Nephrology Commons^™

Advances In Pediatric Acute Kidney Injury Pharmacology And Nutrition: A Report From The 26th Acute Disease Quality Initiative (Adqi) Consensus Conference, Molly Wong Vega, Michelle C Starr, Patrick D Brophy, Prasad Devarajan, Danielle E Soranno, Ayse Akcan-Arikan, Rajit Basu, Stuart L Goldstein, Jennifer R Charlton, Erin Barreto

Faculty, Staff and Students Publications

BACKGROUND: In the past decade, there have been substantial advances in our understanding of pediatric AKI. Despite this progress, large gaps remain in our understanding of pharmacology and nutritional therapy in pediatric AKI.

METHODS: During the 26th Acute Disease Quality Initiative (ADQI) Consensus Conference, a multidisciplinary group of experts reviewed the evidence and used a modified Delphi process to achieve consensus on recommendations for gaps and advances in care for pharmacologic and nutritional management of pediatric AKI. The current evidence as well as gaps and opportunities were discussed, and recommendations were summarized.

RESULTS: Two consensus statements were developed. (1) High-value, …

Pediatric Aki In The Real World: Changing Outcomes Through Education And Advocacy-A Report From The 26th Acute Disease Quality Initiative (Adqi) Consensus Conference, Theresa Mottes, Shina Menon, Andrea Conroy, Jennifer Jetton, Kristin Dolan, Ayse Akcan Arikan, Rajit K Basu, Stuart L Goldstein, Jordan M Symons, Rashid Alobaidi, David J Askenazi, Sean M Bagshaw, Matthew Barhight, Erin Barreto, Benan Bayrakci, O N Bignall Ray, Erica Bjornstad, Patrick Brophy, Jennifer Charlton, Rahul Chanchlani, Andrea L Conroy, Akash Deep, Prasad Devarajan, Dana Fuhrman, Katja M Gist, Stephen M Gorga, Jason H Greenberg, Denise Hasson, Emma Heydari, Arpana Iyengar, Catherine Krawczeski, Leslie Meigs, Catherine Morgan, Jolyn Morgan, Tara Neumayr, Zaccaria Ricci, David T Selewski, Danielle Soranno, Natalja Stanski, Michelle Starr, Scott M Sutherland, Jordan Symons, Marcelo Tavares, Molly Vega, Michael Zappitelli, Claudio Ronco, Ravindra L Mehta, John Kellum, Marlies Ostermann, Adqi 26 Workgroup

Faculty, Staff and Students Publications

BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes.

METHODS: During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary …

Microbial Interactions Among Gardnerella, Prevotella And Fannyhessea Prior To Incident Bacterial Vaginosis: Protocol For A Prospective, Observational Study, Christina A. Muzny, Jacob H. Elnaggar, Lúcia G.V. Sousa, Ângela Lima, Kristal J. Aaron, Isaac C. Eastlund, Keonte J. Graves, Chaoling Dong, Olivia T. Van Gerwen, Meng Luo, Ashutosh Tamhane, Dustin Long, Nuno Cerca, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Introduction The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%–100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key …

The Future Of International Classification Of Diseases Coding In Steatotic Liver Disease: An Expert Panel Delphi Consensus Statement, Hannes Hagström, Leon A Adams, Alina M Allen, Christopher D Byrne, Yoosoo Chang, Ajay Duseja, Henning Grønbæk, Mona H Ismail, Peter Jepsen, Fasiha Kanwal, Jennifer Kramer, Rohit Loomba, Henry E Mark, Philip N Newsome, Mary E Rinella, Ian A Rowe, Seungho Ryu, Arun Sanyal, Jörn M Schattenberg, Marina Serper, Nick Sheron, Tracey G Simon, C Wendy Spearman, Elliot B Tapper, Marcela Villota-Rivas, Sarah H Wild, Vincent Wai-Sun Wong, Yusuf Yilmaz, Shira Zelber-Sagi, Fredrik Åberg, Jeffrey V Lazarus

Faculty, Staff and Students Publications

BACKGROUND: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy.

