Nephrology Commons^™

Unveiling The Impact Of Phosphate On Skeletal Muscle Dysfunction In Chronic Kidney Disease, Hiram Garcia, Sowmya Duddu, Erik Hinojosa, Model Zerfu, Nathaniel L. Alvarez, Mohammad Razzaque, Alex Zuo

Research Colloquium

Background: Chronic Kidney Disease (CKD) is characterized by progressive decline in renal function that ultimately culminates in the inability of the kidneys to effectively maintain homeostasis. The kidneys are a key regulator of phosphate, with other organs assisting in regulation including the skeletal system. In CKD, reduced kidney function leads to hyperphosphatemia. While its impact on the skeletal system is moderately studied, its effects on skeletal muscle are less reviewed. In our literature review, we aim to describe the effects of phosphate in the context of patients who have CKD while providing clinical context for this deserving population. We describe …

Small Gtp-Binding Protein Gdp Dissociation Stimulator Influences Cisplatin-Induced Acute Kidney Injury Via Perk-Dependent Er Stress, Yuxue Yang, Ting Xiong, Ti Wang, Xiwei Chen, Ziwei Ma, Bangyun Zuo, Dong Ning, Ruilong Song, Xuesong Liu, Daxin Wang

Children’s Nutrition Research Center Staff Publications

Cisplatin is a common anticancer drug, but its frequent nephrotoxicity limits its clinical use. Small GTP-binding protein GDP dissociation stimulator (smgGDS), a small GTPase chaperone protein, was considerably downregulated during cisplatin-induced acute kidney injury (CDDP-AKI), especially in renal tubular epithelial cells. SmgGDS-knockdown mice was established and found that smgGDS knockdown promoted CDDP-AKI, as demonstrated by an increase in serum creatine, blood urea nitrogen levels and the appearance of tubular patterns. RNA sequencing suggested that protein kinase RNA-like ER kinase (PERK), which bridges mitochondria-associated ER membranes, was involved in smgGDS knockdown following CDDP-AKI, and then identified that smgGDS knockdown increased phosphorylated-PERK …

Recommendations For Clinical Trial Design In Acute Kidney Injury From The 31st Acute Disease Quality Initiative Consensus Conference A Consensus Statement, Alexander Zarbock, Lui G Forni, Jay L Koyner, Samira Bell, Thiago Reis, Melanie Meersch, Sean M Bagshaw, Dana Y Fuhmann, Kathleen D Liu, Neesh Pannu, Ayse Akcan Arikan, Derek C Angus, D'Arcy Duquette, Stuart L Goldstein, Eric Hoste, Michael Joannidis, Niels Jongs, Matthieu Legrand, Ravindra L Mehta, Patrick T Murray, Mitra K Nadim, Marlies Ostermann, John Prowle, Emily J See, Nicholas M Selby, Andrew D Shaw, Nattachai Srisawat, Claudio Ronco, John A Kellum

Faculty, Staff and Students Publications

PURPOSE: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus.

METHODS: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived …

Fluid Overload In Pediatric Acute Respiratory Distress Syndrome After Allogeneic Hematopoietic Cell Transplantation, Colin J Sallee, Julie C Fitzgerald, Lincoln S Smith, Joseph R Angelo, Megan C Daniel, Shira J Gertz, Deyin D Hsing, Kris M Mahadeo, Jennifer A Mcarthur, Courtney M Rowan, Pediatric Acute Lung Injury Sepsis Investigators (Palisi) Network

Faculty, Staff and Students Publications

The aim of the study is to examine the relationship between fluid overload (FO) and severity of respiratory dysfunction in children posthematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS). This investigation was a secondary analysis of a multicenter retrospective cohort of children (1month to 21 years) postallogeneic HCT with PARDS receiving invasive mechanical ventilation (IMV) from 2009 to 2014. Daily FO % (FO%) and daily oxygenation index (OI) were calculated for each patient up to the first week of IMV (day 0 = intubation). Linear mixed-effect regression was employed to examine whether FO% and OI were associated …

The Role Of Complement In Kidney Disease: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Marina Vivarelli, Jonathan Barratt, Laurence H Beck, Fadi Fakhouri, Daniel P Gale, Elena Goicoechea De Jorge, Marta Mosca, Marina Noris, Matthew C Pickering, Katalin Susztak, Joshua M Thurman, Michael Cheung, Jennifer M King, Michel Jadoul, Wolfgang C Winkelmayer, Richard J H Smith, For Conference Participants

