Nephrology Commons^™

Cyclooxygenase-2, Prostaglandin E2, And Prostanoid Receptor Ep2 In Fluid Flow Shear Stress-Mediated Injury In The Solitary Kidney., Tarak Srivastava, Uri S. Alon, Patricia A. Cudmore, Belal Tarakji, Alexander Kats, Robert E. Garola, R Scott Duncan, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Lynda F. Bonewald, Ashraf El-Meanawy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Hyperfiltration subjects podocytes to increased tensile stress and fluid flow shear stress (FFSS). We showed a 1.5- to 2.0-fold increase in FFSS in uninephrectomized animals and altered podocyte actin cytoskeleton and increased synthesis of prostaglandin E2 (PGE2) following in vitro application of FFSS. We hypothesized that increased FFSS mediates cellular changes through specific receptors of PGE2. Presently, we studied the effect of FFSS on cultured podocytes and decapsulated isolated glomeruli in vitro, and on solitary kidney in uninephrectomized sv129 mice. In cultured podocytes, FFSS resulted in increased gene and protein expression of cyclooxygenase (COX)-2 but not COX-1, prostanoid receptor EP2 …

Severe Tubulointerstitial Nephritis From Acute Epstein-Barr Virus Infection, Craig A. Mackaness Do

Department of Medicine

No abstract provided.

Tps Mutational Status Is A Potential Marker For Risk Stratification In Wilms Tumour With Diffuse Anaplasia, Mariana Maschietto, Richard D. Williams, Tasnim Chagtai, Sergey D. Popov, Neil J. Sebire, Gordan Vujanic, Elizabeth Perlman, James R. Anderson, Paul Grundy, Jeffrey S. Dome, Kathy Pritchard-Jones

Pediatrics Faculty Publications

Purpose

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whetherTP53 mutational status confers additional prognostic information.

Patients and Methods

We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. …

Predictors Of Hospital Stay And Mortality In Dengue Virus Infection-Experience From Aga Khan University Hospital Pakistan, Muhammad Abdul Mabood Khalil, Jackson Tan, Muhammd Ashhad Ullah Khalil, Safia Awan, Manickam Rangasami

Section of Nephrology

Background: Dengue virus infection (DVI) is very common infection. There is scarcity of data on factor associated with increased hospitalstay and mortality in dengue virus infection (DVI). This study was done to know about factors associated with increased hospital stay and mortality in patients admitted with DVI.

Results: Out of 532 patients, two third (72.6%) had stay ≤3 days while one third (27.4%) had stay greater than 3 days. The mean length of hospital stay was 3.46 ± 3.45 days. Factors associated with increased hospital stay (>3 days) included AKI (acute kidney injury) (Odd ratio 2.98; 95% CI 1.66-5.34), …

Eculizumab In The Successful Treatment Of Postpartum Hemolytic Uremic Syndrome - A Case Report, Craig A. Mackaness Do, Frederick S. Fleszler Md

Department of Medicine

No abstract provided.

Babesiosis: An Under-Recognized Tick Bourne Illness, Michael N. Daniels Do, Katie Mastoris Do, Mark Knouse Md, Stacey Smith Md, Facp

Department of Medicine

No abstract provided.

Update On Membranoproliferative Gn, N. Masani, K. D. Jhaveri, S. Fishbane

Journal Articles

Membranoproliferative GN represents a pattern of injury seen on light microscopy. Historically, findings on electron microscopy have been used to further subclassify this pathologic entity. Recent advances in understanding of the underlying pathobiology have led to a proposed classification scheme based on immunofluorescence findings. Dysregulation of the complement system has been shown to be a major risk factor for the development of a membranoproliferative GN pattern of injury on kidney biopsy. Evaluation and treatment of this complex disorder rest on defining the underlying mechanisms.

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

Journal Articles

No abstract provided.

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

Journal Articles

No abstract provided.

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

Journal Articles

No abstract provided.

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 …

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 …

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.

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 …

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 …

Necrotizing Rpgn With Linear Anti Igg Deposits In A Patient With History Of Granulomatosis With Polyangiitis: A Case Report, N. Parekh, E. Epstein, S. El-Sayegh

Journal Articles

INTRODUCTION: Diagnosing the etiology of a rapidly progressive glomerulonephritis is of vital importance to guide appropriate therapeutic management. This case highlights the complexity involved in establishing diagnosis when presentation is atypical. In certain cases diagnosis cannot be established based on clinical presentation or biopsy findings alone, and critical analysis of biopsy findings in context of clinical presentation is crucial to guide the clinical decision-making process. CASE PRESENTATION: A 47-year-old Hispanic male with history of granulomatosis with polyangiitis (GPA) in remission on azathioprine, presented with fatigue and lethargy. Physical examination was unremarkable. Laboratory data revealed elevated creatinine and otherwise normal electrolytes. …

Renin Angiotensin System Modulates Mtor Pathway Through At2r In Hivan, P. Rai, R. Lederman, S. Hague, S. Rehman, V. Kumar, K. Sataranatrajan, A. Malhotra, B. S. Kasinath, P. C. Singhal