METHODS: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries.

RESULTS: Consensus ranged from 88.8% to 96.9% (mean = 92.3%).

CONCLUSIONS: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic …

Rationale And Design Of The Nephrotic Syndrome Study Network (Neptune) Match In Glomerular Diseases: Designing The Right Trial For The Right Patient, Today, Howard Trachtman, Hailey Desmond, Amanda L Williams, Laura H Mariani, Sean Eddy, Wenjun Ju, Laura Barisoni, Heather K Ascani, Wendy R Uhlmann, Cathie Spino, Lawrence B Holzman, John R Sedor, Crystal Gadegbeku, Lalita Subramanian, Chrysta C Lienczewski, Tina Manieri, Scott J Roberts, Debbie S Gipson, Matthias Kretzler, Neptune Investigators

Faculty, Staff and Student Publications

Glomerular diseases are classified using a descriptive taxonomy that is not reflective of the heterogeneous underlying molecular drivers. This limits not only diagnostic and therapeutic patient management, but also impacts clinical trials evaluating targeted interventions. The Nephrotic Syndrome Study Network (NEPTUNE) is poised to address these challenges. The study has enrolled >850 pediatric and adult patients with proteinuric glomerular diseases who have contributed to deep clinical, histologic, genetic, and molecular profiles linked to long-term outcomes. The NEPTUNE Knowledge Network, comprising combined, multiscalar data sets, captures each participant's molecular disease processes at the time of kidney biopsy. In this editorial, we …

Intradialytic Hypotension And Mortality In Adolescents And Young Adults With Kidney Failure Receiving Maintenance Hemodialysis, Xixi Zhao, Tara I Chang, Wolfgang C Winkelmayer, Jin Long, Sai Liu, Olivera Marsenic

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Intradialytic hypotension (IDH) is associated with mortality in adults with kidney failure requiring hemodialysis (HD); however, large-scale pediatric studies are lacking. Moreover, there is no evidence-based consensus definition of IDH in pediatric literature. We aimed to examine the association of commonly used definitions of IDH with mortality in adolescents and young adults.

STUDY DESIGN: This was a retrospective observational cohort study.

SETTING & PARTICIPANTS: In total, 1,199 adolescents and young adults (N = 320, aged 10-18 years and N = 879, aged 19-21 years) who initiated HD in a large dialysis organization were included.

EXPOSURES: This study …

Rates, Patterns, And Predictors Of Specialty Palliative Care Consultation Among Patients With Acute-On-Chronic Liver Failure, Arpan Patel, Anne Walling, Fasiha Kanwal, Marina Serper, Ruben Hernaez, Vinay Sundaram, David Kaplan, Tamar Taddei, Nadim Mahmud

Faculty, Staff and Students Publications

BACKGROUND & AIMS: There is growing acceptance that principles of palliative care should be integrated into the management of serious illnesses affecting the liver, such as acute-on-chronic liver failure (ACLF). However, rates, patterns, and predictors of specialty palliative care consultation among patients with ACLF have not been well-described.

METHODS: We performed a retrospective cohort study of patients hospitalized with ACLF between 1/1/2008 and 12/31/2018 using the VOCAL cohort. Patients were followed until 6/2021. We used mixed-effects regression analyses to identify significant patient and facility factors associated with palliative care consultation. We examined timing of consultation, the influence of ACLF characteristics, …

The Yap1/Taz-Tead Transcriptional Network Regulates Gene Expression At Neuromuscular Junctions In Skeletal Muscle Fibers, Lea Gessler, Danyil Huraskin, Yongzhi Jian, Nane Eiber, Zhaoyong Hu, Tomasz J Prószyński, Said Hashemolhosseini

Faculty, Staff and Students Publications

We examined YAP1/TAZ-TEAD signaling pathway activity at neuromuscular junctions (NMJs) of skeletal muscle fibers in adult mice. Our investigations revealed that muscle-specific knockouts of Yap1 or Taz, or both, demonstrate that these transcriptional coactivators regulate synaptic gene expression, the number and morphology of NMJs, and synaptic nuclei. Yap1 or Taz single knockout mice display reduced grip strength, fragmentation of NMJs, and accumulation of synaptic nuclei. Yap1/Taz muscle-specific double knockout mice do not survive beyond birth and possess almost no NMJs, the few detectable show severely impaired morphology and are organized in widened endplate bands; and with motor nerve endings being …

