Nephrology Commons^™

Endothelin Receptor Antagonists In Resistant Hypertension And Proteinuric Kidney Disease: Receptor Strategy And Volume Management, Corey Keith Goldman, Jesse M. Goldman

Division of Nephrology Faculty Papers

This narrative review examines how endothelin receptor antagonists (ERAs) can be used at the intersection of difficult-to-control hypertension, chronic kidney disease (CKD), and albuminuria or proteinuria. For clinicians, the central question is not receptor selectivity alone, but whether a specific agent, indication, dose, background therapy, and monitoring plan can deliver meaningful blood-pressure or kidney benefit without unacceptable fluid retention. Pulmonary arterial hypertension established the pharmacology and major safety liabilities of the class; the current implementation questions for hypertension and kidney specialists arise in systemic hypertension and proteinuric kidney disease. Aprocitentan is the first and only ERA approved for hypertension; in …

Target Trial Of Glucagon-Like Peptide-1 Agonists Versus Dipeptidyl Peptidase-4 Inhibitors And Mortality In Hemodialysis, Dustin Le, Duncan Kilpatrick, Walter K. Kraft, Morgan E. Grams, Bernard G. Jaar, Jung-Im Shin

Division of Nephrology Faculty Papers

INTRODUCTION: The comparative effectiveness of glucagon-like peptide-1 (GLP-1) agonists (GLP-1s) versus dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4s) in hemodialysis is unknown.

METHODS: Using 2011 to 2021 US Renal Data System and Medicare claims data, we emulated a target trial comparing new users of GLP-1s versus DPP-4s with patients who survived ≥ 90 days on in-center hemodialysis before medication initiation. We used inverse probability of treatment weighting (IPTW) and Cox proportional hazards models to estimate hazard ratios (HRs).

RESULTS: We identified 3671 GLP-1 and 12,039 DPP-4 users. After IPTW, mean age was 63 years, 52% male, 63% White, and mean body mass …

Improving Vaccination In People With Ckd: Report From A National Kidney Foundation Working Group, Susan F. Massengill, Kenneth A. Andreoni, Keith A. Bellovich, Cheryl Courtlandt, Vimal K. Derebail, David L. Feldman, Gia J. Oh, John W. Sleasman, Kristina A. Bryant, Improving Vaccination In Ckd Working Group

Department of Surgery Faculty Papers

People with chronic kidney disease (CKD) are particularly vulnerable to vaccine-preventable infections. Therefore, the National Kidney Foundation organized a multidisciplinary working group, including people with CKD and family care partners, to develop recommendations to improve vaccination rates, vaccination effectiveness, and health care for the CKD population. A modified Delphi process was used to achieve consensus on the recommendations. Recommendations on vaccination in CKD patients were organized into these categories: (1) patient preferences; (2) assessing the vaccination status of patients with CKD; (3) assessing vaccine response in patients with CKD; (4) vaccination of immunocompromised patients; (5) vaccination in posttransplant patients; (6) …

Primary Membranoproliferative Glomerulonephritis: Natural History, Pathogenesis, And Treatment, Edward J. Filippone, John L. Farber

Division of Nephrology Faculty Papers

Primary membranoproliferative glomerulonephritis (MPGN) is an ultrarare disease characterized by immunofluorescence microscopy as either immune-complex mediated (IC-MPGN) or C3 glomerulopathy (C3), the latter subdivided by electron microscopy to C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both IC-MPGN and C3G typically have obvious C3 staining differentiating them from other causes of MPGN histology. Secondary causes must be excluded, including infections, autoimmune disease, and neoplasia. Clinical presentations are variable, including urinary sediment abnormalities, nephrotic syndrome, or a rapidly progressive course. The prognosis is unfavorable with about 50% reaching kidney failure by 10 years. Recurrence following transplantation is frequent, and allograft survival …

Primary Care Use And Clinical Outcomes In A Prevalent Cohort Of Patients Receiving Hemodialysis, Dustin Le, Hatem Najar, Zoheb Backer, Rohanit Singh, Byoungjun Kim, Morgan E. Grams, Laura Plantinga, Bernard G. Jaar

Division of Nephrology Faculty Papers

Rationale & Objective - Primary care is associated with improved health outcomes, but whether this is true for patients receiving dialysis is unclear. We evaluated the association of primary care use in the previous year and clinical outcomes using a prevalent cohort of patients receiving hemodialysis.

Study Design - Retrospective cohort study.

