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Gout: HELP
Articles from Baltimore
Based on 37 articles published since 2008
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These are the 37 published articles about Gout that originated from Baltimore during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Gout and Association with Erectile Dysfunction. 2015

Gelber, Allan C. ·Professor of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. agelber@jhmi.edu. ·J Rheumatol · Pubmed #26429202.

ABSTRACT: -- No abstract --

2 Review Cross-sectional imaging of adult crystal and inflammatory arthropathies. 2016

Soldatos, Theodoros / Pezeshk, Parham / Ezzati, Fatemeh / Karp, David R / Taurog, Joel D / Chhabra, Avneesh. ·Department of Radiology, Mediterraneo Hospital, Athens, Greece. · Musculoskeletal Radiology and Orthopaedic Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9178, USA. · Division of Rheumatic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA. · Musculoskeletal Radiology and Orthopaedic Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-9178, USA. avneesh.chhabra@utsouthwestern.edu. · Musculoskeletal Radiology, Russell H. Morgan Department of Radiology & Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. avneesh.chhabra@utsouthwestern.edu. ·Skeletal Radiol · Pubmed #27209200.

ABSTRACT: This article highlights the key aspects and current perspectives of the role of cross-sectional imaging in adult crystal and inflammatory arthropathies in adults, briefly discussing CT, and particularly focusing on MRI and US imaging as it supplements the conventional radiography. The role of conventional and advanced MR imaging techniques and imaging findings in this domain is discussed and illustrated with case examples. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article contains images and data, which were collected from patients as a part of a retrospective IRB from the institutional teaching files and informed consent was waived.

3 Review Dual-Energy Computed Tomography of the Knee, Ankle, and Foot: Noninvasive Diagnosis of Gout and Quantification of Monosodium Urate in Tendons and Ligaments. 2016

Fritz, Jan / Henes, Joerg C / Fuld, Matthew K / Fishman, Elliot K / Horger, Marius S. ·Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases, Department of Internal Medicine II (Oncology, Hematology, Immunology, Rheumatology, Pulmonology), Eberhard Karls-University Tübingen, Tübingen, Germany. · Siemens Medical Solutions, Malvern, Pennsylvania. · Department of Diagnostic and Interventional Radiology, Eberhard Karls-University Tübingen, Tübingen, Germany. ·Semin Musculoskelet Radiol · Pubmed #27077593.

ABSTRACT: Gout is a true crystal deposition arthropathy caused by the precipitation of monosodium urate into joints and periarticular soft tissues. It is the most common inflammatory arthropathy in men and women of older age with a male-to-female ratio of 3 to 8:1. The disease may progress from asymptomatic hyperuricemia through symptomatic acute gout attacks with asymptomatic periods into chronic symptomatic tophaceous gout. Although invasive arthrocentesis and demonstration of monosodium urate crystals on polarized light microscopy is definitive for the diagnosis of gout, dual-energy computed tomography (CT) allows for noninvasive visualization and reproducible volume quantification of monosodium urate crystals. Based on the high diagnostic performance, dual-energy CT has been included in the 2015 American College of Rheumatology/European League Against Rheumatism Collaborative Initiative Classification Criteria for Gout. Increasing evidence indicates the usefulness of dual-energy CT to guide the management of patients with suspected gout and monitor the effectiveness of urate-lowering medical therapy.

4 Review Imaging as a potential outcome measure in gout studies: A systematic literature review. 2016

Durcan, Laura / Grainger, Rebecca / Keen, Helen I / Taylor, William J / Dalbeth, Nicola. ·Department of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland; Department of Rheumatology, Johns Hopkins University School of Medicine, 1830 East Monument St, Baltimore, MD 21287. Electronic address: ldurcan1@jhmi.edu. · Department of Medicine, University of Otago, Wellington, New Zealand. · University of Western Australia, Perth, Australia. · Division of Medicine, University of Auckland, Auckland, New Zealand. ·Semin Arthritis Rheum · Pubmed #26522139.

ABSTRACT: OBJECTIVE: Despite major progress in the imaging of gout, it is unclear which domains these techniques can evaluate and whether imaging modalities have the potential to provide valid outcome measures. The aim of this study was to assess the use of imaging instruments in gout according to the Outcomes in Rheumatology Clinical Trials (OMERACT) filter to inform the development of imaging as an outcome measure. METHODS: A systematic literature search of imaging modalities for gout was undertaken. Articles were assessed by two reviewers to identify imaging domains and summarize information according to the OMERACT filter. RESULTS: The search identified 78 articles (one abstract). Modalities included were conventional radiography (CR) (16 articles), ultrasound (US) (29), conventional computed tomography (CT) (11), dual energy computed tomography (DECT) (20), and magnetic resonance imaging (MRI) (16). Three domains were identified as follows: urate deposition, joint damage, and inflammation. Although sufficient data were available to assess feasibility, validity, and reliability, comprehensive assessment of discrimination was not possible due to the paucity of prospective imaging studies. CR is widely accessible, inexpensive with a validated damage scoring system. US and MRI offer radiation-free methods of evaluating urate deposition, damage and inflammation, but may be limited by accessibility. DECT provides excellent definition of urate deposition and bone damage, but has restricted availability and requires radiation. CONCLUSIONS: Imaging methods can detect urate deposition, damage, and inflammation in gout. More than one modality may be required depending on the domains and therapeutic agent of interest. No single imaging method currently fulfils all aspects of the OMERACT filter for any domain.

5 Review ABCG2: the molecular mechanisms of urate secretion and gout. 2015

Woodward, Owen M. ·Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland OWoodward@som.umaryland.edu. ·Am J Physiol Renal Physiol · Pubmed #26136557.

