Nephrology Commons^™

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.

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 …

Urinary Tissue Inhibitor Of Metalloproteinase-2 And Insulin-Like Growth Factor-Binding Protein 7 For Risk Stratification Of Acute Kidney Injury In Patients With Sepsis., Patrick M Honore, H Bryant Nguyen, Michelle Gong, Lakhmir S. Chawla, Sean M Bagshaw, Antonio Artigas, Jing Shi, Olivier Joannes-Boyau, Jean-Louis Vincent, John A Kellum

Anesthesiology and Critical Care Medicine Faculty Publications

Objectives:

To examine the performance of the urinary biomarker panel tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with sepsis at ICU admission. To investigate the effect of nonrenal organ dysfunction on tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in this population.

Method:

In this ancillary analysis, we included patients with sepsis who were enrolled in either of two trials including 39 ICUs across Europe and North America. The primary endpoint was moderate-severe acute kidney injury (equivalent to Kidney Disease Improving Global Outcome stage 2–3) within 12 hours of enrollment. We assessed biomarker …

Adenovirus Induced Rhabdomyolysis Causing Hemodialysis Dependent Acute Renal Failure, Deepika Jain Md, Andres Zirlinger Md, Matthew J. Miles Do

Department of Medicine

No abstract provided.

Pharmacologic Diuresis Is Safer Than Ultrafiltration For Cardiorenal Syndrome, Grace Choong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Bart BA, Goldsmith SR, Lee KL et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012;367:2296-2304. doi: 10.1056/NEJMoa1210357

Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp

Electronic Theses and Dissertations

Cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury (AKI) in 30% of patients. Although recovery can occur after one episode of cisplatin-induced AKI, studies have indicated multiple episodes may lead to the development of chronic kidney disease (CKD), an irreversible disease with no current treatments. The standard mouse model of cisplatin-induced AKI consists of one, high dose of cisplatin (> 20 mg/kg) that is lethal to the animal three days later. This model doesn’t accurately reflect the repeated dosing regimen patients receive, and doesn’t allow for long-term outcome studies of pathologies associated with CKD. We have developed a …

It Is Reasonable To Treat Patients With Type 1 Hepatorenal Syndrome With Midodrine And Octreotide, William Kane

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Esrailian E, Pantangco ER, Kyulo NL, Hu KQ, Runyon BA. Octreotide/midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci. 2007;52(3):742-748. doi: 10.1007/s10620-006-9312-0

Distal Renal Tubular Acidosis And Diabetes Insipidus Leading To The Diagnosis Of Sjögren's Syndrome, Loheetha Ragupathi, Md, Elijah Grillo, Md, Jonathan Yadlosky, Md, Ravi Sunderkrishnan, Md

The Medicine Forum

INTRODUCTION

Sjögren's syndrome is a chronic inflammatory disease characterized by the infiltration and progressive destruction of salivary and lacrimal glands. A common presentation involves the complaints of dry eyes and dry mouth, known as the “sicca complex.” Extra-glandular involvement is not uncommon, and is known to involve the lungs, vascular and peripheral nervous system, and kidney.1 The reported renal involvement ranges broadly from 2 – 67%,and is variably defined: the most commonly reported renal pathology is an a tubulo- interstitial nephritis resulting in tubular dysfunction and immune-mediated glomerular disease; however distal renal tubular acidosis (RTA) in particular can be present …

Magic Study: Aims, Design And Methods Using Systemchange™ To Improve Immunosuppressive Medication Adherence In Adult Kidney Transplant Recipients., Cynthia L. Russell, Shirley Moore, Donna Hathaway, An-Lin Cheng, Guoqing Chen, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Among adult kidney transplant recipients, non-adherence to immunosuppressive medications is the leading predictor of poor outcomes, including rejection, kidney loss, and death. An alarming one-third of kidney transplant patients experience medication non-adherence even though the problem is preventable. Existing adherence interventions have proven marginally effective for those with acute and chronic illnesses and ineffective for adult kidney transplant recipients. Our purpose is to describe the design and methods of the MAGIC (Medication Adherence Given Individual SystemCHANGE™) trial

METHODS/DESIGN: We report the design of a randomized controlled trial with an attention-control group to test an innovative 6-month SystemCHANGE™ intervention designed …

Common Chronic Conditions Do Not Affect Performance Of Cell Cycle Arrest Biomarkers For Risk Stratification Of Acute Kidney Injury, Michael Heung, Luis Ortega, Lakhmir S. Chawla, Richard G. Wunderink, Wesley H. Self, Jay Koyner, Jing Shi, John A. Kellum

Anesthesiology and Critical Care Medicine Faculty Publications

Background Identification of acute kidney injury (AKI) can be challenging in patients with underlying chronic disease, and biomarkers often perform poorly in this population. In this study we examined the performance characteristics of the novel biomarker panel of urinary tissue inhibitor of metalloproteinases-2 (TIMP2) and insulin-like growth factor-binding protein 7 ([IGFBP7]) in patients with a variety of comorbid conditions.

