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Hemodialysis.com. Hemodialysis research, author interviews, dialysis updates and information on chronic kidney disease and end stage renal failure. Editor: Marie Benz, MD [email protected] December 1 5 2012 For Informational Purposes Only: Not for Specific Medical Advice.

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Hemodialysis com

Hemodialysis.com

Hemodialysis research, author interviews, dialysis updates and information on chronic kidney disease and end stage renal failure.

Editor: Marie Benz, [email protected]

December 15 2012

For Informational Purposes Only: Not for Specific Medical Advice.

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Hemodialysis com interviews december 6 16 2012

Hemodialysis.com InterviewsDecember 6-16 2012

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Medical disclaimer terms and conditions

Medical Disclaimer | Terms and Conditions

  • The contents of the Hemodialysis.com Site, such as text, graphics, images, and other material contained on the Hemodialysis.com Site ("Content") are for informational purposes only. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on the Hemodialysis.com Site!

  • If you think you may have a medical emergency, call your doctor or 911 immediately. Hemodialysis.com does not recommend or endorse any specific tests, physicians, products, procedures, opinions, or other information that may be mentioned on the Site. Reliance on any information provided by Hemodialysis.com or other Eminent Domains Inc (EDI) websites, EDI employees, others appearing on the Site at the invitation of Hemodialysis.com or EDI, or other visitors to the Site is solely at your own risk.

  • The Site may contain health- or medical-related materials that are sexually explicit. If you find these materials offensive, you may not want to use our Site. The Site and the Content are provided on an "as is" basis.

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Hemodialysis com

Local Complement-Targeted Intervention in Periodontitis: Proof-of-Concept Using a C5a Receptor (CD88) AntagonistHemodialysis.com Author Interview: George Hajishengallis, D.D.S., Ph.D.Professor, Dept. of Microbiology University of Pennsylvania School of Dental Medicine

  • Hemodialysis.com Editor Marie Benz: What are the main findings of the study?

  • Our study showed that the complement system synergizes with Toll-like receptors to induce destructive inflammation in the periodontal tissue. Specifically, maximal inflammation in preclinical models of periodontitis required a crosstalk between the complement C5a receptor (C5aR) and Toll-like receptor 2 (TLR2).

  • Importantly, pharmacological blockade of just one of the receptors involved (C5aR) inhibited inflammation and the destruction of bone that supports the teeth. This treatment was applied locally in the gingiva and was effective regardless of whether the C5aR antagonist was administered in a preventive or a therapeutic mode.

  • Hemodialysis.com: Were any of the findings unexpected?

  • Since destructive inflammation and bone loss required both C5aR and TLR2, one might have expected that both receptors had to be blocked to prevent or halt the disease. However, significant inhibition of disease activity was seen by just blocking C5aR alone, indicating a true synergy between C5aR and TLR2.

  • What was completely unexpected was discovered in our previous work; C5aR does not only mediate destructive inflammation but is also hijacked by certain periodontal bacteria to escape immune clearance.

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Hemodialysis com

Local Complement-Targeted Intervention in Periodontitis: Proof-of-Concept Using a C5a Receptor (CD88) AntagonistHemodialysis.com Author Interview: George Hajishengallis, D.D.S., Ph.D.Professor, Dept. of Microbiology University of Pennsylvania School of Dental Medicine (cont)

  • Hemodialysis.com: What should clinicians and patients take away from your report? 

  • Periodontitis affects more than 47% of the U.S.  adult population, and in its most severe form, which affects 8.5% of adults, can affect systemic health. Our findings suggest that complement therapeutics may offer treatment solutions for periodontitis patients and thereby reduce their risk for associated systemic diseases.

  • Hemodialysis.com: What recommendations do you have for future research as a result of this study?  

  • A better understanding of the role of the various complement pathways in periodontitis may identify additional targets for even better treatment solutions. For instance, blocking complement activity upstream of C5aR may be more beneficial if additional pathways contribute to the disease. We are currently testing these ideas in various periodontal disease animal models and hopefully we can initiate human clinical trials in the near future.

  • Reference:

  • Local Complement-Targeted Intervention in Periodontitis: Proof-of-Concept Using a C5a Receptor (CD88) AntagonistToshiharu Abe, Kavita B. Hosur, EvlambiaHajishengallis, Edimara S. Reis, Daniel Ricklin, John D. Lambris, and George HajishengallisJ Immunol 2012 189:5442-5448; published ahead of print October 22, 2012, doi:10.4049/jimmunol.1202339

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Plasma metabolomic profiles in different stages of CKDHemodialysis.com Author Interview: Vallabh O. Shah, PhD,*   David L. Vander Jagt, PhD,* Raymond R. Townsend, MD, + Harold I. Feldman, MD+  *University of New Mexico Health Sciences Center, Albuquerque NM;  University of Pennsylvania, Perelman School of Medicine, Philadelphia PA

  • Hemodialysis.com Editor Marie Benz: What are the main findings of the study?