ABSTRACT: The human propensity for high levels of serum uric acid (SUA) is a trait that has defied explanation. Is it beneficial? Is it pathogenic? Its role in the human diseases like gout and kidney stones was discovered over a century ago [Richette P, Bardin T. Lancet 375: 318-328, 2010; Rivard C, Thomas J, Lanaspa MA, Johnson RJ. Rheumatology (Oxford) 52: 421-426, 2013], but today emerging new genetic and epidemiological techniques have revived an age-old debate over whether high uric acid levels (hyperuricemia) independently increase risk for diseases like hypertension and chronic kidney disease [Feig DI. J Clin Hypertens (Greenwich) 14: 346-352, 2012; Feig DI, Madero M, Jalal DI, Sanchez-Lozada LG, Johnson RJ. J Pediatr 162: 896-902, 2013; Feig DI, Soletsky B, Johnson RJ. JAMA 300: 924-932, 2008; Wang J, Qin T, Chen J, Li Y, Wang L, Huang H, Li J. PLoS One 9: e114259, 2014; Zhu P, Liu Y, Han L, Xu G, Ran JM. PLoS One 9: e100801, 2014]. Part of the mystery of the role uric acid plays in human health stems from our lack of understanding of how humans regulate uric acid homeostasis, an understanding that could shed light on the historic role of uric acid in human adaptation and its present role in human pathogenesis. This review will highlight the recent work to identify the first important human uric acid secretory transporter, ABCG2, and the identification of a common causal ABCG2 variant, Q141K, for hyperuricemia and gout.

6 Review ABCG transporters and disease. 2011

Woodward, Owen M / Köttgen, Anna / Köttgen, Michael. ·Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. ·FEBS J · Pubmed #21554546.

ABSTRACT: ATP-binding cassette (ABC) transporters form a large family of transmembrane proteins that facilitate the transport of specific substrates across membranes in an ATP-dependent manner. Transported substrates include lipids, lipopolysaccharides, amino acids, peptides, proteins, inorganic ions, sugars and xenobiotics. Despite this broad array of substrates, the physiological substrate of many ABC transporters has remained elusive. ABC transporters are divided into seven subfamilies, A-G, based on sequence similarity and domain organization. Here we review the role of members of the ABCG subfamily in human disease and how the identification of disease genes helped to determine physiological substrates for specific ABC transporters. We focus on the recent discovery of mutations in ABCG2 causing hyperuricemia and gout, which has led to the identification of urate as a physiological substrate for ABCG2.

7 Clinical Trial Efficacy and safety of febuxostat extended release and immediate release in patients with gout and moderate renal impairment: phase II placebo-controlled study. 2018

Gunawardhana, Lhanoo / Becker, Michael A / Whelton, Andrew / Hunt, Barbara / Castillo, Majin / Saag, Kenneth. ·Takeda Pharmaceuticals, One Takeda Parkway, Deerfield, IL, 60015, USA. lhanoo.gunawardhana@takeda.com. · University of Chicago Pritzker School of Medicine, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA. · Johns Hopkins University, 1737 Beaver Brook Lane, Hunt Valley, MD, 21030, USA. · Takeda Pharmaceuticals, One Takeda Parkway, Deerfield, IL, 60015, USA. · Birmingham VA Medical Center, 700 S. 19th Street, Birmingham, AL, 35233, USA. · University of Alabama at Birmingham, Faculty Office Tower, Suite 820, 1720 2nd Avenue South, Birmingham, AL, 35294, USA. ·Arthritis Res Ther · Pubmed #29848361.

ABSTRACT: BACKGROUND: Febuxostat immediate release (IR), a xanthine oxidase inhibitor, is indicated for the management of hyperuricemia in patients with gout by lowering urate levels. An extended release (XR) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure. The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and moderate renal impairment (estimated glomerular filtrate rate ≥ 30 and < 60 ml/min). METHODS: This was an exploratory, 3-month, phase II, multicenter, placebo-controlled, double-blind proof-of-concept study. Patients (n = 189) were randomized 1:1:1:1:1 to receive placebo or febuxostat IR 40 mg, XR 40 mg, IR 80 mg, or XR 80 mg once daily. Endpoints included: proportion of patients with serum uric acid (sUA) < 5.0 mg/dl at month 3 (primary endpoint), proportion of patients with sUA < 6.0 mg/dl at month 3, and proportion of patients with ≥ 1 gout flare requiring treatment over 3 months. RESULTS: At month 3, all febuxostat treatment groups were associated with greater proportions of patients achieving sUA < 5.0 mg/dl (p < 0.05 vs placebo). A greater proportion of patients receiving XR 40 mg achieved sUA < 5.0 mg/dl versus those receiving IR 40 mg (p = 0.034); proportions were similar in the IR 80 mg and XR 80 mg groups. Higher proportions of febuxostat-treated patients achieved sUA < 6.0 mg/dl at month 3 (p < 0.05 vs placebo) and experienced ≥ 1 gout flare (significant for all comparisons, except XR 40 mg). Incidences of treatment-related adverse events were low across all treatment groups; the majority were mild or moderate with no apparent trends correlating with IR or XR doses. The most common treatment-emergent adverse event was hypertension. One death (unrelated to the study drug) was reported. CONCLUSIONS: These exploratory data demonstrate that febuxostat (XR and IR) formulations were effective and well tolerated in patients with gout and moderate renal impairment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02128490 Registered on 29 April 2014.

8 Article Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. 2018

White, William B / Saag, Kenneth G / Becker, Michael A / Borer, Jeffrey S / Gorelick, Philip B / Whelton, Andrew / Hunt, Barbara / Castillo, Majin / Gunawardhana, Lhanoo / Anonymous1481001. ·From the University of Connecticut School of Medicine, Farmington (W.B.W.) · the University of Alabama, Birmingham (K.G.S.) · University of Chicago Medicine, Chicago (M.A.B.), and Takeda Development Center Americas, Deerfield (B.H., M.C., L.G.) - both in Illinois · the State University of New York, Downstate Medical Center, Brooklyn (J.S.B.) · Michigan State University College of Human Medicine, Grand Rapids (P.B.G.) · and Johns Hopkins University School of Medicine, Baltimore (A.W.). ·N Engl J Med · Pubmed #29527974.

ABSTRACT: BACKGROUND: Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease. METHODS: We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization). RESULTS: In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis. CONCLUSIONS: In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035 .).

9 Article Risk of Heart-Related Death From Gout Medication. 2018

Aschenbrenner, Diane S. ·Diane S. Aschenbrenner is an assistant professor at Notre Dame of Maryland University in Baltimore. She also coordinates Drug Watch: daschenbrenner@ndm.edu. ·Am J Nurs · Pubmed #29470212.

