Nephrology Commons^™

Persistent Increase In Serum Ferritin Levels Despite Converting To Permanent Vascular Access In Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study., Ali Mirza Onder, Md Abu Yusuf Ansari, Fang Deng, Matthew M. Grinsell, Larry Patterson, Jennifer Jetton, Sahar Fathallah-Shaykh, Daniel Ranch, Diego Aviles, Lawrence Copelovitch, Eileen Ellis, Vimal Chadha, Ayah Elmaghrabi, Jen-Jar Lin, Lavjay Butani, Maha Haddad, Olivera Marsenic, Paul Brakeman, Raymond Quigley, H Stella Shin, Rouba Garro, Rupesh Raina, Craig B. Langman

Manuscripts, Articles, Book Chapters and Other Papers

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). …

Chromatin Alternates Between A And B Compartments At Kilobase Scale For Subgenic Organization, Hannah L Harris, Huiya Gu, Moshe Olshansky, Ailun Wang, Irene Farabella, Yossi Eliaz, Achyuth Kalluchi, Akshay Krishna, Mozes Jacobs, Gesine Cauer, Melanie Pham, Suhas S P Rao, Olga Dudchenko, Arina Omer, Kiana Mohajeri, Sungjae Kim, Michael H Nichols, Eric S Davis, Dimos Gkountaroulis, Devika Udupa, Aviva Presser Aiden, Victor G Corces, Douglas H Phanstiel, William Stafford Noble, Guy Nir, Michele Di Pierro, Jeong-Sun Seo, Michael E Talkowski, Erez Lieberman Aiden, M Jordan Rowley

Faculty, Staff and Students Publications

Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops are generally studied at a finer scale, but the impact of looping on proximal interactions remains enigmatic. Here, we critically examine nuclear compartments and CTCF loop-proximal interactions using a combination of in situ Hi-C at unparalleled depth, algorithm development, and biophysical modeling. Producing a large Hi-C map with 33 billion contacts in conjunction with an algorithm for performing principal component analysis on sparse, super massive matrices (POSSUMM), we resolve compartments to 500 bp. Our results demonstrate that essentially all …

Comparative Analyses Define Differences Between Bhd-Associated Renal Tumour And Sporadic Chromophobe Renal Cell Carcinoma, Ryosuke Jikuya, Todd A Johnson, Kazuhiro Maejima, Jisong An, Young-Seok Ju, Hwajin Lee, Kyungsik Ha, Woojeung Song, Youngwook Kim, Yuki Okawa, Shota Sasagawa, Yuki Kanazashi, Masashi Fujita, Seiya Imoto, Taku Mitome, Shinji Ohtake, Go Noguchi, Sachi Kawaura, Yasuhiro Iribe, Kota Aomori, Tomoyuki Tatenuma, Mitsuru Komeya, Hiroki Ito, Yusuke Ito, Kentaro Muraoka, Mitsuko Furuya, Ikuma Kato, Satoshi Fujii, Haruka Hamanoue, Tomohiko Tamura, Masaya Baba, Toshio Suda, Tatsuhiko Kodama, Kazuhide Makiyama, Masahiro Yao, Brian M Shuch, Christopher J Ricketts, Laura S Schmidt, W Marston Linehan, Hidewaki Nakagawa, Hisashi Hasumi

Faculty, Staff and Student Publications

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated.

METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated …

An International Delphi Consensus Statement On Metabolic Dysfunction-Associated Fatty Liver Disease And Risk Of Chronic Kidney Disease, Dan-Qin Sun, Giovanni Targher, Christopher D Byrne, David C Wheeler, Vincent Wai-Sun Wong, Jian-Gao Fan, Herbert Tilg, Wei-Jie Yuan, Christoph Wanner, Xin Gao, Michelle T Long, Mehmet Kanbay, Mindie H Nguyen, Sankar D Navaneethan, Yusuf Yilmaz, Yuli Huang, Rino A Gani, Pierluigi Marzuillo, Jérôme Boursier, Huijie Zhang, Chan-Young Jung, Jin Chai, Luca Valenti, George Papatheodoridis, Giovanni Musso, Yu-Jun Wong, Mohamed El-Kassas, Nahum Méndez-Sánchez, Silvia Sookoian, Michael Pavlides, Ajay Duseja, Adriaan G Holleboom, Junping Shi, Wah-Kheong Chan, Yasser Fouad, Junwei Yang, Sombat Treeprasertsuk, Helena Cortez-Pinto, Masahide Hamaguchi, Manuel Romero-Gomez, Mamun Al Mahtab, Ponsiano Ocama, Atsushi Nakajima, Chunsun Dai, Mohammed Eslam, Lai Wei, Jacob George, Ming-Hua Zheng

Faculty, Staff and Students Publications

BACKGROUND: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no …

Longer Time To Recovery From Acute Kidney Injury Is Associated With Major Adverse Kidney Events In Patients With Cirrhosis, Kavish R Patidar, Mobasshir A Naved, Shaowli Kabir, Ananth Grama, Andrew S Allegretti, Giuseppe Cullaro, Sumeet K Asrani, Astin Worden, Archita P Desai, Marwan S Ghabril, Lauren D Nephew, Eric S Orman

Faculty, Staff and Students Publications

BACKGROUND: In patients with cirrhosis and acute kidney injury (AKI), longer time to AKI-recovery may increase the risk of subsequent major-adverse-kidney-events (MAKE).

AIMS: To examine the association between timing of AKI-recovery and risk of MAKE in patients with cirrhosis.

METHODS: Hospitalised patients with cirrhosis and AKI (n = 5937) in a nationwide database were assessed for time to AKI-recovery and followed for 180-days. Timing of AKI-recovery (return of serum creatinine7-days. Primary outcome was MAKE at 90-180-days. MAKE is an accepted clinical endpoint in AKI and defined as the composite outcome of ≥25% decline in estimated-glomerular-filtration-rate (eGFR) compared with baseline with …

Distinguishing Renal Cell Carcinoma From Normal Kidney Tissue Using Mass Spectrometry Imaging Combined With Machine Learning, Vishnu Shankar, Kanchustambham Vijayalakshmi, Rosalie Nolley, Geoffrey A Sonn, Chia-Sui Kao, Hongjuan Zhao, Ru Wen, Livia S Eberlin, Robert Tibshirani, Richard N Zare, James D Brooks

Faculty, Staff and Students Publications

PURPOSE: Accurately distinguishing renal cell carcinoma (RCC) from normal kidney tissue is critical for identifying positive surgical margins (PSMs) during partial and radical nephrectomy, which remains the primary intervention for localized RCC. Techniques that detect PSM with higher accuracy and faster turnaround time than intraoperative frozen section (IFS) analysis can help decrease reoperation rates, relieve patient anxiety and costs, and potentially improve patient outcomes.

MATERIALS AND METHODS: Here, we extended our combined desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and machine learning methodology to identify metabolite and lipid species from tissue surfaces that can distinguish normal tissues from clear cell …

Physiological Age By Artificial Intelligence-Enhanced Electrocardiograms As A Novel Risk Factor Of Mortality In Kidney Transplant Candidates, Elizabeth C Lorenz, Isabella Zaniletti, Bradley K Johnson, Tanya M Petterson, Walter K Kremers, Carrie A Schinstock, Hatem Amer, Andrea L Cheville, Nathan K Lebrasseur, Wolfgang C Winkelmayer, Sankar D Navaneethan, Abraham Baez-Suarez, Zachi I Attia, Francisco Lopez-Jimenez, Paul A Friedman, Cassie C Kennedy, Andrew D Rule

Faculty, Staff and Students Publications

BACKGROUND: Mortality risk assessment before kidney transplantation (KT) is imperfect. An emerging risk factor for death in nontransplant populations is physiological age as determined by the application of artificial intelligence to the electrocardiogram (ECG). The aim of this study was to examine the relationship between ECG age and KT waitlist mortality.

