Medicine and Health Sciences Commons^™

Legionnaire's Disease Presenting With Severe Rhabdomyolysis And Acute Renal Failure: A Case Report, Benjamin Plotz, Victoria K. Shanmugam

GW Research Days 2016 - 2020

Legionnaire's disease is caused by Legionella species, and is a recognized but rare cause of rhabdomyolysis. Legionella species live in water, and exposure to inoculated water systems leads to transmission of the disease, and commonly causes pneumonia in infected individuals. While the mechanism of muscle destruction legionella infection causes is not fully understood, the prevailing theory is that rhabdomyolysis is linked to an endotoxin released by the bacteria into the blood stream. Massive muscle necrosis manifests as limb weakness, muscle pain, swelling, and gross pigmenturia due to the release of electrolytes, myoglobin, and other sarcoplasmic proteins into the bloodstream. A …

Evaluating The Impact Of A Standardized Education Class On A Person Diagnosed With Chronic Kidney Disease, Stage Iv, Nancy K. Uhland, Dnp, Msn, Rn, Fnp-C

Doctor of Nursing Practice Projects

Background: Chronic kidney disease (CKD) is a complex, progressive, and costly disease impacting more than 26 million Americans. Providing effective education is necessary so the patient may actively participate in managing the disease process, but the effectiveness of the delivery of education to the patient with CKD is not well-known.

Objective: To evaluate the effectiveness of a standardized education class on the basic kidney knowledge of persons diagnosed with CKD, stage IV.

Method: This pilot study, using a one-group pre and post-test design, was conducted in an outpatient nephrology clinic located in Washington, D.C. The study participants, recruited using census …

Nephron Segment-Specific Gene Expression Using Aav Vectors., Laureano D Asico, Santiago Cuevas, Xiaobo Ma, Pedro A Jose, Ines Armando, Prasad R Konkalmatt

Medicine Faculty Publications

AAV9 vector provides efficient gene transfer in all segments of the renal nephron, with minimum expression in non-renal cells, when administered retrogradely via the ureter. It is important to restrict the transgene expression to the desired cell type within the kidney, so that the physiological endpoints represent the function of the transgene expressed in that specific cell type within kidney. We hypothesized that segment-specific gene expression within the kidney can be accomplished using the highly efficient AAV9 vectors carrying the promoters of genes that are expressed exclusively in the desired segment of the nephron in combination with administration by retrograde …

Cardiovascular Effects Of Metabolic Syndrome After Transplantation: Convergence Of Obesity And Transplant-Related Factors., Kristen Sgambat, Sarah Clauss, Asha Moudgil

Pediatrics Faculty Publications

Children are at increased risk of developing metabolic syndrome (MS) after kidney transplantation, which contributes to long-term cardiovascular (CV) morbidities and decline in allograft function. While MS in the general population occurs due to excess caloric intake and physical inactivity, additional chronic kidney disease and transplant-related factors contribute to the development of MS in transplant recipients. Despite its significant health consequences, the interplay of the individual components in CV morbidity in pediatric transplant recipients is not well understood. Additionally, the optimal methods to detect early CV dysfunction are not well defined in this unique population. The quest to establish clear …

Fluid Balance Concepts In Medicine: Principles And Practice., Maria-Eleni Roumelioti, Robert H Glew, Zeid J Khitan, Helbert Rondon-Berrios, Christos P Argyropoulos, Deepak Malhotra, Dominic S Raj, Emmanuel I Agaba, Mark Rohrscheib, Glen H Murata, Joseph I Shapiro, Antonios H Tzamaloukas

Medicine Faculty Publications

The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. …

Physical Therapy Considerations For Chronic Kidney Disease And Secondary Sarcopenia, Michael O. Harris-Love, Haniel J. Hernandez, Gideon Obamwonyi

Exercise and Nutrition Sciences Faculty Publications

Chronic kidney disease (CKD) is a progressive condition that may negatively affect musculoskeletal health. These comorbidities may include malnutrition, osteoporosis, and decreased lean body mass. Secondary sarcopenia due to CKD may be associated with mobility limitations and elevated fall risk. Physical therapists are well-positioned among the health care team to screen for secondary sarcopenia in those with CKD and for the treatment of musculoskeletal comorbid conditions that may affect functional performance. Given the consequences of both low muscle mass and low bone mineral density, appropriate and timely physical therapy is important for fall risk assessment and intervention to minimize the …

Gut Microbiota And Cardiovascular Uremic Toxicities, Manuel T. Velasquez, Patricia Centron, Ian Barrows, Rama Dwivedi, Dominic S. Raj

Medicine Faculty Publications

Cardiovascular disease (CVD) remains a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Numerous CVD risk factors in CKD patients have been described, but these do not fully explain the high pervasiveness of CVD or increased mortality rates in CKD patients. In CKD the loss of urinary excretory function results in the retention of various substances referred to as “uremic retention solutes”. Many of these molecules have been found to exert toxicity on virtually all organ systems of the human body, leading to the clinical syndrome of uremia. In recent years, an increasing body …