ABSTRACT: -- No abstract --

10 Article Gouty involvement of the patella and extensor mechanism of the knee mimicking aggressive neoplasm. A case series. 2018

Kester, Christopher / Wallace, Matthew T / Jelinek, James / Aboulafia, Albert. ·Department of Orthopaedics, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA. · Orthopaedic Oncology, National Center for Bone and Soft Tissue Tumors, MedStar Franklin Square Medical Center, 9103 Franklin Square Drive Suite 2300, Baltimore, MD, 21237, USA. Matthew.T.Wallace@medstar.net. · Department of Radiology, MedStar Washington Hospital Center, Washington, DC, USA. · National Center for Bone and Soft Tissue Tumors, MedStar Franklin Square Medical Center, Baltimore, MD, USA. ·Skeletal Radiol · Pubmed #29332201.

ABSTRACT: Gout is a common inflammatory crystal deposition disease that occurs in many joints throughout the body. Active gout is most often associated with painful synovitis causing searing joint pains, but gout can also produce large masses of space-occupying deposits called tophi. Tophi are most frequently seen in juxta-articular locations with or without bony erosion and are often misdiagnosed as degenerative joint disease. Soft tissue deposits and tendon involvement are also known manifestations of gout, but can present with indeterminate and alarming findings on imaging. We present three cases of tophaceous gout mimicking aggressive neoplasms in the extensor mechanism of the knee. All cases presented as extensor tendon masses eroding into the patella, with imaging findings initially concerning for primary musculoskeletal malignancy.

11 Article Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension. 2017

Juraschek, Stephen P / Appel, Lawrence J / Miller, Edgar R. ·The Johns Hopkins University School of Medicine, Division of General Internal Medicine, The Johns Hopkins Bloomberg School of Public Health, and The Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, Maryand, USA. ·Am J Hypertens · Pubmed #28830083.

ABSTRACT: BACKGROUND: There is little evidence guiding selection of nondiuretic, antihypertensive agents with a goal of lowering uric acid (SUA) and minimizing gout risk. METHODS: In the African American Study of Kidney Disease and Hypertension (AASK) trial, African Americans with chronic kidney disease were randomly assigned to metoprolol (a beta-blocker), ramipril (an angiotensin-converting enzyme inhibitors [ACEi]), or amlodipine (a dihydropyridine calcium-channel blocker). SUA was measured at baseline and 12 months. Gout-related hospitalizations were based on ICD9 codes. Gout-related medication use (GRMs) was based on active prescriptions of allopurinol, colchicine, or probenecid during the baseline visit of the AASK cohort phase. We examined the effect of drug assignment on 12-month SUA (linear regression), gout-related hospitalization (Cox regression), and GRM (logistic regression). RESULTS: Of the 630 participants, 40% were female with a mean age of 55 years (SD, 10), mean SUA of 8.2 mg/dl (2.0), and mean serum creatinine of 1.8 mg/dl (0.6). After 12 months, metoprolol increased SUA by 0.3 mg/dl, while ramipril or amlodipine had no effect on SUA. Compared to ramipril, metoprolol significantly increased 12-month SUA (0.40; 0.10, 0.70 mg/dl; P = 0.009), nonsignificantly increased risk of gout-related hospitalization (hazard ratio: 3.87; 0.82, 18.26; P = 0.09), and significantly increased the odds of GRM (odds ratio: 1.62; 1.03, 2.54; P = 0.04). While metoprolol was associated with a higher 12-month SUA compared with amlodipine (0.57; 0.18, 0.95; P = 0.004), there was no difference in gout-related hospitalizations or GRM. CONCLUSIONS: Metoprolol increased SUA and GRM in African American adults. Health professionals treating patients with kidney disease at risk for gout should avoid metoprolol and possibly consider an ACEi. CLINICAL TRIALS REGISTRATION: Trial Number NCT00582777.

12 Article Decrystallization of Crystals Using Gold "Nano-Bullets" and the Metal-Assisted and Microwave-Accelerated Decrystallization Technique. 2016

Thompson, Nishone / Boone-Kukoyi, Zainab / Shortt, Raquel / Lansiquot, Carisse / Kioko, Bridgit / Bonyi, Enock / Toker, Salih / Ozturk, Birol / Aslan, Kadir. ·Department of Chemistry, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA. nitho9@morgan.edu. · Department of Chemistry, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA. zaboo2@morgan.edu. · Department of Chemistry, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA. rasho4@morgan.edu. · Department of Chemistry, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA. calan1@morgan.edu. · Department of Chemistry, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA. brkio1@morgan.edu. · Department of Chemistry, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA. enbon1@morgan.edu. · Department of Chemistry, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA. salih.toker@morgan.edu. · Department of Physics and Engineering Physics, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA. birol.ozturk@morgan.edu. · Department of Chemistry, Morgan State University, 1700 East Cold Spring Lane, Baltimore, MD 21251, USA. Kadir.Aslan@morgan.edu. ·Molecules · Pubmed #27763557.

ABSTRACT: Gout is caused by the overproduction of uric acid and the inefficient metabolism of dietary purines in humans. Current treatments of gout, which include anti-inflammatory drugs, cyclooxygenase-2 inhibitors, and systemic glucocorticoids, have harmful side-effects. Our research laboratory has recently introduced an innovative approach for the decrystallization of biological and chemical crystals using the Metal-Assisted and Microwave-Accelerated Evaporative Decrystallization (MAMAD) technique. In the MAMAD technique, microwave energy is used to heat and activate gold nanoparticles that behave as "nano-bullets" to rapidly disrupt the crystal structure of biological crystals placed on planar surfaces. In this study, crystals of various sizes and compositions were studied as models for tophaceous gout at different stages (i.e., uric acid as small crystals (~10-100 μm) and l-alanine as medium (~300 μm) and large crystals (~4400 μm). Our results showed that the use of the MAMAD technique resulted in the reduction of the size and number of uric acid and l-alanine crystals up to >40% when exposed to intermittent microwave heating (up to 20 W power at 8 GHz) in the presence of 20 nm gold nanoparticles up to 120 s. This study demonstrates that the MAMAD technique can be potentially used as an alternative therapeutic method for the treatment of gout by effective decrystallization of large crystals, similar in size to those that often occur in gout.

