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Presentation on theme: "Hemodialysis.com Hemodialysis research, author interviews, dialysis updates and information on chronic kidney disease and end stage renal failure. Editor:"— Presentation transcript:

1 Hemodialysis.com Hemodialysis research, author interviews, dialysis updates and information on chronic kidney disease and end stage renal failure. Editor: Marie Benz, MD info@hemodialysis.com info@hemodialysis.com January 20 2013 For Informational Purposes Only: Not for Specific Medical Advice. Read more interviews on Hemodialysis.com For Informational Purposes Only. Not for Specific Medical Advice

2 Hemodialysis.com Interviews January 20 2013 Read more interviews on Hemodialysis.com For Informational Purposes Only. Not for Specific Medical Advice

3 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. Read more interviews on Hemodialysis.com For Informational Purposes Only. Not for Specific Medical Advice

4 Social adaptability and substance abuse: Predictors of depression among hemodialysis patients? Hemodialysis.com Author Interview: Paulo Roberto Santos and Francisco Plácido Arcanjo Sobral School of Medicine Federal University of Ceará, Brazil Hemodialysis.com Editor Marie Benz: What are the main findings of the study? A composite index comprising employment status, education level, marital status, income and substance abuse was not associated with depression among end-stage renal disease patients undergoing hemodialysis. Hemodialysis.com: Were any of the findings unexpected? Yes. The index we used has been associated with morbidity and mortality among hemodialysis patients in other studies. So, we were expecting that the socioeconomic factors covered by the index could also predict depression. Our finding reinforces the idea that predictors of objective clinical outcomes and self-perceived outcomes may be quite different, depending on the group of patients. Hemodialysis.com: What should clinicians and patients take away from your report? Depression is very common among hemodialysis patients. Predictors are useful for identifying patients at risk and for early diagnosis. Based on our results, despite predicting several clinical outcomes among hemodialysis and transplanted patients, the social adaptability index is not useful to predict depression. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Socioeconomic aspects of patients are modulated by personality traits, ways of coping and social support, for example. We think that future research should focus on how modulating variables of patients interact with socioeconomic status. Moreover, we think that substance abuse among chronic disease patients is a very complex question, and deserves to be studied separately rather than as an item of a composite index. Reference: Social adaptability and substance abuse: Predictors of depression among hemodialysis patients? Santos PR, Arcanjo FP. BMC Nephrol. 2013 Jan 15;14(1):12. [Epub ahead of print] For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

5 Selecting renal replacement therapies: what do African American and non-African American patients and their familie s think others should know? A mixed methods study Hemodialysis.com Author Interview: L. Ebony Boulware, MD, MPH, FACP Associate Professor of Medicine and Epidemiology Johns Hopkins Medical Institutions Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Patients frequently selected factors pertaining to morbidity or mortality (e.g., living longer), autonomy (e.g., control over treatment schedule), treatment delivery (e.g., finding a living donor), and symptoms (e.g., feeling tired) as important to address in educational resources about renal replacement therapy selection decisions. Similar to patients, family members most frequently selected factors pertaining to the effect of RRT on patients’ morbidity or mortality, autonomy, experiences with treatment delivery, and their symptoms as important to address in educational resources. Within domains, family members sometimes chose different factors than patients. Family members also discussed the influence of renal replacement therapy selection on patients’ psychological well-being and finances more often than patients. In terms of experiences with various end stage renal disease treatments, patients with no prior experience reported that they felt it important to have educational resources address a broader range of factors compared to patients with experience on various treatments for end stage renal disease. Hemodialysis.com: Were any of the findings unexpected? In light of well-documented race differences in the types of renal replacement therapies initiated in the United States, we hypothesized that patients’ and families’ informational needs might vary by race. However, we did not detect substantial differences in participants’ reported information needs according to their race or ethnicity with the exception of African American patients and families more frequently identifying the influence of renal replacement therapy on personal relationships and finances as important factors to address relative to their non-African American counterparts. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

6 Selecting renal replacement therapies: what do African American and non-African American patients and their families think others should know? A mixed methods study Hemodialysis.com Author Interview: L. Ebony Boulware, MD, MPH, FACP Associate Professor of Medicine and Epidemiology Johns Hopkins Medical Institutions Selecting renal replacement therapies: what do African American and non-African American patients and their families think others should know? A mixed methods study Hemodialysis.com Author Interview: L. Ebony Boulware, MD, MPH, FACP Associate Professor of Medicine and Epidemiology Johns Hopkins Medical Institutions (cont) Hemodialysis.com: What should clinicians and patients take away from your report? Educational resources addressing factors that patients and families deem most important to their renal replacement therapy selection decisions could facilitate a treatment choice well-aligned with their personal values and needs. Patients should evaluate the factors they believe are most relevant to them prior to making a renal replacement therapy selection; clinicians should facilitate patients’ decision making process by guiding them toward the treatment choice that best aligns with these factors. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Our findings suggest that family members may broaden the range of considerations influencing renal replacement therapy decisions beyond considerations commonly expressed by patients; efforts to include information about factors deemed important to family members could not only help families better understand the health risks and benefits of various renal replacement therapies but may also help them set reasonable expectations regarding the logistical and psychological burden certain treatment choices may place on patients’ families. Our findings also highlight the potential importance of tailoring educational resources to meet the needs of patients and their families based on their prior experiences with end stage renal disease treatments. Future research should therefore view family members as playing an important and influential role in patients’ renal replacement therapy selection as well as tailor their study aims to account for patients’ degree of prior experience with end stage renal disease treatments. Reference: Selecting renal replacement therapies: what do African American and non-African American patients and their families think others should know? A mixed methods study DePasquale N, Ephraim PL, Ameling J, LewisBoy?r L, Crews DC, Greer RC, Rabb H, Powe NR et al. BMC Nephrology 2013, 14:9 (14 January 2013) For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

7 Electrocardiographic Assessment of Incident Atrial Fibrillation in Hemodialysis Patients Hemodialysis.com Author Interview: Shoichi Fujimoto Keiko Nishi Dialysis Division, University of Miyazaki Hospital, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan Hemodialysis.com Editor Marie Benz: What are the main findings of the study? We found that the presence of a P-terminal force > 0.04 mm.sec., one of electrocardiographic findings, was an independent predictor of new-onset AF in HD patients. Our study is novel in that it reveals the relation between electrocardiographic findings and incident AF in HD patients systematically. Hemodialysis.com: Were any of the findings unexpected? We were surprised to see that AF occurred within 72 months of the start of HD in about 50% of patients with newly diagnosed AF Hemodialysis.com: What should clinicians and patients take away from your report? If clinicians find a P-terminal force > 0.04 mm.sec. in the patient’sECG findings, they should give attention to avoid volume overload during intermittent HD session. In addition, it would be better for HD patients with P- terminal force > 0.04 mm.sec. in their ECG findings to use angiotensin converting enzyme inhibitor or angiotensin II receptor blocker that are revealed to suppress the development of structural remodeling of right atrium which leads to atrial fibrillation. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Ideally, a large study including data from both electrocardiography and echocardiography are needed. Reference: Electrocardiographic Assessment of Incident Atrial Fibrillation in Hemodialysis Patients Keiko Nishi, Shouichi Fujimoto, Shuichi Hisanaga, Osamu Ogawa, Kazuo Kitamura Therapeutic Apheresis and Dialysis Article first published online: 13 DEC 2012 DOI: 10.1111/j.1744-9987.2012.01137.x For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