Managing Renal Cell Carcinoma Associated Paraneoplastic Syndrome With Nephron-Sparing Surgery In A Patient With Von Hippel-Lindau., John M Dibianco, Julie Y An, Sally Tanakchi, Zachary Stanik, Aidan Mcgowan, Mahir Maruf, Abhinav Sidana, Amit Lodha Jain, Akhil Muthigi, Arvin K George, Christopher Bayne, W Marston Linehan, Shawna L Boyle, Adam R Metwalli

Urology Faculty Publications

A patient with germline von Hippel-Lindau (VHL) gene alteration and history of multiple tumors present with classical paraneoplastic syndrome (PNS) associated with renal cell carcinoma (RCC). She underwent open nephron sparing surgery with resolution of symptoms. She remained without recurrence of RCC for the initial 2 years of her follow-up. To the best of our knowledge, this case represents the first in which PNS was specifically resolved using a partial nephrectomy in a patient with VHL. This case report provides initial evidence for the potential role of nephron sparing surgery in the management of paraneoplastic symptoms associated with hereditary RCC.

Plk2 Plays An Essential Role In High D-Glucose-Induced Apoptosis, Ros Generation And Inflammation In Podocytes., Hong-Hong Zou, Ping-Ping Yang, Tian-Lun Huang, Xiao-Xu Zheng, Gao-Si Xu

Medicine Faculty Publications

Diabetic kidney disease (DKD) is a serious complication of hyperglycemia. Currently, there is no effective therapeutic intervention for DKD. In this study, we sought to provide a set of gene profile in diabetic kidneys. We identified 338 genes altered in diabetes-induced DKD glomeruli, and PLK2 exhibited the most dramatic change. Gene set enrichment analysis (GSEA) indicated multiple signaling pathways are involved DKD pathogenesis. Here, we investigated whether PLK2 contributes to podocyte dysfunction, a characteristic change in the development of DKD. High D-glucose (HDG) significantly increased PLK2 expression in mouse podocytes. Suppressing PLK2 attenuated HDG-induced apoptosis and inflammatory responses both in …

Hypoxia Inducible Factor 1: A Urinary Biomarker Of Kidney Disease., S Movafagh, Dominic Raj, M Sanaei-Ardekani, D Bhatia, K Vo, M Mahmoudieh, R Rahman, E H Kim, Arthur F Harralson

Medicine Faculty Publications

Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF-1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF-1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF-1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF-1a mRNA is of kidney origin, we examined colocalization of HIF-1a mRNA with two kidney specific markers in urine cells. We found that HIF-1a mRNA is readily quantifiable …

Hypertension In The Pediatric Kidney Transplant Recipient., Olga Charnaya, Asha Moudgil

Pediatrics Faculty Publications

Hypertension after kidney transplant is a frequent occurrence in pediatric patients. It is a risk factor for graft loss and contributes to the significant burden of cardiovascular disease (CVD) in this population. The etiology of posttransplant hypertension is multifactorial including donor factors, recipient factors, medications, and lifestyle factors similar to those prevalent in the general population. Ambulatory blood pressure monitoring has emerged as the most reliable method for measuring hypertension in pediatric transplant recipients, and many consider it to be essential in the care of these patients. Recent technological advances including measurement of carotid intima-media thickness, pulse wave velocity, and …

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 …

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 …

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 …

Membranoproliferative Glomerulonephritis Recurrence After Kidney Transplantation: Using The New Classification., Sami Alasfar, Naima Carter-Monroe, Avi Z Rosenberg, Robert A Montgomery, Nada Alachkar

Pathology Faculty Publications

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon glomerular disorder that may lead to end stage renal disease (ESRD). With new understanding of the disease pathogenesis, the classical classification as MPGN types I, II, III has changed. Data on post-transplant MPGN, in particular with the newly refined classification, is limited. We present our center's experience of MPGN after kidney transplantation using the new classification.

METHODS: This is a retrospective study of 34 patients with ESRD due to MPGN who received 40 kidney transplants between 1994 and 2014. We reviewed the available biopsies' data using the new classification. We assessed post transplantation …

Interleukin-6 Is A Risk Factor For Atrial Fibrillation In Chronic Kidney Disease: Findings From The Cric Study., Richard L. Amdur, Monica Mukherjee, Alan Go, Ian R Barrows, Ali Ramezani, Jun Shoji, Dominic S. Raj, +13 Additional Authors

Surgery Faculty Publications

Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic kidney disease (CKD). In this study, we examined the association between inflammation and AF in 3,762 adults with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. AF was determined at baseline by self-report and electrocardiogram (ECG). Plasma concentrations of interleukin(IL)-1, IL-1 Receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, transforming growth factor-β, high sensitivity C-Reactive protein, and fibrinogen, measured at baseline. At baseline, 642 subjects had history of AF, but only 44 had AF in ECG recording. During a mean follow-up of 3.7 years, 108 subjects …

Recurrence Of Acute Page Kidney In A Renal Transplant Allograft., Rajan Kapoor, Carlos Zayas, Laura Mulloy, Muralidharan Jagadeesan

Medicine Faculty Publications

Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft.

