Nephrology Commons^™

The Effect Of Body Mass Index On Graft Function And Kidney Transplant Outcomes, Morgan Galle

Theses & Dissertations

Background: When determining eligibility for kidney transplantation, body mass index (BMI) is often a debatable criterion for transplant due to the clinical indication, an elevated BMI has adverse effects on kidney transplant outcomes. There is a current gap in research on the effect BMI has on kidney transplant outcomes.

Purpose: The purpose of this study was to determine the role BMI plays in post-kidney transplant clinical outcomes including delayed graft function, new onset diabetes after transplant, wound complications, hospital length of stay, albumin, and readmissions to the hospital from initial hospitalization and at six months following kidney transplantation. The primary …

Effects Of Acceptance Of Disability On Death Or Dialysis In Chronic Kidney Disease Patients: A 3-Year Prospective Cohort Study, Hsin-Hung Chiang, Hanoch Livneh, How-Ran Guo, Mei-Ling Yen, Tzung-Yi Tsai

Counselor Education Faculty Publications and Presentations

Background: Acceptance of disability (AOD) is a useful construct that assesses the ability of a patient to psychologically cope with chronic diseases, but its effect on long-term outcomes of patients with chronic kidney disease (CKD) remains unclear. This study aimed to evaluate the relation between AOD level and clinical outcomes in a cohort of CKD patients in Taiwan.

Methods: 262 CKD patients without dialysis at a hospital in Taiwan were consecutively recruited, from 2010 to 2011, and followed up for 3 years. At enrollment, demographic and clinical data were obtained, including baseline level measurement of AOD, using the …

Effect Of Kidney Function On Drug Kinetics And Dosing In Neonates, Infants, And Children., Frederique Rodieux, Melanie Wilbaux, Johannes N. Van Den Anker, Marc Pfister

Pediatrics Faculty Publications

Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood …

Sotatercept Improves Anemia, Vascular Calcification, And Bone Loss In Patients With End-Stage Kidney Disease On Hemodialysis, John Havill, Nelson Kopyt Do, Fasn, Facp, Daniel Coyne, Michael Weiswasser, William T. Smith

Department of Medicine

No abstract provided.

Alkali Therapy In Lactic Acidosis, Zeid J. Khitan, Md, Deepak Malhotra, Md, Dominic S. Raj, Md, Antonios H. Tzamaloukas, Md, Joseph I. Shapiro, Md

Marshall Journal of Medicine

This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate.

Enhanced Fitness And Renal Function In Type 2 Diabetes., Eric S. Nylen, S. M. Gandhi, Raya E. Kheirbek, Peter Kokkinos

Medicine Faculty Publications

Aims

To investigate the renal effects of fitness in people with diabetes with mild renal dysfunction.

Methods

The effect of a 12-week exercise programme on estimated GFR in 128 people with diabetes was evaluated.

Results

All cardiometabolic variables improved after 12 weeks of supervised exercise. Although there was a modest 3.9% increase in estimated GFR from baseline in the 128 people who completed the study, those with baseline chronic kidney disease stages 2 and 3 were found to have significant (6 and 12%, respectively; p < 0.01) improvements in post-exercise estimated GFR. Moreover, 42% of the people with chronic kidney disease stage 3 improved to chronic kidney disease stage 2 after the intervention.

Conclusion

Short-term exercise improves renal function in those with more moderate baseline chronic kidney disease. …

Janus Kinase 2/Signal Transducer And Activator Of Transcription 3 Inhibitors Attenuate The Effect Of Cardiotrophin-Like Cytokine Factor 1 And Human Focal Segmental Glomerulosclerosis Serum On Glomerular Filtration Barrier., Mukut Sharma, Jianping Zhou, Jean-François Gauchat, Ram Sharma, Ellen T. Mccarthy, Tarak Srivastava, Virginia J. Savin