8 Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism Hemodialysis.com Author Interview: Dr Pablo Urena MD Clinique Du Landy, Saint-Ouen, France Hemodialysis.com Editor Marie Benz: What are the main findings of the study? The main results of this study are that in CKD-V patients just initiating the treatment by dialysis (mean duration time of 7.2 months) and presenting a biological secondary hyperparathyroidism, as evidenced by a serum PTH > 300 pg/ml, a treatment by the calcimimetic Cinacalcet+low dose of active vitamin D (< 6 mcg/week) was more efficient that a treatment by flexible doses of active vitamin D sterol, if prescribed. There was a significant difference in the achievement of the primary endpoint (≥30% PTH reduction at 6 months) between cinacalcet-treated subjects and controls in both the entire cohort (63 versus 38%) and the subgroup of subjects not receiving active vitamin D at enrollment (70 versus 44). Hemodialysis.com: Were any of the findings unexpected? Most of the findings were expected including the better control of PTH, calcium and phosphate levels in the cinacalcet-treated patients compared with patients receiving active vitamin D therapy. However, what was unexpected was that after a 4-week washout of cinacalcet and/or vitamin D analogs at the end of the study, there was a rapid rise in serum PTH levels to values approaching those at baseline. This suggests that neither treatment approach over a 12-month period had a significant impact on the degree of parathyroid hyperplasia and support the concept that secondary hyperparathyroidism in CKD dialysis patients is a chronic disease that is better managed with early prevention and long-term uninterrupted therapy. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

9 Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism Hemodialysis.com Author Interview: Dr Pablo Urena MD Clinique Du Landy, Saint-Ouen, France Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism Hemodialysis.com Author Interview: Dr Pablo Urena MD Clinique Du Landy, Saint-Ouen, France (cont) Hemodialysis.com: What should clinicians and patients take away from your report? That both treatment approaches cinacalcet and active vitamin D are efficient decreasing serum PTH levels. However, cinacalcet therapy reduced serum PTH concentration to a significantly greater degree than flexible doses of active vitamin D alone. Treatment by cinacalcet is associated with lower serum calcium and phosphate concentrations than treatment with active vitamin D, which might be beneficial for these patients in the long-term. That both treatments cinacalcet and active vitamin D should be kept for long-time and interrupted in order to control PTH secretion and probably parathyroid gland growth. Hemodialysis.com: What recommendations do you have for future research as a result of this study? The first recommendation for future research in the same population of CKD patients would be to perform the same study but of longer duration, 2-3 years. This longer study should be associated with functional (calcium "set-point", PTH suppresion test) and morphological study looking at the parathyroid gland size (ultrasound, CT, MRI, scintigraphy, etc). The second recommendation would be performing similar study but this time comparing "head-to-head" cinacalcet treatment with other two groups treated by either controlled escalating doses of calcium salts or escalating doses of active vitaminD analogs. The third recommendation would be performing similar study with a more robust diagnosis of secondary hyperparathyroidism at the time of prescribing cinacalcet or active vitamin D, that means by combining PTH values with markers of bone remodeling such bone alkaline phosphatase or crosslinked collagen peptides (CTX). Reference: Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism Pablo Ureña-Torres, Ian Bridges, Cynthia Christiano, Serge H. Cournoyer, Kerry Cooper, Mourad Farouk, Nelson P. Kopyt, Mariano Rodriguez, Daniel Zehnder, and Adrian Covic Nephrol. Dial. Transplant. first published online January 16, 2013 doi:10.1093/ndt/gfs568 For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

10 High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients Hemodialysis.com Author Interview: Eiichiro Kanda, M.D. M.P.H. Ph.D. Department of Nephrology Tokyo Kyosai Hospital Bioethics Research Center, Tokyo Medical and Dental University Hemodialysis.com Editor Marie Benz: What are the main findings of the study? The main findings are that, in elderly CKD patients, serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level within the normal range is associated with a low risk of CKD progression. Hemodialysis.com: Were any of the findings unexpected? The K/DOQI guidelines 2000 recommend that the serum bicarbonate level should be maintained at or above 22 mEq/l, which is in the normal range. Our study showed that the patients with a serum bicarbonate level lower than 25.5 mEq/l had a high risk of CKD progression. It was suggested that the bicarbonate level 22 to 25.5 mEq/l, which is within the normal range, is not enough to prevent the CKD progression. Hemodialysis.com: What should clinicians and patients take away from your report? Our data showed a possibility that a high serum bicarbonate level within the normal range may effectively prevent CKD progression in elderly CKD patients. Because measuring bicarbonate level at a Clinic or Hospital is easy, it is important to follow up bicarbonate level and GFR. Hemodialysis.com: What recommendations do you have for future research as a result of this study? For the prevention of CKD progression, there are issues that should be resolved: when to start the treatment with sodium bicarbonate and how much sodium bicarbonate should be administered. Clinical trials using a large sample size are required to obtain strong evidence that can help guide therapies with sodium bicarbonate. Reference: High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients Kanda E, Ai M, Yoshida M, Kuriyama R, Shiigai T. Department of Nephrology, Tokyo Kyosai Hospital, Nakameguro 2-3-8, Meguroku, Tokyo, 153-8934, Japan. Tokyo BMC Nephrol. 2013 Jan 9;14:4. doi: 10.1186/1471-2369-14-4. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

11 Determinants of renal function at hospital discharge of patients treated with renal replacement therapy in the intensive care unit. Hemodialysis.com Author Interview: Gijs Fortrie PhD student Dept. of Nephrology Erasmus Medical Center Rotterdam The Netherlands Hemodialysis.com Editor Marie Benz: What are the main findings of the study? In the our study, the clinical determinants for the degree of renal function at hospital discharge in a large group of critically ill patient with acute kidney injury treated with renal replacement therapy during their ICU stay were analyzed. We found that more than half of the patients with an assumed normal renal function prior to hospital admission left the hospital with an impaired renal function. About 8% percent of all patients were chronic dialysis dependent at this time point. Furthermore, the elderly patient and particular the patient with pre-existent chronic kidney disease had a high risk for modest to severely impaired renal function at hospital discharge. Hemodialysis.com: Were any of the findings unexpected? It is noteworthy that such a large amount of patients left the hospital with an impaired renal function, while these patients are rarely referred to the nephrologic outpatient clinic afterwards. Furthermore, the underlying cause of acute kidney injury (sepsis, ischemia, intoxication, other) and comorbidity like diabetes mellitus, hypertension and cardiovascular disease had no significant impact on renal function at hospital discharge at all. In addition, we evaluated the number of investigations involving iodine containing contrast fluid during hospital admission because this might represent a nephrotoxic factor adding up to the renal impairment at hospital discharge. To our surprise we found a protective independent association with renal function at hospital discharge. One of the possible explanations might be that patients with limited renal recovery were considered to have a contraindication for contrast to protect their residual renal function and therefore ruled out for radiologic imaging involving contrast. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

12 Determinants of renal function at hospital discharge of patients treated with renal replacement therapy in the intensive care unit. Hemodialysis.com Author Interview: Gijs Fortrie PhD student Dept. of Nephrology Erasmus Medical Center Rotterdam The Netherlands Determinants of renal function at hospital discharge of patients treated with renal replacement therapy in the intensive care unit. Hemodialysis.com Author Interview: Gijs Fortrie PhD student Dept. of Nephrology Erasmus Medical Center Rotterdam The Netherlands (cont) Hemodialysis.com: What should clinicians and patients take away from your report? It is important to keep in mind that acute kidney injury is more than just an innocent reversible condition. It is a multifactorial syndrome and often the result of multiple pathophysiological pathways including complex interplay between hypoperfusion, ischaemia, inflammation and toxicity. The impact of acute kidney injury should never be underestimated and it will have a major negative effect on quality of life and life expectancy. Therefore, these patients should be monitored closely and the use of nephrotoxic medication should be avoided. Every effort should be made to conserve renal function in those with an impaired renal function at hospital discharge and close observation of renal function by a nephrologist seems warranted in most patients. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Because therapeutic options for acute kidney are lacking, the most important goal for future research will be to focus on the prevention and early detection of this syndrome. Furthermore, besides the need for chronic dialysis the predictive implications of renal function at hospital discharge are unknown so it is of interest to know how this affects the long-term prognosis. Reference: Determinants of renal function at hospital discharge of patients treated with renal replacement therapy in the intensive care unit. Fortrie G, Stads S, de Geus HR, Groeneveld AB, Zietse R, Betjes MG. Department of Nephrology, Erasmus Medical Center, Rotterdam, The Netherlands. J Crit Care. 2012 Dec 19. pii: S0883-9441(12)00369-3. doi: 10.1016/j.jcrc.2012.10.013. [Epub ahead of print] For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