METHODS: We applied a previously developed convolutional neural network to the ECGs of KT candidates evaluated 2014 to 2019 to determine ECG age. We used a Cox proportional hazard model to examine whether ECG age was associated with waitlist mortality.

RESULTS: Of the 2183 patients evaluated, 59.1% were male, …

Validation Of A Predictive Model For Hospital-Acquired Acute Kidney Injury With Emergence Of Sars-Cov-2 Variants, Meredith C Mcadams, Pin Xu, Michael Li, L Parker Gregg, Sameh N Saleh, Mauricio Ostrosky-Frid, Duwayne L Willett, Ferdinand Velasco, Christoph U Lehmann, S Susan Hedayati

Faculty, Staff and Students Publications

We previously developed and validated a model to predict acute kidney injury (AKI) in hospitalized coronavirus disease 2019 (COVID-19) patients and found that the variables with the highest importance included a history of chronic kidney disease and markers of inflammation. Here, we assessed model performance during periods when COVID-19 cases were attributable almost exclusively to individual variants. Electronic Health Record data were obtained from patients admitted to 19 hospitals. The outcome was hospital-acquired AKI. The model, previously built in an

Steroidal Or Non-Steroidal Mras: Should We Still Enable Raasi Use Through K Binders?, L Parker Gregg, Sankar D Navaneethan

Faculty, Staff and Students Publications

Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions …

Cellular And Molecular Mechanisms Of Liver Fibrosis In Patients With Nafld, Jessica I Sanchez, Edwin R Parra, Jingjing Jiao, Luisa M Solis Soto, Debora A Ledesma, Omar A Saldarriaga, Heather L Stevenson, Laura Beretta

Faculty, Staff and Student Publications

The expression of immune- and cancer-related genes was measured in liver biopsies from 107 NAFLD patients. The strongest difference in overall gene expression was between liver fibrosis stages F3 and F4, with 162 cirrhosis-associated genes identified. Strong correlations with fibrosis progression from F1 to F4 were observed for 91 genes, including CCL21, CCL2, CXCL6, and CCL19. In addition, the expression of 21 genes was associated with fast progression to F3/F4 in an independent group of eight NAFLD patients. These included the four chemokines, SPP1, HAMP, CXCL2, and IL-8. A six-gene signature including SOX9, THY-1, and CD3D had the highest performance …

Apolipoprotein E Dyslipidemia And Nephrotic Syndrome: A Rare Connection, Sahana Tito, Avica Atri, Shivaraj Patil, Saima Dean, Sweta Carpenter

Einstein Health Papers

Severe hyperlipidemia warrants an extensive evaluation. We report a case of a 25-year-old man of Chinese descent seen in the cardiology-lipid clinic. He was found to have a serum low-density lipoprotein cholesterol of 12.12 mmol/L (468 mg/dL) and serum triglycerides of 2.29 mmol/L (203 mg/dL) during routine screening. Work-up revealed nephrotic-range proteinuria, and renal biopsy showed dilated glomerular capillary loops with lipid deposits, pathognomonic of lipoprotein glomerulopathy. Genetic studies showed apolipoprotein E3/E4 phenotype. He was treated with a high-intensity statin and fibrate therapy, which resulted in a marked improvement in dyslipidemia and proteinuria.