13 Article Serum uric acid, gout, and venous thromboembolism: The atherosclerosis risk in communities study. 2016

Kubota, Yasuhiko / McAdams-DeMarco, Mara / Folsom, Aaron R. ·Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States; Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: kubot007@umn.edu. · Departments of Epidemiology and Surgery, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States. · Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States. ·Thromb Res · Pubmed #27337701.

ABSTRACT: INTRODUCTION: Inflammatory diseases increase risk of venous thromboembolism (VTE). Whether gout, the most common rheumatologic inflammatory arthritis, or its cause, elevated serum uric acid (SUA), is associated with VTE incidence is unknown. MATERIALS AND METHODS: The Atherosclerosis Risk in Communities Study measured SUA in 14126 participants aged 45-64, without a history of VTE or gout and not using anticoagulants/gout medications, and obtained information on incident gout between 1987 and 1998 from 10247. We followed them for VTE occurrence from 1987 to 2011. Hazard ratios (HRs) of VTE were estimated using Cox proportional hazards models. RESULTS: We documented 632 incident cases of VTE (236 unprovoked and 396 provoked). Age, sex, and race-adjusted HRs for total VTE were 1, 1.40, 1.43, 1.91, 1.71, and 3.25 (P for trend<0.001) across levels of SUA (range mg/dL: ≤4.9, 5.0-5.9, 6.0-6.9, 7.0-7.5, 7.6-8.7, and ≥8.8). After adjustment for other VTE risk factors, those in the highest level of SUA had HRs [95% confidence interval] of 2.13 (1.47-3.07) for total VTE, 2.07 (1.17-3.67) for unprovoked VTE and 2.16 (1.33-3.50) for provoked VTE. Those with incident gout had a nonsignificantly increased risk of total VTE [HR (95% CI): 1.33 (0.95-1.86)]. CONCLUSIONS: Elevated SUA was associated with an increased risk of VTE, suggesting that SUA might be a novel risk factor or marker for VTE. Further studies are needed to assess the association between gout and VTE.

14 Article Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment. 2016

Saag, Kenneth G / Whelton, Andrew / Becker, Michael A / MacDonald, Patricia / Hunt, Barbara / Gunawardhana, Lhanoo. ·Birmingham VA Medical Center, Birmingham, Alabama, and University of Alabama at Birmingham. · Johns Hopkins University, Baltimore, Maryland. · University of Chicago Pritzker School of Medicine, Chicago, Illinois. · Takeda Pharmaceuticals, Deerfield, Illinois. ·Arthritis Rheumatol · Pubmed #26894653.

ABSTRACT: OBJECTIVE: Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ). METHODS: Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12. RESULTS: At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses. CONCLUSION: Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function.

15 Article Dual-energy computed tomography has limited sensitivity for non-tophaceous gout: a comparison study with tophaceous gout. 2016

Baer, Alan N / Kurano, Tracie / Thakur, Uma J / Thawait, Gaurav K / Fuld, Matthew K / Maynard, Janet W / McAdams-DeMarco, Mara / Fishman, Elliot K / Carrino, John A. ·Department of Medicine (Rheumatology), Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Suite 4000, Mason Lord Center Tower, Baltimore, MD, 21224, USA. alanbaer@jhmi.edu. · Department of Medicine (Rheumatology), Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Suite 4000, Mason Lord Center Tower, Baltimore, MD, 21224, USA. tkurano@gmail.com. · Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. uma.j.thakur@gmail.com. · Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. gthawai1@jhmi.edu. · Siemens Medical Solutions USA Inc., Malvern, PA, USA. matthew.fuld@siemens.edu. · Department of Medicine (Rheumatology), Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Suite 4000, Mason Lord Center Tower, Baltimore, MD, 21224, USA. janetmaynard@gmail.com. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. mara@jhu.edu. · Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. efishman@jhmi.edu. · Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. carrinoj@hss.edu. ·BMC Musculoskelet Disord · Pubmed #26891750.

ABSTRACT: BACKGROUND: Dual-energy computed tomography (DECT) is a new diagnostic tool for gout, but its sensitivity has not been established. Our goal was to assess the sensitivity of DECT for the detection of monosodium urate (MSU) deposits in non-tophaceous and tophaceous gout, both at the level of the patient and that of the individual joint or lesion. METHODS: DECT was performed on 11 patients with crystal-proven non-tophaceous gout and 10 with tophaceous gout and included both the upper and lower extremities in 20/21 patients. DECT images were simultaneously acquired at 80 and 140 kV and then processed on a workstation with proprietary software using a two-material decomposition algorithm. MSU deposits were color coded as green by the software and fused onto grey-scale CT images. The number and location of these deposits was tallied independently by two DECT-trained radiologists blinded to the clinical characteristics of the patient. Sensitivity of DECT was defined as the proportion of patients with a confirmed diagnosis of gout which was correctly identified as such by the imaging technique. All patients provided informed consent to participate in this IRB-approved study. RESULTS: MSU deposits were detected by DECT in ≥1 joint area in 7/11 (64 %) patients with non-tophaceous gout, but were only detected in 3/12 (25 %) joints proven by aspiration to be affected with gout. Inclusion of the upper extremity joints in the scanning protocol did not improve sensitivity. All 10 patients with tophaceous gout had MSU deposits evident by DECT. The sensitivity of DECT for individual gouty erosions was assessed in 3 patients with extensive foot involvement. MSU deposits were detected by DECT within or immediately adjacent to 13/26 (50 %) erosions. CONCLUSIONS: A DECT protocol that includes all lower extremity joints has moderate sensitivity in non-tophaceous and high sensitivity in tophaceous gout. However, DECT has lower sensitivity when restricted to individual crystal-proven gouty joints in non-tophaceous disease or individual erosive lesions in tophaceous gout. The detection of MSU deposits by DECT relates to their size and density and the detection parameters of the DECT scanner and adjustment of the latter might improve sensitivity.

16 Article Gout in Older Adults: The Atherosclerosis Risk in Communities Study. 2016

Burke, Bridget Teevan / Köttgen, Anna / Law, Andrew / Grams, Morgan / Baer, Alan N / Coresh, Josef / McAdams-DeMarco, Mara A. ·Department of Epidemiology, JHU Bloomberg School of Public Health, Baltimore, Maryland. · Department of Epidemiology, JHU Bloomberg School of Public Health, Baltimore, Maryland. Division of Nephrology, University Medical Center Freiburg, Germany. · Department of Surgery. · Division of Nephrology, and. · Division of Rheumatology, JHU School of Medicine, Baltimore, Maryland. · Department of Epidemiology, JHU Bloomberg School of Public Health, Baltimore, Maryland. Department of Surgery, mara@jhu.edu. ·J Gerontol A Biol Sci Med Sci · Pubmed #26714568.