Journal Articles

Mammalian target of rapamycin (mTOR) has been reported to contribute to the development of HIV-associated nephropathy (HI VAN). We hypothesized that HIV may be activating renal tissue mTOR pathway through renin angiotensin system (RAS) via Angiotensin Receptor Type II receptor (AT2R). Renal tissues of Vpr transgenic and Tg26 (HIVAN) mice displayed enhanced phosphorylation of mTOR and p70S6K. Aliskiren, a renin inhibitor attenuated phosphotylation of both mTOR and p70S6K in renal tissues of HIVAN mice. Interestingly, Angiotensin Receptor Type I (AT1R) blockade did not modulate renal tissue phosphorylation of mTOR in HIVAN mice; on the other hand, AT2R blockade attenuated renal …

A 12-Week, Double-Blind, Placebo-Controlled Trial Of Ferric Citrate For The Treatment Of Iron Deficiency Anemia And Reduction Of Serum Phosphate In Patients With Ckd Stages 3-5, G. A. Block, S. Fishbane, M. Rodriguez, G. Smits, S. Shemesh, P. E. Pergola, M. Wolf, G. M. Chertow

Journal Articles

BACKGROUND: Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality. STUDY DESIGN: Double-blind, placebo-controlled, randomized trial. SETTING & PARTICIPANTS: 149 patients with estimated glomerular filtration rates < 60mL/min/1.73m2, iron deficiency anemia (hemoglobin, 9.0-12.0g/dL; transferrin saturation [TSAT]/= 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited. INTERVENTION: Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo. OUTCOMES & MEASUREMENTS: Coprimary end points were change in TSAT and serum phosphate level from baseline to end of study. Secondary outcomes included change from baseline to end of treatment in values for ferritin, hemoglobin, intact fibroblast growth factor 23 (FGF-23), urinary phosphate excretion, and estimated glomerular filtration rate. RESULTS: Ferric citrate treatment increased mean TSAT from 22% +/- 7% (SD) to 32% +/- 14% and reduced serum phosphate levels from 4.5+/-0.6 to 3.9+/-0.6mg/dL, while placebo exerted no effect on TSAT (21% +/- 8% to 20% +/- 8%) and less effect on serum phosphate level (4.7+/-0.6 to 4.4+/-0.8mg/dL; between-group P

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 …

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.

Spla2 Ib Induces Human Podocyte Apoptosis Via The M-Type Phospholipase A2 Receptor, Y. B. Pan, J. X. Wan, Y. P. Liu, Q. Yang, W. Liang, P. C. Singhal, M. A. Saleem, G. H. Ding

Journal Articles

The M-type phospholipase A2 receptor (PLA2R) is expressed in podocytes in human glomeruli. Group IB secretory phospholipase A2 (sPLA2 IB), which is one of the ligands of the PLA2R, is more highly expressed in chronic renal failure patients than in controls. However, the roles of the PLA2R and sPLA2 IB in the pathogenesis of glomerular diseases are unknown. In the present study, we found that more podocyte apoptosis occurs in the kidneys of patients with higher PLA2R and serum sPLA2 IB levels. In vitro, we demonstrated that human podocyte cells expressed the PLA2R in the cell membrane. After binding with …

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 …

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 …

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), …

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 …

Discovery Of Pharmacological Compounds That Stimulate Renal Mitochondrial Biogenesis And Restore Kidney Function, Sean Robert Jesinkey

MUSC Theses and Dissertations

Dysfunctional mitochondria are a primary pathological consequence of acute kidney injury (AKI). Mitochondrial homeostasis is disrupted up to 144 h after ischemia-reperfusion (I/R) induced-AKI in the renal cortical tissue of mice. Stimulation of mitochondrial biogenesis in renal cells after oxidant injury restores mitochondrial function. The primary goals of this project were to identify novel pharmacological compounds capable of inducing mitochondrial biogenesis in the renal proximal tubule and evaluate if this induction would promote the recovery of mitochondrial and/or renal function after in vivo AKI. The secondary goal was to employ our mitochondrial approach for drug discovery towards identifying a novel …

Serotonergic Stimulation Of Mitochondrial Biogenesis And Their Cheminformatic Models, Richard Edwin Trager Iii

MUSC Theses and Dissertations

Kidney disease and toxicity is increasingly being tied to mitochondrial dysfunction. Cheminformatic modeling and high-throughput phenotypic screens can discover discrete subsets of selective ligands that correlate with mitochondrial biogenesis (MB) and accelerate recovery from acute kidney injury (AKI). Serotonergic (5-HT) stimulation has been shown to cause MB. Subtype specific ligands for 5-HT1F and 5-HTA/C receptors show increased uncoupled oxygen consumption rate (OCR). Our overall goal, in a screening assay, is to discover small molecules that increase MB to be used as drugs in the treatment of diseases that exhibit mitochondrial dysfunction. To achieve this goal we created pharmacophore models of …

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 …

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 …