate Clinical Overlap, Yesha K. Shah Do, Emilee E. Kurtz Do, Sharon E. Maynard Md, Mohammad Saqib Md

Department of Medicine

No abstract provided.

Bone Quality In Chronic Kidney Disease Patients: Current Concepts And Future Directions – Part Ii, Kamyar Asadipooya, Mohamed Abdalbary, Yahya Ahmad, Elijah Kakani, Marie-Claude Monier-Faugere, Amr El-Husseini

Internal Medicine Faculty Publications

Background: Patients with chronic kidney disease (CKD) have an increased risk of osteoporotic fractures, which is due not only to low bone volume and mass but also poor microarchitecture and tissue quality. The pharmacological and nonpharmacological interventions detailed, herein, are potential approaches to improve bone health in CKD patients. Various medications build up bone mass but also affect bone tissue quality. Antiresorptive therapies strikingly reduce bone turnover; however, they can impair bone mineralization and negatively affect the ability to repair bone microdamage and cause an increase in bone brittleness. On the other hand, some osteoporosis therapies may cause a redistribution …

Bone Quality In Ckd Patients: Current Concepts And Future Directions – Part I, Kamyar Asadipooya, Mohamed Abdalbary, Yahya Ahmad, Elijah Kakani, Marie-Claude Monier-Faugere, Amr El-Husseini

Internal Medicine Faculty Publications

Background: There is ample evidence that patients with CKD have an increased risk of osteoporotic fractures. Bone fragility is not only influenced by low bone volume and mass but also by poor microarchitecture and tissue quality. More emphasis has been given to the quantitative rather than qualitative assessment of bone health, both in general population and CKD patients. Although bone mineral density (BMD) is a very useful clinical tool in assessing bone strength, it may underestimate the fracture risk in CKD patients. Serum and urinary bone biomarkers have been found to be reflective of bone activities and predictive of fractures …

Differential Effects Of Kim-1 In Subcutaneous And Orthotopic Renca Models Of Kidney Cancer, Demitra M. Yotis Dy

Electronic Thesis and Dissertation Repository

Renal Cell Carcinoma (RCC) is the most common and fatal type of kidney cancer. Over 30% of patients that are diagnosed with RCC exhibit metastases. Almost 88% of patients with distant metastases succumb to the disease within 5 years of diagnosis. Kidney Injury Molecule-1 (KIM-1) is a cell surface glycoprotein that is not expressed in a healthy kidney but becomes highly expressed on proximal tubular epithelial cells (PTECs) following injury. Data from the Cancer Genome Atlas (TCGA) reveals that >90% of RCC tumours express KIM-1 mRNA and that higher expression levels correlate with increased overall survival rates of patients. The …

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 …