Setting & Participants - United States Renal Data System registry of prevalent patients requiring maintenance in-center on January 1, 2019, linked with Medicare claims data.

Exposure - Primary care use was defined as ≥ 1 outpatient visit to a provider with the specialty of Family, General, Geriatric, or …

Serum Factors In Primary Podocytopathies, Edward J. Filippone, John L. Farber

Division of Nephrology Faculty Papers

Primary podocytopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), are caused by a circulating factor or factors injurious to the podocyte. An immunologic origin seems likely based on responsiveness to corticosteroids or other immunosuppressive agents, including calcineurin inhibitors targeting T-cells and rituximab targeting B-cells. Potential non-antibody-mediated circulating factors have been identified, including cardiotrophin-like cytokine 1, soluble urokinase plasminogen activator receptor, and angiopoietin-like 4, among others. More recent research supports a primary antibody pathogenesis, with anti-nephrin antibodies found in a significant percentage of cases. Such antibodies also predict recurrence after transplantation. Other potential antigenic targets besides nephrin include …

Parvovirus B19 Infection In Kidney Transplant Recipients, Hatem Najar, Kiran Goli, Maria P. Martinez Cantarin

Division of Nephrology Faculty Papers

On August 14, 2024, the Centers for Disease Control issued a Health Alert Network (HAN) health advisory due to a surge in Parvovirus B19 (B19V) infections in the United States. Our report presents two cases of suspected donor-derived Parvovirus B19 infection in kidney transplant patients. Both cases had refractory anemia requiring treatment with intravenous immunoglobulin. These cases highlight the importance of awareness and monitoring of B19V infection in the context of recent epidemiologic trends to improve clinical outcomes in kidney transplant recipients.

The Road Ahead: Emerging Therapies For Primary Iga Nephropathy, Edward J. Filippone, Rakesh Gulati, John Farber

Division of Nephrology Faculty Papers

Primary IgA nephropathy (IgAN) is the most common form of primary glomerulopathy. A slowly progressive disease presenting in the young to middle-aged, most patients with reduced eGFR or proteinuria will progress to end-stage kidney disease (ESKD) in their lifetimes. The pathogenesis involves increased production of galactose-deficient IgA1 (Gd-IgA1) that forms immune complexes that deposit in the glomerulus, eliciting mesangial cell proliferation, inflammation, and complement activation. The backbone of therapy is supportive, including lifestyle modifications, strict blood pressure control, and renin-angiotensin system inhibition targeting proteinuria < 300 mg/day. Sodium-glucose transporter 2 inhibitors are indicated for persisting proteinuria or declining eGFR. Sparsentan is indicated for persisting proteinuria. Immunosuppression should be considered for all patients at risk for progression (persisting proteinuria and/or declining eGFR). To reduce Gd-IgA1 production, targeted-release budesonide is approved. Agents targeting B cell survival factors APRIL or BAFF/APRIL have significantly reduced Gd-IgA1 production and proteinuria in phase 2 trials but await phase 3 data for approval. To reduce inflammation, high-dose steroids are ineffective and toxic in Caucasian patients, although lower-dose regimens may be effective in Chinese patients. Complement inhibition is being actively studied. The factor B inhibitor iptacopan has conditional approval. The terminal pathway inhibitors cemdisiran and ravulizumab show promise in phase 2 studies. Our current approach for those requiring immunosuppression involves combining the reduction of Gd-IgA1 (nefecon) with suppressing the effects of inflammation (iptacopan). The optimal duration of such therapy is uncertain. Clearly, there is more to be learned with many trials underway.

A Conceptual Framework To Assess The Health, Socioeconomic And Environmental Burden Of Chronic Kidney Disease, Charlotte Johnston-Webber, Isaac Bencomo-Bermudez, George Wharton, Robin Van Kessel, Salvatore Barone, Francisco Brotons Muntó, Steven Chadban, Juan Jose Garcia Sanchez, Janwillem Kocks, Kyra Obolensky, Petra Sandow, Neil Skolnik, Ming-Hui Zhao, Alexei Volaco, David Wheeler, Alistair Mcguire, Elias Mossialos

Department of Medicine Faculty Papers

Chronic kidney disease (CKD) is a global health challenge that affects patients, caregivers, healthcare systems, the environment and national economies. Despite its far-reaching impact, there is no framework to systematically evaluate national CKD prevention and management programmes or evaluate the societal burden of disease. This paper has two objectives: first, to introduce a comprehensive framework to assess national programmes, which recognises gaps and weaknesses and identifies feasible policy interventions to reduce overall CKD burden; second, to present some key challenges and success stories in delivering CKD services delivered in eight different country settings. A literature review informed an initial version …

Defining Renal Recovery In Patients With Hepatorenal Syndrome-Acute Kidney Injury: Experience From North American Studies, Muhammad A. Mujtaba, Hussien Elsiesy, Sara Faiz, Syed A. Hussain, Ann Kathleen N. Gamilla-Crudo, Aftab Karim, Mohammad I. Khan, Muhammad W. Khattak, Zunaira Zafar, Michael Kueht, Khurram Jamil

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

INTRODUCTION: The degree of improvement in serum creatinine (SCr) has previously been suggested as a sensitive indicator of treatment response in patients with hepatorenal syndrome-acute kidney injury (HRS-AKI), while HRS reversal remains the primary endpoint in clinical trials.

METHODS: A total of ≥ 30% SCr improvement was analyzed as an exploratory prespecified endpoint in the CONFIRM trial. In this post hoc analysis, intent-to-treat population data from three Phase 3 studies (OT-0401, REVERSE, and CONFIRM) conducted in North America in patients with HRS-AKI were pooled to assess the incidence of > 30% improvement in SCr and its association with clinical outcomes.

RESULTS: …

Commentary: Obstructive Sleep Apnea In The Hemodialysis Population: Are Clinicians Putting Existing Scientific Evidence Into Practice?, Aleena Jamal, Som Singh, Fawad Qureshi

SKMC Student Presentations and Publications

No abstract provided.

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 …

Real-Life Experience On The Effect Of Sglt2 Inhibitors Vs. Finerenone Vs. Combination On Albuminuria In Chronic Kidney Disease, Mohamad Hanouneh, Dustin Le, Bernard G. Jaar, Christina Tamargo, C. Elena Cervantes

Division of Nephrology Faculty Papers

BACKGROUND: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting.

METHODS: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m² and a urine albumin-to-creatinine ratio (UACR) ≥ …

Invasive Hemodynamic Changes Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Abiodun Idowu, Olayinka Adebolu, Casipit Bruce, Bede Nriagu, Endurance Evbayekha, Kevin Bryan Lo, Olayinka Afolabi-Brown, Janani Rangaswami

Einstein Health Papers

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to lower incident heart failure (HF) and HF hospitalizations, but the mechanisms of benefit in relation to invasive hemodynamics remain unclear. Using PRISMA guidelines, we systematically reviewed multiple online databases for randomized trials evaluating the effect of SGLT2i on invasive hemodynamics. Rest and peak exercise invasive hemodynamics were measured via right heart catheterization pre- and postintervention. Random effects model meta-analysis at a 95% confidence interval was done using RevMan 5.0. A total of 3 studies with a total of 145 patients were included in the meta-analysis. SGLT2i was significantly associated with a reduction …

Finding Ways To Decrease The Number Of Pediatric Type 1 Diabetes Patients With A Hba1c Over 8.5%, Abigayle Hoover, Bs, Ashley Medina, Dhsc, Kimberly Shoe Moyer, Apm, Evan G. Graber, Do, Patrick C. Hanley. Md

Health Equity and Quality Improvement (HEQI) Summit

Background

Problem Statement:

Hemoglobin A1c is the standard of care for monitoring the metabolic control of patients with Type 1 Diabetes.¹ Patients should have HbA1c checked every 3 months.

Higher HbA1cs are linked to higher morbidity and mortality in patients with diabetes.²

Project AIM:

Develop, implement, and evaluate different methods to engage patients with an

Expanding The Access To Kidney Transplantation: Strategies For Kidney Transplant Programs, Angie Nishio Lucar, Ankita Patel, Shikha Mehta, Anju Yadav, Mona Doshi, Megan Urbanski, Beatrice Concepcion, Neeraj Singh, M. Lee Sanders, Arpita Basu, Jessica Harding, Ana Rossi, Oluwafisayo Adebiyi, Milagros Samaniego-Picota, Kenneth Woodside, Ronald Parsons

Department of Medicine Faculty Papers

Kidney transplantation is the most successful kidney replacement therapy available, resulting in improved recipient survival and societal cost savings. Yet, nearly 70 years after the first successful kidney transplant, there are still numerous barriers and untapped opportunities that constrain the access to transplant. The literature describing these barriers is extensive, but the practices and processes to solve them are less clear. Solutions must be multidisciplinary and be the product of strong partnerships among patients, their networks, health care providers, and transplant programs. Transparency in the referral, evaluation, and listing process as well as organ selection are paramount to build such …

Assessing Kidney Transplantation Using Ecmo-Supported Donors Within A Kdpi-Based Allocation System, Peter J. Altshuler, Devon J. Pace, William A. Preston, Sage Vincent, Ashesh P. Shah, Jaime M. Glorioso, Warren R. Maley, Adam M. Frank, Carlo B. Ramirez, Sharon West, Richard Hasz Jr., Adam S. Bodzin

Department of Surgery Faculty Papers

Background.

