Istvan Mucsi

Bio: Istvan Mucsi is an academic researcher from University Health Network. The author has contributed to research in topics: Kidney disease & Kidney transplantation. The author has an hindex of 42, co-authored 185 publications receiving 6358 citations. Previous affiliations of Istvan Mucsi include McGill University Health Centre & Semmelweis University.

Elevated Fibroblast Growth Factor 23 is a Risk Factor for Kidney Transplant Loss and Mortality

Abstract: An increased circulating level of fibroblast growth factor 23 (FGF23) is an independent risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease (CKD), but its role in transplant allograft and patient survival is unknown. We tested the hypothesis that increased FGF23 is an independent risk factor for all-cause mortality and allograft loss in a prospective cohort of 984 stable kidney transplant recipients. At enrollment, estimated GFR (eGFR) was 51 ± 21 ml/min per 1.73 m2 and median C-terminal FGF23 was 28 RU/ml (interquartile range, 20 to 43 RU/ml). Higher FGF23 levels independently associated with increased risk of the composite outcome of all-cause mortality and allograft loss (full model hazard ratio: 1.46 per SD increase in logFGF23, 95% confidence interval: 1.28 to 1.68, P < 0.001). The results were similar for each component of the composite outcome and in all sensitivity analyses, including prespecified analyses of patients with baseline eGFR of 30 to 90 ml/min per 1.73 m2. In contrast, other measures of phosphorus metabolism, including serum phosphate and parathyroid hormone (PTH) levels, did not consistently associate with outcomes. We conclude that a high (or elevated) FGF23 is an independent risk factor for death and allograft loss in kidney transplant recipients.

Central role for Rho in TGF-β1-induced α-smooth muscle actin expression during epithelial-mesenchymal transition

Abstract: New research suggests that, during tubulointerstitial fibrosis, α-smooth muscle actin (SMA)-expressing mesenchymal cells might derive from the tubular epithelium via epithelial-mesenchymal transiti...

Integrity of Cell-Cell Contacts Is a Critical Regulator of TGF-β1-Induced Epithelial-to-Myofibroblast Transition : Role for β-Catenin

Abstract: Injury of the tubular epithelium and TGF-β1-induced conversion of epithelial cells to α-smooth muscle actin (SMA)-expressing myofibroblasts are key features of kidney fibrosis. Since injury damages intercellular junctions and promotes fibrosis, we hypothesized that cell contacts are critical regulators of TGF-β1-triggered epithelial-to-mesenchymal transition (EMT). Here we show that TGF-β1 was unable to induce EMT in intact confluent monolayers, but three different models of injury-induced loss of epithelial integrity (subconfluence, wounding, and contact disassembly by Ca2+-removal) restored its EMT-inducing effect. This manifested in loss of E-cadherin, increased fibronectin production and SMA expression. TGF-β1 or contact disassembly alone only modestly stimulated the SMA promoter in confluent layers, but together exhibited strong synergy. Since β-catenin is a component of intact adherens junctions, but when liberated from destabilized contacts may act as a transcriptional co-activator, we investigated its role in TGF-β1-provoked EMT. Contact disassembly alone induced degradation of E-cadherin and β-catenin, but TGF-β1 selectively rescued β-catenin and stimulated the β-catenin-driven reporter TopFLASH. Moreover, chelation of free β-catenin with the N-cadherin cytoplasmic tail suppressed the TGF-β1 plus contact disassembly-induced SMA promoter activation and protein expression. These results suggest a β-catenin-dependent two-hit mechanism in which both an initial epithelial injury and TGF-β1 are required for EMT.

Restless legs syndrome, insomnia and quality of life in patients on maintenance dialysis

Abstract: Background. In a cross-sectional study, we analysed the complex relationship between restless legs syndrome (RLS), insomnia and specific insomnia symptoms and health-related quality of life (QoL) in patients on maintenance dialysis. Methods. Data were obtained from 333 patients on chronic maintenance dialysis. To assess the prevalence of RLS, we used the RLS Questionnaire (RLSQ). The Athens Insomnia Scale (AIS) was used to assess insomnia and QoL was measured with the Kidney Disease Quality-of-Life Questionnaire. Results. The prevalence of RLS was 14%. The number of comorbid conditions was significantly higher in patients with vs without RLS (median: three vs two; P<0.05). RLS patients were twice as likely to have significant insomnia as patients without RLS (35% vs 16%; P<0.05). Furthermore, RLS was associated with impaired overall sleep quality (median AIS score: 8 vs 4; P<0.01) and poorer QoL. RLS was a significant and independent predictor of several of the QoL domains after statistical adjustment for clinical and socio-demographic covariables. Importantly, this association remained significant even after adjusting for sleep quality. Conclusions. RLS is associated with poor sleep, increased odds for insomnia and impaired QoL in patients on maintenance dialysis. Based on the present results, we suggest that both sleep-related and sleep-independent factors may confer the effect of RLS on QoL.

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

Abstract: WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Blaha, MD, MPH Stephanie E. Chiuve, ScD Mary Cushman, MD, MSc, FAHA Sandeep R. Das, MD, MPH, FAHA Rajat Deo, MD, MTR Sarah D. de Ferranti, MD, MPH James Floyd, MD, MS Myriam Fornage, PhD, FAHA Cathleen Gillespie, MS Carmen R. Isasi, MD, PhD, FAHA Monik C. Jiménez, ScD, SM Lori Chaffin Jordan, MD, PhD Suzanne E. Judd, PhD Daniel Lackland, DrPH, FAHA Judith H. Lichtman, PhD, MPH, FAHA Lynda Lisabeth, PhD, MPH, FAHA Simin Liu, MD, ScD, FAHA Chris T. Longenecker, MD Rachel H. Mackey, PhD, MPH, FAHA Kunihiro Matsushita, MD, PhD, FAHA Dariush Mozaffarian, MD, DrPH, FAHA Michael E. Mussolino, PhD, FAHA Khurram Nasir, MD, MPH, FAHA Robert W. Neumar, MD, PhD, FAHA Latha Palaniappan, MD, MS, FAHA Dilip K. Pandey, MBBS, MS, PhD, FAHA Ravi R. Thiagarajan, MD, MPH Mathew J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Rodriguez, MD, MPH, FAHA Gregory A. Roth, MD, MPH Wayne D. Rosamond, PhD, FAHA Comilla Sasson, MD, PhD, FAHA Amytis Towfighi, MD Connie W. Tsao, MD, MPH Melanie B. Turner, MPH Salim S. Virani, MD, PhD, FAHA Jenifer H. Voeks, PhD Joshua Z. Willey, MD, MS John T. Wilkins, MD Jason HY. Wu, MSc, PhD, FAHA Heather M. Alger, PhD Sally S. Wong, PhD, RD, CDN, FAHA Paul Muntner, PhD, MHSc On behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2017 Update

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

Abstract: March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Abstract: Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.