Faculty, Staff and Students Publications

Uncontrolled complement activation can cause or contribute to glomerular injury in multiple kidney diseases. Although complement activation plays a causal role in atypical hemolytic uremic syndrome and C3 glomerulopathy, over the past decade, a rapidly accumulating body of evidence has shown a role for complement activation in multiple other kidney diseases, including diabetic nephropathy and several glomerulonephritides. The number of available complement inhibitor therapies has also increased during the same period. In 2022, Kidney Diseases: Improving Global Outcomes (KDIGO) convened a Controversies Conference, "The Role of Complement in Kidney Disease," to address the expanding role of complement dysregulation in the …

Mitochondrial Complex I Promotes Kidney Cancer Metastasis, Divya Bezwada, Luigi Perelli, Nicholas P Lesner, Ling Cai, Bailey Brooks, Zheng Wu, Hieu S Vu, Varun Sondhi, Daniel L Cassidy, Stacy Kasitinon, Sherwin Kelekar, Feng Cai, Arin B Aurora, Mckenzie Patrick, Ashley Leach, Rashed Ghandour, Yuanyuan Zhang, Duyen Do, Phyllis Mcdaniel, Jessica Sudderth, Dennis Dumesnil, Sara House, Tracy Rosales, Alan M Poole, Yair Lotan, Solomon Woldu, Aditya Bagrodia, Xiaosong Meng, Jeffrey A Cadeddu, Prashant Mishra, Javier Garcia-Bermudez, Ivan Pedrosa, Payal Kapur, Kevin D Courtney, Craig R Malloy, Giannicola Genovese, Vitaly Margulis, Ralph J Deberardinis

Faculty, Staff and Student Publications

Most kidney cancers are metabolically dysfunctional1-4, but how this dysfunction affects cancer progression in humans is unknown. We infused 13C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2-13C]acetate and [U-13C]glutamine infusions in patients, coupled with measurements of respiration in isolated human …

Atypical Hemolytic Uremic Syndrome Following Influenza B: A Case Report, Kathryn E. Mcgraw, Amanda P. Porter, Alyssa M. Moffitt, Marina E M Golden, Heather Stewart

HCA Healthcare Journal of Medicine

Background

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy that presents with a triad of hemolytic anemia, thrombocytopenia, and acute kidney impairment. It can be attributed to mutations in an array of different complement proteins leading to the overactivation of the complement system, the most impacted being the alternative pathway. Though rare, influenza B has been documented as a potential trigger to the development of aHUS.

Case Presentation

We discuss a 10-year-old girl with a history of aHUS who was found to have a repeat episode of aHUS following an influenza B infection. There have only been a few …

Vitamin D And Metabolic Bone Disease In Prolonged Continuous Kidney Replacement Therapy: A Prospective Observational Study., Peace Dorothy Imani, Molly Vega, Naile Tufan Pekkucuksen, Poyyapakkam Srivaths, Ayse Akcan Arikan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Complications of prolonged continuous kidney replacement therapy (CKRT) have not been well described. Our objective was to describe mineral metabolism and bone findings in children who required prolonged CKRT.

METHODS: In this single center prospective observational study, we enrolled 37 patients who required CKRT for ≥ 28 days with regional citrate anticoagulation. Exposure was duration on CKRT and outcomes were 25-hydroxy vitamin D and osteopenia and/or fractures.

RESULTS: The prevalence of vitamin D deficiency and insufficiency was 17.2% and 69.0%, respectively. 29.7% of patients had radiographic findings of osteopenia and/or fractures. There was no association between vitamin D deficiency …

Epigenetic Mechanisms Differentially Regulate Blood Pressure And Renal Dysfunction In Male And Female Npr1 Haplotype Mice, Prerna Kumar, Kandasamy Neelamegam, Chandramohan Ramasamy, Ramachandran Samivel, Huijing Xia, Daniel R. Kapusta, Kailash N. Pandey

School of Graduate Studies Faculty Publications

We determined the epigenetic mechanisms regulating mean arterial pressure (MAP) and renal dysfunction in guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene-targeted mice. The Npr1 (encoding NPRA) gene-targeted mice were treated with class 1 specific histone deacetylase inhibitor (HDACi) mocetinostat (MGCD) to determine the epigenetic changes in a sex-specific manner. Adult male and female Npr1 haplotype (1-copy; Npr1+/−), wild-type (2-copy; Npr1+/+), and gene-duplicated heterozygous (3-copy; Npr1++/+) mice were intraperitoneally injected with MGCD (2 mg/kg) for 14 days. BP, renal function, histopathology, and epigenetic changes were measured. One-copy male mice showed significantly increased MAP, renal dysfunction, and fibrosis than 2-copy and 3-copy mice. …