  • GC/LC mass spectrometry was used to assess metabolites in plasma samples from non-diabetic men, with 10 participants each in CKD stages 2, 3, and 4. Major differences in metabolite profiles with increasing stage of CKD were observed, which pointed to altered arginine metabolism and elevated coagulation/inflammation. This was based upon the observation of marked increases in dimethylarginine and fibrinopeptide-A in progression from CKD-stage 2 to CKD-stage 3. This global metabolite profiling not only identified potential stage-specific biomarkers but also provided a potential, testable hypothesis regarding progression of CKD.

  • Hemodialysis.com: Were any of the findings unexpected?

  • It was unexpected that such a small sample size would give a clear delineation of the key metabolites. Generally a much larger sample size is required.

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Hemodialysis com

Plasma metabolomic profiles in different stages of CKDHemodialysis.com Author Interview: Vallabh O. Shah, PhD,*   David L. Vander Jagt, PhD,* Raymond R. Townsend, MD, + Harold I. Feldman, MD+  *University of New Mexico Health Sciences Center, Albuquerque NM; +University of Pennsylvania, Perelman School of Medicine, Philadelphia PA (cont)

  • Hemodialysis.com: What should clinicians and patients take away from your report? 

  • This study suggests that there are distinct changes in well-defined domains that may help us to understand the graded increase in CVD risk as kidney function worsens, particularly regarding involvement of inflammation and coagulation.

  • Hemodialysis.com: What recommendations do you have for future research as a result of this study?  

  • This initial study involved only non-diabetic men with CKD and was a cross-sectional study. Future longitudinal studies should evaluate both non-diabetic and diabetic populations, should determine differences related to gender and ethnicity, and should compare all stages of CKD up to ESRD and include transplant populations.

  • Reference:

  • Plasma metabolomic profiles in different stages of CKDVallabh O. Shah, PhD,*   David L. Vander Jagt, PhD,* Raymond R. Townsend, MD, + Harold I. Feldman, MD+  *University of New Mexico Health Sciences Center, Albuquerque NM;  +University of Pennsylvania, Perelman School of Medicine, Philadelphia PA

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Hemodialysis com

Cystatin C in children on chronic hemodialysis.Hemodialysis.com Author Interview: OliveraMarsenicCouloures M.D. Pediatric Nephrology, Oklahoma University Health Sciences Center, 1200 N. Phillips Ave., Suite 14200, Oklahoma City, OK, 73104, USA

  • Hemodialysis.com Editor Marie Benz: What are the main findings of the study?

  • Our study showed that Cystatin C (CyC), and likely other middle molecules are not removed with standard low-flux HD that is routine practice in children. This increases the risk of poor outcomes. We also showed that CyC does not rise between HD and is not removed by very low residual renal function (RRF), and remains at steady-state. This suggests that its elimination in end-stage renal disease is extrarenal.

  • We also found that in absence of its removal, CyC levels increase with patient age and size.

  • Hemodialysis.com: Were any of the findings unexpected?

  • Absence of removal of CyC with high HD doses achieved in children and a discrepancy in CyC levels seen in smaller and larger anuric children.

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Hemodialysis com

Cystatin C in children on chronic hemodialysis.Hemodialysis.com Author Interview: Olivera Marsenic Couloures M.D. Pediatric Nephrology, Oklahoma University Health Sciences Center, 1200 N. Phillips Ave., Suite 14200, Oklahoma City, OK, 73104, USA(Cont.)

  • Hemodialysis.com: What should clinicians and patients take away from your report? 

  • High-flux and other more intensified HD modalities should become routine in children in order to remove larger molecules.CyC should further be investigated as a marker of adequacy of these intensified HD regimens. If using CyC for estimation of RRF, physicians should keep in mind that very low RRF does not affect CyC elimination and that in end stage disease serum CyC levels are dependant on patient age and size.

  • Hemodialysis.com: What recommendations do you have for future research as a result of this study?  

  • Our findings require confirmation on larger number of children of various ages, with both anuria and a wider range of RRF.

  • Reference:

  • Cystatin C in children on chronic hemodialysis.

  • Marsenic O, Wierenga A, Wilson DR, Anderson M, Shrivastava T, Simon GA, Beck AM, Swanson TJ, Studnicka K, Elberg D, Couloures K, Turman MA.Pediatric Nephrology, Oklahoma University Health Sciences Center, 1200 N. Phillips Ave., Suite 14200, Oklahoma City, OK, 73104, USAPediatrNephrol. 2012 Nov 21. [Epub ahead of print]

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Elevated Serum Bone Morphogenetic Protein 4 in Patients with Chronic Kidney Disease and Coronary Artery Disease.Hemodialysis.com Author Interview: T. Cooper Woods, Ph.D.Head, Laboratory of Molecular Cardiology Institute for Translational ResearchOchsner Clinic Foundation

  • Hemodialysis.com Editor Marie Benz: What are the main findings of the study?

  • Chronic Kidney Disease is associated with increased vascular calcification. We found that serum levels of an osteogenic growth factor, Bone Morphogenetic Protein-4, were elevated in subjects with both chronic kidney disease and coronary artery disease.  Furthermore, increases in serum BMP-4 levels correlated with increased coronary artery calcification.

  • Hemodialysis.com: Were any of the findings unexpected?

  • Overall, I don’t think the findings were unexpected, however given the small sample size, we were surprised at the strength of some of the associations.

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Hemodialysis com

Elevated Serum Bone Morphogenetic Protein 4 in Patients with Chronic Kidney Disease and Coronary Artery Disease.Hemodialysis.com Author Interview: T. Cooper Woods, Ph.D.Head, Laboratory of Molecular Cardiology Institute for Translational ResearchOchsner Clinic Foundation (cont)

  • Hemodialysis.com: What should clinicians and patients take away from your report? 

  • This is a small observational study that serves as a first step in examining the relationship between coronary artery disease, chronic kidney disease, and serum BMP-4.  The study alerts clinicians and patients to the potential of osteogenic factors as future targets for the diagnosis and treatment of coronary artery disease in the kidney disease population.

  • Hemodialysis.com: What recommendations do you have for future research as a result of this study?  

  • Larger prospective studies examining the relationship between serum concentrations of osteogenic factors and the extent of coronary artery disease in subjects with chronic kidney disease may lead to therapeutic or diagnostic tools for treating this high risk population.

  • Reference:

  • Elevated Serum Bone Morphogenetic Protein 4 in Patients with Chronic Kidney Disease and Coronary Artery Disease.Stahls PF 3rd, Lightell DJ Jr, Moss SC, Goldman CK, Woods TC.Department of Cardiology, Ochsner Clinic Foundation, New Orleans, LA, USA.J CardiovascTransl Res. 2012 Dec 4. [Epub ahead of print]

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Hemodialysis com

Preoperative Statin Use and Postoperative Acute Kidney InjuryHemodialysis.com Author Interview: Steven M. Brunelli, MD, MSCEHarvard Medical School, Boston, MassachusettsRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MassachusettsChanning Laboratory, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts(cont)

  • Hemodialysis.com Editor Marie Benz: What are the main findings of the study?

  • The primary finding of the study is that ongoing statin use was independently associated with 20-26% relative reduction in the risk of developing post-operative acute kidney injury.

  • Hemodialysis.com: Were any of the findings unexpected?

  • We were surprised that the benefit of statins was less among patients undergoing cardiac surgery versus other types of surgery.

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Hemodialysis com

Preoperative Statin Use and Postoperative Acute Kidney InjuryHemodialysis.com Author Interview: Steven M. Brunelli, MD, MSCEHarvard Medical School, Boston, MassachusettsRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MassachusettsChanning Laboratory, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

  • Hemodialysis.com: What should clinicians and patients take away from your report? 

  • Clinicians should be aware that these data, in association with other data suggesting ameliorative effects on other post operative complications, support the continuation of statins in the peri-operative period.

  • Hemodialysis.com: What recommendations do you have for future research as a result of this study?  

  • Future studies are needed to evaluate whether it is safe, efficacious, and efficient to initiate statins prior to surgery among patients at high risk for post-operative acute kidney injury.

  • Reference:

  • Preoperative Statin Use and Postoperative Acute Kidney InjurySteven M. Brunelli, Sushrut S. Waikar, Brian T. Bateman, Tara I. Chang, Joyce Lii, Amit X. Garg, Wolfgang C. Winkelmayer, Niteesh K. ChoudhryThe American Journal of Medicine - December 2012 (Vol. 125, Issue 12, Pages 1195-1204.e3, DOI: 10.1016/j.amjmed.2012.06.021)

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