Nephrology Commons^™

Thrombotic Microangiopathy, An Unusual Form Of Monoclonal Gammopathy Of Renal Significance: Report Of 3 Cases And Literature Review., Edward J. Filippone, Eric D. Newman, Li Li, Rakesh Gulati, John L. Farber

Department of Medicine Faculty Papers

Monoclonal gammopathies result from neoplastic clones of the B-cell lineage and may cause kidney disease by various mechanisms. When the underlying clone does not meet criteria for a malignancy requiring treatment, the paraprotein is called a monoclonal gammopathy of renal significance (MGRS). One rarely reported kidney lesion associated with benign paraproteins is thrombotic microangiopathy (TMA), provisionally considered as a combination signifying MGRS. Such cases may lack systemic features of TMA, such as a microangiopathic hemolytic anemia, and the disease may be kidney limited. There is no direct deposition of the paraprotein in the kidney, and the presumed mechanism is disordered …

Closing Gaps In The Care Of Patients With Heart-Kidney Disease: The Time Is Now., Janani Rangaswami

Department of Medicine Faculty Papers

No abstract present.

Therapeutic Potential Of Hla-I Polyreactive Mabs Mimicking The Hla-I Polyreactivity And Immunoregulatory Functions Of Ivig, Mepur H Ravindranath, Fatiha El Hilali, Edward Filippone

Department of Medicine Faculty Papers

HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing mice with HLA-E monomeric, α-heavy chain (αHC) open conformers (OCs). Two mAbs (TFL-006 and TFL-007) were bound to the αHC’s coated on a solid matrix. The binding was inhibited by the peptide117AYDGKDY123, present in all alleles of the six HLA-I isoforms but masked by β2-microglobulin (β2-m) in intact HLA-I trimers (closed conformers, CCs). IVIg preparations administered to lower anti-HLA Abs in pre-and post-transplant patients have also shown HLA-I polyreactivity. We hypothesized that the mAbs that mimic IVIg HLA-I polyreactivity might also possess the immunomodulatory …

Angiotensin Converting Enzyme Inhibitors And Angiotensin Receptor Blockers In Acute Heart Failure: Invasive Hemodynamic Parameters And Clinical Outcomes., Kevin Bryan Lo, Hesam Mostafavi Toroghi, Grace Salacup, Jiahui Jiang, Ruchika Bhargav, Eduardo Quintero, Kira Balestrini, Anum Shahzad, Roy O Mathew, Peter A Mccullough, Janani Rangaswami

Department of Medicine Faculty Papers

There are limited data regarding the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) in acute heart failure (AHF). The purpose is to determine the patterns of ACEi/ARB use at the time of admission and discharge in relation to invasive hemodynamic data, mortality, and heart failure (HF) readmissions. This is a retrospective single-center study in patients with AHF who underwent right heart catheterization between January 2010 and December 2016. Patients on dialysis, evidence of shock, or incomplete follow up were excluded. Multivariate logistic regression analysis was used to analyze the factors associated with continuation of ACEi/ARB use on discharge …

Covid-19 In Solid Organ Transplantation: Disease Severity And Clinical Update., Akanksha Arya, Michael Li, Nana Aburjania, Pooja Singh, Tricia. Royer, Sean Moss, Katherine A. Belden

Department of Medicine Faculty Papers

BACKGROUND: Solid organ transplant (SOT) recipients are a complex, immunocompromised population in whom greater coronavirus disease 2019 (COVID-19) mortality has been reported compared with the general population.

METHODS: We examined a retrospective cohort of 58 SOT recipients with first-wave COVID-19, comparing patients with severe and nonsevere illness. Additionally, SOT recipients are compared with general patients with first-wave COVID-19.

RESULTS: Organs transplanted included 38 kidneys, 8 livers, 5 hearts, and 3 pancreases. Average SOT recipient age was 57.4 years; 62% were male; 46.6% were African American 36.2% were white. Comorbidities included hypertension (86%), chronic kidney disease (86%), diabetes mellitus (50%), coronary …

Macrophage And Adipocyte Interaction As A Source Of Inflammation In Kidney Disease, Cristina Martos-Rus, Goni Katz-Greenberg, Zhao Lin, Eurico Serrano, Diana Whitaker Menezes, Marina Domingo-Vidal, Megan Roche, Kavitha Ramaswamy, D. Craig Hooper, Bonita Falkner, Maria P Martinez Cantarin

Kimmel Cancer Center Faculty Papers

In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue …

Patient And Renal Outcomes Of Posttransplant Lymphoproliferative Disorder Following Solid Organ Transplantations - A Single Center Experience, Kashka Mallari, Goni Katz-Greenberg, Maria Martinez Cantarin

Phase 1

Introduction: Post-transplant Proliferative Disorder (PTLD) is a significant complication after solid organ transplantation (SOT). Major risk factors that contribute to the development of PTLD include Epstein-Barr Virus (EBV) infection and degree of immunosuppression. Despite novel therapies, the 5-year survival rate of PTLD only improved from 40% to 50% over the years. The reported 5-year survival rate of PTLD also remains significantly lower compared to around 90% in other malignancies such as breast and colon cancer. In our center, we hypothesize better transplant outcomes compared to those reported in preceding literatures.