13 Pancreas–kidney transplantation is associated with reduced fracture risk compared with kidney-alone transplantation in men with type 1 diabetes Hemodialysis.com Author Interview: Thomas Nickolas, MD, MS Assistant Professor of Clinical Medicine Division of Nephrology, Columbia University Medical Center, New York, New York 10032, USA Hemodialysis.com Editor Marie Benz: What are the main findings of the study? This study demonstrated that among patients with T1DM, significantly more fractures resulting in hospitalization occurred in solitary kidney transplant recipients, compared with those who received a simultaneous pancreas-kidney. A 31% decrease in fracture risk over five years was noted in men with T1DM who received simultaneous pancreas-kidney transplant, independent of other fracture risk factors. Hemodialysis.com: Were any of the findings unexpected? It was surprising that the fracture risk reduction benefit of simultaneous pancreas-kidney transplantation was present for men but not for women. Hemodialysis.com: What should clinicians and patients take away from your report? No single treatment has been proven effective at reducing fracture risk after kidney transplantation. This lack of effective medical therapy is troubling, given the significant mortality associated with fractures post transplantation. Given the results of this study, simultaneous pancreas- kidney transplantation may potentially serve as an important fracture preventative measure in this especially vulnerable patient population. Hemodialysis.com: What recommendations do you have for future research as a result of this study? It will be important, in future research, to investigate the microstructural and biochemical mechanisms that underlie fracture risk in patients with T1DM and CKD both before and after simultaneous pancreas-kidney transplantation, as this may aid the development of effective fracture prevention treatments for both men and women. Reference: Pancreas-kidney transplantation is associated with reduced fracture risk compared with kidney-alone transplantation in men with type 1 diabetes. Nikkel LE, Iyer SP, Mohan S, Zhang A, McMahon DJ, Tanriover B, Cohen DJ, Ratner L, Hollenbeak CS, Rubin MR, Shane E, Nickolas TL. Penn State Hershey College of Medicine, Hershey, Pennsylvania, USA. Kidney Int. 2013 Jan 2. doi: 10.1038/ki.2012.430. [Epub ahead of print] For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

14 Hemodynamic response magnetic resonance imaging: application for renal hemodynamic characterization Hemodialysis.com Author Interview: Dr. Rinat Abramovitch Goldyne Savad Institute of Gene Therapy Hadassah University Medical Center P.O.B. 12000 Jerusalem, 91120 Israel Hemodialysis.com Editor Marie Benz: What are the main findings of the study? The use of contrast materials for imaging in patients with impaired renal function is limited. In our study Hemodynamic Response Imaging (HRI), a functional MRI method combined with hypercapnia and hyperoxia, was shown to be sensitive to the known renal hemodynamic changes during pharmacological intervention with nitric oxide synthase and cycloxygenase inhibition, in mice. Moreover, renal-HRI maps, that were acquired 4 days after the induction of rhabdomyolysis-induced AKI, revealed significantly attenuated reactivity to hypercapnia and reduced renal oxygenation and perfusion. Hemodialysis.com: Were any of the findings unexpected? Hypercapnia caused 30% decline in renal-HRI maps in contrast to the positive response in other tissues (i.e. the brain). Moreover, hypercapnic-hyperoxia following hypercapnia caused a 50% increase in renal T2*-weighted SI, markedly enhancing the sensitivity of this method compared to the previous studies which showed only 3-4% change. Hemodialysis.com: What should clinicians and patients take away from your report? The comprehensive information provided by adding hypercapnic challenge to the basic BOLD-MRI routine, as done in HRI, makes it a useful tool for the assessment of renal perfusion and oxygenation as well as vascular reactivity during pathological conditions. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Our experiments were performed on anesthetized mice; therefore, further research is required to establish clinical applicability of this technique in awake humans. Reference: Hemodynamic response magnetic resonance imaging: application for renal hemodynamic characterization Zohar Milman, Samuel N. Heyman, Nathalie Corchia, Yifat Edrei, Jonathan H. Axelrod, Chrisitian Rosenberger, Galia Tsarfati, and Rinat Abramovitch Nephrol. Dial. Transplant. first published online January 4, 2013 doi:10.1093/ndt/gfs541 For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

15 Exhaled breath and fecal volatile organic biomarkers of chronic kidney disease Hemodialysis.com Author Interview: Nick Vaziri, M.D., M.A.C.P. Professor of Medicine, Physiology & Biophysics Division of Nephrology & Hypertension Schools of Medicine and Biological Science University of California Irvine Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Although great deal is known about the changes in composition of body fluids in chronic kidney disease (CKD) very little is known about the effect of CKD on the composition of the gases found in the exhaled breath or those produced by the intestinal microbial flora. Fermentation of substrates by the gut microbial flora leads to formation of various gases the nature of which depends on the available substrate and the biological properties of the microbial community residing in the intestinal tract. In a recent study (Vaziri N.D., Wong J., Pahl M.V., Piceno Y.M., Yuan J., DeSantis T.Z., Ni Z., Nguyen T.H., Andersen G.L. Chronic kidney disease alters the composition of intestinal microbial flora. Kidney Int. 2012 Sep 19. doi: 10.1038/ki.2012.345. [Epub ahead of print] PMID: 22992469) we found significant differences in the composition of intestinal microbiome in humans and animals with CKD compared to their healthy control counterparts. In this study we tested the hypothesis that uremia-induced changes in cellular metabolism and intestinal microbiome may change the volatile organic metabolites generated by intestinal flora and gases found in the exhaled breath. To this end we used CKD rats 6 weeks after subtotal nephrectomy or sham-operation. To isolate the effect of CKD the CKD and control rats were fed the same food and kept under identical condition. Exhaled breath was collected by enclosing each animal in a glass chamber flushed with clean air, then sealed for 45 minutes at which time the trapped air was collected. In addition we collected their feces which were dissolved in pure water, incubated at 37º C in glass reactors for 24 hours and collected the trapped air. Collected gases were analyzed by gas chromatography. We found over 50 organic gases in the exhaled breath and 36 gases produced by cultured feces. Many of the volatile organic compounds found in the exhaled breath were the same as those generated by the cultured fecal microbes. Four gases in exhaled breath and 4 generated by cultured feces were significantly different in the two groups. The exhaled breath in CKD rats contained a significantly greater amount of isoprene and significantly lower amounts of linear aldehydes. The cultured feces from the CKD animals released larger amounts of dimethyldisulfide, dimethyltrisulfide, and two thioesters which were either absent or present at much lower levels in the normal control group. Thus the study revealed that the previously demonstrated CKD-induced changes in the composition of intestinal microbial flora leads to significant changes in the volatile organic compounds produced in the intestinal tract. Identification of these gaseous compounds along with several previously-identified uremic retained solutes generated by the gut microbial flora (i.e. indoxyl sulfate and P-cresol sulfate) illustrate the contribution of microbial flora to the uremic toxicity. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

16 Exhaled breath and fecal volatile organic biomarkers of chronic kidney disease Hemodialysis.com Author Interview: Nick Vaziri, M.D., M.A.C.P. Professor of Medicine, Physiology & Biophysics Division of Nephrology & Hypertension Schools of Medicine and Biological Science University of California Irvine Exhaled breath and fecal volatile organic biomarkers of chronic kidney disease Hemodialysis.com Author Interview: Nick Vaziri, M.D., M.A.C.P. Professor of Medicine, Physiology & Biophysics Division of Nephrology & Hypertension Schools of Medicine and Biological Science University of California Irvine (cont) Hemodialysis.com: Were any of the findings unexpected? Based on our earlier demonstration of marked changes in the composition of the intestinal microbiome we expected see differences in the gaseous byproducts of the microbial flora between uremic and normal animals and by extension humans. Hemodialysis.com: What should clinicians and patients take away from your report? The findings of the study have identified a previously unrecognized consequence of advanced CKD which by itself is rewarding. In addition it can lead to further studies aimed at restoring symbiotic relationship between the host and the microbial flora that prevails in normal condition. Hemodialysis.com: What recommendations do you have for future research as a result of this study? The next step is to explore the efficacy of appropriate prebiotics or probiotics which might favorably modify the structure and function of microbiome in CKD. Reference: Exhaled breath and fecal volatile organic biomarkers of chronic kidney disease Meinardi S, Jin KB, Barletta B, Blake DR, Vaziri ND.. Biochim Biophys Acta. 2012 Dec 26. doi:pii: S0304-4165(12)00352-2. 10.1016/j.bbagen.2012.12.006. [Epub ahead of print] For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