Manuscripts, Articles, Book Chapters and Other Papers

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) after renal transplantation is believed to be caused by a circulating factor(s). We detected cardiotrophin-like cytokine factor 1 (CLCF1), a member of the interleukin 6 family, in the plasma from patients with recurrent FSGS. We hypothesized that CLCF1 contributes to the effect of FSGS serum on the glomerular filtration barrier in vitro. Presently, we studied the effect of CLCF1 on isolated rat glomeruli using an in vitro assay of albumin permeability (P(alb)). CLCF1 (0.05-100 ng/mL) increased P(alb) and caused maximal effect at 5-10 ng/mL (P < 0.001). The increase in Palb was analogous to the effect of FSGS serum. Anti-CLCF1 monoclonal antibody blocked the CLCF1-induced increase in P(alb) and significantly attenuated the effect of FSGS serum (P < 0.001). The heterodimer composed of CLCF1 and cosecreted molecule cytokine receptor-like factor 1 (CRLF1) attenuated the increase in P(alb) caused by CLCF1 or FSGS serum. Western blot analysis showed that CLCF1 upregulated phosphorylation of signal transducer and activator of transcription 3 (STAT3) (Tyr705) in glomeruli. This effect was diminished by the heterodimer CLCF1-CRLF1. Janus kinase 2 (JAK2) inhibitor BMS-1119543 or STAT3 inhibitor Stattic significantly blocked the effect of CLCF1 or FSGS serum on P(alb) (P < 0.001). These novel findings suggest that when monomeric CLCF1 increases P(alb), the heterodimer CLCF1-CRLF1 may protect the glomerular filtration barrier. We speculate that albuminuria in FSGS is related to qualitative or quantitative changes in the CLCF1-CRLF1 complex, and that JAK2 or STAT3 inhibitors may be novel therapeutic agents to treat FSGS.

Efficacy Of Galactose And Adalimumab In Patients With Resistant Focal Segmental Glomerulosclerosis: Report Of The Font Clinical Trial Group., Howard Trachtman, Suzanne Vento, Emily Herreshoff, Milena Radeva, Jennifer Gassman, Daniel T. Stein, Virginia J. Savin, Mukut Sharma, Jochen Reiser, Changli Wei, Michael Somers, Tarak Srivastava, Debbie S. Gipson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with resistant focal segmental glomerulosclerosis (FSGS) who are unresponsive to corticosteroids and other immunosuppressive agents are at very high risk of progression to end stage kidney disease. In the absence of curative treatment, current therapy centers on renoprotective interventions that reduce proteinuria and fibrosis. The FONT (Novel Therapies for Resistant FSGS) Phase II clinical trial (NCT00814255, Registration date December 22, 2008) was designed to assess the efficacy of adalimumab and galactose compared to standard medical therapy which was comprised of lisinopril, losartan, and atorvastatin.

METHODS: Key eligibility criteria were biopsy confirmed primary FSGS or documentation of a causative …

Hla-Dqa1 And Plcg2 Are Candidate Risk Loci For Childhood-Onset Steroid-Sensitive Nephrotic Syndrome., Rasheed A. Gbadegesin, Adebowale Adeyemo, Nicholas J A Webb, Larry A A. Greenbaum, Asiri Abeyagunawardena, Shenal Thalgahagoda, Arundhati Kale, Debbie Gipson, Tarak Srivastava, Jen-Jar Lin, Deepa Chand, Tracy E. Hunley, Patrick D. Brophy, Arvind Bagga, Aditi Sinha, Michelle N. Rheault, Joanna Ghali, Kathy Nicholls, Elizabeth Abraham, Halima S. Janjua, Abiodun Omoloja, Gina-Marie Barletta, Yi Cai, David D. Milford, Catherine O'Brien, Atif Awan, Vladimir Belostotsky, William E. Smoyer, Alison Homstad, Gentzon Hall, Guanghong Wu, Shashi Nagaraj, Delbert Wigfall, John Foreman, Michelle P. Winn, Mid-West Pediatric Nephrology Consortium

Manuscripts, Articles, Book Chapters and Other Papers

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were …

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Association Between Inflammation And Cardiac Geometry In Chronic Kidney Disease: Findings From The Cric Study., Jayanta Gupta, Elizabeth Dominic, Jeffrey C. Fink, Akinlolu O. Ojo, Ian R. Barrows, Muredach Reilly, Raymond R. Townsend, Marshall Joffe, Sylvia Rosas, Melanie Wolman, Samir Patel, Martin Keane, Harold I. Feldman, John W. Kusek, Dominic S. Raj

Medicine Faculty Publications

Background

Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.