ABSTRACT: BACKGROUND: It is unclear whether traditional and genetic risk factors in middle age predict the onset of gout in older age. METHODS: We studied the incidence of gout in older adults using the Atherosclerosis Risk in Communities study, a prospective U.S. population-based cohort of middle-aged adults enrolled between 1987 and 1989 with ongoing follow-up. A genetic urate score was formed from common urate-associated single nucleotide polymorphisms for eight genes. The adjusted hazard ratio and 95% confidence interval of incident gout by traditional and genetic risk factors in middle age were estimated using a Cox proportional hazards model. RESULTS: The cumulative incidence from middle age to age 65 was 8.6% in men and 2.5% in women; by age 75 the cumulative incidence was 11.8% and 5.0%. In middle age, increased adiposity, beer intake, protein intake, smoking status, hypertension, diuretic use, and kidney function (but not sex) were associated with an increased gout risk in older age. In addition, a 100 µmol/L increase in genetic urate score was associated with a 3.29-fold (95% confidence interval: 1.63-6.63) increased gout risk in older age. CONCLUSIONS: These findings suggest that traditional and genetic risk factors in middle age may be useful for identifying those at risk of gout in older age.

17 Article Physical Function, Hyperuricemia, and Gout in Older Adults. 2015

Burke, Bridget Teevan / Köttgen, Anna / Law, Andrew / Windham, Beverly Gwen / Segev, Dorry / Baer, Alan N / Coresh, Josef / McAdams-DeMarco, Mara A. ·Johns Hopkins University, Baltimore, Maryland. · Johns Hopkins University, Baltimore, Maryland, and University of Freiburg, Freiburg, Germany. · University of Mississippi Medical Center, Jackson. ·Arthritis Care Res (Hoboken) · Pubmed #26138016.

ABSTRACT: OBJECTIVE: Gout prevalence is high in older adults and those affected are at risk of physical disability, yet it is unclear whether they have worse physical function. METHODS: We studied gout, hyperuricemia, and physical function in 5,819 older adults (age ≥65 years) attending the 2011-2013 Atherosclerosis Risk in Communities Study visit, a prospective US population-based cohort. Differences in lower extremity function (Short Physical Performance Battery [SPPB] and 4-meter walking speed) and upper extremity function (grip strength) by gout status and by hyperuricemia prevalence were estimated in adjusted ordinal logistic regression (SPPB) and linear regression (walking speed and grip strength) models. Lower scores or times signify worse function. The prevalence of poor physical performance (first quartile) by gout and hyperuricemia was estimated using adjusted modified Poisson regression. RESULTS: Ten percent of participants reported a history of gout and 21% had hyperuricemia. There was no difference in grip strength by history of gout (P = 0.77). Participants with gout performed worse on the SPPB test; they had 0.77 times (95% confidence interval [95% CI] 0.65, 0.90, P = 0.001) the prevalence odds of a 1-unit increase in SPPB score and were 1.18 times (95% CI 1.07, 1.32, P = 0.002) more likely to have poor SPPB performance. Participants with a history of gout had slower walking speed (mean difference -0.03; 95% CI -0.05, -0.01, P < 0.001) and were 1.19 times (95% CI 1.06, 1.34, P = 0.003) more likely to have poor walking speed. Similarly, SPPB score and walking speed, but not grip strength, were worse in participants with hyperuricemia. CONCLUSION: Older adults with gout and hyperuricemia are more likely to have worse lower extremity, but not upper extremity, function.