Dialysis Modality, Transplant Characteristics, And Incident Atrial Fibrillation After Kidney Transplant: An Observational Study Using Usrds Data, Leonardo Pozo Garcia, Sai Liu, Colin R Lenihan, Maria E Montez-Rath, Tara I Chang, Wolfgang C Winkelmayer, Pascale Khairallah

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Atrial fibrillation is the most common arrhythmia and is increasing in prevalence. The prevalence of atrial fibrillation is high among patients receiving dialysis, affecting ∼21.3% of the patients receiving hemodialysis and 15.5% of those receiving peritoneal dialysis. The association of previous dialysis modality with incident atrial fibrillation in patients after receiving their first kidney transplant has not been studied.

STUDY DESIGN: We used the United States Renal Data System to retrospectively identify adult, Medicare-insured patients who received their first kidney transplant between January 1, 2005, and September 30, 2012 and who had not previously been diagnosed with …

Prevalence And Patterns Of Cardiovascular Risk Factors In Young Hypertensive Patients, *Raghu V S R Tanuku Dr., Major Venkata Shree Krishna Dr., Sreedhar Tanuku Dr

Digital Journal of Clinical Medicine

Hypertension ranks among the top ten causes of mortality, with around 4% attributed to hypertensive complications. High salt intake, Type 2 diabetes, smoking, elevated serum lipids, a sedentary lifestyle, a diet heavy in saturated fat, genetic predisposition, as well as stress are among the factors that contribute to hypertension. Hypertension affects about 1 billion people worldwide, with considerable differences between populations and ethnic groups [2]. The Framingham Heart Study indicates that a person's lifetime risk of developing hypertension is 90% if they are normotensive at age 55. According to the NHANES IV (4th National Health and Nutrition Examination Survey), the …

Bridging The Gap: Assessing Cmv Dnaemia In Kidney Transplant Recipients With Previous Solid Organ Transplants, Goni Katz-Greenberg, Julie M Steinbrink, Krishna Shah, Jennifer S Byrns

Faculty, Staff and Students Publications

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive …

High Prevalence Of A-Β+ Ketosis-Prone Diabetes In Children With Type 2 Diabetes And Diabetic Ketoacidosis At Diagnosis: Evidence From The Rare And Atypical Diabetes Network (Radiant), Elizabeth Kubota-Mishra, Xiaofan Huang, Charles G Minard, Marcela Astudillo, Ahmad Refaey, Graciela Montes, Stephanie Sisley, Nalini Ram, William E Winter, Rochelle N Naylor, Ashok Balasubramanyam, Maria J Redondo, Mustafa Tosur, Radiant Study Group

Faculty, Staff and Students Publications

BACKGROUND:A−β+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved β-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at “T2D” onset and determined the prevalence and characteristics of pediatric A−β+ KPD within this cohort.

METHODS: We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the …

Treatment Guidelines For Hyponatremia: Stay The Course, Richard H Sterns, Helbert Rondon-Berrios, Horacio J Adrogué, Tomas Berl, Volker Burst, David M Cohen, Mirjam Christ-Crain, Martin Cuesta, Guy Decaux, Michael Emmett, Aoife Garrahy, Fabrice Gankam-Kengne, John K Hix, Ewout J Hoorn, Kamel S Kamel, Nicolaos E Madias, Alessandro Peri, Julie Refardt, Mitchell H Rosner, Mark Sherlock, Stephen M Silver, Alain Soupart, Chris J Thompson, Joseph G Verbalis

Faculty, Staff and Students Publications

International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago. After reviewing the history of that controversy, the evidence supporting …

