Apol1 Risk Variants Enhance Podocyte Necrosis Through Compromising Lysosomal Membrane Permeability, X. Q. Lan, A. Jhaveri, K. Cheng, H. X. Wen, M. A. Saleem, P. W. Mathieson, S. Aviram, A. Malhotra, K. Skorecki, P. C. Singhal, +1 Additional Author

Journal Articles

Development of higher rates of nondiabetic glomerulosclerosis (GS) in African Americans has been attributed to two coding sequence variants (G1 and G2) in the APOL1 gene. To date, the cellular function and the role of APOL1 variants (Vs) in GS are still unknown. In this study, we examined the effects of overexpressing wild-type (G0) and kidney disease risk variants (G1 and G2) of APOL1 in human podocytes using a lentivirus expression system. Interestingly, G0 inflicted podocyte injury only at a higher concentration; however, G1 and G2 promoted moderate podocyte injury at lower and higher concentrations. APOL1Vs expressing podocytes displayed diffuse …

The Authors Reply, K. D. Jhaveri, H. H. Shah, J. Radhakrishnan

Journal Articles

No abstract provided.

Chief's Seminar: Turning Interns Into Clinicians, C. Dittus, V. Grover, G. Panagopoulos, K. Jhaveri

Journal Articles

BACKGROUND: Recent changes in healthcare delivery have necessitated residency education reform. To adapt to these changes, graduate medical education can adopt a chief resident-led clinical curriculum. Chief residents are ideal clinical instructors, as they are recent graduates who have excelled in their residency programs. To effectively use the limited time available for education, chief residents can implement active learning techniques. We present a chief resident-led, small-group, problem-based curriculum for teaching first-year internal medicine residents, and provide preliminary data supporting the efficacy of this approach. METHODS: The seminar consisted of 11 4-week modules. Week 1 was a team-based crossword competition. Weeks …

Glomerular Diseases: Entering A New Era, K. D. Jhaveri, S. Fishbane

Journal Articles

No abstract provided.

Hypersensitivity Reactions To Intravenous Iron: Guidance For Risk Minimization And Management, D. Rampton, J. Folkersen, S. Fishbane, M. Hedenus, S. Howaldt, F. Locatelli, S. Patni, J. Szebeni, G. Weiss

Journal Articles

Intravenous iron is widely used for the treatment of iron deficiency anemia when oral iron is inappropriate, ineffective or poorly tolerated. Acute hypersensitivity reactions during iron infusions are very rare but can be life-threatening. This paper reviews their frequency, pathogenesis and risk factors, and provides recommendations about their management and prevention. Complement activation-related pseudo-allergy triggered by iron nanoparticles is probably a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple …

Intravenous Iron Exposure And Outcomes In Patients On Hemodialysis, S. Fishbane, A. T. Mathew, R. Wanchoo

Journal Articles

No abstract provided.

Intravenous Albumin Infusion Is An Effective Therapy For Hyponatremia In Patient With Malignant Ascites, K. D. Jhaveri, A. Chawla, C. Xu, A. Hazzan

Journal Articles

There are few reports about the treatment of moderate to severe hyponatremia associated with malignant liver metastasis. Here, we report using intravenous salt poor albumin infusion to treat hypervolemic cirrhosis related hyponatremia. A 58-year-old female with ascites secondary to metastatic breast cancer was referred to our department with symptomatic hyponatremia (serum sodium concentration of 121 mEq/L). The serum sodium level was corrected slowly over 2 days with intravenous albumin infusion and the patient's symptoms - fatigue, nausea, dizziness and headache improved.

Modulation Of Renin Angiotensin System Predominantly Alters Sclerotic Phenotype Of Glomeruli In Hivan, A. Plagov, X. Q. Lan, P. Rai, D. Kumar, R. Lederman, S. Rehman, A. Malhotra, G. H. Ding, P. N. Chander, P. C. Singhal

Journal Articles

HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with African ancestry in general and with APOL1 gene risk variants in particular. Although collapsing glomerulopathy is considered a hallmark of HIVAN, significant numbers of glomeruli in patients with HIVAN also display other variants of focal segmental glomerulosclerosis (FSGS). We propose that collapsed glomeruli as well as glomeruli with other variants of FSGS are manifestations of HIVAN and their prevalence depends on associated host factors. We explored the role of the renin-angiotensin system (RAS) in the manifestation of any specific glomerular phenotype in HIVAN. To evaluate the role …