Methods

Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted …

Elevated Serum Bicarbonate Concentration In Chronic Kidney Disease: A Call To Find The Cause, Zeid J. Khitan

Internal Medicine

In this issue, Dobre et al1 reported an observational study looking at results of annually measured serum bicarbonate concentration in participants with chronic kidney disease (CKD) enrolled in the Chronic Renal Insufficiency Cohort (CRIC) using the marginal structural model, a validated statistical method,2 to estimate the cumulative effect over the period of the study and their effects on adjudicated heart failure events, atherosclerotic events, renal disease progression, and mortality. In their analysis, they included patients aged 21 to 74 years with estimated glomerular filtration rate of 20 to 70 mL/min per 1.73 m2 and excluded patients with NYHA Class III/IV …

A Rare Case Of Non-Cardiogenic Pulmonary Edema, Talal Alzahrani, Kelly Zhang, Angela Ryan, Yasir Alfi, Jeffrey Zweig

GW Research Days 2015

INTRODUCTION:

Nephrotic syndrome is identified by a significant proteinuria more than 3.5 g/day, hypoalbuminemia less than 3.5 g/dl, and peripheral edema. It associated with risks of thrombosis, infection, and hyperlipidemia due to loss of plasma protein. Several studies have shown patients with nephrotic syndrome do not develop non-cardiogenic pulmonary edema. However, we report a case of nephrotic syndrome caused by diabetic nephropathy and presented with non-cariogenic pulmonary edema.

CASE REPORT:

A 37-year old man with a past medical history of diabetes mellitus, hypertension, dyslipidemia, Charcot foot, who presented with dyspnea, orthopnea, and non-productive cough for two days. He had been …

On The Safety Of Intravenous Iron, Evidence Trumps Conjecture, M. Auerbach, J. Adamson, A. Bircher, C. Breymann, S. Fishbane, A. Gafter-Gvili, C. Gasche, J. Gilreath, G. Grazzini, A. Shander, +7 Additional Authors

Journal Articles

No abstract provided.

Ferric Pyrophosphate Citrate (Triferic) Administration Via The Dialysate Maintains Hemoglobin And Iron Balance In Chronic Hemodialysis Patients, S. N. Fishbane, A. K. Singh, S. H. Cournoyer, K. K. Jindal, P. Fanti, C. D. Guss, V. H. Lin, R. D. Pratt, A. Gupta

Journal Articles

BACKGROUND: Administration of ferric pyrophosphate citrate (FPC, Triferic) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. METHODS: Two identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 microM FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from …

Full-Length Soluble Urokinase Plasminogen Activator Receptor Down-Modulates Nephrin Expression In Podocytes, M. Alfano, P. Cinque, G. Giusti, S. Proietti, M. Nebuloni, S. Danese, S. D'Alessio, M. Genua, P. C. Singhal, J. Mikulak, +5 Additional Authors

Journal Articles

Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms' tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of alpha v beta 3 integrin RGDfv blocked suPAR-induced suppression of …

Harvest, A Longitudinal Patient Record Summarizer, J. S. Hirsch, J. S. Tanenbaum, S. Lipsky Gorman, C. Liu, E. Schmitz, D. Hashorva, A. Ervits, D. Vawdrey, M. Sturm, N. Elhadad

Journal Articles

OBJECTIVE: To describe HARVEST, a novel point-of-care patient summarization and visualization tool, and to conduct a formative evaluation study to assess its effectiveness and gather feedback for iterative improvements. MATERIALS AND METHODS: HARVEST is a problem-based, interactive, temporal visualization of longitudinal patient records. Using scalable, distributed natural language processing and problem salience computation, the system extracts content from the patient notes and aggregates and presents information from multiple care settings. Clinical usability was assessed with physician participants using a timed, task-based chart review and questionnaire, with performance differences recorded between conditions (standard data review system and HARVEST). RESULTS: HARVEST displays …

Hypersensitivity To Intravenous Iron: Classification, Terminology, Mechanisms And Management, J. Szebeni, S. Fishbane, M. Hedenus, S. Howaldt, F. Locatelli, S. Patni, D. Rampton, G. Weiss, J. Folkersen

Journal Articles

Intravenous (IV) iron therapy is widely used in iron deficiency anemias when oral iron is not tolerated or ineffective. Administration of IV iron is considered a safe procedure, but severe hypersensitivity reactions (HSRs) can occur at a very low frequency. Recently, new guidelines have been published by the European Medicines Agency (EMA) with the intention of making IV-iron therapy safer; however, the current protocols are still non-specific, non-evidence-based empiric measures which neglect the fact that the majority of IV-iron reactions are not Ig-E-mediated anaphylactic reactions. The field would benefit from new specific and effective methods for the prevention and treatment …

Integrating Real Time Data To Improve Outcomes In Acute Kidney Injury, J. S. Hirsch, S. Mohan