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery Of Cyclosporine And Dithranol: In-Vitro, Ex-Vivo, And In-Vivo Studies, Sammar Fathy Elhabal, Nashwa Abdelaal, Saeed A S Al-Zuhairy, Mohamed Fathi Mohamed Elrefai, Mohamed Mansour Khalifa, Mohammad Ahmad Khasawneh, Ahmed Mohsen Elsaid Hamdan, Passant M Mohie, Rania A Gad, Soad L Kabil, Mohamed Kandeel El-Ashery, Bhaskara R Jasti, Nahla A Elzohairy, Nehal Elfar, Tayseer Elnawawy, Fatma E Hassan, Mohamed Ahmed El-Nabarawi

Faculty, Staff and Students Publications

PURPOSE: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. …

Enhancement Pattern Mapping For Early Detection Of Hepatocellular Carcinoma In Patients With Cirrhosis, Newsha Nikzad, David Thomas Fuentes, Millicent Roach, Tasadduk Chowdhury, Matthew Cagley, Mohamed Badawy, Ahmed Elkhesen, Manal Hassan, Khaled M Elsayes, Laura Beretta, Eugene Jon Koay, Prasun Kumar Jalal

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Limited methods exist to accurately characterize the risk of malignant progression of liver lesions. Enhancement pattern mapping (EPM) measures voxel-based root mean square deviation (RMSD) of parenchyma and the contrast-to-noise (CNR) ratio enhances in malignant lesions. This study investigates the utilization of EPM to differentiate between HCC versus cirrhotic parenchyma with and without benign lesions.

METHODS: Patients with cirrhosis undergoing MRI surveillance were studied prospectively. Cases (n=48) were defined as patients with LI-RADS 3 and 4 lesions who developed HCC during surveillance. Controls (n=99) were patients with and without LI-RADS 3 and 4 lesions who did not …

Pre-Clinical Protective Potentials Of Carica Papaya Constituents In Experimentally Induced Anemia, Hassan Abdulsalam Adewuyi, Adamu Yusuf Kabiru, Hadiza Lami Muhammad, Halimat Yusuf Lukman, Mayowa Solomon Owolabi, Ibrahim Jonathan, Ahmed M El-Gazzar, Mohamed H Mahmoud, Gaber El-Saber Batiha, Bashir Lawal

Faculty, Staff and Students Publications

OBJECTIVE: Anemia is a pathological condition characterized by reduced oxygen bioavailability and/or changes in hematological parameters. This study investigated the anti-anemic activities of

METHOD: Twenty-seven rats were randomized into nine groups of three rats as follows; group 1 was the normal (non-induced) group, 2-9 were anemic rats administered 1 mL distilled water, standard drug (3 mg/kg body weight (bw) ferrous sulphate), 100, 300 and 500 mg/kg bw of crude methanolic extract of CP (CMECP) of the leaf and 100, 300 and 500 mg/kg bw of CMECP of the seed respectively in the first stage of the study. In the second …

Efficacy And Safety Of Lumasiran For Infants And Young Children With Primary Hyperoxaluria Type 1: 30-Month Analysis Of The Phase 3 Illuminate-B Trial, Yaacov Frishberg, Wesley Hayes, Hadas Shasha-Lavsky, David J Sas, Mini Michael, Anne-Laure Sellier-Leclerc, Julien Hogan, Richard Willey, John M Gansner, Daniella Magen

Faculty, Staff and Students Publications

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a genetic disorder resulting in overproduction of hepatic oxalate, potentially leading to recurrent kidney stones, nephrocalcinosis, chronic kidney disease, and kidney failure. Lumasiran, the first RNA interference therapeutic approved for infants and young children, is a liver-directed treatment that reduces hepatic oxalate production. Lumasiran demonstrated sustained efficacy with an acceptable safety profile over 12 months in infants and young children (age <6 >years) with PH1 in ILLUMINATE-B (clinicaltrials.gov: NCT03905694), an ongoing, Phase 3, multinational, open-label, single-arm study.