Methods We analyzed data from two multicenter studies of critically ill patients in which [TIMP2]•[IGFBP7] was validated for prediction of Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2 or 3 AKI within 12 h. We constructed receiver operating characteristic (ROC) curves …

Clinical Adjudication In Acute Kidney Injury Studies: Findings From The Pivotal Timp-2*Igfbp7 Biomarker Study, Kathleen D. Liu, Anitha Vijayan, Mitchell H. Rosner, Jing Shi, Lakhmir S. Chawla, John A. Kellum

Anesthesiology and Critical Care Medicine Faculty Publications

Background The NEPROCHECK test (Astute Medical, San Diego, CA, USA) combines urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) to identify patients at high risk for acute kidney injury (AKI). In a US Food and Drug Administration registration trial (NCT01573962), AKI was determined by a three-member clinical adjudication committee. The objectives were to examine agreement among adjudicators as well as between adjudicators and consensus criteria for AKI and to determine the relationship of biomarker concentrations and adjudicator agreement.

Methods Subjects were classified as AKI 3/3, 2/3, 1/3 or 0/3 according to the …

Chronic Kidney Disease And Acute Myocardial Infarction: The Story After 1 Year, Paulette S. Wehner, William A. Nitardy

Internal Medicine

When chronic kidney disease (CKD) is part of the clinical history for a patient with acute myocardial infarction, the interventional cardiologist experiences an increased anxiety level. An acute myocardial infarction with renal disease requires more attention to dye load and fluid status, and general opinion exists regarding the negative outcomes of these “sicker” patients.

Mark Navarro and colleagues completed a thorough study from a different angle. We know the interventionalists’ concerns are justified acutely as these CKD patients have a higher level of inpatient complications, but these authors chose to look at the patients 1 year from their event to …

Renal Stress Testing In The Assessment Of Kidney Disease, Lakhmir S. Chawla, Claudio Ronco

Anesthesiology and Critical Care Medicine Faculty Publications

As part of human evolutionary development, many human organ systems have innate mechanisms to adapt to increased “work demand” or stress. This reserve capacity can be informative and is used commonly in cardiology to assess cardiac function (e.g., treadmill test). Similarly, the kidney possesses reserve capacity, which can be demonstrated in at least 2 of the following renal domains: glomerular and tubular. When appropriate stimulants are used, healthy patients with intact kidneys can significantly increase their glomerular filtration rate and their tubular secretion. This approach has been used to develop diagnostics for the assessment of renal function. This article reviews …

Use Of Surface-Enhanced Laser Desorption/Ionization With Time Of Flight (Seldi-Tof) Of The Urine In The Assessment Of Acute Kidney Injury (Aki), David J. Kennedy, Phd, Joseph M. Chan, Dinkar Kaw, Md, Anand M. Ravindaran, Md, Shobha Ratnam, Md, Phd, Deepak Malhotra, Md, Phd, Joseph I. Shapiro Md

Marshall Journal of Medicine

Background: Urinalysis is an important component in the assessment of acute kidney injury (AKI). Proteonomics is a rapidly developing approach in the analysis of physiological states. Several techniques have been developed to screen for protein populations. In this regard SELDI-TOF is a technique based on mass spectroscopy that is being utilized in proteonomics research.

Methods:For this study, clean catch or catheterized urine was collected from normals (n=18) and patients referred to the renal service with AKI. Based upon urine and serum chemistries, clinical parameters, and microscopic urinalysis, the urines were separated into those consistent with prerenal azotemia (n=17) and acute …

Kidney Disease Progression In Autosomal Recessive Polycystic Kidney Disease., Katherine M. Dell, Matthew Matheson, Erum A. Hartung, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort.

STUDY DESIGN: GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test.

RESULTS: Annualized GFR change in subjects …

Strengthening Instrumental Variables Through Weighting, Douglas Lehmann, Yun Li, Rajiv Saran, Yi Li

The University of Michigan Department of Biostatistics Working Paper Series

Instrumental variable (IV) methods are widely used to deal with the issue of unmeasured confounding and are becoming popular in health and medical research. IV models are able to obtain consistent estimates in the presence of unmeasured confounding, but rely on assumptions that are hard to verify and often criticized. An instrument is a variable that influences or encourages individuals toward a particular treatment without directly affecting the outcome. Estimates obtained using instruments with a weak influence over the treatment are known to have larger small-sample bias and to be less robust to the critical IV assumption that the instrument …

Techniques And Approaches To Genetic Analyses In Nephrological Disorders., Laurel K. Willig

Manuscripts, Articles, Book Chapters and Other Papers

Inherited renal disease is a leading cause of morbidity and mortality in pediatric nephrology. High throughput advancements in genomics have led to greater understanding of the biologic underpinnings of these diseases. However, the underlying genetic changes explain only part of the molecular biology that contributes to disease manifestation and progression. Other omics technologies will provide a more complete picture of these cellular processes. This review discusses these omics technologies in the context of pediatric renal disease.

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 …