Contemporary Review Of Iga Nephropathy, Edward Filippone, Rakesh Gulati, John Farber

Division of Nephrology Faculty Papers

IgA nephropathy (IgAN) is considered the most common primary glomerulonephritis worldwide with a predilection for Asian-Pacific populations and relative rarity in those of African descent. Perhaps 20%–50% of patients progress to kidney failure. The pathogenesis is incompletely understood. Mesangial deposition of immune complexes containing galactose-deficient IgA1 complexed with anti-glycan IgG or IgA antibodies results in mesangial cell activation and proliferation, inflammatory cell recruitment, complement activation, and podocyte damage. Diagnosis requires a biopsy interpreted by the Oxford criteria. Additional pathologic features include podocytopathy, thrombotic microangiopathy, and C4d staining. Biomarkers predicting adverse outcomes include proteinuria, reduced GFR, hypertension, and pathology. Acceptable surrogate …

Pembrolizumab Induced Hyponatremia. A Case Report, Mouna Reghis, Taanvi Gowdar, Arjun Sekar

Advances in Clinical Medical Research and Healthcare Delivery

Hyponatremia is the most common electrolyte abnormality inpatient. Medications are a common cause of this. Cancer treatment has evolved with immune check point inhibitors replacing conventional chemotherapy agents. Pembrolizumab, which is a program cell death receptor-1 ligand has been shown to cause endocrinopathies. We describe a case of hyponatremia due to pembrolizumab

Renal Mass Imaging Modalities: Does Body Mass Index (Bmi) Matter?, Young Son, Mark E Quiring, Raeann M Dalton, Brian Thomas, Noah Davidson, Dayna Devincentz, Collin Payne, Sahil H Parikh, Benjamin A Fink, Thomas Mueller, Gordon Brown

Rowan-Virtua School of Osteopathic Medicine Departmental Research

PURPOSE: Accurate measurement of renal mass size is crucial in the management of renal cancer. With the burdensome cost of imaging yet its need for management, a better understanding of the variability among patients when determining mass size remains of urgent importance. Current guidelines on optimal imaging are limited, especially with respect to body mass index (BMI). The aim of this study is to discern which modalities accurately measure renal mass size and whether BMI influences such accuracy.

METHODS: A multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between 2018 and 2021, with 236 patients …

379. Sglt Inhibitors: The Biology Of Sglt Inhibition With Dr. Katherine Tuttle, Katherine Tuttle

Articles, Abstracts, and Reports

No abstract provided.

Horizons-Easd Elearning, Katherine Tuttle

Articles, Abstracts, and Reports

No abstract provided.

Associations Between Il-1Β, Il-6, And Tnfα Polymorphisms And Longitudinal Trajectories Of Cognitive Function In Non-Demented Older Adults, Karen A. Lawrence, Elana M. Gloger, Cristina N. Pinheiro, Frederick A. Schmitt, Suzanne C. Segerstrom

Neurology Faculty Publications

Inflammation is implicated in Alzheimer’s disease (AD), and specific single nucleotide polymorphisms (SNPs) in inflammatory cytokine genes are associated with increased AD risk. Whether the same polymorphisms also predict domain-specific cognitive change in cognitively healthy older adults is unclear. Specific SNPs in three cytokine genes, IL-1β (rs16944), IL-6 (rs1800795), and TNFα (rs1800629) were assessed for association with longitudinal trajectories spanning up to 16 years of global cognitive function, episodic memory, attention and working memory, and executive function in a sample of 324 non-demented older adults. Only rs1800629 (TNFα) was associated with significant change in global cognitive function over time [γ …

Derivation And Validation Of An Optimal Neutrophil Gelatinase-Associated Lipocalin Cutoff To Predict Stage 2/3 Acute Kidney Injury (Aki) In Critically Ill Children, Stuart L Goldstein, Ayse Akcan-Arikan, Natasha Afonso, David J Askenazi, Abby M Basalely, Rajit K Basu, Hostensia Beng, Julie C Fitzgerald, Katja Gist, Sarah Kizilbash, David Kwiatkowski, Christopher W Mastropietro, Shina Menon, Megan Soohoo, Avram Z Traum, Christopher A Bird

Faculty, Staff and Students Publications

INTRODUCTION: Acute kidney injury (AKI) defined by changes in serum creatinine (SCr), or oliguria is associated with increased morbidity and mortality in children who are critically ill. We derived and validated a clinical cutoff value for urine neutrophil gelatinase-associated lipocalin (NGAL), in a prospective multicenter study of children who were critically ill. We report the clinical performance of urine NGAL (uNGAL) to aid in pediatric AKI risk assessment.