17 Role of Urea in Intestinal Barrier Dysfunction and Disruption of Epithelial Tight Junction in Chronic Kidney Disease Nick Vaziri, M.D., M.A.C.P. Professor of Medicine, Physiology & Biophysics Division of Nephrology & Hypertension Schools of Medicine and Biological Science University of California Irvine Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Chronic kidney disease (CKD) is invariably associated with systemic inflammation which plays a central role in the pathogenesis of cardiovascular disease and numerous other complications in this population. In a series of recent studies we found heavy losses of the key protein constituents of colonic epithelial tight junction in rats with CKD (Vaziri ND, Yuan J, Norris K. Role of Urea in Intestinal Barrier Dysfunction and Disruption of Epithelial Tight Junction in Chronic Kidney Disease. Am J Nephrol. 2012 Dec 19;37(1):1-6. [Epub ahead of print). The depletion of the intestinal epithelial tight junction which is the principal barrier against influx of endotoxin and other noxious luminal contents into the systemic circulation shown in that study unraveled the source of endotoxemia which is commonly present and is a major cause of inflammation in CKD. In a subsequent study (Vaziri ND, Goshtasbi N, Yuan J, Jellbauer S, Moradi H, Raffatellu M, Kalantar-Zadeh K. Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium. Am J Nephrol. 2012;36(5):438-443) we asked whether CKD- induced disruption of intestinal epithelial barrier is caused by some retained uremic toxins or metabolites and if so whether they can be removed by dialysis. To address this question we compared the effects of pre- and post-hemodialysis plasma samples from ESRD patients and plasma from healthy controls on the epithelial barrier function and structure in cultured human colonic epithelial cells seeded on Transwell plates to form a polarized, impermeable monolayer that simulates characteristics of intestinal epithelium in vivo. The study showed that compared with the control plasma, incubation in media containing pre-dialysis plasma from ESRD patients caused a marked drop in trans-epithelial electrical resistance denoting increased epithelial permeability. This was accompanied by significant loss of the tight junction proteins. The severity of the epithelial barrier damage and dysfunction was significantly less in cells exposed to the post-dialysis than per-dialysis plasma pointing to the role of some dialyzable uremic retained product(s). In our latest study we tested the hypothesis that the breakdown of the intestinal barrier in CKD is at least in part mediated by the heavy influx of urea into the gastrointestinal tract, its conversion by microbial urease to ammonia [CO(NH2)2 +H2O à CO2+2NH3] and formation of ammonium hydroxide [NH3 + H2OàNH4OH], a caustic compound which can dissolve the tight junction proteins. To test this hypothesis we incubated the fully polarized human enterocytes in the culture media containing clinically-relevant concentrations of urea. To simulate the presence of microbial flora we repeated the experiments by adding urea plus urease to the culture media. The study revealed that at clinically-relevant concentrations, urea caused a concentration-dependent fall in trans-epithelial electrical resistance and a significant reduction of the tight junction proteins. The effects of urea were dramatically amplified by urease which caused cells detachment, dissipation of trans-epithelial electrical resistance, and massive loss of the tight junction proteins. These experiments documented, for the first time, that uremia-induced disruption of intestinal barrier function is, in part, mediated by urea which has heretofore been considered to be a nontoxic retained metabolite. These findings revealed a novel mechanism for the previously documented salutary effect of urea-lowering strategies e.g. low protein diet and longer and more frequent dialysis regimens in advanced CKD. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

18 Role of Urea in Intestinal Barrier Dysfunction and Disruption of Epithelial Tight Junction in Chronic Kidney Disease Nick Vaziri, M.D., M.A.C.P. Professor of Medicine, Physiology & Biophysics Division of Nephrology & Hypertension Schools of Medicine and Biological Science University of California Irvine Role of Urea in Intestinal Barrier Dysfunction and Disruption of Epithelial Tight Junction in Chronic Kidney Disease Nick Vaziri, M.D., M.A.C.P. Professor of Medicine, Physiology & Biophysics Division of Nephrology & Hypertension Schools of Medicine and Biological Science University of California Irvine (cont) Hemodialysis.com: Were any of the findings unexpected? Identification of urea which has been generally viewed as an inert nontoxic uremic retained metabolite as being a major mediator of inflammation and the associated morbidity and mortality in CKD and ESRD population is a novel finding and has significant therapeutic implications. Hemodialysis.com: What should clinicians and patients take away from your report? Low protein diet in CKD patients and longer and more frequent dialysis treatments in ESRD patients can reduce inflammation and lower the risk of cardiovascular and related complication. Hemodialysis.com: What recommendations do you have for future research as a result of this study? We are currently conducting a series of in vivo studies to test the hypothesis that administration of activated charcoal may attenuate the intestinal barrier damage and dysfunction by adsorbing ammonia and, thereby, limiting the formation of the caustic ammonium hydroxide in the uremic animals. Reference: Vaziri ND, Yuan J, Norris K. Role of Urea in Intestinal Barrier Dysfunction and Disruption of Epithelial Tight Junction in Chronic Kidney Disease. Vaziri ND, Yuan J, Norris K. Am J Nephrol. 2012 Dec 19;37(1):1-6. [Epub ahead of print] For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

19 Degree of Acute Kidney Injury before Dialysis Initiation and Hospital Mortality in Critically Ill Patients Hemodialysis.com Author Interview: Charuhas V Thakar, MD, FASN Chief of the Section of Nephrology at Cincinnati VA Medical Center and an Associate Professor of Medicine in the Division of Nephrology and Hypertension at the University of Cincinnati. Hemodialysis.com Editor Marie Benz: What are the main findings of the study? The main findings of the study are that within those patients who develop AKI requiring dialysis in ICU, the degree of mortality risk is proportional to the degree of AKI sustained prior to dialysis initiation. This prognostic information has important implications in terms of anticipated outcomes, and future clinical research. Additionally, the data also describes the natural history of these patients in ICU – and notes that majority of those who require dialysis in ICU, do so within first 3 – 4 days after admission. Thus, our efforts to conduct clinical trials in ICU AKI-D patients need significantly improved methods of rapid risk stratification within first 24 hours of ICU admission. Hemodialysis.com: Were any of the findings unexpected? The clinicians should review the degree of kidney injury sustained prior to dialysis initiation, as that will have an important implication on the expected outcome during hospitalization. Hemodialysis.com: What should clinicians and patients take away from your report? The clinicians should review the degree of kidney injury sustained prior to dialysis initiation, as that will have an important implication on the expected outcome during hospitalization. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Future research should look at ways to improve rapid risk stratification or prediction of those who will require dialysis in ICU. Additionally, trials on intervention in dialysis should take into consideration the degree of injury sustained prior to dialysis initiation as an important determinant of outcome. Reference: Degree of Acute Kidney Injury before Dialysis Initiation and Hospital Mortality in Critically Ill Patients Charuhas V. Thakar, Annette Christianson, Peter Almenoff, Ron Freyberg, and Marta L. Render, “Degree of Acute Kidney Injury before Dialysis Initiation and Hospital Mortality in Critically Ill Patients,” International Journal of Nephrology, vol. 2013, Article ID 827459, 7 pages, 2013. doi:10.1155/2013/827459 For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