Journal Articles

Critically ill patients with acute kidney injury requiring renal replacement therapy have a poor prognosis. Despite well-known factors, which contribute to outcomes, including dose delivery, patients frequently miss the target dose and volume removal. One major barrier to effective care of these patients is the traditional dissociation of dialysis device data from other clinical information systems, notably the electronic health record (EHR). This lack of integration and the resulting manual documentation leads to errors and biases in documentation and missed opportunities to intervene in a timely fashion. This review summarizes the technological advancements facilitating direct connection of dialysis devices to …

Apolipoprotein L1 (Apol1) Variants (Vs) A Possible Link Between Heroin-Associated Nephropathy (Han) And Hiv-Associated Nephropathy (Hivan), X. Lan, T. K. Rao, P. N. Chander, K. Skorecki, P. C. Singhal

Journal Articles

In 1970s, Heroin-associated Nephropathy (HAN), one form of focal and segmental glomerulosclerosis (FSGS), was a predominant cause of End-stage Kidney Disease (ESKD) in African-Americans (AAs). In 1980s, with the surge of Acquired Immune Deficiency Syndrome (AIDS) in AAs, HAN more or less disappeared, and the incidence of Human Immunodeficiency Virus associated Nephropathy (HIVAN) markedly increased. Recent studies in AAs have identified APOL1 variants (Vs) as a major risk factor for the development and progression of non-diabetic kidney diseases including idiopathic FSGS and hypertension-attributed nephrosclerosis. These observations have also offered partial insights into the mechanisms of development, and higher rate of …

Cardiorenal Syndrome And The Role Of The Bone-Mineral Axis And Anemia, D. M. Charytan, S. Fishbane, J. Malyszko, P. A. Mccullough, D. Goldsmith

Journal Articles

The association between chronic kidney disease (CKD) and cardiovascular disease (CVD) is well established, and there is mounting evidence of interorgan cross talk that may accelerate pathologic processes and the progression of organ dysfunction in both systems. This process, termed cardiorenal syndrome (CRS) by the Acute Dialysis Quality Initiative, is considered a major health problem: patients with CKD and CVD are at much higher risk of mortality than patients with either condition alone. To date, the majority of CRS research has focused on neurohormonal mechanisms and hemodynamic alterations. However, mounting evidence suggests that abnormalities in the normal pathophysiology of the …

Challenges And Opportunities In Late-Stage Chronic Kidney Disease, S. Fishbane, A. D. Hazzan, C. Halinski, A. T. Mathew

Journal Articles

There is increasing recognition that chronic diseases are a major challenge for health delivery systems and treasuries. These are highly prevalent and costly diseases and frequency is expected to increase greatly as the population of many countries ages. Chronic kidney disease (CKD) has not received the same attention as other chronic diseases such as congestive heart failure; yet, the prevalence and costs of CKD are substantial. Greater recognition and support for CKD may require that the disease no longer be viewed as one continuous disease state. Early CKD stages require less complex care and generate lower costs. In contrast, late-stage …

Mllt1 Yeats Domain Mutations In Clinically Distinctive Favourable Histology Wilms Tumours., Elizabeth J Perlman, Samantha Gadd, Stefan T Arold, Anand Radhakrishnan, Daniela S Gerhard, Jeffrey S. Dome, +19 Additional Authors

Pediatrics Faculty Publications

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar …

A Review Of The Nonpressor And Nonantidiuretic Actions Of The Hormone Vasopressin, G. P. Mavani, M. V. Devita, M. F. Michelis

Journal Articles

The pressor and antidiuretic actions of arginine vasopressin (AVP) have been well documented. This review focuses on the less widely appreciated actions of AVP which also have important physiologic functions and when better understood may provide important insights into common disease states. These actions include effects on pain perception and bone structure as well as important relationships to the varied components of metabolic syndrome. These include effects on blood glucose, lipid levels, and blood pressure. AVP may also play a role in the progression of chronic kidney disease and effect physiologic changes relating to aging, abnormal social behavior, and cognitive …

Tubular Cell Phenotype In Hiv-Associated Nephropathy: Role Of Phospholipid Lysophosphatidic Acid, K. R. Ayasolla, P. Rai, S. Rahimipour, M. Hussain, A. Malhotra, P. C. Singhal