Organ donors supported by extracorporeal membrane oxygenation (ECMO) have historically been considered high-risk and are judiciously utilized. This study examines transplant outcomes using renal allografts from donors supported on ECMO for nondonation purposes.

Methods.

Retrospective review of the Gift of Life (Pennsylvania, New Jersey, Delaware) organ procurement organization database, cross-referenced to the Organ Procurement and Transplantation Network database, assessed kidney transplants using donors supported on venoarterial (VA) and venovenous (VV) ECMO for nondonation purposes. Transplants using VA- and VV-ECMO donors were compared with Kidney Donor Profile Index (KDPI)-stratified non-ECMO donors. Regression modeling of the entire ECMO and non-ECMO populations …

The Effectiveness Of Tirzepatide (Gip/Glp-1 Receptor Co-Agonist) Vs Glp-1 Receptor Agonists On Lowering A1c In Adults With Type 2 Diabetes Mellitus, Madison Laplante

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Introduction

In the United States, 34.2 million people are currently diagnosed with diabetes mellitus, which accounts for 10.5% of the total population.¹ Type 2 diabetes mellitus (T2DM) holds 94.2% of all diabetes diagnoses. The American Association of Diabetes estimates approximately $327 billion annually and is broken up as follows:¹

Prevention Of Intradialytic Hypotension In Hemodialysis Patients: Current Challenges And Future Prospects, Seyed Mehrdad Hamrahian, Salem Vilayet, Johann Herberth, Tibor Fülöp

Division of Nephrology Faculty Papers

Intradialytic hypotension, defined as rapid decrease in systolic blood pressure of greater than or equal to 20 mmHg or in mean arterial pressure of greater than or equal to 10 mmHg that results in end-organ ischemia and requires countermeasures such as ultrafiltration reduction or saline infusion to increase blood pressure to improve patient’s symptoms, is a known complication of hemodialysis and is associated with several potential adverse outcomes. Its pathogenesis is complex and involves both patient-related factors such as age and comorbidities, as well as factors related to the dialysis prescription itself. Key factors include the need for volume removal …

Biopsy-Proven Anticoagulant-Related Nephropathy: A Case Report And Review Of The Literature, Hussam Al Hennawi, Muhammad Shan Ul Abedin, Rui Song, Majid Khan

Abington Jefferson Health Papers

Anticoagulant-related nephropathy is a type of acute kidney injury that may follow warfarin and other anticoagulants. Anticoagulant-related nephropathy has been shown to be associated with irreversible kidney injury and increased risk for morbidity. Accurate diagnosis and management remain to be challenging. We describe a case of a 62-year-old man with significant cardiac history who presented with impaired kidney function associated with supratherapeutic international normalized ratio. Kidney biopsy findings suggested anticoagulant-related nephropathy.

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.

Adipose Tissue Metabolic Changes In Chronic Kidney Disease, Eurico Serrano, Prashamsa Shenoy, Maria Paula Martinez Cantarin

Division of Nephrology Faculty Papers

Adipose tissue is a complex organ whose functions go beyond being an energy reservoir to sustain proper body energy homeostasis. Functioning as an endocrine organ, the adipose tissue has an active role in the body's metabolic balance regulation through several secreted factors generally termed as adipokines. Thus, adipose tissue dysregulation in chronic kidney disease (CKD) can have a deep impact in the pathophysiology of diseases associated with metabolic dysregulation including metabolic syndrome, insulin resistance (IR), atherosclerosis, and even cachexia. CKD is a progressive disorder linked to increased morbidity and mortality. Despite being characterized by renal function loss, CKD is accompanied …

A Scoping Review Of Microwave Ablation Versus Partial Nephrectomy For Treatment Of Renal Cell Carcinoma, Benjamin Odumah

Master of Science in Applied Health Economics and Outcomes Research Capstone Presentations

