Author Interviews, Kidney Disease, Nature / 27.10.2015

MedicalResearch.com Interview with: Daniele Zink PhD Institute of Bioengineering and Nanotechnology Singapore  Medical Research: What is the background for this study? Dr. Zink: The kidney is one of the main target organs for toxic effects of drugs, environmental toxicants and other compounds. Renal proximal tubular cells (PTCs) are frequently affected due to their roles in compound transport and metabolism. Validated and accepted assays for the prediction of PTC toxicity in humans currently do not exist. Recently, we have developed the first and only pre-validated assays for the accurate prediction of PTC toxicity in humans 1, 2. This previous work was performed with human primary renal proximal tubular cells (HPTCs) or embryonic stem cell-derived HPTC-like cells. HPTCs are associated with a variety of issues that apply to all kinds of primary cells, such as cell sourcing problems, inter-donor variability and limited proliferative capacity. Embryonic stem cell-derived cells are associated with ethical and legal issues. These are the main reasons why induced pluripotent stem cell (iPSC)-derived cells are currently a favored cell source for in vitro toxicology and other applications. The problem was that stem cell-based approaches were not well-established with respect to the kidney. Recently, the group of IBN Executive Director Prof. Jackie Y. Ying developed the first protocol for differentiating embryonic stem cells into HPTC-like cells, and my group has contributed to characterizing these cells and publishing the results 3.  In the work published in Scientific Reports ,4we have applied a modified version of this protocol to iPSCs. In this way, we have established the simplest and fastest protocol ever for differentiating iPSCs into HPTC-like cells. The cells can be used for downstream applications after just 8 days of differentiation. These cells can also be applied directly without further purification due to their high purity of > 90%. By using these cells, we have developed the first and only iPSC-based model for the prediction of PTC toxicity in humans. This was achieved by combining our iPSC-based differentiation protocol with our previously developed assay based on interleukin (IL)6/IL8 induction 1, 2 and machine learning methods 5. Machine learning methods were used for data analysis and for determining the predictive performance of the assay. The test accuracy of the predictive iPSC-based model is 87%, and the assay is suitable for correctly identifying injury mechanisms and compound-induced cellular pathways. (more…)
Author Interviews, Genetic Research, Kidney Disease, Nature, Stem Cells / 24.10.2015

MedicalResearch.com Interview with: Benjamin Freedman, Ph.D. Assistant Professor | University of Washington Department of Medicine | Division of Nephrology Member, Kidney Research Institute Member, Institute for Stem Cell and Regenerative Medicine Seattle WA 98109  Medical Research: What is the background for this study? What are the main findings? Dr. Freedman: We are born with a limited number of kidney tubular subunits called nephrons. There are many different types of kidney disease that affect different parts of the nephron. The common denominator between all of these diseases is the irreversible loss of nephrons, which causes chronic kidney disease in 730 million patients worldwide, and end stage renal disease in 2.5 million. Few treatments have been discovered that specifically treat kidney disease, and the therapeutic gold standards, dialysis and transplant, are of limited availability and efficacy. Pluripotent stem cells are a renewable source of patient-specific human tissues for regeneration and disease analysis. In our study, we investigated the potential of pluripotent cells to re-create functional kidney tissue and disease in the lab. Pluripotent cells treated with a simple chemical cocktail matured into mini-kidney 'organoids' that closely resembled nephrons. Using an advanced gene editing technique called CRISPR, we created stem cells with genetic mutations linked to two common kidney diseases, polycystic kidney disease (PKD) and glomerulonephritis. Mini-kidneys derived from these genetically engineered cells showed specific 'symptoms' of these two different diseases in the petri dish. (more…)
Author Interviews, Bipolar Disorder, Kidney Disease, Lancet, Mental Health Research, Pharmacology / 24.10.2015