Ragd Auto-Activating Mutations Impair Mit/Tfe Activity In Kidney Tubulopathy And Cardiomyopathy Syndrome, Irene Sambri, Marco Ferniani, Giulia Campostrini, Marialuisa Testa, Viviana Meraviglia, Mariana E G De Araujo, Ladislav Dokládal, Claudia Vilardo, Jlenia Monfregola, Nicolina Zampelli, Francesca Del Vecchio Blanco, Annalaura Torella, Carolina Ruosi, Simona Fecarotta, Giancarlo Parenti, Leopoldo Staiano, Milena Bellin, Lukas A Huber, Claudio De Virgilio, Francesco Trepiccione, Vincenzo Nigro, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Heterozygous mutations in the gene encoding RagD GTPase were shown to cause a novel autosomal dominant condition characterized by kidney tubulopathy and cardiomyopathy. We previously demonstrated that RagD, and its paralogue RagC, mediate a non-canonical mTORC1 signaling pathway that inhibits the activity of TFEB and TFE3, transcription factors of the MiT/TFE family and master regulators of lysosomal biogenesis and autophagy. Here we show that RagD mutations causing kidney tubulopathy and cardiomyopathy are "auto- activating", even in the absence of Folliculin, the GAP responsible for RagC/D activation, and cause constitutive phosphorylation of TFEB and TFE3 by mTORC1, without affecting the phosphorylation …

Tfeb And Tfe3 Drive Kidney Cystogenesis And Tumorigenesis, Chiara Di Malta, Angela Zampelli, Letizia Granieri, Claudia Vilardo, Rossella De Cegli, Laura Cinque, Edoardo Nusco, Salvatore Pece, Daniela Tosoni, Francesca Sanguedolce, Nicolina Cristina Sorrentino, Maria J Merino, Deborah Nielsen, Ramaprasad Srinivasan, Mark W Ball, Christopher J Ricketts, Cathy D Vocke, Martin Lang, Baktiar Karim, Luisa Lanfrancone, Laura S Schmidt, W Marston Linehan, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Birt-Hogg-Dubé (BHD) syndrome is an inherited familial cancer syndrome characterized by the development of cutaneous lesions, pulmonary cysts, renal tumors and cysts and caused by loss-of-function pathogenic variants in the gene encoding the tumor-suppressor protein folliculin (FLCN). FLCN acts as a negative regulator of TFEB and TFE3 transcription factors, master controllers of lysosomal biogenesis and autophagy, by enabling their phosphorylation by the mechanistic Target Of Rapamycin Complex 1 (mTORC1). We have previously shown that deletion of Tfeb rescued the renal cystic phenotype of kidney-specific Flcn KO mice. Using Flcn/Tfeb/Tfe3 double and triple KO mice, we now show that both Tfeb …

Brash Syndrome Case Report And Brief Review, Kelly Schuitema

Rowan-Virtua Research Day

BRASH syndrome is an acronym that stands for bradycardia, renal failure, AV node blocker, shock and hyperkalemia. The syndrome is precipitated by synergism from AV nodal blocking agents and hyperkalemia. The combination of the AV nodal blockade and renal failure leads to a cycle of severe bradycardia and hyperkalemia. We will discuss a case of BRASH syndrome with a 68 year old female who presented with generalized weakness and was found to be hypotensive, bradycardia, in acute renal failure with hyperkalemia likely related to metoprolol and amlodipine use.

Renal Toxicity Warnings And Precautions Of Drugs Marketed In The Us, Mohammad Al Ghamdi

Pharmaceutical Sciences (MS) Theses

INTRODUCTION: The use of drugs can lead to renal adverse effects prompting the need to include warnings and precautions on medication labels. Studies evaluating renal warnings and precautions need to be improved. This study assessed the characteristics of FDA renal toxicity warnings and precautions included in the labels of drugs approved by the FDA and marked in the US. The study also evaluated the potential factors of including a boxed warning on a drug label.

METHODS: We extracted the labels of human prescription drugs with renal toxicity boxed warnings and warnings and precautions from the “FDA Label: Full-Text Search of …

Artificial Intelligence In Continuous Kidney Replacement Therapy, Lucas J. Liu, Tomonori Takeuchi, Jin Chen, Javier A. Neyra

Markey Cancer Center Faculty Publications

Over the past decade, artificial intelligence (AI) through machine learning (ML) has been increasingly used in health care applications. The use of AI/ML to enhance the provision of continuous kidney replacement therapy (CKRT) is an area of active investigation because of the growing clinical needs of critically ill patients and the abundance of multimodal data from the electronic health records (EHRs) and the CKRT machine itself. Importantly, best clinical practices of CKRT have not been sufficiently standardized, so there is considerable heterogeneity in utilization and deliverables. In this context, AI/ML-based tools could facilitate informed decisions to enhance CKRT goal-oriented deliver- …

Qt-Prolonging Antibiotics, Serum-To-Dialysate Potassium Gradient, And Risk Of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis, Patrick H Pun, Magdalene M Assimon, Lily Wang, Sana M Al-Khatib, M Alan Brookhart, David J Weber, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin.