METHODS: Eligible subjects were aged ≥ 90 days to < 22 years, admitted to an intensive care unit (ICU), and had 1 or more of the following: mechanical ventilation, vasoactive medication administration, solid organ or bone marrow transplantation, or hypotension within 24-hours of admission. uNGAL was assessed within 24-hours of admission. The primary outcome was SCr-based stage 2/3 AKI presence at 48- to 72-hours.

RESULTS: Twenty-five (12.3%) derivation study patients had stage 2/3 AKI at 48- to 72-hours. uNGAL concentration of 125 ng/ml was the optimal cutoff. …

Predicting Wait Time For Pediatric Kidney Transplant: A Novel Index, Alexandra Alvarez, Ashley Montgomery, Nhu Thao Nguyen Galván, Eileen D Brewer, Abbas Rana

Faculty, Staff and Students Publications

BACKGROUND: Over one thousand pediatric kidney transplant candidates are added to the waitlist annually, yet the prospective time spent waiting is unknown for many. Our study fills this gap by identifying variables that impact waitlist time and by creating an index to predict the likelihood of a pediatric candidate receiving a transplant within 1 year of listing. This index could be used to guide patient management by giving clinicians a potential timeline for each candidate's listing based on a unique combination of risk factors.

METHODS: A retrospective analysis of 3757 pediatric kidney transplant candidates from the 2014 to 2020 OPTN/UNOS …

Endotrophin As A Biomarker For Severe Acute Kidney Injury And Major Adverse Kidney Events, Alexander H Flannery, Dawei Bu, Madison Botkins, Fabiola Gianella, Ningyan Zhang, Zhiqiang An, Orson W Moe, Philipp E Scherer, Javier A Neyra

Faculty, Staff and Student Publications

Key Points:

• Endotrophin (ETP), a circulating marker of fibroinflammation, is elevated in critically ill patients with AKI.
• ETP is independently associated with major adverse kidney events at hospital discharge.
• Sustained elevations of ETP at 5–7 days are associated with major adverse kidney events.

Background: The search for novel biomarkers in AKI continues, both for being able to predict adverse events in AKI but also for confirming pathogenic pathways as potential therapeutic targets. Endotrophin (ETP) is an emerging biomarker in a number of fibroinflammatory diseases. We sought to test the association of ETP with the development of a major adverse kidney …

Bile Acid-Sensitive Human Norovirus Strains Are Susceptible To Sphingosine-1-Phosphate Receptor 2 Inhibition, Victoria Tenge, B Vijayalakshmi Ayyar, Khalil Ettayebi, Sue E Crawford, Nicole M Hayes, Yi-Ting Shen, Frederick H Neill, Robert L Atmar, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are a diverse group of RNA viruses that cause endemic and pandemic acute viral gastroenteritis. Previously, we reported that many HuNoV strains require bile or bile acid (BA) to infect human jejunal intestinal enteroid cultures. BA was not essential for the replication of a pandemic-causing GII.4 HuNoV strain. We found the hydrophobic BA glycochenodeoxycholic acid (GCDCA) promotes the replication of the BA-dependent strain GII.3 in jejunal enteroids. Furthermore, we found that inhibition of the G-protein-coupled BA receptor, sphingosine-1-phosphate receptor 2 (S1PR2), by JTE-013, reduced GII.3 infection dose-dependently and inhibited GII.3 cellular uptake in enteroids. Herein, we sought …

Salvage Of A Kidney Transplant With A Mycotic Extrarenal Pseudoaneursym Using Donor Vessels, Audrey Horn, Kelli L. Summers, William Fuell, Adarsh Vijay, Hoonbae Jeon, Melissa Donovan, Kiara Tulla, Anil Paramesh

School of Medicine Faculty Publications

A 63-year-old male developed a mycotic pseudoaneurysm (MPA) two months after a renal transplant at the anastomotic site. He presented with uncontrolled hypertension and elevated creatinine. The pseudoaneurysm occurred at the anastomosis between the two donor renal arteries and the left external iliac artery. We describe a unique surgical reconstruction where the MPA was resected and the vasculature was reconstructed using deceased donor vessels. A deceased donor common iliac artery including superior gluteal and inferior gluteal branches were used as a jump graft from the contralateral common iliac artery to the two transplanted renal arteries. The external iliac artery was …