MedicalResearch.com Interview with: Dr. Stefan Clos MSc Applied Health Statistics Psychiatrist Murray Royal Hospital Scotland UK Medical Research: What is the background for this study? Dr. Clos: For more than 40 years there has been a debate about the long-term effect of lithium maintenance therapy on renal function. There is a lack of good quality data from randomized clinical trials and two previous meta-analyses from 2010 and 2012 suggest that little evidence exists for a clinically significant reduction in renal function in most patients who are on lithium therapy. However, the two publications point out the poor quality of available study data, emphasising the need for large scale epidemiological studies that control for confounders. Several population-based studies have since attempted to address this problem, but had insufficient ability to adjust for confounders or had limitations because of inappropriate cross-sectional study design or did not include an appropriate comparator group.  (more…)
Anemia, Author Interviews, Infections, Kidney Disease, UCSF / 21.10.2015

Dr. Julie H. Ishida MD San Francisco Veterans Affairs Medical Center Nephrology Section San Francisco, CAMedicalResearch.com Interview with: Dr. Julie H. Ishida MD San Francisco Veterans Affairs Medical Center Nephrology Section San Francisco, CA Medical Research: What is the background for this study? What are the main findings? Dr. Ishida: Intravenous iron is important in the treatment of anemia of end-stage renal disease, but it is biologically plausible that iron may increase infection risk. While results from epidemiologic studies evaluating the association between intravenous iron and infection in hemodialysis patients have been conflicting, guidelines for the treatment of anemia of chronic kidney disease have recommended caution in prescribing, avoidance and withholding of intravenous iron in the setting of active infection. However, no data specifically support the recommendation to withhold intravenous iron during active infection. Our study observed that among hemodialysis patients hospitalized for bacterial infection who had been receiving intravenous iron as an outpatient, continued receipt of intravenous iron was not associated with higher all-cause mortality, readmission for infection, or longer hospital stay. (more…)
Author Interviews, Calcium, Kidney Disease, Kidney Stones, Supplements, Vitamin D / 20.10.2015

MedicalResearch.com Interview with: Christopher Loftus M.D. candidate Cleveland Clinic Lerner College of Medicine Medical Research: What is the background for this study? What are the main findings? Response: Most kidney stones are made, at least partially, of calcium composite. In a prospective study of nurses in the post-menopausal age, it was found that diets that contained high amounts of calcium were beneficial in preventing kidney stones in this population. In the gut, calcium can bind to oxalate which prevents it from being absorbed into the body and decreases the concentration of calcium in the urine. However there has been debate as to whether supplemental calcium (calcium pills) has the same beneficial effects as calcium in the diet. Supplemental calcium enters the gut in large quantities all at once so it may enter the blood stream in higher concentrations over smaller amounts of time. By the same token, vitamin D plays a role in the management and balance of calcium in the body and could potentially have an effect on stone formation as well.  It has also been debated whether vitamin D supplementation has major effect on patients who are known to be stone formers.  So we reviewed CT scans of patients and 24 hour urine collections (both male and female of adult age) who were known to have kidney stones and measured the growth of stones over a period of time. Our main findings were that supplementary calcium increased the rate of stone formation in these patients. We also found that vitamin D had a protective effect and patients taking only vitamin D had a slower rate of stone progression. (more…)
Author Interviews, Cleveland Clinic, Heart Disease, JACC, Kidney Disease, Transplantation / 13.10.2015

W.H. Wilson Tang, MD, FACC Assistant Professor in Medicine, Cleveland Clinic Lerner College of Medicine Staff, Section of Heart Failure & Cardiac Transplant Medicine Assistant Program Director, General Clinical Research Center (GCRC) The Cleveland Clinic Cleveland, OHMedicalResearch.com Interview with: W.H. Wilson Tang, MD, FACC  Assistant Professor in Medicine, Cleveland Clinic Lerner College of Medicine Staff, Section of Heart Failure & Cardiac Transplant Medicine Assistant Program Director, General Clinical Research Center The Cleveland Clinic  Cleveland, OH Medical Research: What is the background for this study? What are the main findings? Dr. Tang: Cardiac function is a key determinant of outcomes after surgery, especially transplantation. End-stage renal disease (ESRD) poses a unique scenario, as the metabolic and uremic derangements that result from this condition lead to adverse cardiac remodeling, and kidney transplantation offers a potential for reverse remodeling. We studied patients who underwent kidney transplantation and found that echocardiogram following transplantation demonstrated consistent and significant improvement in cardiac structure and function. Post-transplant improvement in anemia was a vital factor that independently predicted such positive changes, whereas post-transplant changes in blood pressure, renal function at 12 months, and dialysis duration duration did not. Moreover, patients that demonstrated reverse remodeling had outcomes comparable to those with normal baseline cardiac function. (more…)
Author Interviews, Biomarkers, Cleveland Clinic, Heart Disease, JACC, Kidney Disease / 12.10.2015