Renal cell carcinomas (RCC) make up 80 to 85% of primary renal neoplasms. Over 90% are low grade and slow growing with low probability of metastasis. Advantages of percutaneous techniques including microwave ablation (MWA) over surgical approach such as partial nephrectomy (PN), including cost effectiveness, minimally invasive, better renal preservation rates, lower procedure-related morbidity, and reduced hospitalization time make the case compelling. The major limitations for MWA are lack of prospective RCT or long-term follow-up data. The objective of this capstone was to conduct a scoping review on MWA versus PN regarding oncologic, perioperative, and functional outcomes in the treatment …

Emphysematous Pyelonephritis Necessitating Bilateral Radical Nephrectomy: A Case Report And Literature Review., Christine E Wamsley, Arianna Morton, Christopher G Roth, Joseph K Izes, Li Li

Computational Medicine Center Faculty Papers

Emphysematous pyelonephritis (EPN) is a severe, acute necrotizing infection of the kidney with gas accumulation in the renal parenchyma, collecting ducts, and/or perirenal tissue. We report a case of EPN in a 66 year-old male with uncontrolled diabetes mellitus (DM), urinary tract infection and septic shock necessitating emergent bilateral radical nephrectomy. Morphologically, the kidney parenchyma revealed severe acute bacterial pyelonephritis with extensive abscesses, gas cysts, necrosis and foci of infarctions. The uninvolved background cortex parenchyma exhibited diabetic nephropathy (DN), Class IIB. Post-operatively, the patient remained dialysis-dependent with multiple re-admissions for recurrent multi-drug resistant

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 …

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 …

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 …

Clinically Adjudicated Deceased Donor Acute Kidney Injury And Graft Outcomes, Sherry G Mansour, Nadeen Khoury, Ravi Kodali, Sarthak Virmani, Peter P Reese, Isaac E Hall, Yaqi Jia, Yu Yamamoto, Heather R Thiessen-Philbrook, Wassim Obeid, Mona D Doshi, Enver Akalin, Jonathan S Bromberg, Meera N Harhay, Sumit Mohan, Thangamani Muthukumar, Pooja Singh, Francis L Weng, Dennis G Moledina, Jason H Greenberg, Francis P Wilson, Chirag R Parikh

Department of Medicine Faculty Papers

Background: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association.

Methods: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among …

Ramifications Of The Hla-I Allelic Reactivity Of Anti-Hla-E*01:01 And Anti-Hla-E*01:03 Heavy Chain Monoclonal Antibodies In Comparison With Anti-Hla-I Igg Reactivity In Non-Alloimmunized Males, Melanoma-Vaccine Recipients, And End-Stage Renal Disease Patients, Mepur H Ravindranath, Narendranath M Ravindranath, Fatiha El Hilali, Senthamil R Selvan, Edward J Filippone

Department of Medicine Faculty Papers

Serum anti-HLA-I IgG are present in non-alloimmunized males, cancer patients, and transplant recipients. Anti-HLA-I antibodies are also present in intravenous immunoglobulin (IVIg), prepared from the plasma of thousands of healthy donors. However, the HLA-Ia reactivity of IVIg diminishes markedly after passing through HLA-E HC-affinity columns, suggesting that the HLA-I reactivity is due to antibodies formed against HLA-E. Hence, we examined whether anti-HLA-E antibodies can react to HLA-I alleles. Monoclonal IgG antibodies (mAbs) against HCs of two HLA-E alleles were generated in Balb/C mice. The antibodies were analyzed using multiplex bead assays on a Luminex platform for HLA-I reactivity. Beads coated …

Four Faces Of Cell-Surface Hla Class-I: Their Antigenic And Immunogenic Divergence Generating Novel Targets For Vaccines, Mepur H Ravindranath, Narendranath M Ravindranath, Senthamil R Selvan, Edward J Filippone, Carly J Amato-Menker, Fatiha El Hilali

Department of Medicine Faculty Papers

Leukocyte cell-surface HLA-I molecules, involved in antigen presentation of peptides to CD8+ T-cells, consist of a heavy chain (HC) non-covalently linked to β2-microglobulin (β2m) (Face-1). The HC amino acid composition varies across all six isoforms of HLA-I, while that of β2m remains the same. Each HLA-allele differs in one or more amino acid sequences on the HC α1 and α2 helices, while several sequences among the three helices are conserved. HCs without β2m (Face-2) are also observed on human cells activated by malignancy, viral transformation, and cytokine or chemokine-mediated inflammation. In the absence of β2m, the monomeric Face-2 exposes immunogenic …