The Effects Of Dihydrobiopterin And Tetrahydrobiopterin On Hydrogen Peroxide And Nitric Oxide Release During Extracorporeal Shockwave Lithotripsy (Eswl), Brittany Deiling

PCOM Biomedical Studies Student Scholarship

ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H₂O₂) in …

Graphical Model For Three-Way Living Donor Kidney Exchange, Carmen Beatriz Rodriguez

Senior Projects Spring 2014

Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). There are three possible organ sources for these transplants; cadaver, living, and good samaritan donors. The living donors are usually friends or relatives of the patient. The benefits of living donors in kidney exchanges are to increase the patients’ chance of receiving an organ sooner than patients waiting for cadaver donors, as well as providing them with a higher graft survival rate. In cases where a living donor is incompatible with their loved-one in need of a transplant, kidney paired exchanges are possible. Kidney paired exchanges …

Acute Kidney Injury In Lymphoma: A Single Centre Experience, Muhammad Abdul Mabood Khalil, Hira Latif, Abdur Rehman, Waqar Uddin Kashif, Safia Awan, Zarghona Khalil, Uziar Mushtaq, Maria Ahmad, Muhammad Ashhad Ullah Khalil, Manickam Ranga Sami

Section of Nephrology

Background. Acute kidney injury (AKI) is a common but least studied complication of lymphoma.

Objective. To determine the frequency and predictors of AKI in lymphoma and to study the impact of AKI on hospital stay and mortality.

Methods. Retrospective review of medical records of hospitalized lymphoma patients aged ≥14 years between January 2008 and December 2011 was done.

Results. Out of 365 patients, AKI was present in 31.8% (116/365). Multivariate logistic regression analysis showed that independent predictors for AKI included sepsis (odds ratio (OR) 3.76; 95% CI 1.83-7.72), aminoglycosides (OR 4.75; 95% CI 1.15-19.52), diuretics (OR 2.96; 95% CI 1.31-6.69), …

American And Brazilian Children With Primary Urolithiasis: Similarities And Disparities., Maria Goretti Moreira Guimarães Penido, Marcelo De Sousa Tavares, Milena Maria Moreira Guimarães, Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Objectives. Considering the differences in location, socioeconomic background, and cultural background, the aim of this study was to try to identify possible factors associated with the increased incidence of urolithiasis by comparing American and Brazilian children with stones.
Methods. Data of 222 American and 190 Brazilian children with urolithiasis were reviewed including age, gender, body mass index, imaging technique used (ultrasound and computed tomography), and 24-hour urine volume and chemistries.
Results. There were no differences between age and gender at diagnosis. Brazilian children were leaner but in no population did obesity rate exceed that of the general population. Ultrasound was …

Fluid Flow Shear Stress Over Podocytes Is Increased In The Solitary Kidney., Tarak Srivastava, Gianni E. Celsi, Mukut Sharma, Hongying Dai, Ellen T. Mccarthy, Melanie Ruiz, Patricia A. Cudmore, Uri S. Alon, Ram Sharma, Virginia A. Savin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Glomerular hyperfiltration is emerging as the key risk factor for progression of chronic kidney disease (CKD). Podocytes are exposed to fluid flow shear stress (FFSS) caused by the flow of ultrafiltrate within Bowman's space. The mechanism of hyperfiltration-induced podocyte injury is not clear. We postulated that glomerular hyperfiltration in solitary kidney increases FFSS over podocytes.

METHODS: Infant Sprague-Dawley rats at 5 days of age and C57BL/6J 14-week-old adult mice underwent unilateral nephrectomy. Micropuncture and morphological studies were then performed on 20- and 60-day-old rats. FFSS over podocytes in uninephrectomized rats and mice was calculated using the recently published equation …

Considerations And Challenges In Defining Optimal Iron Utilization In Hemodialysis, D. M. Charytan, A. B. Pai, C. T. Chan, D. W. Coyne, A. M. Hung, C. P. Kovesdy, S. Fishbane

Journal Articles

Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and …

A Letter To The Master Clinician, K. D. Jhaveri

Journal Articles

In this commentary, the author writes a letter to the Master Clinician about his concerns regarding the teaching responsibilities of current faculty members during ward rounds. This short essay highlights the transition that has been noticed in medical training in the last decade.