20 Combined Association of Creatinine, Albuminuria, and Cystatin C with All-Cause Mortality and Cardiovascular and Kidney Outcomes Hemodialysis.com Authors' Interview: Professor Josef Coresh, MD, PhD, MHS SALMAN WAHEED MD, MPH Johns Hopkins University Hemodialysis.com Editor Marie Benz: What is the background of the study? We followed 9,489 participants of the Atherosclerosis Risk in Communities (ARIC) cohort for a median of 11.2 years, and investigated the joint association of eGFRcreatinine, eGFRcystatin and urine albumin to creatinine ratio with mortality, coronary heart disease, heart failure, acute kidney injury and end stage renal disease. We also investigated if addition of urine albumin to creatinine ratio to eGFRcreatinine plus all other predictors or further addition of eGFRcystatin to both eGFRcreatinine and urine albumin to creatinine ratio improves risk classification. Hemodialysis.com: What are the main findings of the study? Overall, eGFRcreatinine 60 mL/min/1.73m2, eGFRcystatin >60 mL/min/1.73m2 and ACR 60 mL/min/1.73m2 and urine albumin creatinine ratio<30 mg/g compared to those without CKD, while risk of kidney outcomes remained elevated. We also found that there is significant improvement in risk classification with the addition of either urine albumin to creatinine ratio to eGFRcreatinine, or further addition of eGFRcystatin to both eGFRcreatinine and urine albumin to creatinine ratio. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

21 Combined Association of Creatinine, Albuminuria, and Cystatin C with All-Cause Mortality and Cardiovascular and Kidney Outcomes Hemodialysis.com Authors' Interview: Professor Josef Coresh, MD, PhD, MHS SALMAN WAHEED MD, MPH Johns Hopkins University Combined Association of Creatinine, Albuminuria, and Cystatin C with All-Cause Mortality and Cardiovascular and Kidney Outcomes Hemodialysis.com Authors' Interview: Professor Josef Coresh, MD, PhD, MHS SALMAN WAHEED MD, MPH Johns Hopkins University (cont) Hemodialysis.com: Were any of the findings unexpected? We noted that risk associations were weaker with coronary heart disease compared to those with all cause mortality or heart failure. While it is poorly understood why associations were weaker for coronary heart disease compared to mortality or heart failure, some of the other studies have also observed similar weaker association with coronary heart disease compared to those observed for all-cause mortality or heart failure. Potential explanations include the possibility that CKD is predominantly a micro vascular disease and thus shares a risk factor profile of micro vascular disease in the heart and brain which may lead to more cardiac dysfunction (heart failure) and stroke than atherosclerosis and coronary heart disease. Similarly, anemia, hypervolemia and electrolyte abnormalities increase cardiac risk and mortality through mechanisms other than atherosclerosis. It is also possible that increased risk of mortality from non-coronary heart disease such as heart failure, arrhythmia and stroke provides a competing risk that reduces the risk of coronary heart disease. However, exact mechanism remains unclear. Hemodialysis.com: What should clinicians and patients take away from your report? Following are the most important take home messages from this report: a: In our cohort, 42% of those with eGFRcreatinine 60 mL/min/1.73m2). This is important to know because this group was not observed to be at increased risk for any of the non-kidney outcomes compared to those with no CKD. This suggests that eGFRcystatin and ACR can be used as confirmatory markers for future risk in those with eGFRcreatinine <60 mL/min/1.73m2. This approach improves risk classification, and provides reassurance to a large group of individuals with eGFRcreatinine <60 mL/min/1.73m2. b: For kidney outcomes, low eGFRcreatinine conferred to increased risk similar to eGFRcystatin independent of other two markers. However, even for kidney outcomes, if we only measure eGFRcreatinine and ignore urine albumin to creatinine ratio and eGFRcystatin, we misclassify a large proportion of individuals into the higher risk category when their actual risk is several folds lower if the other two markers are not in the CKD range. We propose that cystatin C should be used in clinical practice as a confirmatory marker for evaluating clinical risk in those with stage 3 CKD based on serum creatinine, particularly when albuminuria is not elevated. Hemodialysis.com: What recommendations do you have for future research as a result of this study? One important question that arises is that since eGFRcystatin is overall less biased compared to eGFRcreatinine, is a better risk predictor than creatinine, and is associated with increased risk of outcomes even after accounting for the other two markers, should cystatin C replace creatinine in clinical practice without the need for this multimarker approach? Although we believe cystatin C is definitely a superior marker than creatinine, using cystatin C as a first line marker in clinical practice would involve testing a large number of individuals. Since it is costlier to measure cystatin C on everyone than serum creatinine, this approach may not be practical until we have studies on cost-benefit analysis. Reference: Combined Association of Creatinine, Albuminuria, and Cystatin C with All-Cause Mortality and Cardiovascular and Kidney Outcomes Salman Waheed, Kunihiro Matsushita, Brad C. Astor, Ron C. Hoogeveen, Christie Ballantyne, and Josef Coresh CJASN CJN.04960512; published ahead of print December 20, 2012, doi:10.2215/CJN.04960512 For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

22 Bisphenol A exposure is associated with low-grade urinary albumin excretion in children of the United States Hemodialysis.com Author Interview: Howard Trachtman, MD NYU School of Medicine's Department of Pediatrics Hemodialysis.com Editor Marie Benz: What are the main findings of the study? We demonstrated that in healthy US children who were part of the 2009-10 NHANES study, low grade albuminuria was higher in the children with greater levels of BPA exposure. The increased albuminuria was not related to BP, weight, or other known factors that impact on urinary albumin excretion. Hemodialysis.com: Were any of the findings unexpected? The findings are not entirely unexpected because they are consistent with observations made a year ago in adults living in China. However, they are surprising because they imply that children are as susceptible as adults to the impact of BPA on low grade albuminuria. Hemodialysis.com: What should clinicians and patients take away from your report? The findings suggest that adverse effects of BPA exposure are noticeable in children. The change in albumin excretion is not clinically significant at the time was measured so parents and pediatricians should not worry about the immediate health of their children/patients. But, changes in the order of magnitude that we observed in our study are associated with increased cardiovascular risk in adulthood. If risk is cumulative, parents and clinicians might want to adopt strategies to minimize exposure to BPA for their children and to advocate together for the banning of BPA use in the US. Hemodialysis.com: What recommendations do you have for future research as a result of this study? I would suggest confirming the finding in other cohorts of healthy children. In addition, the effects of BPA on albuminuria should be studied in children at higher risk of cardiovascular disease such as those with chronic kidney disease or heart disease. Hopefully these data will help regulatory agencies make the proper decision regarding use of BPA in the US. Reference: Bisphenol A exposure is associated with low-grade urinary albumin excretion in children of the United States Leonardo Trasande, Teresa M Attina and Howard Trachtman Kidney Int advance online publication, January 9, 2013; doi:10.1038/ki.2012.422 Bisphenol A exposure is associated with low-grade urinary albumin excretion in children of the United States For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

23 Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti- inflammatory drugs and risk of acute kidney injury: nested case-control study Hemodialysis.com Author Interview: Samy Suissa, PhD James McGill Professor of Epidemiology, Biostatistics and Medicine, McGill University Director, Centre for Clinical Epidemiology Lady Davis Research Institute - Jewish General Hospital Montreal, Quebec H3T 1E2 Canada Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Patients who take a combination of diuretics and either angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to, which NSAIDs are added, have a 31% increase in the risk of acute kidney injury. This risk is particularly elevated during the first month of triple combination treatment, with an 82% increase in the risk. Hemodialysis.com: Were any of the findings unexpected? A double therapy combination of a diuretic, an ACE inhibitor or an ARB with an NSAID was not associated with an increased risk of kidney injury, though the numbers were not sufficiently large to firmly conclude safety. We agree with the accompanying editorial that "the jury is still out on whether double drug combinations are indeed safe." Hemodialysis.com: What should clinicians and patients take away from your report? Clinicians should advise patients of the risks and be vigilant for signs of drug associate d acute kidney injury during the first month of use. These drugs are commonly prescribed together, particularly in elderly people with several chronic conditions. Although the absolute risk of acute kidney injury for individuals is low, it is a major public health concern, occurring in more than 20% of hospital inpatients and is associated with around half of all potentially preventable deaths in hospital. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Like all research, these findings should be confirmed in other settings and the question of double therapy combination of an antihypertensive with an NSAID should be assessed in a larger population. Reference: Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study Lapi F,Azoulay L,Yin H,Nessim SJ,Suissa S. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ 2013;346:e8525 For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