Methods: We retrospectively reviewed the electronic medical records of …

Severe Hypophosphatemia In A Patient With A Relapsing Lymphoma, Xiaoying Deng, Md, Phd, Edgar Guzman-Suarez, Md, Anju Yadav, Md, Rakesh Gulati, Md

Department of Medicine Posters

Hypophosphatemia in cancer patients is commonly ascribed to chemotherapy, renal wasting or malnutrition from anorexia and poor PO intake. We report a case caused by rapid cancer cell proliferation. 61-year-old woman with history of marginal zone lymphoma diagnosed in 2017 who presented with fatigue, poor oral intake and undetectable phosphate levels (Phos) for 5 days. Her outpatient medications included Acyclovir 400 mg by mouth daily, Allopurinol 100 mg PO daily and Enoxaparin 60 mg under the skin every 12 hours. Blood work revealed phosphate levels less than1 mg/dl (normal 2.4-4.5mg/dl). Her intact PTH level was normal. Her phosphate level further …

Effects Of The 2017 Clinical Practice Guidelines On Hypertension In Children And Adolescents: A Commentary, Bonita Falkner

Department of Medicine Faculty Papers

No abstract provided.

Maternal And Gestational Influences On Childhood Blood Pressure., Bonita Falkner

Department of Medicine Faculty Papers

Exposures that contribute to a sub-optimal intrauterine environment can have an effect on the developing fetus. Impaired fetal growth that results in low birth weight is an established risk factor for cardio-metabolic disorders later in life. Recent epidemiologic and prospective cohort studies that include the maternal and gestational period have identified maternal and gestational conditions that confer increased risk for subsequent cardio-metabolic disorders in the absence of low birth weight. Maternal pre-conception health status, including chronic obesity and type 2 diabetes, increase risk for childhood obesity and obesity-related higher blood pressure (BP) in child offspring. Maternal gestational exposures, including gestational …

Improving Transitions Of Care For Inpatients With An Egfr < 20ml/Min, Brianna Shinn, Md, Brandon Menachem, Md, Robert Park, Md, Sarah Houtmann, Md, Zachary Lee, Md, Thomas Holden, Md, Tomoyuki Hongo, Md, Vincent Yeung, Md, Goni Katz-Greenberg, Md, Peter Burke, Do, Mba

House Staff Quality Improvement and Patient Safety Conference (2016-2019)

In this study we conducted an analysis of 22 inpatients with an eGFR<20 that revealed there was a greater prevalence of patients without permanent AV access for HD initiation when compared to national data. These findings demonstrated the need for improved transitions of care and timely creation of AV access for this patient population, thus we sought to improve this. This is the first inpatient initiative that our group is aware with the aim of improving timely AV access and transitions of care for an inpatient population (Figure 1).

Idiopathic Nodular Glomerulosclerosis In A Chronic Marijuana User; A Case Report And Review Of The Literature, Mehri Mollaee, Tibor Fülöp, Sohil Abdul Salim, Seyed Mehrdad Hamrahian

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Nodular glomerulosclerosis is a characteristic histological finding of diabetic nephropathy (DN) with thickened glomerular basement membrane (GBM) and hyalinized arterioles. Idiopathic nodular glomerulosclerosis (ING), a rare distinct clinicopathologic entity, is the term used to denote classic DN confirmed by light microscopy, immuno-fluorescence, and electron microscopy in the absence of diabetes mellitus (DM). ING has been linked to heavy tobacco smoking, chronic hypertension, obesity and insulin resistance. Its association with marijuana use is unknown. Case Presentation: We report a case of biopsy-proved ING in the absence of pre-existing history of DM and heavy smoking. This report addresses the possible accentuation …

The Nephrotoxicity Of Vancomycin., Edward J. Filippone, Walter K. Kraft, John L. Farber

Department of Medicine Faculty Papers

No abstract provided.

Fibulin-4 Is Essential For Maintaining Arterial Wall Integrity In Conduit But Not Muscular Arteries., Carmen M. Halabi, Thomas J. Broekelmann, Michelle Lin, Vivian S. Lee, Mon-Li Chu, Robert P. Mecham

Department of Dermatology and Cutaneous Biology Faculty Papers

Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder characterized by significant cardiovascular abnormalities, including abnormal elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B. Fbln4^E57K/E57K mice were hypertensive and developed arterial elongation, tortuosity, and ascending aortic aneurysms. Smooth muscle cell organization within the arterial wall of large conducting vessels was abnormal, and elastic fibers were fragmented and had a moth-eaten appearance. …

Distal Renal Tubular Acidosis And Diabetes Insipidus Leading To The Diagnosis Of Sjögren's Syndrome, Loheetha Ragupathi, Md, Elijah Grillo, Md, Jonathan Yadlosky, Md, Ravi Sunderkrishnan, Md