METHODS: Here, we report interim efficacy and safety findings from ILLUMINATE-B following 30 months of lumasiran treatment. …

Trajectories Of Egfr And Risk Of Albuminuria In Youth With Type 2 Diabetes: Results From The Today Cohort Study, Laure El Ghormli, Hui Wen, Diane Uschner, Morey W Haymond, Kara S Hughan, Katherine Kutney, Lori Laffel, Sherida E Tollefsen, Elia N Escaname, Jane Lynch, Petter Bjornstad, Today Study Group

Faculty, Staff and Students Publications

BACKGROUND: We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated. Hyperfiltration peak is the greatest eGFR inflection point during follow-up. Latent class modeling was applied to identify distinct eGFR trajectories.

RESULTS: At baseline, participants' mean age …

Machine Learning For Dynamic And Early Prediction Of Acute Kidney Injury After Cardiac Surgery, Christopher T Ryan, Zijian Zeng, Subhasis Chatterjee, Matthew J Wall, Marc R Moon, Joseph S Coselli, Todd K Rosengart, Meng Li, Ravi K Ghanta

Faculty, Staff and Students Publications

OBJECTIVE: Acute kidney injury after cardiac surgery increases morbidity and mortality. Diagnosis relies on oliguria or increased serum creatinine, which develop 48 to 72 hours after injury. We hypothesized machine learning incorporating preoperative, operative, and intensive care unit data could dynamically predict acute kidney injury before conventional identification.

METHODS: Cardiac surgery patients at a tertiary hospital (2008-2019) were identified using electronic medical records in the Medical Information Mart for Intensive Care IV database. Preoperative and intraoperative parameters included demographics, Charlson Comorbidity subcategories, and operative details. Intensive care unit data included hemodynamics, medications, fluid intake/output, and laboratory results. Kidney Disease: Improving …

Acute And Chronic Kidney Injury During Therapy For Pediatric Acute Leukemia: A Report From The Leukemia Electronic Abstraction Of Records Network (Learn), Wendy Hsiao, Yimei Li, Kelly Getz, Lusha Cao, Edward Krause, Mark Ramos, Judy Lee, Maria Monica Gramatges, Karen R Rabin, Michael E Scheurer, Richard Aplenc, Michelle Denburg, Tamara P Miller

Center for Medical Ethics and Health Policy Staff Publications

Children with acute leukemia are at increased risk of kidney injury. Using electronic health record data from three centers between 2010 and 2018, this study retrospectively described acute kidney injury (AKI) and chronic kidney disease (CKD) prevalence in children with acute lymphoblastic or myeloid leukemia (ALL, AML) using Common Terminology Criteria for Adverse Events (CTCAE) and Kidney Disease Improving Global Outcomes (KDIGO) definitions. AKI during therapy was 25% (ALL) and 32% (AML) using CTCAE, versus 84% (ALL) and 74% (AML) using KDIGO. CKD prevalence was low and Grade 1/Stage 2. Further investigation is needed to optimally define kidney injury in …

Challenges In The Management Of The Kidney Allograft: From Decline To Failure: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Michelle A Josephson, Yolanda Becker, Klemens Budde, Bertram L Kasiske, Bryce A Kiberd, Alexandre Loupy, Jolanta Małyszko, Roslyn B Mannon, Burkhard Tönshoff, Michael Cheung, Michel Jadoul, Wolfgang C Winkelmayer, Martin Zeier, For Conference Participants

Faculty, Staff and Students Publications

In March 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a virtual Controversies Conference to address the important but rarely examined phase during which the kidney transplant is failing or has failed. In addition to discussing the definition of a failing allograft, 4 broad areas were considered in the context of a declining functioning graft: prognosis and kidney failure trajectory; immunosuppression strategies; management of medical and psychological complications, and patient factors; and choice of kidney replacement therapy or supportive care following graft loss. Identifying and paying special attention to individuals with failing allografts was felt to be important in order …

Risk Stratification Model For Hepatocellular Cancer In Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Jennifer R Kramer, Xian Yu, Yumei Cao, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis.

METHODS: We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating …

A Network Pharmacology And Molecular-Docking-Based Approach To Identify The Probable Targets Of Short-Chain Fatty-Acid-Producing Microbial Metabolites Against Kidney Cancer And Inflammation, Md Rezaul Karim, Md Niaj Morshed, Safia Iqbal, Shahnawaz Mohammad, Ramya Mathiyalagan, Deok Chun Yang, Yeon Ju Kim, Joon Hyun Song, Dong Uk Yang

Faculty, Staff and Student Publications

(1) Background: A large and diverse microbial population exists in the human intestinal tract, which supports gut homeostasis and the health of the host. Short-chain fatty acid (SCFA)-secreting microbes also generate several metabolites with favorable regulatory effects on various malignancies and immunological inflammations. The involvement of intestinal SCFAs in kidney diseases, such as various kidney malignancies and inflammations, has emerged as a fascinating area of study in recent years. However, the mechanisms of SCFAs and other metabolites produced by SCFA-producing bacteria against kidney cancer and inflammation have not yet been investigated. (2) Methods: We considered 177 different SCFA-producing microbial species …

Market Competition And Anemia Management In The United States Following Dialysis Payment Reform, Anshul Bhatnagar, Vishnupriyadevi Parvathareddy, Wolfgang C Winkelmayer, Glenn M Chertow, Kevin F Erickson

Faculty, Staff and Students Publications

BACKGROUND: Whether market competition influences health care provider responses to national reimbursement reforms is unknown.

OBJECTIVES: We examined whether changes in anemia management after the expansion of Medicare's dialysis payment bundle varied with market competition.

RESEARCH DESIGN: With data from the US dialysis registry, we used a difference-in-differences (DID) design to estimate the independent associations of market competition with changes in anemia management after dialysis reimbursement reform.

SUBJECTS: A total of 326,150 patients underwent in-center hemodialysis in 2009 and 2012, representing periods before and after reimbursement reform.

MEASURES: Outcomes were erythropoiesis-stimulating agent (ESA) and intravenous iron dosage, the probability of …

Trends And Perspectives For Improving Quality Of Chronictrends And Perspectives For Improving Quality Of Chronic Kidney Disease Care: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference Kidney Disease Care: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Kai-Uwe Eckardt, Cynthia Delgado, Hiddo J L Heerspink, Roberto Pecoits-Filho, Ana C Ricardo, Bénédicte Stengel, Marcello Tonelli, Michael Cheung, Michel Jadoul, Wolfgang C Winkelmayer, Holly Kramer, Conference Participants

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) affects over 850 million people globally, and the need to prevent its development and progression is urgent. During the past decade, new perspectives have arisen related to the quality and precision of care for CKD, owing to the development of new tools and interventions for CKD diagnosis and management. New biomarkers, imaging methods, artificial intelligence techniques, and approaches to organizing and delivering healthcare may help clinicians recognize CKD, determine its etiology, assess the dominant mechanisms at given time points, and identify patients at high risk for progression or related events. As opportunities to apply the concepts …

Mmp-2 Associates With Incident Heart Failure And Atrial Fibrillation: The Aric Study, Leo F Buckley, Ali M Agha, Pranav Dorbala, Brian L Claggett, Bing Yu, Aliza Hussain, Vijay Nambi, Lin Yee Chen, Kunihiro Matsushita, Ron C Hoogeveen, Christie M Ballantyne, Amil M Shah

Faculty, Staff and Student Publications

BACKGROUND: MMP (matrix metalloproteinase)-2 participates in extracellular matrix regulation and may be involved in heart failure (HF), atrial fibrillation (AF), and coronary heart disease.

