Nephrology Commons^™

Epigenetic Basis Of Diabetic Vasculopathy, Theja Bhamidipati, Manishekhar Kumar, Sumit S. Verma, Sedat Kacar, Diamond Reese, Michelle M. Martinez, Malgorzata M. Kamocka, Kenneth W. Dunn, Chandan K. Sen, Kanhaiya Singh

Einstein Health Papers

Type 2 diabetes mellitus (T2DM) causes peripheral vascular disease because of which several blood-borne factors, including vital nutrients fail to reach the affected tissue. Tissue epigenome is sensitive to chronic hyperglycemia and is known to cause pathogenesis of micro- and macrovascular complications. These vascular complications of T2DM may perpetuate the onset of organ dysfunction. The burden of diabetes is primarily because of a wide range of complications of which nonhealing diabetic ulcers represent a major component. Thus, it is imperative that current research help recognize more effective methods for the diagnosis and management of early vascular injuries. This review addresses …

Expression Of P-Stat3 And C-Myc Correlates With P2-Hnf4Α Expression In Nonalcoholic Fatty Liver Disease (Nafld), Mamoun Younes, Lin Zhang, Baharan Fekry, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

We studied the expression of two hepatocyte nuclear factor 4 alpha (HNF4α) isoforms, p-STAT3. and c-Myc in 49 consecutive liver biopsies with nonalcoholic fatty liver disease (NAFLD) using immunohistochemistry. All 49 biopsies (100%) were positive for nuclear expression of P1-HNF4α. Twenty-eight (57%) cases were positive for P2-HNF4α, 6 (12%) were positive for p-STAT3 and 5 (10%) were positive for c-Myc. All 6 (100%) p-STAT3-positive cases were also positive for P2-HNF4α (p = 0.03). p-STAT3-positive cases were more likely to be positive for c-Myc (67% vs. 2%, p = 0.0003). Four cases were positive for P2-HNF4α, p-STAT3 and c-Myc. p-STAT3 …

Acute Kidney Injury In Hospitalized Children With Sickle Cell Anemia, Anthony Batte, Sahit Menon, John Ssenkusu, Sarah Kiguli, Robert Kalyesubula, Joseph Lubega, Edrisa Ibrahim Mutebi, Robert Opoka, Chandy John, Michelle Starr

Paediatrics and Child Health, East Africa

Background: Children with sickle cell anemia (SCA) are at increased risk of acute kidney injury (AKI) that may lead to death or chronic kidney disease. This study evaluated AKI prevalence and risk factors in children with SCA hospitalized with a vaso-occlusive crisis (VOC) in a low-resource setting. Further, we evaluated whether modifcations to the Kidney Disease: Improving Global Outcomes (KDIGO) defnition would infuence clinical outcomes of AKI in children with SCA hospitalized with a VOC.

Methods: We prospectively enrolled 185 children from 2 – 18 years of age with SCA (Hemoglobin SS) hospitalized with a VOC at a tertiary hospital …

Association Between Cause Of Kidney Failure And Fracture Incidence In A National Us Dialysis Population Cohort Study, Susan Ziolkowski, Sai Liu, Maria E Montez-Rath, Michelle Denburg, Wolfgang C Winkelmayer, Glenn M Chertow, Michelle M O'Shaughnessy

Faculty, Staff and Students Publications

Background: Bradycardia and asystole events are common among patients treated with maintenance hemodialysis. However, triggers of these events in patients on maintenance hemodialysis (HD), particularly during the long interdialytic period when these events cluster, are uncertain.

Methods: The Monitoring in Dialysis Study (MiD) enrolled 66 patients on maintenance HD who were implanted with loop recorders and followed for 6 months. We analyzed associations of predialysis laboratory values with clinically significant bradyarrhythmia or asystole (CSBA) during the 12 hours before an HD session. Associations with CSBA were analyzed with mixed-effect models. Adjusted negative binomial mixed-effect regression was used to estimate incidence …

Chronic Kidney Disease In Public Renal Practices In Queensland, Australia, 2011–2018, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Vishal Diwan, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative

Faculty, Staff and Student Publications

AIM: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland.

METHODS: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years.

RESULTS: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons …

Association Of Bradycardia And Asystole Episodes With Dialytic Parameters: An Analysis Of The Monitoring In Dialysis (Mid) Study, Qandeel H Soomro, Nisha Bansal, Wolfgang C Winkelmayer, Bruce A Koplan, Alexandru I Costea, Prabir Roy-Chaudhury, James A Tumlin, Vijay Kher, Don E Williamson, Saurabh Pokhariyal, Candace K Mcclure, David M Charytan, Mid Investigators

Faculty, Staff and Students Publications

BACKGROUND: Bradycardia and asystole events are common among patients treated with maintenance hemodialysis. However, triggers of these events in patients on maintenance hemodialysis (HD), particularly during the long interdialytic period when these events cluster, are uncertain.

METHODS: The Monitoring in Dialysis Study (MiD) enrolled 66 patients on maintenance HD who were implanted with loop recorders and followed for 6 months. We analyzed associations of predialysis laboratory values with clinically significant bradyarrhythmia or asystole (CSBA) during the 12 hours before an HD session. Associations with CSBA were analyzed with mixed-effect models. Adjusted negative binomial mixed-effect regression was used to estimate incidence …

Getting Ahead: A Resident Led Quality Improvement Project To Increase Diabetic Nephropathy Screening In An Underserved Hispanic-Predominant Population, Stephanie Luu, Jose Rivera, Daniel Aragon, Victor Zamora, Irma Huayanay, Reham Majzoub, Andreina Baird, Cristina Escobar, Eric Sanchez, Juan Carlos Lopez-Alvarenga, Daniela Hernandez, Chelsea Chang

Journal of Community Hospital Internal Medicine Perspectives

Introduction: Diabetes is the leading cause of end-stage renal disease (ESRD) in the United States (US), with 37 million having chronic kidney disease. Despite national guidelines recommendations for diabetic nephropathy screening with urine albumin-to-creatinine ratio (UACR), less than 50% receive full screening.

Our Internal Medicine residents led a quality improvement project to increase diabetic nephropathy screening rate with UACR in our resident clinic by 50% in one academic year.

Methods: We conducted the resident-led quality improvement project from July 2021 to April 2022. We reviewed the electronic medical records (EMR) from our clinic pre-intervention July 2020 to June 2021 and …

Uremic Myopathy And Mitochondrial Dysfunction In Kidney Disease, Eurico Serrano, Diana Whitaker-Menezes, Zhao Lin, Megan Roche, Maria Paula Martinez Cantarin

Kimmel Cancer Center Faculty Papers

Alterations in muscle structure and function in chronic kidney disease (CKD) patients are associated with poor outcomes. As key organelles in muscle cell homeostasis, mitochondrial metabolism has been studied in the context of muscle dysfunction in CKD. We conducted a study to determine the contribution of oxidative metabolism, glycolysis and fatty acid oxidation to the muscle metabolism in CKD. Mice developed CKD by exposure to adenine in the diet. Muscle of CKD mice showed significant weight loss compared to non-CKD mice, but only extensor digitorum longus (EDL) muscle showed a decreased number of fibers. There was no difference in the …

Letter To The Editor, Magdalene M Assimon, Patrick H Pun, Lily Wang, Sana M Al-Khatib, M Alan Brookhart, David J Weber, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

No abstract provided.

A Review Of Ferric Citrate Clinical Studies, And The Rationale And Design Of The Ferric Citrate And Chronic Kidney Disease In Children (Fit4kid) Trial., Mark R. Hanudel, Marciana L. Laster, Anthony A. Portale, Aditi Dokras, Raymond P. Quigley, German A Lozano Guzman, Joshua J. Zaritsky, Nicole A. Hayde, Frederick J. Kaskel, Mark M. Mitsnefes, Jorge A. Ramirez, Peace D. Imani, Poyyapakkam R. Srivaths, Amy J. Kogon, Michelle R. Denburg, Tom D. Blydt-Hansen, Loretta Z. Reyes, Larry A. Greenbaum, Darcy K. Weidemann, Bradley A. Warady, David A. Elashoff, Susan R. Mendley, Tamara Isakova, Isidro B. Salusky

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production-dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use …

A Case Report Of Concurrent Cryptococcal And Tuberculous Meningitis In An Immunosuppressed Renal Transplant Patient, Linda Barasa, Ahmed Sokwala, Felix Riunga, Dilraj Sokhi

Internal Medicine, East Africa

Infections after renal transplant are a common cause of morbidity and are commonly due to Cytomegalovirus (CMV), Cryptococcus, Mycobacterium tuberculosis, and Aspergillus. Concurrent infections with both cryptococcal and tuberculous aetiologies are rare within the central nervous system (CNS). We present a case of a 67-year-old male patient who presented with three weeks of headaches, confusion, unsteady gait, and seizures. He had type 2 diabetes mellitus and hypertension. He had a kidney transplant three years prior and was on three immunosuppressive agents. He was HIV-negative. He was evaluated and found to have cryptococcal meningitis and received appropriate treatment with liposomal amphotericin …

Prevent Vascular Access Complications By Adopting A Vascular Access Assessment Improvement Process In The Adultdialysis Unit, Ana Lopez Franco

St. Joseph Hospital, Orange, CA. Evidence Based Practice Conference

No abstract provided.

Contrast Induced Nephropathy, Tessa Cicchella

St. Joseph Hospital, Orange, CA. Evidence Based Practice Conference

No abstract provided.

Pathologic Predictors Of Response To Treatment Of Immune Checkpoint Inhibitor-Induced Kidney Injury, Ala Abudayyeh, Liye Suo, Heather Lin, Omar Mamlouk, Noha Abdel-Wahab, Amanda Tchakarov

Faculty, Staff and Student Publications

Background: Immune-related adverse events are a management challenge in patients receiving immune checkpoint inhibitors (ICIs). The most common renal immune-related adverse event, acute interstitial nephritis (AIN), is associated with patient morbidity and mortality. AIN, characterized by infiltration of renal tissue with immune cells, may be analogous to kidney transplant rejection. We evaluated clinical variables and pathologic findings to identify predictors of renal response and overall survival (OS) in patients with ICI-induced AIN. Design, setting, participants, and measurements: We reviewed the records and biopsy specimens of all 35 patients treated for ICI-induced AIN at our institution, between August 2007 and August …

Cgas-Sting Activation Contributes To Podocyte Injury In Diabetic Kidney Disease, Nan Zang, Chen Cui, Xinghong Guo, Jia Song, Huiqing Hu, Mengmeng Yang, Mingyue Xu, Lingshu Wang, Xinguo Hou, Qin He, Zheng Sun, Chuan Wang, Li Chen

Faculty, Staff and Students Publications

Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases. DKD does not have efficacious treatment. The cGAS-STING pathway is activated in podocytes at the early stage of kidney dysfunction, which is associated with the activation of STING downstream effectors TBK1 and NF-κB but not IRF3. Lipotoxicity induces mitochondrial damage and mtDNA leakage to the cytosol through Bcl-2 associated X protein (BAX) in podocytes. BAX-mediated mtDNA cytosolic leakage can activate the cGAS-STING pathway in the absence of lipotoxicity and is sufficient to cause podocyte injury. Depletion of cytosolic mtDNA, genetic STING knockdown, or pharmacological inhibition of STING or …

The Modifying Effect Of The Serum-To-Dialysate Potassium Gradient On The Cardiovascular Safety Of Ssris In The Hemodialysis Population: A Pharmacoepidemiologic Study, Magdalene M Assimon, Patrick H Pun, Sana M Al-Khatib, Maurice Alan Brookhart, Bradley N Gaynes, Wolfgang C Winkelmayer, Jennifer E Flythe

Faculty, Staff and Students Publications

Background: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs).

Methods: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus < 4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study.

Results: …

[Nomenclature For Kidney Function And Kidney Diseases - Improving Assessment And Prognosis Through Precision And Comprehensibility], Kai-Uwe Eckardt, Isabelle Binet, Kirsten De Groot, Jürgen Floege, Jan C Galle, Isabelle Jordans, Andreas Kribben, Rainer Oberbauer, Hermann Pavenstädt, Alexander Rosenkranz, Marcus Säemann, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Kidney disease represents an increasing global health problem. Its mitigation requires effective communication between all stakeholders involved in assessment, diagnosis and therapy and individuals affected by kidney disease. However, as of today the nomenclature for kidney function and kidney disease is far from uniform. In 2019, the international non-profit organization Kidney Disease: Improving Global Outcomes (KDIGO) has implemented a consensus process to develop a glossary in English language to standardize the nomenclature for kidney function, kidney structure and kidney disease. Guiding principles for this process were (1) precision, (2) patient-centeredness and (3) consistency with KDIGO guidelines. The current position paper …

Role Of Hla-I Structural Variants And The Polyreactive Antibodies They Generate In Immune Homeostasis, Mepur H Ravindranath, Fatiha El Hilali, Carly J Amato-Menker, Hajar El Hilali, Senthamil R Selvan, Edward J Filippone

Department of Medicine Faculty Papers

Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes changes upon activation by pathological conditions with the expression of β2m-free HCs (Face-2) resulting in exposure of β2m-masked sequences shared by almost all alleles and the generation of HLA-polyreactive antibodies (Abs) against them. Face-2 may homodimerize or heterodimerize with the same (Face-3) or different alleles (Face-4) preventing exposure of shared epitopes. Non-allo immunized males naturally carry HLA-polyreactive …

The Lawnmower And The Pediatric Lower Extremity: A Catastrophic Combination, Alvaro Tamayo-Gutierrez, Hassan N Ibrahim

Faculty, Staff and Student Publications

Heart failure can lead to renal impairment, an interaction now termed "cardiorenal syndrome." The prevalent physiological explanation for the renal impairment that accompanies heart failure centers around the forward failure hypothesis, which emphasizes the role of left ventricular dysfunction in causing edema, and the backward failure hypothesis, which singles out venous congestion as the dominant mechanism of edema and reduced glomerular filtration rate. In this review, we provide an appraisal on venous congestion, an extremely important contributor that has received little attention. We also summarize the pharmacology of loop diuretics, explain current understanding of diuretic resistance, and address controversies regarding …

Hypertension Management In Patients With Chronic Kidney Disease, Sean A Hebert, Hassan N Ibrahim

Faculty, Staff and Student Publications

Hypertension and chronic kidney disease are closely linked. Patients with chronic kidney disease have hypertension almost universally and uncontrolled hypertension accelerates the decline in kidney function. The pathophysiology of hypertension in chronic kidney disease is complex, but is largely related to reduced nephron mass, sympathetic nervous system overactivation, involvement of the renin-angiotensin-aldosterone system, and generalized endothelial dysfunction. Consensus guidelines for blood pressure targets have adopted a blood pressure <120/80 mm Hg in native chronic kidney disease and <130/80 mm Hg in kidney transplant recipients. Guidelines also strongly advocate for renin-angiotensin-aldosterone system blockade as the first-line therapy.