The Medicine Forum

INTRODUCTION

Sjögren's syndrome is a chronic inflammatory disease characterized by the infiltration and progressive destruction of salivary and lacrimal glands. A common presentation involves the complaints of dry eyes and dry mouth, known as the “sicca complex.” Extra-glandular involvement is not uncommon, and is known to involve the lungs, vascular and peripheral nervous system, and kidney.1 The reported renal involvement ranges broadly from 2 – 67%,and is variably defined: the most commonly reported renal pathology is an a tubulo- interstitial nephritis resulting in tubular dysfunction and immune-mediated glomerular disease; however distal renal tubular acidosis (RTA) in particular can be present …

The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner

Department of Medicine Faculty Papers

Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis …

Secondary Membranous Nephropathy Associated With Guillain-Barré Syndrome., Edward J Filippone, Mitul Kanzaria, Rodney Bell, Eric Newman, John L Farber

Department of Medicine Faculty Papers

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome (NS) in adults. It may be primary, usually mediated by IgG4 anti-phospholipase A2 autoantibodies or secondary to various other conditions. Guillain- Barré syndrome (GBS) has been associated with MN, but a cause and effect relation has not been proven. We present a case of concurrent development of GBS and severe NS, with renal biopsy demonstrating MN. IgG4 stain was negative, indicating that most likely, the MN was secondary and probably caused by the underlying GBS.

A Kidney For Christmas, Stephen Scholand

The Medicine Forum

When Asmar Lawrence first walked into the small examining room in the Jefferson Hospital Ambulatory Practice (JHAP) Clinic, we both had no idea what the future would hold. It was July, 1998 and I was fresh from medical school. Each week, I looked forward to the JHAP experience to develop my clinical skills and follow patients longitudinally. No longer was my learning prescribed from a textbook, this was the 'real world' of medicine where anything could happen and I was supposed to be in control of it. The long white coat probably helped perpetuate some of that illusion. Fortunately our …

Hematuria Status Post Renal Biopsy, Bill Mcelhaugh

The Medicine Forum

This is a case of a 66 year old Caucasian woman admitted to the hospital following a ureteroscopic biopsy of the left renal pelvis. The biopsy was performed for asymptomatic hematuria, with a retrograde intravenous pyelogram revealing a mass in the left renal pelvis. The patient developed lightheadedness and left flank pain 12-24 hours following the procedure and was found to have a 3 gram drop in hemoglobin compared to blood work performed during the previous week.

Primary Provider Beliefs And Practice Patterns Contribute To The Lack Of Hiv/Hcv Coinfected Patients Undergoing Liver Transplantation In The United States, Jonathan M. Fenkel, Md, Victor J. Navarro, Md

Division of Gastroenterology and Hepatology Faculty Papers

Conclusions:

1. The majority of primary providers were ambivalent toward or against LT for HIV/HCV coninfected patients.

2. Half of all respondents were unlikely to refer cirrhotic coinfected patients for LT evaluation.

3. HIV specialists were significantly more likely to believe transplant should be offered, but reported no difference in likelihood of LT referral.

4. These findings suggest that primary provider beliefs and self-reported practice patterns may partially explain the paucity of coinfected US liver transplant recipients.

Assessment Of Adherence To Guidelines For Hepatocellular Carcinoma Screening In Hiv/Hcv Coinfected Patients, Jonathan M. Fenkel, Md, Victor J. Navarro, Md

Division of Gastroenterology and Hepatology Faculty Papers

Conclusions:

1. Self-reported adherence with published guidelines for HCC screening is poor among primary providers for HIV/HCV coinfected patients, including HIV specialists and University-based providers.

2. Unnecessary imaging is also frequently ordered on non-cirrhotics, particularly by University-based providers.

3. Improved adherence to guidelines is needed among primary providers as over 50% of HCC's may be missed, and many patients many not be referred for subspecialty GI or Liver care, where screening practices may differ.

A Phase I/Iia Clinical Trial Of A Recombinant Rho Protein Antagonist In Acute Spinal Cord Injury., Michael G Fehlings, Nicholas Theodore, James Harrop, Gilles Maurais, Charles Kuntz, Chris I Shaffrey, Brian K Kwon, Jens Chapman, Albert Yee, Allyson Tighe, Lisa Mckerracher

Department of Neurosurgery Faculty Papers

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or …

Hypertension In Children And Adolescents: Epidemiology And Natural History., Bonita Falkner

Department of Medicine Faculty Papers

Primary hypertension is detectable in children and adolescents and, as in adults, is associated with a positive family history of hypertension, obesity, and life-style factors. Owing to the well-established childhood obesity epidemic, the population prevalence of high blood pressure (BP) in the young is increasing. Hypertension in childhood is commonly associated with other cardiovascular risk factors as well as obesity. Although death and cardiovascular disability do not occur in hypertensive children, intermediate markers of target organ damage, such as left ventricular hypertrophy, thickening of the carotid vessel wall, retinal vascular changes, and even subtle cognitive changes, are detectable in children …

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy., Katalin Susztak, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin P Böttinger

Department of Medicine Faculty Papers

BACKGROUND: Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.

METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC) apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced …