Nephrology Commons^™

Incidental Ring-Hyperenhancing Liver Micronodules At Ct Hepatic Arteriography-Guided Percutaneous Thermal Ablation Of Colorectal Liver Metastases, Jessica Albuquerque, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Ching-Wei Tzeng, Jean-Nicolas Vauthey, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of …

Associations Between Anemia And Fgf23 In The Ckid Study., Elizabeth Thomas, Alexandra M. Klomhaus, Marciana L. Laster, Susan L. Furth, Bradley A. Warady, Isidro B. Salusky, Mark R. Hanudel

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in chronic kidney disease-mineral bone disorder and is associated with CKD progression and cardiovascular morbidity. Factors related to CKD-associated anemia, including iron deficiency, can increase FGF23 production. This study aimed to assess whether anemia and/or iron deficiency are associated with increased circulating concentrations of FGF23 in the large, well-characterized Chronic Kidney Disease in Children (CKiD) study cohort.

METHODS: Hemoglobin concentrations, iron parameters, C-terminal (total) FGF23, intact FGF23, and relevant covariables were measured in cross-sectional analysis of CKiD study subjects.

RESULTS: In 493 pediatric patients with …

Environmental Justice: A Missing Core Tenet Of Global Health, Redeat Workneh, Merhawit Abadi, Krystle Perez, Sharla Rent, Elliott Mark Weiss, Stephanie Kukora, Olivia Brandon, Gal Barbut, Sahar Rahiem, Shaphil Wallie, Joseph Mhango, Benjamin C Shayo, Friday Saidi, Gesit Metaferia, Mahlet Abayneh, Gregory C Valentine

Faculty, Staff and Students Publications

No abstract provided.

Spectrophotometric Analysis Of Purple Urine Secondary To Methylene Blue And Hydroxocobalamin Co-Administration, Jeremy Hardin, Henrik Galust, Richard Franklin Clark, Binh Ly, Raymond Theodore Suhandynata

Faculty, Staff and Student Publications

BACKGROUND: The development of purple urine after methylene blue (methylthioninium chloride) and hydroxocobalamin co-administration is a rare clinical entity that has not been fully elucidated. A 47-year-old male presented to the emergency department with hypotension, cyanosis, and depressed mental status. The patient was noted to have profound peripheral and central cyanosis, as well as chocolate-colored arterial blood. He was treated with both methylene blue and hydroxocobalamin and developed purple urine for approximately 1 week.

METHODS: Color chromatography was performed by placing the patient's urine directly onto absorbent filter paper. Urine spectrophotometry was performed utilizing the NanoDrop One/One C UV-Vis Spectrophotometer. …

Programs And Processes For Advancing Pediatric Acute Kidney Support Therapy In Hospitalized And Critically Ill Children: A Report From The 26th Acute Disease Quality Initiative (Adqi) Consensus Conference, Tara M Neumayr, Benan Bayrakci, Rahul Chanchlani, Akash Deep, Jolyn Morgan, Ayse Akcan Arikan, Rajit K Basu, Stuart L Goldstein, David J Askenazi

Faculty, Staff and Students Publications

Pediatric acute kidney support therapy (paKST) programs aim to reliably provide safe, effective, and timely extracorporeal supportive care for acutely and critically ill pediatric patients with acute kidney injury (AKI), fluid and electrolyte derangements, and/or toxin accumulation with a goal of improving both hospital-based and lifelong outcomes. Little is known about optimal ways to configure paKST teams and programs, pediatric-specific aspects of delivering high-quality paKST, strategies for transitioning from acute continuous modes of paKST to facilitate rehabilitation, or providing effective short- and long-term follow-up. As part of the 26th Acute Disease Quality Initiative Conference, the first to focus on a …

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, …

Real-World Evidence On The Dosing And Safety Of C.E.R.A. In Pediatric Dialysis Patients: Findings From The International Pediatric Dialysis Network Registries., Laura Kohlhas, Milena Studer, Loes Rutten-Jacobs, Sylvie Meyer Reigner, Anja Sander, Hui-Kim Yap, Karel Vondrak, Paula A. Coccia, Francisco Cano, Claus Peter Schmitt, Bradley A. Warady, Franz Schaefer, Ipdn Collaborators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: This retrospective real-world study used data from two registries, International Pediatric Peritoneal Dialysis Network (IPPN) and International Pediatric Hemodialysis Network (IPHN), to characterize the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) in pediatric patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) or hemodialysis (HD).

METHODS: IPPN and IPHN collect prospective data (baseline and every 6 months) from pediatric PD and HD centers worldwide. Demographics, clinical characteristics, dialysis information, treatment, laboratory parameters, number and causes of hospitalization events, and deaths were extracted for patients on C.E.R.A. treatment (IPPN: 2007-2021; IPHN: 2013-2021).

RESULTS: We analyzed 177 patients …

Clonal Hematopoiesis Of Indeterminate Potential Is Associated With Acute Kidney Injury, Caitlyn Vlasschaert, Cassianne Robinson-Cohen, Jianchun Chen, Elvis Akwo, Alyssa C Parker, Samuel A Silver, Pavan K Bhatraju, Hannah Poisner, Shirong Cao, Ming Jiang, Yinqiu Wang, Aolei Niu, Edward Siew, Joseph C Van Amburg, Holly J Kramer, Anna Kottgen, Nora Franceschini, Bruce M Psaty, Russell P Tracy, Alvaro Alonso, Dan E Arking, Josef Coresh, Christie M Ballantyne, Eric Boerwinkle, Morgan Grams, Ming-Zhi Zhang, Bryan Kestenbaum, Matthew B Lanktree, Michael J Rauh, Raymond C Harris, Alexander G Bick