METHODS: Among the 4693 ARIC study (Atherosclerosis Risk in Communities) participants (mean age, 75±5 years; 42% women) without prevalent HF, multivariable Cox proportional hazard models were used to estimate associations of plasma MMP-2 levels with incident HF, HF with preserved ejection fraction (≥50%), HF with reduced ejection fraction (

RESULTS: Compared with the 3 lower quartiles, the highest MMP-2 quartile associated with greater risk of incident HF overall (adjusted hazard ratio, 1.48 [95% CI, 1.21-1.81]), incident …

Sptan1/Numb Axis Senses Cell Density To Restrain Cell Growth And Oncogenesis Through Hippo Signaling, Dongxue Su, Yuxi Li, Weiji Zhang, Huan Gao, Yao Cheng, Yongqiang Hou, Junhong Li, Yi Ye, Zhangjian Lai, Zhe Li, Haitao Huang, Jiaxin Li, Jinhuan Li, Mengyu Cheng, Cheng Nian, Na Wu, Zhien Zhou, Yunzhi Xing, Yu Zhao, He Liu, Jiayu Tang, Qinghua Chen, Lixin Hong, Wengang Li, Zhihai Peng, Bin Zhao, Randy L Johnson, Pingguo Liu, Wanjin Hong, Lanfen Chen, Dawang Zhou

Faculty, Staff and Student Publications

The loss of contact inhibition is a key step during carcinogenesis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is an important regulator of cell growth in a cell density-dependent manner. However, how Hippo signaling senses cell density in this context remains elusive. Here, we report that high cell density induced the phosphorylation of spectrin α chain, nonerythrocytic 1 (SPTAN1), a plasma membrane-stabilizing protein, to recruit NUMB endocytic adaptor protein isoforms 1 and 2 (NUMB1/2), which further sequestered microtubule affinity-regulating kinases (MARKs) in the plasma membrane and rendered them inaccessible for phosphorylation and inhibition of the Hippo kinases sterile 20-like kinases MST1 and …

Müllerian-Type Clear Cell Carcinoma Of Donor Origin In A Male Patient With A Kidney Transplant: Ascertained By Molecular Testing, J Bryan Iorgulescu, Leah K Shaw, Asif Rashid, Priya Rao, Sreedhar Mandayam, Keyur P Patel, Kathleen M Schmeler, Richard K Yang, Pavlos Msaouel

Faculty, Staff and Student Publications

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem …

Chronic Kidney Disease Promotes Atrial Fibrillation Via Inflammasome Pathway Activation, Jia Song, Jose Alberto Navarro-Garcia, Jiao Wu, Arnela Saljic, Issam Abu-Taha, Luge Li, Satadru K Lahiri, Joshua A Keefe, Yuriana Aguilar-Sanchez, Oliver M Moore, Yue Yuan, Xiaolei Wang, Markus Kamler, William E Mitch, Gema Ruiz-Hurtado, Zhaoyong Hu, Sandhya S Thomas, Dobromir Dobrev, Xander Ht Wehrens, Na Li

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) is associated with a higher risk of atrial fibrillation (AF). The mechanistic link between CKD and AF remains elusive. IL-1β, a main effector of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, is a key modulator of conditions associated with inflammation, such as AF and CKD. Circulating IL-1β levels were elevated in patients with CKD who had AF (versus patients with CKD in sinus rhythm). Moreover, NLRP3 activity was enhanced in atria of patients with CKD. To elucidate the role of NLRP3/IL-1β signaling in the pathogenesis of CKD-induced AF, Nlrp3-/- and WT mice were subjected to …

Erythrocyte Ent1-Ampd3 Axis Is An Essential Purinergic Hypoxia Sensor And Energy Regulator Combating Ckd In A Mouse Model, Changhan Chen, Tingting Xie, Yujin Zhang, Yiyan Wang, Fang Yu, Lizhen Lin, Weiru Zhang, Benjamin C Brown, Xin Zhang, Rodney E Kellems, Angelo D'Alessandro, Yang Xia

Faculty, Staff and Student Publications

Significance statement: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear. In this study, we demonstrated in a mouse model that erythrocyte ENT1-AMPD3 is a master energy regulator of the intracellular purinergic hypoxic compensatory response that promotes rapid energy supply from extracellular adenosine, eAMPK-dependent metabolic reprogramming, and O 2 delivery, which combat renal hypoxia and progression of CKD. ENT1-AMPD3-AMPK-BPGM comprise a group of circulating erythroid-specific biomarkers, providing early diagnostic and novel therapeutic targets for CKD.

Background: Hypoxia drives kidney damage …