Dr. Wilson Tang MD Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Director of the Center for Clinical Genomics Cleveland ClinicMedicalResearch.com Interview with: Dr. Wilson Tang MD Professor of Medicine Cleveland Clinic Lerner College of Medicine Case Western Reserve University Director of the Center for Clinical Genomics Cleveland Clinic  Medical Research: What is the background for this study? What are the main findings? Dr. Tang: Renal impairment has long been associated with worse outcomes in acute heart failure. Administration of diuretic therapy often obscures accurate assessment of renal function by urine output.  Despite extensive literature suggesting the poor outcomes in those with a rise in creatinine following treatment, recent data has suggested that in the presence of effective diuresis, this phenomenon likely represents hemoconcentration and azotemia rather than acute kidney injury.  We observed that using a novel and sensitive biomarker that identified acute kidney injury, specific to tubular injury, we can identify those at higher risk of adverse outcomes in patents admitted for acute heart failure.   However, after adjusting for standard risk factors, the prognostic value was clearly attenuated. (more…)
Author Interviews, Kidney Disease / 03.10.2015

Austin G. Stack MD., MSc., FRCPI. Professor and Foundation Chair of Medicine, Graduate Entry Medical School (GEMS),Consultant Nephrologist, University Hospital LimerickMedicalResearch.com Interview with: Austin G. Stack MD., MSc., FRCPI. Professor and Foundation Chair of Medicine, Graduate Entry Medical School (GEMS),Consultant Nephrologist, University Hospital Limerick Medical Research: What is the background for this study? Dr. Stack: Height is an important proxy for nutritional health and published studies in the general population have generally shown that taller individuals liver longer. Dialysis patients have life spans that may be 1/5th that of the general population, and it is important to identify those characteristics that are associated with greatest survival. Few studies have described the relationship between adult height and survival in patients undergoing dialysis in the Unites States. Our study, using data from the US Renal Registry, is the largest study ever conducted that has investigated the relationship with height and mortality risk in patients undergoing dialysis. (more…)
Author Interviews, Kidney Disease, Mayo Clinic, Sugar / 30.09.2015

Wisit Cheungpasitporn, MD Nephrology Fellow Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MNMedicalResearch.com Interview with: Wisit Cheungpasitporn, MD Nephrology Fellow Departments of Nephrology and Hypertension Program director: Suzanne Norby, MD Co-authors: Charat Thongprayoon, MD, Oisin A O'Corragain, MD, Peter J Edmonds, BS, Wonngarm Kittanamongkolchai, MD, Stephen B Erickson, MD Project mentor: Stephen B. Erickson, MD Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MN Medical Research: What is the background for this study? Dr. Cheungpasitporn: High-fructose corn syrup consumption in the form of sugar-sweetened soda has dramatically increased worldwide and associated with risk factors for chronic kidney disease (CKD) including diabetes mellitus (DM) and metabolic syndrome. Recently, artificial sweeteners have become commonly used in soda marketed as ‘diet’ alternatives. Recent studies have demonstrated that diet soda consumption may also be associated with weight gain, metabolic syndrome and cardiovascular disease. The risks of CKD in individuals with sugar-sweetened or diet soda consumption, however, were conflicting. We therefore conducted a meta-analysis to assess the associations between CKD and the consumption of sugar sweetened and diet soda. The findings of our study were recently published in Nephrology (Carlton). 2014; 19(12):791-7. Medical Research: What are the main findings? Dr. Cheungpasitporn: Five studies (2 prospective cohort studies, 2 cross-sectional studies and a case-control study) were included in our analysis of the association between consumption of sugar-sweetened soda (≥1-2 drinks of sugary soda/day) and CKD. We found an overall 1.58-fold increase CKD risk in individuals who regularly consumed sugar-sweetened soda with the pooled risk ratio (RR) of 1.58 (95% CI 1.00–2.49). Four studies (2 prospective cohort studies, a cross-sectional studies and a case-control study) were included to assess the association between CKD and diet soda consumption (≥1-2 drinks of diet soda/day). Despite a trend of chronic kidney disease risk in individuals with diet soda consumption with the pooled RR of 1.33 (95% CI 0.82–2.15), this association was not statistically significant. (more…)
Author Interviews, Gout, Heart Disease, Kidney Disease, Mayo Clinic / 14.09.2015