18 Article Modulation of genetic associations with serum urate levels by body-mass-index in humans. 2015

Huffman, Jennifer E / Albrecht, Eva / Teumer, Alexander / Mangino, Massimo / Kapur, Karen / Johnson, Toby / Kutalik, Zoltán / Pirastu, Nicola / Pistis, Giorgio / Lopez, Lorna M / Haller, Toomas / Salo, Perttu / Goel, Anuj / Li, Man / Tanaka, Toshiko / Dehghan, Abbas / Ruggiero, Daniela / Malerba, Giovanni / Smith, Albert V / Nolte, Ilja M / Portas, Laura / Phipps-Green, Amanda / Boteva, Lora / Navarro, Pau / Johansson, Asa / Hicks, Andrew A / Polasek, Ozren / Esko, Tõnu / Peden, John F / Harris, Sarah E / Murgia, Federico / Wild, Sarah H / Tenesa, Albert / Tin, Adrienne / Mihailov, Evelin / Grotevendt, Anne / Gislason, Gauti K / Coresh, Josef / D'Adamo, Pio / Ulivi, Sheila / Vollenweider, Peter / Waeber, Gerard / Campbell, Susan / Kolcic, Ivana / Fisher, Krista / Viigimaa, Margus / Metter, Jeffrey E / Masciullo, Corrado / Trabetti, Elisabetta / Bombieri, Cristina / Sorice, Rossella / Döring, Angela / Reischl, Eva / Strauch, Konstantin / Hofman, Albert / Uitterlinden, Andre G / Waldenberger, Melanie / Wichmann, H-Erich / Davies, Gail / Gow, Alan J / Dalbeth, Nicola / Stamp, Lisa / Smit, Johannes H / Kirin, Mirna / Nagaraja, Ramaiah / Nauck, Matthias / Schurmann, Claudia / Budde, Kathrin / Farrington, Susan M / Theodoratou, Evropi / Jula, Antti / Salomaa, Veikko / Sala, Cinzia / Hengstenberg, Christian / Burnier, Michel / Mägi, Reedik / Klopp, Norman / Kloiber, Stefan / Schipf, Sabine / Ripatti, Samuli / Cabras, Stefano / Soranzo, Nicole / Homuth, Georg / Nutile, Teresa / Munroe, Patricia B / Hastie, Nicholas / Campbell, Harry / Rudan, Igor / Cabrera, Claudia / Haley, Chris / Franco, Oscar H / Merriman, Tony R / Gudnason, Vilmundur / Pirastu, Mario / Penninx, Brenda W / Snieder, Harold / Metspalu, Andres / Ciullo, Marina / Pramstaller, Peter P / van Duijn, Cornelia M / Ferrucci, Luigi / Gambaro, Giovanni / Deary, Ian J / Dunlop, Malcolm G / Wilson, James F / Gasparini, Paolo / Gyllensten, Ulf / Spector, Tim D / Wright, Alan F / Hayward, Caroline / Watkins, Hugh / Perola, Markus / Bochud, Murielle / Kao, W H Linda / Caulfield, Mark / Toniolo, Daniela / Völzke, Henry / Gieger, Christian / Köttgen, Anna / Vitart, Veronique. ·Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom. · Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany. · King's College London, St. Thomas' Hospital Campus, London, United Kingdom. · Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland. · William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. · Institute for Maternal and Child Health-Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) "Burlo Garofolo", Trieste, Italy; University of Trieste, Trieste, Italy. · Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy. · Department of Psychology, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland. · Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America. · Clinical Research Branch, National Institute on Aging, Baltimore, MD, United States of America. · Member of Netherlands Consortium for Healthy Aging (NCHA) sponsored by Netherlands Genomics Initiative (NGI), Leiden, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. · Institute of Genetics and Biophysics "A. Buzzati-Traverso"-Consiglio Nazionale delle Ricerche (CNR), Naples, Italy. · Biology and Genetics section, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy. · Icelandic Heart Association Research Institute, Kopavogur, Iceland; University of Iceland, Reykjavik, Iceland. · Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. · Institute of Population Genetics, National Research Council of Italy, Sassari, Italy. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Uppsala Clinical Research Center, Uppsala University Hospital, Upsalla, Sweden; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden. · Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy; Affiliated Institute of the University of Lübeck, Lübeck, Germany. · Faculty of Medicine, University of Split, Croatia, Soltanska 2, Split, 21000, Croatia. · Estonian Genome Center, University of Tartu, Tartu, Estonia; Broad Institute, Cambridge, MA, United States of America; Children's Hospital Boston, Boston, MA, United States of America. · Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom; Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom. · Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom. · Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Edinburgh, United Kingdom; Roslin Institute, The University of Edinburgh, Edinburgh, United Kingdom. · Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany. · Icelandic Heart Association Research Institute, Kopavogur, Iceland. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Welch Center for Prevention, Epidemiology and Clinical Research, John Hopkins University, Baltimore, MD, United States of America. · Institute for Maternal and Child Health-Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) "Burlo Garofolo", Trieste, Italy. · Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland. · Tallinn University of Technology, Department of Biomedical Engineering, Chair of Medical Physics, Tallinn, Estonia; Centre of Cardiology, North Estonia Medical Centre, Tallinn, Estonia. · Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-University, Munich, Germany. · Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-University, Munich, Germany; Klinikum Grosshadern, Munich, Germany. · Bone and Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Medicine, University of Otago, Christchurch, New Zealand. · Department of Psychiatry/EMGO Institute, VU University Medical Centre, Amsterdam, the Netherlands. · Laboratory of Genetics, National Institute on Aging (NIA), Baltimore, MD, United States of America. · Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Turku, Finland. · University Hospital Regensburg, Regensburg, Germany. · Department of Medicine, Nephrology Division, Lausanne University Hospital, Lausanne, Switzerland. · Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-University, Munich, Germany. · Max Planck Institute of Psychiatry, Munich, Germany. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Turku, Finland; Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom; University of Helsinki, Institute of Molecular Medicine, Helsinki, Finland. · Department of Mathematics and Informatics, Università di Cagliari, Cagliari, Italy; Department of Statistics, Universidad Carlos III de Madrid, Madrid, Spain. · Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom. · Faculty of Medicine, University of Split, Croatia, Soltanska 2, Split, 21000, Croatia; Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom. · Queen Mary, University of London, London, United Kingdom. · Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands; Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. · Department of Epidemiology, Subdivision Genetic Epidemiology, Erasmus MC, Rotterdam, The Netherlands. · Institute of Internal Medicine, Renal Program, Columbus-Gemelli University Hospital, Catholic University, Rome, Italy. · Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden. · on behalf of PROCARDIS; Department of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. · Estonian Genome Center, University of Tartu, Tartu, Estonia; Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland; University of Helsinki, Institute of Molecular Medicine, Helsinki, Finland. · University Institute of Social and Preventive Medicine, Lausanne, Switzerland. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America; Renal Division, Freiburg University Hospital, Freiburg, Germany. ·PLoS One · Pubmed #25811787.

ABSTRACT: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

19 Article Plasma Urate and Risk of a Hospital Stay with AKI: The Atherosclerosis Risk in Communities Study. 2015

Greenberg, Keiko I / McAdams-DeMarco, Mara A / Köttgen, Anna / Appel, Lawrence J / Coresh, Josef / Grams, Morgan E. ·Departments of Medicine and kgreenb4@jhmi.edu. · Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; · Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Renal Division, University Medical Center Freiburg, Freiburg, Germany; and. · Departments of Medicine and Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland. · Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland. ·Clin J Am Soc Nephrol · Pubmed #25717072.

ABSTRACT: BACKGROUND AND OBJECTIVES: Higher urate levels are associated with higher risk of CKD, but the association between urate and AKI is less established. This study evaluated the risk of hospitalized AKI associated with urate concentrations in a large population-based cohort. To explore whether urate itself causes kidney injury, the study also evaluated the relationship between a genetic urate score and AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 11,011 participants from the Atherosclerosis Risk in Communities study were followed from 1996-1998 (baseline) to 2010. The association between baseline plasma urate and risk of hospitalized AKI, adjusted for known AKI risk factors, was determined using Cox regression. Interactions of urate with gout and CKD were tested. Mendelian randomization was performed using a published genetic urate score among the participants with genetic data (n=7553). RESULTS: During 12 years of follow-up, 823 participants were hospitalized with AKI. Overall, mean participant age was 63.3 years, mean eGFR was 86.3 ml/min per 1.73 m(2), and mean plasma urate was 5.6 mg/dl. In patients with plasma urate >5.0 mg/dl, there was a 16% higher risk of hospitalized AKI for each 1-mg/dl higher urate (adjusted hazard ratio, 1.16; 95% confidence interval, 1.10 to 1.23; P<0.001). When stratified by history of gout, the association between higher urate and AKI was significant only in participants without a history of gout (P for interaction=0.02). There was no interaction of CKD and urate with AKI, nor was there an association between genetic urate score and AKI. CONCLUSIONS: Plasma urate >5.0 mg/dl was independently associated with risk of hospitalized AKI; however, Mendelian randomization did not provide evidence for a causal role of urate in AKI. Further research is needed to determine whether lowering plasma urate might reduce AKI risk.