24 Serum Magnesium and Calcium on the Association between Adiponectin Levels and All-Cause Mortality in End-Stage Renal Disease Patients Hemodialysis.com Author Interview: Dr. John Kyriazis MD Department of Nephrology, General Hospital of Chios, Chios, Greece Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Studies of the impact of adiponectin (ADPN) on clinical outcomes in end-stage renal disease (ESRD) patients have yielded contradictory results so far. This study aimed at unraveling the existing controversy in the literature. This is the first study to document the existence of strong positive and negative associations of ADPN levels with serum magnesium (s-Mg) and calcium (s-Ca), respectively, in ESRD patients. These associations were independent of each other and independent of body composition, nutritional and inflammatory status. High ADPN levels were an independent predictor of all-cause mortality in ESRD patients.There was asignificant 7 % increased risk for death from any cause for each 1-μg/ml increment of ADPN, after multivariate adjustment for possible confounders. The chief finding of this study was that s-Mg and s-Ca emerged as important effect modifiers of the association between ADPN and all-cause mortality. Survival analysis stratified by s-Mg levels (below and above the median value of 2.45 mg/dl) and s-Ca levels (below and above the median value of 9.3 mg/dl), revealed ADPN as an independent predictor of total mortality only in the low s-Mg and high s-Ca groups. Hemodialysis.com: Were any of the findings unexpected? In line with previous evidence, this study showed that low s-Mg and high s-Ca levels were independently associated with malnutrition, inflammation, arterial stiffening and risk of death. However, the fact that s-Mg and s-Ca levels could be also factors capable of influencing the relationship between ADPN and all-cause mortality was an unexpected finding. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

25 Serum Magnesium and Calcium on the Association between Adiponectin Levels and All-Cause Mortality in End-Stage Renal Disease Patients Hemodialysis.com Author Interview: Dr. John Kyriazis MD Department of Nephrology, General Hospital of Chios, Chios, Greece Serum Magnesium and Calcium on the Association between Adiponectin Levels and All-Cause Mortality in End-Stage Renal Disease Patients Hemodialysis.com Author Interview: Dr. John Kyriazis MD Department of Nephrology, General Hospital of Chios, Chios, Greece (cont) Hemodialysis.com: What should clinicians and patients take away from your report? The predictive value of ADPN in all-cause mortality in ESRD patients appears to be critically dependent on s-Mg and s-Ca levels. Therefore, s-Mg and s-Ca levels should be taken into consideration when assessing the role of ADPN on outcomes in ESRD. Given that s-Mg and s-Ca levels are strongly dependent on dialysate Mg and Ca concentration, respectively, the use of high dialysate Mg concentrations (0.75 mmol/l) and low dialysate concentrations (1.25 mmol/l), besides other beneficial effects, may also reduce the risk of death attributed to the markedly increased ADPN in the plasma of uremic patients. Hemodialysis.com: What recommendations do you have for future research as a result of this study? An hypothesis, based on previously published evidence, that could provide a plausible explanation for the modifying effects of s-Mg and s-Ca on the ADPN-mortality association is that low s-Ca and/or potentially high s- Mg levels may be associated with increased low molecular weight ADPN isomers and better outcomes, whereas high s-Ca and/or potentially low s-Mg levels may be associated with high molecular weight ADPN isomers and poor prognosis. Given that we measured total ADPN and not it’s various isomers, further assessment of ADPN isomers along with s-Mg and s-Ca concentrations (and/or Mg and Ca concentrations in the dialysis bath) will be necessary to verify this intriguing hypothesis. Reference: Hemodialysis.com Author Interview: Dr. John Kyriazis The Role of Serum Magnesium and Calcium on the Association between Adiponectin Levels and All-Cause Mortality in End-Stage Renal Disease Patients Anastasia Markaki, John Kyriazis, Kostas Stylianou, George A. Fragkiadakis, Kostas Perakis, Andrew N. Margioris, Emmanuel S. Ganotakis, Eugene Daphnis Research Article | published 20 Dec 2012 | PLOS ONE 10.1371/journal.pone.0052350 The Role of Serum Magnesium and Calcium on the Association between Adiponectin Levels and All-Cause Mortality in End-Stage Renal Disease Patients For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

26 The fat-mass and obesity-associated gene (FTO) predicts mortality in chronic kidney disease of various severity. Hemodialysis.com Authors' Interview: Dr. Belinda Spoto, CNR-IBIM and Nephrology, Dialysis and Transplantation Unit of Reggio Calabria, Reggio Calabria, Italy Dr. Carmine Zoccali CNR-IBIM Epidemiologia Clinica e Fisiopatologia delle Malattie Renali e dell'Ipertensione Arteriosa, Ospedali Riuniti, Reggio Cal, Italy Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Our results show that the fat-mass and obesity-related (FTO) gene, an important determinant of body weight associated with type 2 diabetes, hypertension and cancer, is a relevant genetic factor in determining mortality in patients with chronic kidney disease (CKD) of various severity. In particular, the A allele of the novel FTO rs708259 polymorphism associates to a higher death risk both in pre-dialysis and dialysis patients and in a pooled analysis including three independent dialysis cohorts and an additional cohort of stage 2-5 CKD patients the excess risk of death associated to this allele was 42%, a figure of high statistical significance (p=0.002). Hemodialysis.com: Were any of the findings unexpected? The relationship between obesity and the risk of death in CKD and dialysis patients is a complex matter and studies performed so far provided conflicting results. Our finding that a polymorphism in an obesity-susceptible gene contributes to explain mortality in pre-dialysis and dialysis patients apparently gives credit to the hypothesis that alterations in BMI produce unfavourable outcomes in CKD, like in the general population. The unexpected finding was that this polymorphism on CKD was largely independent from BMI, a phenomenon suggesting that CKD profoundly modifies the link between this polymorphism and alterations in BMI and/or that the same polymorphism impacts upon clinical outcomes independently on mechanism(s) independently of body mass in this population. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

27 The fat-mass and obesity-associated gene (FTO) predicts mortality in chronic kidney disease of various severity. Hemodialysis.com Authors' Interview: Dr. Belinda Spoto, CNR-IBIM and Nephrology, Dialysis and Transplantation Unit of Reggio Calabria, Reggio Calabria, Italy Dr. Carmine Zoccali CNR-IBIM Epidemiologia Clinica e Fisiopatologia delle Malattie Renali e dell'Ipertensione Arteriosa, Ospedali Riuniti, Reggio Cal, Italy The fat-mass and obesity-associated gene (FTO) predicts mortality in chronic kidney disease of various severity. Hemodialysis.com Authors' Interview: Dr. Belinda Spoto, CNR-IBIM and Nephrology, Dialysis and Transplantation Unit of Reggio Calabria, Reggio Calabria, Italy Dr. Carmine Zoccali CNR-IBIM Epidemiologia Clinica e Fisiopatologia delle Malattie Renali e dell'Ipertensione Arteriosa, Ospedali Riuniti, Reggio Cal, Italy (cont) Hemodialysis.com: What should clinicians and patients take away from your report? Our results have no direct clinical implication. Yet we believe that our study is of interest because generates the hypothesis that the gene product(s) of FTO rs708259 polymorphism may have adverse health effects in CKD patients. Hemodialysis.com: What recommendations do you have for future research as a result of this study? The FTO gene codes for an enzyme that oxidatively demethylates single-stranded DNA and, by this mechanism, it may modulate relevant epigenetic modifications of other genes regulating various biological processes. However, while the association between the FTO rs708259 polymorphism and mortality in pre-dialysis and dialysis patients in our data is statistically robust, the functional significance of this SNP is unknown and we can only speculate that this polymorphism may enhance the risk of mortality via DNA methylation. In this respect, functional studies in appropriate models are needed to define the mechanism(s) whereby this polymorphism impacts upon survival in this population. Reference: The fat-mass and obesity-associated gene (FTO) predicts mortality in chronic kidney disease of various severity. Belinda Spoto, Francesco Mattace-Raso, Eric Sijbrands, Francesca Mallamaci, Daniela Leonardis, Filippo Aucella, Alessandra Testa, Antonio Gesuete, Maria C. Sanguedolce, Graziella D'Arrigo, Rosa M. Parlongo, Anna Pisano, Claudia Torino, Giuseppe Enia, Giovanni Tripepi, Maurizio Postorino, and Carmine Zoccali Nephrol. Dial. Transplant. (2012) 27(suppl 4): iv58-iv62 doi:10.1093/ndt/gfs550 For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