Magnesium Protects Against Cisplatin-Induced Acute Kidney Injury By Regulating Platinum Accumulation, M. H. Solanki, P. K. Chatterjee, M. Gupta, X. Y. Xue, A. Plagov, M. H. Metz, R. Mintz, P. C. Singhal, C. N. Metz

Journal Articles

Despite its success as a potent antineoplastic agent, similar to 25% of patients receiving cisplatin experience acute kidney injury (AKI) and must discontinue therapy. Impaired magnesium homeostasis has been linked to cisplatin-mediated AKI, and because magnesium deficiency is widespread, we examined the effect of magnesium deficiency and replacement on cisplatin-induced AKI in physiologically relevant older female mice. Magnesium deficiency significantly increased cisplatin-associated weight loss and markers of renal damage (plasma blood urea nitrogen and creatinine), histological changes, inflammation, and renal cell apoptosis and modulated signaling pathways (e.g., ERK1/2, p53, and STAT3). Conversely, these damaging effects were reversed by magnesium. Magnesium …

Mutations In The Gene That Encodes The F-Actin Binding Protein Anillin Cause Fsgs, R. A. Gbadegesin, G. Hall, A. Adeyemo, N. Hanke, I. Tossidou, J. Burchette, G. H. Wu, A. Homstad, P. C. Singhal, M. P. Winn, +17 Additional Authors

Journal Articles

FSGS is characterized by segmental scarring of the glomerulus and is a leading cause of kidney failure. Identification of genes causing FSGS has improved our understanding of disease mechanisms and points to defects in the glomerular epithelial cell, the podocyte, as a major factor in disease pathogenesis. Using a combination of genome-wide linkage studies and whole-exonne sequencing in a kindred with familial FSGS, we identified a missense mutation R431C in anillin (ANLN), an F-actin binding cell cycle gene, as a cause of FSGS. We screened 250 additional families with FSGS and found another variant, G618C, that segregates with disease in …

Clinically Significant Contrast Induced Acute Kidney Injury After Non-Emergent Cardiac Catheterization--Risk Factors And Impact On Length Of Hospital Stay., Waqar Kashif, Ali Khawaja, Syed Ather Hussain

Department of Medicine

Objective: To evaluate the frequency and risk factors associated with clinically significant contrast-induced nephropathy(CIN) in patients undergoing non-emergent coronary angiography.

Study Design: Descriptive study.

Place and Duration of Study: The Aga Khan University Hospital, Karachi, from January 2005 to December 2007.

Methodology: Case records of patients who underwent coronary angiography with a serum creatinine of ≥ 1.5 mg/dl atthe time of procedure were evaluated. Clinically significant contrast induced nephropathy (CSCIN) was defined as either doubling of serum creatinine from baseline value within a week following the procedure or need for emergency hemodialysis after the procedure.Results: One hundred …

Características Sociodemográficas E Aspectos Clínicos De Pacientes Com Doença Renal Policística Do Adulto Submetidos À Hemodiálise; Sociodemographic Characteristics And Clinical Features Of Patients With Adult Polycystic Kidney Disease Undergoing Hemodialysis, Everton Alves, Luiza Tsuneto, Sueli Borelli, Renata Cadidé, Rosane De Freitas, Ângela Gravena, Sandra Pelloso, Maria Dalva Carvalho

Everton Fernando Alves

Aims: To analyze the socio-demographic and clinical characteristics of patients with adult polycystic kidney disease

admitted to hemodialysis services in Northwestern Paraná state, Brazil.

Methods: This was an observational, descriptive and retrospective longitudinal study. Medical records of patients

with polycystic kidneys who initiated hemodialysis between 1995 and 2012, in four centers that treat patients of the

coverage area of the 15th Regional Health Region of Paraná state where analyzed.

Results: We found that 10.3% of hemodialysis patients had polycystic kidney disease as a leading cause of stage 5 of

chronic kidney disease. The mean age of patients was 54.9±9.4 years …

Effect Of Fluid Loss Following Hemodialysis On Tibialis Anterior Muscle Strength In People With End-Stage Renal Disease, Anuradha Sawant

Electronic Thesis and Dissertation Repository

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the effect of fluid loss following hemodialysis (HD) on tibialis anterior (TA) strength in participants with end-stage renal disease. Issues concerning measures of skeletal muscle hydration and efficacy of exercise as an anabolic intervention were also addressed.

METHODS: Data from published literature were combined in a meta-analysis to establish efficacy of exercise in participants on HD. Three clinical studies were undertaken using data acquired from healthy volunteers and participants on HD. Hydration of the calf muscles was estimated using bioelectrical impedance spectroscopy (BIS) [extracellular (ECF) and intracellular (ICF) fluid] …