20 Article Arsenic exposure, hyperuricemia, and gout in US adults. 2015

Kuo, Chin-Chi / Weaver, Virginia / Fadrowski, Jeffrey J / Lin, Yu-Sheng / Guallar, Eliseo / Navas-Acien, Ana. ·Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Kidney Institute and Division of Nephrology, Department of Internal Medicine, China Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan. · Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Pediatric Nephrology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Environmental and Occupational Health, University of North Texas Health Science Center, Fort Worth, TX, USA. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA. ·Environ Int · Pubmed #25499256.

ABSTRACT: BACKGROUND: There is very limited information on the association between arsenic and serum uric acid levels or gout. The aim of this study was to investigate the association of arsenic with hyperuricemia and gout in US adults. METHODS: A cross-sectional study was conducted in 5632 adults aged 20years or older from the National Health and Nutrition Examination Survey (NHANES) 2003-2010 with determinations of serum uric acid and urine total arsenic and dimethylarsinate (DMA). Hyperuricemia was defined as serum uric acid higher than 7.0mg/dL for men and 6.0mg/dL for women. Gout was defined based on self-reported physician diagnosis and medication use. RESULTS: After adjustment for sociodemographic factors, comorbidities and arsenobetaine levels, the increase in the geometric means of serum uric acid associated with one interquartile range increase in total arsenic and DMA levels was 3% (95% CI 2-5) and 3% (2-5), respectively, in men and 1% (0-3) and 2% (0-4), respectively, in women. In men, the adjusted odds ratio for hyperuricemia comparing the highest to lowest quartiles of total arsenic was 1.84 (95% CI, 1.26-2.68) and for DMA it was 1.41 (95% CI, 1.01-1.96). The corresponding odds ratios in women were 1.26 (0.77, 2.07) and 1.49 (0.96, 2.31), respectively. The odds ratio for gout comparing the highest to lowest tertiles was 5.46 (95% CI, 1.70-17.6) for total arsenic and 1.98 (0.64-6.15) for DMA among women older than 40years old. Urine arsenic was not associated with gout in men. CONCLUSION: Low level arsenic exposures may be associated with the risk of hyperuricemia in men and with the prevalence of gout in women. Prospective research focusing on establishing the direction of the relationship among arsenic, hyperuricemia, and gout is needed.

21 Article Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study. 2015

Jing, Jiaojiao / Kielstein, Jan T / Schultheiss, Ulla T / Sitter, Thomas / Titze, Stephanie I / Schaeffner, Elke S / McAdams-DeMarco, Mara / Kronenberg, Florian / Eckardt, Kai-Uwe / Köttgen, Anna / Anonymous6300811. ·Renal Division, Medical Center-University of Freiburg, Freiburg, Germany. · Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany. · Department of Medicine, Ludwig-Maximilians-University Hospital, Munich, Germany. · Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany. · Division of Nephrology and Intensive Care Medicine, Charité University Medicine, Berlin, Germany. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. · Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria. ·Nephrol Dial Transplant · Pubmed #25395390.

ABSTRACT: BACKGROUND: Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. METHODS: Data from 5085 CKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of 30-<60 mL/min/1.73 m(2) or eGFR ≥60 and overt proteinuria at recruitment and non-missing values for self-reported gout, medications and urate measurements from a central laboratory were evaluated. RESULTS: The overall prevalence of gout was 24.3%, and increased from 16.0% in those with eGFR ≥60 mL/min/1.73 m(2) to 35.6% in those with eGFR <30. Of those with self-reported gout, 30.7% of individuals were not currently taking any gout medication and among gout patients on urate lowering therapy, 47.2% still showed hyperuricaemia. Factors associated with gout were serum urate, lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip ratio, higher triglyceride and C-reactive protein (CRP) concentrations, alcohol intake and diuretics use. While lower eGFR categories showed significant associations with gout in multivariable-adjusted models (prevalence ratio 1.46 for eGFR <30 compared with eGFR ≥60, 95% confidence interval 1.21-1.77), associations between gout and higher urinary albumin-to-creatinine ratio in this CKD population were not significant. CONCLUSIONS: Self-reported gout is common among patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study.

22 Article Gout, urate-lowering therapy, and uric acid levels among adults in the United States. 2015

Juraschek, Stephen P / Kovell, Lara C / Miller, Edgar R / Gelber, Allan C. ·Johns Hopkins Bloomberg School of Public Health, Welch Center for Prevention, Epidemiology and Clinical Research, and Johns Hopkins University School of Medicine, Baltimore, Maryland. ·Arthritis Care Res (Hoboken) · Pubmed #25201123.

ABSTRACT: OBJECTIVE: Evidence strongly suggests that delivery of gout care is suboptimal. The 2012 American College of Rheumatology (ACR) guidelines emphasize a serum uric acid (SUA) target of <6 mg/dl when utilizing urate-lowering therapy (ULT). However, the proportion and characteristics of Americans with gout receiving ULT, or with a ULT indication, who are achieving this target is unknown. METHODS: We identified US adults with gout receiving ULT, and those with an indication for ULT, using the National Health and Nutrition Examination Surveys from 2007-2010. Using the ACR guidelines, a ULT indication comprised chronic kidney disease (CKD) stage 2-5, a history of nephrolithiasis, or current ULT use. Demographic and clinical factors associated with an SUA ≥6 mg/dl were determined using Poisson regression. RESULTS: In 2007-2010, an estimated 4.5 million US adults with gout had an indication for ULT; two-thirds had an SUA ≥6 mg/dl. In adjusted analyses among those with gout and CKD or nephrolithiasis, those age ≥70 years were less likely (prevalence ratio [PR] 0.77, 95% confidence interval [95% CI] 0.61-0.97) to have an SUA ≥6 mg/dl. Regarding those taking ULT, hypertension was related to a reduced prevalence (PR 0.51, 95% CI 0.30-0.87), whereas diabetes mellitus (PR 1.42, 95% CI 1.06-1.90) and obesity (PR 1.74, 95% CI 1.19-2.56) were each associated with a higher prevalence of an SUA value ≥6 mg/dl. CONCLUSION: Half of all Americans with gout receiving ULT, and two-thirds with an indication for ULT, have an SUA above target. This study furnishes a meaningful baseline for assessing the effectiveness of the ACR guidelines in future years.