28 Mononuclear Leukocyte Apoptosis and Inflammatory Markers in Patients with Chronic Kidney Disease Hemodialysis.com Author Interview: Kostas C. Siamopoulos, MSc, MD, FRSH, FERA Professor of Medicine/Nephrology Department of Nephrology Medical School, University of Ioannina University Avenue, Ioannina, GR451 10, Greece Hemodialysis.com Editor Marie Benz: What are the main findings of the study? In this study, we investigated levels of specific apoptosis and inflammatory markers in non-dialysis patients with CKD stages 1-4. The main findings, which confirmed our initial hypothesis, were that apoptotic markers and an inflammatory response started to increase early in the course of CKD, as soon as patients entered stage 3 of CKD and even earlier. Moreover, we demonstrated that kidney disease remained significant predictor for the aggregate of the assessed markers after adjusting for variables that were expected to influence them. Hemodialysis.com: Were any of the findings unexpected? We did not find a strong negative correlation between IL-6 and CRP levels with eGFR, which according to the existing literature has been shown in CKD patients. Possible explanations to our finding could be first, the diversity in the expression of inflammatory markers in the CKD population and second the fact that CRP and IL-6 levels have been shown to fluctuate over time, being mainly influenced by comorbidity and subclinical infections. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

29 Mononuclear Leukocyte Apoptosis and Inflammatory Markers in Patients with Chronic Kidney Disease Hemodialysis.com Author Interview: Kostas C. Siamopoulos, MSc, MD, FRSH, FERA Professor of Medicine/Nephrology Department of Nephrology Medical School, University of Ioannina University Avenue, Ioannina, GR451 10, GreeceMononuclear Leukocyte Apoptosis and Inflammatory Markers in Patients with Chronic Kidney Disease Hemodialysis.com Author Interview: Kostas C. Siamopoulos, MSc, MD, FRSH, FERA Professor of Medicine/Nephrology Department of Nephrology Medical School, University of Ioannina University Avenue, Ioannina, GR451 10, Greece (cont) Hemodialysis.com: What should clinicians and patients take away from your report? Apoptosis and especially inflammation are established non-traditional, uremia-related cardiovascular risk factors in CKD population. Considering that these risk factors start to be disturbed so early in the course of CKD, we clinicians have to act soon and effectively by the implementation of strategies that have shown a positive effect on the control of these factors. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Future research could concentrate on the investigation of a causal association between chronic kidney injury and the disturbance of pathopysiologic mechanisms such as apoptosis and inflammation. Another area of ​​investigation could be the prospective, repeated monitoring of apoptotic and inflammatory factors in a CKD population starting from the early stages of the disease and the association between levels of these factors with the deterioration of renal function and the appearance of a cardiovascular event. Reference: Mononuclear Leukocyte Apoptosis and Inflammatory Markers in Patients with Chronic Kidney Disease 1Evangelia Dounousi, 1Elli Koliousi, 2Aikaterini Papagianni, 3Kyriakos Ioannou, 1Xanthi Zikou, 1Konstantinos Katopodis, 3Apostolos Kelesidis, 4Dimitrios Tsakiris, 1Kostas C. Siamopoulos Departments of Nephrology of 1University Hospital of Ioannina, 2General Hospital of Thessaloniki “Hippokration”, 3General Hospital of Veria, and 4General Hospital of Thessaloniki “Papageorgiou”, Greece Am J Nephrol. 2012;36(6):531-6. doi: 10.1159/000345352. Epub 2012 Nov 29.. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

30 Conversion from epoetin alfa to darbepoetin alfa: effects on patients' hemoglobin and costs to canadian dialysis centres. Hemodialysis.com Author Interview: Marisa Battistella, BSc Phm, Pharm D, ACPR Pharmacy Clinician Scientist Assistant Professor Leslie Dan Faculty of Pharmacy, University of Toronto Clinical Pharmacist-Nephrology University Health Network Hemodialysis.com Editor Marie Benz: What are the main findings of the study? In this retrospective, open-label, observational study, 3 hospital-based hemodialysis centres in Ontario, Canada, converted patients from erythropoietin to darbepoietin over the period July 2004 to April 2006. Data were collected for a total of 442 patients. The median dose-conversion ratio for each hemodialysis centre ranged from 288:1 to 400:1, and the average annual per-patient savings varied between $2140 and $4711. Hemodialysis.com: Were any of the findings unexpected? One site collected data with respect to ESA administration and found that with darbepoietin, the relative risk of medication administration errors was reduced by 72% (p < 0.001). Although the numbers were small at this site, the results should not be overlooked. Hemodialysis.com: What should clinicians and patients take away from your report? Both ESA agents work at increasing Hb, however the ratios reported in the product monographs are not accurate and much less darbepoietin is required when converting patients and this has an effect on cost as the price in Canada was set at a 200:1 ratio. Hemodialysis.com: What recommendations do you have for future research as a result of this study? This retrospective design study was performed prior to the publications of CHOIR, CREATE and TREAT and with the new KDIGO guidelines suggesting lower Hb targets, a new analysis should be performed as the ratio may be lower, that is closer to 250:1 – 300:1. Reference: Conversion from epoetin alfa to darbepoetin alfa: effects on patients' hemoglobin and costs to canadian dialysis centres. Jordan J, Breckles J, Leung V, Hopkins M, Battistella M.,BScPharm, is a Pharmacist Consultant with Toronto East General Hospital, Toronto, Ontario. Can J Hosp Pharm. 2012 Nov;65(6):443-9. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

31 Obesity-related chronic kidney disease is associated with spleen-derived IL-10 Hemodialysis.com Author Interview: Koro Goto Department of Internal Medicine 1, Faculty of Medicine, Oita University, Hasama, Yufu, Japan Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Obesity is associated with systemic low-grade inflammation and a risk factor for chronic kidney disease (CKD), but the molecular mechanism remains uncertain. We suggest that obesity reduces IL-10 induction from spleen and spleen-derived IL-10 may protect against the development of CKD induced by obesity. Hemodialysis.com: Were any of the findings unexpected? No. Previously, we demonstrated the role of spleen-derived IL-10 in diet-induced changes due to inflammatory responses in the white adipose tissue and liver, and thus suggested a role in the etiology of obesity-related metabolic abnormalities. As we expected, spleen-derived IL-10 downregulates the severity of obesity-related CKD. Hemodialysis.com: What should clinicians and patients take away from your report? We have identified that high-fat feeding decreased the synthesis of IL-10 from spleen probably due to oxidative stress in previous study and that obesity-related CKD may be characterized by promotion of pro-inflammatory pathways accompanied by diminished spleen-derived IL-10 in this study. Thus, it is important to protect the ability of IL-10 synthesis from spleen. There is the possibility that anti-oxidant drugs such as vitamin E might be effective to prevent the development of obesity-related CKD. Hemodialysis.com: What recommendations do you have for future research as a result of this study? We have demonstrated a critical role for spleen-derived IL-10 in the inflammation of kidneys in the obese state. Although additional work is needed to understand why obesity elicits an inflammatory response, our data indicate that a more comprehensive understanding of the interactions between obesity and the spleen may provide a therapeutic strategy for treating CKD. Reference Obesity-related chronic kidney disease is associated with spleen-derived IL-10 Koro Gotoh, Megumi Inoue, Takayuki Masaki, Seiichi Chiba, Kentaro Shiraishi, Takanobu Shimasaki, Kazue Matsuoka, Hisae Ando, Kansuke Fujiwara, Naoya Fukunaga, Kohei Aoki, Tomoko Nawata, Isao Katsuragi, Tetsuya Kakuma, Masataka Seike, and Hironobu Yoshimatsu For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

32 Enoxaparin Outcomes in Patients With Moderate Renal Impairment Hemodialysis.com Author Interview: Douglas D. DeCarolis, PharmD Clinical Assistant Professor, University of Minnesota Pharmacy Program Manager: Research/Investigational Drugs) College of Pharmacy Board Certified Pharmacotherapy Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Caution is advised when using full, therapeutic doses of enoxaparin (1mg/kg q12h) in patients with moderate renal impairment defined as an eGFR (or eCrCl) of 30-50 ml/min. Of particular concern is therapy greater than 5-7 days. It is advisable to determine an eGFR (in ml/min) in patients at risk or with existing CKD prior to therapy to properly evaluate benefit versus risks. Others have recommended reduced doses or the monitoring of AntiFactor Xa level (if available), however, there is evidence is lacking regarding these strategies. Also, consider the above risk when using enoxaparin to oral anticoagulation. Particularly with bridging for cardiac ablation procedures, we observed a significant risk of bleeding. Caution is advised interpreting this finding as it was a post-hoc analysis and represents a reduced number of patients to be conclusive. However, this finding did contribute to an immediate change of practice at our institution. Of note, some have recommended using ½ dose enoxaparin (0.5mg/kg q12h)1 based on expert opinion while others have studied continuing warfarin without bridging for cardiac ablation procedures. 39. European Heart Rhythm Association (EHRA); European Cardiac Arrhythmia Society (ECAS); American College of Cardiology (ACC); American Heart Association (AHA); Society of Thoracic Surgeons (STS), Calkins H, Brugada J, Packer DL, et al. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation [published correction appears in Heart Rhythm. 2009;6(1):148]. Heart Rhythm. 2007;4(6):816-861. 40. Ahmed I, Gertner E, Nelson WB, et al. Continuing warfarin therapy is superior to interrupting warfarin with or without bridging anticoagulation therapy in patients undergoing pacemaker and defibrillator implantation. Heart Rhythm. 2010; 7(6):745-749. 41. Di Biase L, Burkhardt JD, Mohanty P, et al. Periprocedural stroke and management of major bleeding complications in patients undergoing catheter ablation of atrial fibrillation: the impact of periprocedural therapeutic international normalized ratio. Circulation. 2010;121(23):2550-2556. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

33 Enoxaparin Outcomes in Patients With Moderate Renal Impairment Hemodialysis.com Author Interview: Douglas D. DeCarolis, PharmD Clinical Assistant Professor, University of Minnesota Pharmacy Program Manager: Research/Investigational Drugs) College of Pharmacy Board Certified Pharmacotherapy Enoxaparin Outcomes in Patients With Moderate Renal Impairment Hemodialysis.com Author Interview: Douglas D. DeCarolis, PharmD Clinical Assistant Professor, University of Minnesota Pharmacy Program Manager: Research/Investigational Drugs) College of Pharmacy Board Certified Pharmacotherapy (cont) Hemodialysis.com: Were any of the findings unexpected? Due to the well-known pharmacokinetic profile of enoxaparin, reliance on kidney function for elimination, and previous studies, a difference was hypothesized. However the magnitude of difference was unexpected. The very high rate of bleeding when bridging for cardiac ablation procedures in this population was unexpected. Hemodialysis.com: What should clinicians and patients take away from your report? Be more cognizant of the potential risks of major bleeding in this patient population with renal impairment. This includes using enoxaparin for bridging purposes. Consider renal function assessment for a better benefit vs. risk analysis when selecting an anticoagulant. If enoxaparin is selected and therapy becomes longer than originally planned, consideration of this increased risk in patients with renal impairment may prevent serious and unnecessary adverse effect. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Validation of our results in a more heterogeneous population (vs. VA population) is needed. We feel there is sufficient data already collected in many of the large trials that could be re-analyzed to assess differences in bleeding based renal function and length of therapy. This would provide more definitive data and would be valuable to practicing clinicians. Reference: DeCarolis DD, Thorson JG, Clairmont MA, Leuthner AM, Rector TS, Johnson GJ. Enoxaparin Outcomes in Patients With Moderate Renal Impairment. Arch Intern Med. 2012;172(22):1713-1718. doi:10.1001/2013.jamainternmed.369. For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

34 Exploring the role of pharmacists in outpatient dialysis centers: a qualitative study of nephrologist views Hemodialysis.com Author Interview: Author's Interview: Ms. Teresa Salgado and Fernando Fernandez-Llimos, Ph.D., Pharm.D., M.B.A Assistant Professor Department of Social Pharmacy University of Lisbon Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Nephrologists in Australia and in Portugal hold different views regarding the future provision of pharmacy services in outpatient dialysis centers. While Australian nephrologists reflected positive attitudes and showed receptiveness towards the future implementation of pharmacy services in outpatient dialysis centres, Portuguese nephrologists demonstrated some reluctance and manifested concern with professional boundaries. In addition, Australian nephrologists were more aware of pharmacists’ skills comparing to the Portuguese nephrologists, voicing several types of pharmacy services that could be beneficial to dialysis patients. Hemodialysis.com: Were any of the findings unexpected? No indeed. As we expected, a previous history of pharmacy services implementation is a good predictor for nephrologists’ acceptance and their acquaintance with clinical pharmacists’ skills. Hemodialysis.com: What should clinicians and patients take away from your report? Collaboration between physicians and clinical pharmacists in this setting could be a way of addressing a wider range of patient medication needs and improving the quality of care delivered. This would increase the effectiveness of the health care system and potentiate the capabilities of both the pharmacy and medical professions. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Future research should focus on the benefits of a collaborative practice between clinical pharmacists and nephrologists in countries that are lacking or are in the process of considering interprofessional collaborative care at this level. Reference: Exploring the role of pharmacists in outpatient dialysis centers: a qualitative study of nephrologist views Teresa M. Salgado, Rebekah Moles, Shalom I. Benrimoj, and Fernando Fernandez-Llimos Nephrol. Dial. Transplant. first published online December 30, 2012 doi:10.1093/ndt/gfs436 For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com

35 Incident Atrial Fibrillation and Risk of End-Stage Renal Disease in Adults with Chronic Kidney Disease Hemodialysis.com Author Interview: Nisha Bansal, MD, MAS Assistant Professor, Division of Nephrology University of California, San Francisco Hemodialysis.com Editor Marie Benz: What are the main findings of the study? Our study found that among adults with CKD, incident atrial fibrillation was independently associated with a 67% increased risk of ESRD. Hemodialysis.com: What should clinicians and patients take away from your report? Atrial fibrillation is very common among patients with CKD and has very important clinical consequences, including an association with subsequent ESRD as was seen in our study. Hemodialysis.com: What recommendations do you have for future research as a result of this study? Further research is needed to study mechanisms that link atrial fibrillation and progression of CKD. Exploration of these mechanisms may identify potential modifiable pathways. Reference: Incident Atrial Fibrillation and Risk of End-Stage Renal Disease in Adults with Chronic Kidney Disease Nisha Bansal, Dongjie Fan, Chi-yuan Hsu, Juan D. Ordonez, Gregory M. Marcus, and Alan S. Go Circulation. 2012;CIRCULATIONAHA.112.123992published online before print December 28 2012, doi:10.1161/CIRCULATIONAHA.112.123992 For Informational Purposes Only. Not for Specific Medical Advice Read more interviews on Hemodialysis.com


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