Faculty, Staff and Student Publications

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased risk for several chronic diseases associated with aging. Here we sought to test whether CHIP increases the risk of AKI. In three population-based epidemiology cohorts, we found that CHIP was associated with a greater risk of incident AKI, which was more pronounced in patients with AKI requiring dialysis and in individuals with somatic mutations in genes other than DNMT3A, including mutations in TET2 and JAK2. Mendelian randomization analyses supported a causal …

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 …

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 …

Improved Mortality Prediction For Pediatric Acute Liver Failure Using Dynamic Prediction Strategy, Ruosha Li, Jingyan Wang, Cuihong Zhang, James E Squires, Steven H Belle, Jing Ning, Jianwen Cai, Robert H Squires

Faculty, Staff and Student Publications

OBJECTIVES: To develop and validate a prediction tool for pediatric acute liver failure (PALF) mortality risks that captures the rapid and heterogeneous clinical course for accurate and updated prediction.

METHODS: Data included 1144 participants with PALF enrolled during three phases of the PALF registry study over 15 years. Using joint modeling, we built a dynamic prediction tool for mortality by combining longitudinal trajectories of multiple laboratory and clinical variables. The predictive performance for 7-day and 21-day mortality was assessed using the area under curve (AUC) through cross-validation and split-by-time validation.

RESULTS: We constructed a prognostic joint model that combines the …

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 …

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. …

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 …

Predictive Metabolites For Incident Myocardial Infarction: A Two-Step Meta-Analysis Of Individual Patient Data From Six Cohorts Comprising 7897 Individuals From The Consortium Of Metabolomics Studies, Ana Nogal, Taryn Alkis, Yura Lee, Domagoj Kifer, Jie Hu, Rachel A Murphy, Zhe Huang, Rui Wang-Sattler, Gabi Kastenmüler, Birgit Linkohr, Clara Barrios, Marta Crespo, Christian Gieger, Annette Peters, Jackie Price, Kathryn M Rexrode, Bing Yu, Cristina Menni

Faculty, Staff and Student Publications

AIMS: Myocardial infarction (MI) is a major cause of death and disability worldwide. Most metabolomics studies investigating metabolites predicting MI are limited by the participant number and/or the demographic diversity. We sought to identify biomarkers of incident MI in the COnsortium of METabolomics Studies.

METHODS AND RESULTS: We included 7897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1428 metabolites, of which 168 were present in at least three cohorts with over 80% prevalence) and MI information (1373 cases). We performed a two-stage individual patient data meta-analysis. We first assessed the associations …

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 …

Comparative Study Between Antegrade Flexible Ureteroscopy And Reterograde Intrarenal Surgery In The Management Of Impacted Upper Ureteric Stones 15 Cm Or Larger, Ahmed Mohey, Ahmed A Abdelfattah, Ahmed E Mohammed, Abdelmoniem Marzouk, Amr S El-Dakhakhny

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate the safety and efficacy of antegrade flexible ureteroscopy (FURS) with the following criteria (supine, ultrasonic guided puncture through lower calyx with 14 fr tract, tubeless) versus retrograde intrarenal surgery (RIRS) in the management of large impacted upper ureteric stones ≥ 1.5 cm.

PATIENTS AND METHODS: This study recruited 61 patients with single large impacted upper ureteric stone of ≥ 1.5 cm. The patients were randomly allocated to two groups. Group A, included 31 patients who treated by antegrade FURS, all patients were put in supine modified galadako Valdivia position and the renal access is reached by …

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 …

Differences In The Circulating Proteome In Individuals With Versus Without Sickle Cell Trait, Yanwei Cai, Nora Franceschini, Aditya Surapaneni, Melanie E Garrett, Usman A Tahir, Li Hsu, Marilyn J Telen, Bing Yu, Hua Tang, Yun Li, Simin Liu, Robert E Gerszten, Josef Coresh, Joann E Manson, Genevieve L Wojcik, Charles Kooperberg, Paul L Auer, Matthew W Foster, Morgan E Grams, Allison E Ashley-Koch, Laura M Raffield, Alex P Reiner

Faculty, Staff and Student Publications

BACKGROUND: Sickle cell trait affects approximately 8% of Black individuals in the United States, along with many other individuals with ancestry from malaria-endemic regions worldwide. While traditionally considered a benign condition, recent evidence suggests that sickle cell trait is associated with lower eGFR and higher risk of kidney diseases, including kidney failure. The mechanisms underlying these associations remain poorly understood. We used proteomic profiling to gain insight into the pathobiology of sickle cell trait.

METHODS: We measured proteomics ( N =1285 proteins assayed by Olink Explore) using baseline plasma samples from 592 Black participants with sickle cell trait and 1:1 …

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 …

Lessons Learned From Regional Training Of Paediatric Nephrology Fellows In Africa., Mignon I. Mcculloch, Andrew C. Argent, Brenda Morrow, Peter Nourse, Ashton Coetzee, Christel Du Buisson, Deveshni Reddy, Jonathan Buckley, Paul J. Sinclair, Priya Gajjar, Lucie Semanska, Allison Eddy, John Feehally, Francisco Cano, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Access to care for children with kidney disease is limited in less well-resourced regions of the world and paediatric nephrology (PN) workforce development with good practical skills is critical.

METHODS: Retrospective review of a PN training program and trainee feedback from 1999 to 2021, based at Red Cross War Memorial Children's Hospital (RCWMCH), University of Cape Town.

RESULTS: A regionally appropriate 1-2-year training program enrolled 38 fellows with an initial 100% return rate to their country of origin. Program funding included fellowships from the International Pediatric Nephrology Association (IPNA), International Society of Nephrology (ISN), International Society of Peritoneal Dialysis …

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 …