Journal Articles

Collapsing glomerulopathy and microcysts are characteristic histological features of HIV-associated nephropathy (HIVAN). We have previously reported the role of epithelial mesenchymal transition (EMT) in the development of glomerular and tubular cell phenotypes in HIVAN. Since persistent tubular cell activation of NF kappa B has been reported in HIVAN, we now hypothesize that HIV may be contributing to tubular cell phenotype via lysophosphatidic acid (LPA) mediated downstream signaling. Interestingly, LPA and its receptors have also been implicated in the tubular interstitial cell fibrosis (TIF) and cyst formation in autosomal dominant polycystic kidney disease (PKD). Primary human proximal tubular cells (HRPTCs) were …

Vascular Smooth Muscle Cells Contribute To Apol1-Induced Podocyte Injury In Hiv Milieu, X. Lan, H. Wen, M. A. Saleem, J. Mikulak, A. Malhotra, K. Skorecki, P. C. Singhal

Journal Articles

Clinical reports have demonstrated that higher rates of non-diabetic glomerulosclerosis in African Americans can be attributed to two coding sequence variants (G1 and G2) in the APOL1 gene; however, the underlying mechanism is still unknown. Kidney biopsy data suggest enhanced expression of APOL1/APOL1 variants (Vs) in smooth muscle cells (SMCs) of renal vasculature. Since APOL1 is a secretory protein of relatively low molecular weight (41kDa), SMCs may be a contributory endocrine/paracrine source of APOL1 wild type (WT)/APOL1Vs in the glomerular capillary perfusate percolating podocytes. In the present study, we tested the hypothesis that an HIV milieu stimulated secretion of APOL1 …

Vitamin D Receptor And Epigenetics In Hiv Infection And Drug Abuse, N. Chandel, A. Malhotra, P. C. Singhal

Journal Articles

Illicit drug abuse is highly prevalent and serves as a powerful co-factor for HIV exacerbation. Epigenetic alterations in drug abuse and HIV infection determine expression of several critical genes such as vitamin D receptor (VDR), which participates in proliferation, differentiation, cell death under both physiological and pathological conditions. On that account, active vitamin D, the ligand of VDR, is used as an adjuvant therapy to control infection, slow down progression of chronic kidney diseases, and cancer chemotherapy. Interestingly, vitamin D may not be able to augment VDR expression optimally in several instances where epigenetic contributes to down regulation of VDR; …

An Overlapping Case Of Lupus Nephritis And Igg4-Related Kidney Disease, M. Zaarour, C. Weerasinghe, A. Eter, S. El-Sayegh, E. El-Charabaty

Journal Articles

We report a case of a 71-year-old Filipino female who was admitted to the hospital for abdominal pain, vomiting and diarrhea of 8 days duration. The patient was found to have marked acute kidney injury (AKI), which required hemodialysis in the next 3 days. Extensive workup revealed hematuria, subnephrotic range proteinuria, elevated anti-nuclear antibody (ANA) and elevated total immunoglobulin G (IgG) levels, with normal IgG4 and anti-dsDNA levels. On kidney biopsy, mild membranous glomerulonephritis was found, along with autoimmune tubulointerstitial nephritis (TIN) with a "full-house" pattern of immune deposits. These findings were suggestive of lupus interstitial nephritis. However, IgG4+ plasma …

Presence Of Anti-Glomerular Basement Membrane Antibodies And Myeloperoxidase Anti-Neutrophilic Cytoplasmic Antibodies In A Case Of Rapidly Progressive Glomerulonephritis, G. P. Mavani, M. Pommier, S. Win, M. F. Michelis, J. Rosenstock

Journal Articles

A 69-year-old male had initially presented with low-grade proteinuria, microhematuria, and a positive myeloperoxidase anti-neutrophilic antibody (ANCA). He subsequently developed deterioration of kidney function and developed uremic symptoms. Creatinine was 486.2 mumol/L (5.5 mg/dL). Anti-MPO was positive (titer >8 U, normal

Protein Domains Of Apol1 And Its Risk Variants, X. Q. Lan, H. X. Wen, R. Lederman, A. Malhotra, J. Mikulak, W. Popik, K. Skorecki, P. C. Singhal

Journal Articles

Increasing lines of evidence have demonstrated that the development of higher rates of non-diabetic glomerulosclerosis (GS) in African Americans can be attributed to two coding sequence variants (G1 and G2) in the Apolipoprotein L1 (APOL) gene. Recent studies indicate that the gene products of these APOL1 risk variants have augmented toxicity to kidney cells. However, the biological characteristics of APOL1 and its risk variants are not well elucidated. The APOL1 protein can be divided into several functional domains, including signal peptide (SP), pore forming domain (PFD), membrane address domain (MAD), and SEA-interacting domain. To investigate the relative contribution of each …