The Synergistic Roles Of Cholecystokinin B And Dopamine D5 Receptors On The Regulation Of Renal Sodium Excretion., Xiaoliang Jiang, Wei Chen, Xing Liu, Zihao Wang, Yunpeng Liu, Robin A Felder, John J Gildea, Pedro A. Jose, Chuan Qin, Zhiwei Yang

Medicine Faculty Publications

Renal dopamine D1-like receptors (D1R and D5R) and the gastrin receptor (CCKBR) are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT) cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other's expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was …

Utilizing Electronic Health Records To Predict Acute Kidney Injury Risk And Outcomes: Workgroup Statements From The 15th Adqi Consensus Conference, Scott M. Sutherland, Lakhmir S. Chawla, Sandra Kane-Gill, Raymond K. Hsu, Andrew A. Kramer, Stuart A. Goldstein, John A Kellum, Claudio Ronco, Sean M. Bagshaw, On Behalf Of The 15 Adqi Consensus Group

Anesthesiology and Critical Care Medicine Faculty Publications

The data contained within the electronic health record (EHR) is “big” from the standpoint of volume, velocity, and variety. These circumstances and the pervasive trend towards EHR adoption have sparked interest in applying big data predictive analytic techniques to EHR data. Acute kidney injury (AKI) is a condition well suited to prediction and risk forecasting; not only does the consensus definition for AKI allow temporal anchoring of events, but no treatments exist once AKI develops, underscoring the importance of early identification and prevention. The Acute Dialysis Quality Initiative (ADQI) convened a group of key opinion leaders and stakeholders to consider …

Effect Of Kidney Function On Drug Kinetics And Dosing In Neonates, Infants, And Children., Frederique Rodieux, Melanie Wilbaux, Johannes N. Van Den Anker, Marc Pfister

Pediatrics Faculty Publications

Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood …

Enhanced Fitness And Renal Function In Type 2 Diabetes., Eric S. Nylen, S. M. Gandhi, Raya E. Kheirbek, Peter Kokkinos

Medicine Faculty Publications

Aims

To investigate the renal effects of fitness in people with diabetes with mild renal dysfunction.

Methods

The effect of a 12-week exercise programme on estimated GFR in 128 people with diabetes was evaluated.

Results

All cardiometabolic variables improved after 12 weeks of supervised exercise. Although there was a modest 3.9% increase in estimated GFR from baseline in the 128 people who completed the study, those with baseline chronic kidney disease stages 2 and 3 were found to have significant (6 and 12%, respectively; p < 0.01) improvements in post-exercise estimated GFR. Moreover, 42% of the people with chronic kidney disease stage 3 improved to chronic kidney disease stage 2 after the intervention.

Conclusion

Short-term exercise improves renal function in those with more moderate baseline chronic kidney disease. …

Association Between Inflammation And Cardiac Geometry In Chronic Kidney Disease: Findings From The Cric Study., Jayanta Gupta, Elizabeth Dominic, Jeffrey C. Fink, Akinlolu O. Ojo, Ian R. Barrows, Muredach Reilly, Raymond R. Townsend, Marshall Joffe, Sylvia Rosas, Melanie Wolman, Samir Patel, Martin Keane, Harold I. Feldman, John W. Kusek, Dominic S. Raj

Medicine Faculty Publications

Background

Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.

Methods

Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted …

A Rare Case Of Non-Cardiogenic Pulmonary Edema, Talal Alzahrani, Kelly Zhang, Angela Ryan, Yasir Alfi, Jeffrey Zweig

GW Research Days 2015

INTRODUCTION:

Nephrotic syndrome is identified by a significant proteinuria more than 3.5 g/day, hypoalbuminemia less than 3.5 g/dl, and peripheral edema. It associated with risks of thrombosis, infection, and hyperlipidemia due to loss of plasma protein. Several studies have shown patients with nephrotic syndrome do not develop non-cardiogenic pulmonary edema. However, we report a case of nephrotic syndrome caused by diabetic nephropathy and presented with non-cariogenic pulmonary edema.

CASE REPORT:

A 37-year old man with a past medical history of diabetes mellitus, hypertension, dyslipidemia, Charcot foot, who presented with dyspnea, orthopnea, and non-productive cough for two days. He had been …

Mllt1 Yeats Domain Mutations In Clinically Distinctive Favourable Histology Wilms Tumours., Elizabeth J Perlman, Samantha Gadd, Stefan T Arold, Anand Radhakrishnan, Daniela S Gerhard, Jeffrey S. Dome, +19 Additional Authors

Pediatrics Faculty Publications

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar …

Tps Mutational Status Is A Potential Marker For Risk Stratification In Wilms Tumour With Diffuse Anaplasia, Mariana Maschietto, Richard D. Williams, Tasnim Chagtai, Sergey D. Popov, Neil J. Sebire, Gordan Vujanic, Elizabeth Perlman, James R. Anderson, Paul Grundy, Jeffrey S. Dome, Kathy Pritchard-Jones

Pediatrics Faculty Publications

Purpose

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whetherTP53 mutational status confers additional prognostic information.

Patients and Methods

We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. …