STUDY DESIGN: Retrospective observational cohort study using a new-user study design.

SETTING & POPULATION: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017).

EXPOSURE: Initiation of azithromycin (or …

A Parathyroid Hormone/Salt-Inducible Kinase Signaling Axis Controls Renal Vitamin D Activation And Organismal Calcium Homeostasis, Sung-Hee Yoon, Mark B Meyer, Carlos Arevalo, Murat Tekguc, Chengcheng Zhang, Jialiang S Wang, Christian D Castro Andrade, Katelyn Strauss, Tadatoshi Sato, Nancy A Benkusky, Seong Min Lee, Rebecca Berdeaux, Marc Foretz, Thomas B Sundberg, Ramnik J Xavier, Charles H Adelmann, Daniel J Brooks, Anthony Anselmo, Ruslan I Sadreyev, Ivy A Rosales, David E Fisher, Navin Gupta, Ryuji Morizane, Anna Greka, J Wesley Pike, Michael Mannstadt, Marc N Wein

Faculty, Staff and Student Publications

The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin D activation remain unknown. Here, we demonstrated that salt-inducible kinases (SIKs) orchestrated renal 1,25-vitamin D production downstream of PTH signaling. PTH inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation. Whole-tissue and single-cell transcriptomics demonstrated that both PTH and pharmacologic SIK inhibitors regulated a vitamin D gene module in the proximal tubule. SIK inhibitors increased 1,25-vitamin D production and renal Cyp27b1 mRNA expression in mice and in human embryonic stem cell–derived kidney organoids. Global- and kidney-specific Sik2/Sik3 mutant mice showed Cyp27b1 upregulation, …

Candidate Biomarkers As Predictors Of Future Kidney Disease And Cardiovascular Dysfunction In Adolescents With Type 2 Diabetes, Fida Bacha, Laure El Ghormli, Barbara H Braffett, Amy S Shah, Santica M Marcovina, Lorraine E Levitt Katz, Steven M Willi, Sonia Caprio, Ruban Dhaliwal, Samuel S Gidding

Faculty, Staff and Students Publications

AIMS: Evaluate changes in circulating biomarkers as predictors of kidney disease, and cardiac/vascular dysfunction in participants from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Candidate biomarkers were assessed annually in 507 participants over a mean follow-up of 6.9 ± 2.4 years. Moderate albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g and hyperfiltration as eGFR ≥ 135 mL/min/1.73 m

RESULTS: At baseline, 35.7% were male, with a mean age 13.9 years, diabetes duration 7.8 months, and HbA1c 6.0%. Higher concentrations of E-selectin and proinsulin were associated with incident moderate albuminuria and hyperfiltration. …

Metformin-Associated Lactic Acidosis: A Case Report, Joshua Santoli, Jamie Lee Aldakkour, Hossein Tohidi, Yizhi Lin

HCA Healthcare Journal of Medicine

Introduction

Metformin is considered a first-line therapy for patients with diabetes secondary to its cost efficiency, minimal side effects, and marked improvement in one’s hemoglobin A1c; however, metformin is avoided in patients with renal insufficiency out of concern for drug accumulation and lactic acidosis. In fact, there is a black box warning for metformin, identifying lactic acidosis as the inciting trigger for fatal arrhythmias and death.

Case Presentation

A 62-year-old male presented with multiple episodes of nausea, vomiting, abdominal pain, and decreased urine output for 3 days after working on a roof, all day in the summer heat. He did …