23 Article Gout-causing Q141K mutation in ABCG2 leads to instability of the nucleotide-binding domain and can be corrected with small molecules. 2013

Woodward, Owen M / Tukaye, Deepali N / Cui, Jinming / Greenwell, Patrick / Constantoulakis, Leeza M / Parker, Benjamin S / Rao, Anjana / Köttgen, Michael / Maloney, Peter C / Guggino, William B. ·Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. owenw@jhmi.edu ·Proc Natl Acad Sci U S A · Pubmed #23493553.

ABSTRACT: The multidrug ATP-binding cassette, subfamily G, 2 (ABCG2) transporter was recently identified as an important human urate transporter, and a common mutation, a Gln to Lys substitution at position 141 (Q141K), was shown to cause hyperuricemia and gout. The nature of the Q141K defect, however, remains undefined. Here we explore the Q141K ABCG2 mutation using a comparative approach, contrasting it with another disease-causing mutation in an ABC transporter, the deletion of Phe-508 (ΔF508) in the cystic fibrosis transmembrane conductance regulator (CFTR). We found, much like in ΔF508 CFTR, that the Q141K mutation leads to instability in the nucleotide-binding domain (NBD), a defect that translates to significantly decreased protein expression. However, unlike the CFTR mutant, the Q141K mutation does not interfere with the nucleotide-binding domain/intracellular loop interactions. This investigation has also led to the identification of critical residues involved in the protein-protein interactions necessary for the dimerization of ABCG2: Lys-473 (K473) and Phe-142 (F142). Finally, we have demonstrated the utility of using small molecules to correct the Q141K defect in expression and function as a possible therapeutic approach for hyperuricemia and gout.

24 Article Dose-response association of uncontrolled blood pressure and cardiovascular disease risk factors with hyperuricemia and gout. 2013

Juraschek, Stephen P / Kovell, Lara C / Miller, Edgar R / Gelber, Allan C. ·Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. ·PLoS One · Pubmed #23460805.

ABSTRACT: BACKGROUND: First-line therapy of hypertension includes diuretics, known to exert a multiplicative increase on the risk of gout. Detailed insight into the underlying prevalence of hyperuricemia and gout in persons with uncontrolled blood pressure (BP) and common comorbidities is informative to practitioners initiating antihypertensive agents. We quantify the prevalence of hyperuricemia and gout in persons with uncontrolled BP and additional cardiovascular disease (CVD) risk factors. METHODS AND FINDINGS: We performed a cross-sectional study of non-institutionalized US adults, 18 years and older, using the National Health and Nutrition Examination Surveys in 1988-1994 and 1999-2010. Hyperuricemia was defined as serum uric acid >6.0 mg/dL in women; >7.0 mg/dL in men. Gout was ascertained by self-report of physician-diagnosed gout. Uncontrolled BP was based on measured systolic BP≥140 mmHg and diastolic BP≥90 mmHg. Additional CVD risk factors included obesity, reduced glomerular filtration rate, and dyslipidemia. The prevalence of hyperuricemia was 6-8% among healthy US adults, 10-15% among adults with uncontrolled BP, 22-25% with uncontrolled BP and one additional CVD risk factor, and 34-37% with uncontrolled BP and two additional CVD risk factors. Similarly, the prevalence of gout was successively greater, at 1-2%, 4-5%, 6-8%, and 8-12%, respectively, across these same health status categories. In 2007-2010, those with uncontrolled BP and 2 additional CVD risk factors compared to those without CVD risk factors had prevalence ratios of 4.5 (95% CI 3.5-5.6) and 4.5 (95% CI: 3.1-6.3) for hyperuricemia and gout respectively (P<0.01). CONCLUSIONS: Health care providers should be cognizant of the incrementally higher prevalence of hyperuricemia and gout among patients with uncontrolled BP and additional CVD risk factors. With one in three people affected by hyperuricemia among those with several CVD risk factors, physicians should consider their anti-hypertensive regimens carefully and potentially screen for hyperuricemia or gout.

25 Article Association of kidney disease with prevalent gout in the United States in 1988-1994 and 2007-2010. 2013

Juraschek, Stephen P / Kovell, Lara C / Miller, Edgar R / Gelber, Allan C. ·Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. ·Semin Arthritis Rheum · Pubmed #23312548.

ABSTRACT: OBJECTIVE: To determine the prevalence of gout associated with progressive degrees of kidney disease in the US population. METHODS: We performed a cross-sectional analysis among non-institutionalized adults (age 20 and older) of the National Health and Nutrition Examination Surveys in 1988-1994 and 2007-2010. Gout status was ascertained by self-report of physician-diagnosed gout. Chronic kidney disease (CKD) was defined in stages based on estimated glomerular filtration rate (GFR) and single albuminuria measurements (albumin-to-creatinine ratio). Prevalence ratios comparing successive categories of GFR, albuminuria, and CKD as well as temporal trends over a 22-year interval were determined via Poisson regression. RESULTS: In the US, the crude prevalence of gout was 2-3% among participants without CKD, 4% among participants with CKD stage 1, 6-10% for stage 2, 11-13% for stage 3, and over 30% for stage 4. The adjusted prevalence ratio comparing the CKD stage 4 stratum to participants without CKD was 3.20 (95% CI: 1.96, 5.24) in 2007-2010 and remained significant even after adjustment for serum uric acid. Notably, there was a statistically significant, progressively greater adjusted prevalence ratio of gout associated with successively lower categories of GFR and higher categories of albuminuria. CONCLUSIONS: Among US adults, there exists a strong dose-response association between impaired renal function and prevalent gout. Health providers should be aware of the elevated burden of gout among patients with CKD especially when evaluating new onset joint pain and swelling.

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