Wisit Cheungpasitporn, MD Nephrology Fellow Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MMedicalResearch.com Interview with: Wisit Cheungpasitporn, MD Nephrology Fellow Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MN Program director: Suzanne Norby, MD Co-authors: Charat Thongprayoon, MD, Andrew M. Harrison, BS and Stephen B. Erickson, MD Project mentors: Stephen B. Erickson, MD Departments of Nephrology and Hypertension Mayo Clinic, Rochester, MN   Medical Research: What is the background for this study? Dr. Cheungpasitporn: Uric acid has been linked to acute kidney injury (AKI) through crystal-dependent pathways and crystal-independent mechanisms, including reduced renal blood flow and glomerular filtration rate. Serum uric acid measurement has recently been examined as a marker for early AKI detection, especially in the setting of postoperative AKI following cardiovascular surgery. The effect of admission serum uric acid levels on the risk of in-hospital AKI in the general hospitalized patients, however, was unclear. Thus, we conducted a study to assess the risk of AKI in all hospitalized patients across different serum uric acid levels. The findings of our study data were recently published in Clinical Kidney Journal. (more…)
Author Interviews, Diabetes, Heart Disease, Karolinski Institute, Kidney Disease / 12.09.2015

MedicalResearch.com Interview with: Dr. Daniel Hertzberg M.D., Ph.D. Student Department of Medicine, Solna Karolinska University Hospital Medical Research: What is the background for this study? Dr. Hertzberg: Acute Kidney Injury (AKI) is a common complication in patients undergoing cardiac surgery. It is associated with increased short and long-term mortality, myocardial infarction, heart failure and chronic kidney disease. Diabetes is often considered as a risk factor for AKI. However, when we searched the literature we did not find any studies which specifically studied diabetes as a risk factor for AKI. In addition, in observational studies, it is uncommon that diabetes is subtyped into type 1 or type 2 even though they have different etiologies and thus may have different impact on risk of adverse outcomes. Thus, we designed this study in order to study the association between the two subtypes of diabetes and risk of AKI. (more…)
Author Interviews, Diabetes, JAMA, Kidney Disease / 01.09.2015

George L. Bakris MD Professor of Medicine Director, Comprehensive Hypertension Center University of Chicago MedicineMedicalResearch.com Interview with: George L. Bakris MD Professor of Medicine Director, Comprehensive Hypertension Center University of Chicago Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Bakris: Aldosterone receptor antagonists such as spironolactone are known to reduce mortality from heart failure and reduce albuminuria, a well-known marker of diabetic kidney disease progression. Finerenone is a novel nonsteroidal aldosterone receptor antagonist and is associated with less hyperkalemia (high blood potassium levels) compared to traditional aldosterone receptor blockers like spironolactone. The current study was a dose finding study to ascertain the optimal dose of finerenone for reducing urine albumin (a key risk marker in people with diabetic kidney disease) that is also associated with the smallest rise in serum potassium. The main findings are that in a dose dependent manner finerenone reduced albuminuria and at the highest dose a modest rise in serum potassium. Finerenone was also very well tolerated.  (more…)
Author Interviews, Heart Disease, Kidney Disease / 22.08.2015

Tae-Hyun Yoo MD PhD Department of Internal Medicine, College of Medicine Severance Biomedical Science Institute, Brain Korea 21 PLUS Yonsei University, Seoul, KoreaMedicalResearch.com Interview with: Tae-Hyun Yoo MD PhD Department of Internal Medicine, College of Medicine Severance Biomedical Science Institute, Brain Korea 21 PLUS Yonsei University, Seoul, Korea Medical Research: What is the background for this study? What are the main findings? Dr. Tae-Hyun Yoo: Sarcopenia, reduction in muscle mass, is frequently observed in PEW and is prevalent in chronic kidney disease (CKD) patients. In ESRD patients, sarcopenia is significantly associated with greater mortality. Skeletal muscles produce and release myokines, which  suggested to mediate their protective effects. Irisin, a novel myokine, has been introduced to drive brown-fat-like conversion of white adipose tissue and has beneficial effects of skeletal muscle on energy homeostasis and glucose metabolisms. Therefore, we hypothesized that irisin had significant association with sarcopenia and cardiovascular disease in dialysis patients. In peritoneal dialysis patients, serum irisin was positively correlated with mid-arm muscle circumference and thigh circumference. In addition, serum irisin was a significant independent predictor for carotid atherosclerosis even after adjustment for high-sensitivity C-reactive protein in these patients. This study demonstrated that serum irisin was significantly associated with sarcopenia and carotid atherosclerosis in peritoneal dialysis patients. (more…)
Author Interviews, Kidney Disease, Lancet, Weight Research / 21.08.2015

Dr. Csaba P. Kovesdy MedicalResearch.com Interview with: Dr. Csaba P. Kovesdy, MD Professor of Medicine University of Tennessee Health Science Center Chief of Nephrology Memphis Veterans Affairs Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Kovesdy: Obesity has reached epidemic proportions in modern societies, and has been linked to adverse outcomes such as diabetes mellitus, hypertension, cardiovascular disease and mortality. In addition, obesity is also associated with chronic kidney disease through a variety of mechanisms. Our population is ageing, and previous studies have suggested that the effect of obesity on certain outcomes like mortality may be different in older vs. younger individuals, but this has not been previously examined for chronic kidney disease. We have this examined the association of granular BMI categories with progressive loss of kidney function in a very large cohort of patients with normal estimated GFR in patients of different ages. We found that the association of a BMI of >30 kg/m2 with progressive loss of kidney function was not present in younger individuals (< 40 years of age), and increased as people aged, with >80 years old displaying the strongest associations between obesity and loss of kidney function. In addition to this we also examined the association of BMI with mortality in different age groups, and found uniform U-shaped associations that did not vary by age. (more…)
Author Interviews, Diabetes, Kidney Disease, Lancet / 12.08.2015

MedicalResearch.com Interview with: Prof. Der-Cherng Tarng, MD, PhD Division of Nephrology Taipei Veterans General Hospital, and National Yang-Ming University, Taiwan MedicalResearch: What is the background for this study? What are the main findings? Prof. Tarng: Metformin is generally recommended as a first-line therapy for type 2 diabetes mellitus, but the use of metformin has been limited in patients with impaired kidney function because of the perceived risk of lactic acidosis. More recently, available evidence supports the cautious expansion of metformin use in patients with mild to moderate chronic kidney disease (CKD). However, no studies have yet examined whether metformin can be prescribed more widely to patients with advanced CKD. We conducted a propensity score-matched cohort study using Taiwan’s National Health Insurance Research Database to assess the safety of metformin in patients with type 2 diabetes and serum creatinine levels >6 mg/dL, enrolled between January 1, 2000 and June 30, 2009 and followed-up until December 31, 2009, before Taiwan’s prescribing guidelines for metformin contraindicated its use in patients with CKD. From a consecutive sample of 12350 patients, 1005 (8.1%) were metformin users. Of these, 813 were successfully matched 1:3 to 2439 metformin nonusers. After multivariate adjustment, metformin use remained was an independent risk factor for mortality (hazard ratio 1.35, 95% confidence interval 1.20–1.45; p<0.0001). The increased risk was dose-dependent and was consistent across all subgroup analyses. However, metformin users compared with non-users were associated with a higher but insignificant risk of metabolic acidosis (hazard ratio 1.30, 95% confidence interval 0.88–1.93; p=0.188). (more…)
Author Interviews, Kidney Disease, Mayo Clinic, Radiology / 11.08.2015

MedicalResearJennifer S. McDonald Ph.D Assistant Professor Department of Radiology Mayo Clinicch.com Interview with: Jennifer S. McDonald Ph.D Assistant Professor Department of Radiology Mayo Clinic Medical Research: What is the background for this study? What are the main findings? Dr. McDonald: Our research group is interested in studying contrast-induced nephropathy (CIN), which is the development of acute kidney injury following administration of iodinated contrast material. Iodinated contrast material is frequently administered during CT examinations. Recent publications, including those by our group, suggest that the incidence of contrast-induced nephropathy has been overestimated by prior, uncontrolled studies. The purpose of our study was to better evaluate the incidence and severity of CIN in patients with diminished renal function (eGFR < 60 ml/min/1.73m2). In the current article, we performed a controlled retrospective study comparing patients who received a contrast-enhanced CT scan at our institution to patients who received an unenhanced CT scan. We used propensity score analysis that incorporated numerous variables to match contrast recipients and control patients with similar clinical characteristics. After performing this analysis, we found that the rate of AKI, emergent dialysis, and short-term mortality was similar between contrast recipients and control patients. (more…)
Author Interviews, Emory, JAMA, Kidney Disease / 11.08.2015

Rachel Patzer, PhD, MPH Director of Health Services Research, Emory Transplant Center Assistant Professor Department of Surgery Division of Transplantation Emory University School of MedicineMedicalResearch.com Interview with: Rachel Patzer, PhD, MPH Director of Health Services Research, Emory Transplant Center Assistant Professor Department of Surgery Division of Transplantation Emory University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Patzer: There are two main treatments for patients with end stage kidney disease: dialysis or kidney transplantation.  Kidney transplantation offers the best survival and quality of life compared to dialysis.  However, there is a limited supply of organs in the U.S., so not all patients with end stage organ failure get a kidney transplant. Certain regions of the country have lower access to kidney transplantation than other regions.  The Southeastern United States (GA, NC, and SC) has the lowest rates of kidney transplantation in the nation, and Georgia (GA) is the state that ranks at the very bottom. Our research team and collaborators from the Southeastern Kidney Transplant Coalition sought to examine some of the reasons for why Georgia had the lowest rates of kidney transplantation in the nation.  The transplant centers in our Coalition collaborated to share data on patient referrals from dialysis facilities, where the majority of end stage renal disease patients receive treatment, to transplant centers in Georgia. Referral from a dialysis facility to a transplant center is required for patients to undergo the extensive medical evaluation that is required for a patient to either be placed on the national deceased donor waiting list, or to receive a living donor kidney transplant (e.g. from a friend or family member). There were several major findings: 1)    That overall, referral of patients from a dialysis facility to a kidney transplant center is low (only about 28% of patients with kidney failure are referred to a transplant center within a year of starting dialysis). 2)    There was much variation in referral for transplantation across dialysis facilities in GA, where some facilities referred no patients within a year, and others referred up to 75% of their patient population. (more…)
Anemia, Author Interviews, Biomarkers, Kidney Disease, Mineral Metabolism / 10.08.2015

MedicalResearch.com Interview with: Lac Tran, MD Division of Nephrology and Hypertension Kaiser Permanente Los Angeles Medical Center Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Tran: Abnormal serum phosphorus levels have been associated with adverse cardiovascular outcomes and progression to renal failure.  Given phosphorus’s important biological roles in cellular replication and bone mineral metabolism, we sought to investigate the association between phosphorus levels and anemia in normal kidney function and early chronic kidney disease. Our study is a population-based study among a large racially/ethnically diverse population within the Kaiser Permanente Southern California health system. Among 155, 974 individuals, 4.1% had moderate anemia and 12.9% had mild anemia.  We found that phosphorus levels greater than 3.5 mg/dL and less than 2.0 mg/dL showed a greater likelihood for moderate anemia.  Every 0.5 mg/dL phosphorus level increase demonstrated a 16% greater likelihood for moderate anemia.  The highest phosphorus tertile of our population had a 26% greater likelihood for anemia compared to the middle tertile.  We also found that female sex, Asian race, diabetes, low albumin, and low iron saturation were risk factors for anemia. (more…)
Author Interviews, Blood Pressure - Hypertension, BMJ, Kidney Disease / 10.07.2015

Gijs Van Pottelbergh, MD, PhD Department of Health and Technology Leuven University College Leuven, BelgiumMedicalResearch.com Interview with: Gijs Van Pottelbergh, MD, PhD Department of Health and Technology Leuven University College Leuven, Belgium Medical Research: What is the background for this study? What are the main findings? Response: Earlier research identified arterial hypertension as a cause of chronic kidney disease but in older persons the relation between blood pressure and kidney function is little investigated.This study analyses the relation between dynamic blood pressure measurements and kidney function over time. A decline in blood pressure over time turned out to be a strong risk factor for kidney function decline in all age strata. (more…)
Author Interviews, Kidney Disease, Social Issues / 18.06.2015

Holly Kramer, MD, MPH Department of Public Health Sciences Loyola University Chicago Health Sciences Campus Maywood, ILMedicalResearch.com Interview with: Holly Kramer, MD, MPH Department of Public Health Sciences Loyola University Chicago Health Sciences Campus Maywood, IL MedicalResearch: What is the background for this study? What are the main findings? Dr. Kramer: The U.S. dialysis dependent population continues to grow with  636,905 prevalent cases of end-stage renal disease (ESRD) in the U.S. as of December 31, 2012, , an increase of 3.7% since 2011.  Poverty is a well described risk factor for ESRD because poverty impacts access to care and nutritious foods.  The definitions for poverty in the U.S. have not changed over the past several decades despite marked changes in social structure.  For example, social integration in the U.S. society currently requires a cell phone, computer and internet access and access to transportation.  Healthy foods also cost more now relative to unhealthy foods compared to past decades.  Thus, the link between poverty and any chronic disease or health outcome is likely dynamic due to the evolving financial burden for living in a rapidly changing industrialized society.  Our study defined poverty as living in a zip code defined area with > 20% of the residents living below the federal poverty line.  We show that the prevalence of adults receiving dialysis who are living in poverty has increased over time.  We also show that the association between poverty and ESRD may be getting stronger over time.   (more…)
Author Interviews, Kidney Disease, Telemedicine / 18.06.2015

MedicalResearch.com Interview with: Judy K. Tan, MD Department of Nephrology Mount Sinai Hospital New York, New York MedicalResearch: What is the background for this study? What are the main findings? Dr. Tan: Chronic kidney disease (CKD) is a common life-threatening medical condition, affecting approximately 26 million adults in the U.S. In Veterans Integrated Service Network (VISN) 3, veterans with CKD who reside in the Hudson Valley Veterans Affair Medical Center (VAMC) catchment area travel to the James J. Peters VAMC, a tertiary care facility in the Bronx for their nephrology care. However, because of several barriers such as (1) distance between the two facilities (approximately 60 miles) and (2) patient complexity (medical and psychiatric illnesses), patients referred to the James J. Peters VAMC renal clinic from Hudson Valley VAMC often cancel or “no show”. This poor compliance increases the long-term risk of rapid progression of CKD and the development of complications associated with it.  To address this issue, the division of nephrology at the James J. Peters VAMC, in line with the veterans affairs’ focus on “patient-centered care,” developed a collaborative out-patient telenephrology service as a means to deliver care. The out-patient telenephrology service employs specialized global medical video conferencing equipment with customized medical instruments (ie stethoscopes) and Computerized Patient Record System (CPRS) accessibility to direct real-time evaluation and management of our veterans with CKD while they stay in their local VAMC. As demonstrated by Rohatgi et al, this intervention significantly increased the compliance rate of patients and reduced the travel time, miles, and cost of patients utilizing the telenephrology service.1 The hypothesis of our study is that patients with CKD remotely managed through our telenephrology service would exhibit comparable clinical outcomes and visit compliance as conventional in-person renal care. Our provisional analysis of the subjects followed in the telenephrology service showed 117 unique patients were evaluated between 2011-2014. The mean age was 71±11years old with 98.3% males. 70% of the patients were white and 26.5% African American. The predominant etiology of chronic kidney disease was diabetic nephropathy (31.6%) followed by hypertensive nephrosclerosis (26.5%). In the 87 patients who had 1-year follow up data, estimated glomerular filtration (eGFR) was well preserved over the year (33 mL/min vs. 32 mL/min; p=0.04). Systolic blood pressure (BP) was reduced from 138±20 to 133±16 mm Hg (p=0.03), but no difference was observed in diastolic BP. Urine protein-creatinine ratio fell from 0.58 to 0.25 (p=0.07). 94% of patients had parathyroid levels checked and 70.9% were on ACE inhibitors during the first year of follow up. (more…)
Author Interviews, Biomarkers, Kidney Disease, University of Pittsburgh / 14.06.2015

MedicalResearch.com Interview with: Raghavan Murugan MD, MS, FRCP, FCCP Associate Professor of Critical Care Medicine and Clinical and Translational Science Core Faculty, Center for Critical Care Nephrology, CRISMA Center, Raghavan Murugan MD, MS, FRCP, FCCP Associate Professor of Critical Care Medicine and Clinical and Translational Science Core Faculty, Center for Critical Care Nephrology, CRISMA Center, John Kellum, MD Professor and Vice Chair for Research Director, Bioengineering and Organ Support Program, CRISMA Center Director, Center for Assistance in Research using eRecord (CARe)John Kellum, MD Professor and Vice Chair for Research Director, Bioengineering and Organ Support Program, CRISMA Center Director, Center for Assistance in Research using eRecord (CARe) Department of Critical Care Medicine University of Pittsburgh Pittsburgh, PA Medical Research: What is the background for this study? What are the main findings? Response: In our prior studies, we found that nearly one-half of critically ill patients in the intensive care unit who receive dialysis die by 2 months after acute illness and more than one-third of surviving patients are dialysis dependent. We sought to examine whether simple patient characteristics and inflammatory biomarkers predicted death and non-recovery of kidney function after severe acute kidney injury. We found that a combination of four simple and readily available patient characteristics including older age, lower mean arterial pressure, need for mechanical ventilation, and higher serum bilirubin levels predicted death and dialysis dependence. Higher plasma concentration of interleukin (IL)-8 in combination with the clinical characteristics also increased risk prediction. To our knowledge, this study is the first large study to examine risk prediction for outcomes after severe acute kidney injury using a panel of biomarkers in a large cohort of critically ill patients receiving dialysis. (more…)
Author Interviews, Diabetes, Immunotherapy, Kidney Disease, University of Michigan / 13.06.2015

MedicalResearch.com Interview with: Frank C. Brosius, MD Professor, Internal Medicine and Physiology Chief, Division of Nephrology University of Michigan Ann Arbor, MI Dr. Matthias Kretzler MD Professor, Internal Medicine Research Professor, Computational Medicine and Biology University of Michigan Ann Arbor, MI Katherine R. Tuttle MD Clinical Professor of Medicine, Division of Nephrology Medical & Scientific Director, Providence Medical Research Center/Sacred Heart Center Professor of Basic Medical Sciences, WWAMI Program Washington State University Medical Research: What is the background for this study? Response: Our University of Michigan team had found that JAK-STAT gene expression was increased in kidneys in patients with diabetic kidney disease and that these changes correlated with progression of kidney disease.  We subsequently substantiated these changes in other studies and have found that by increasing expression of just one of these genes, JAK2, in a single kidney cell type (podocytes) in mice that we can make their diabetic kidney disease much worse. At around the same time, investigators at Eli Lilly and Co. had FDA approval to test a JAK1-2 inhibitor, baricitinib, in patients with rheumatoid arthritis.  The Lilly scientists saw our human results and thought about using baricitinib in patients with diabetic kidney disease.  After initial discussions with Dr. Kretzler and myself they concluded that there was good reason to move ahead with this study and just 14 months after the initial meeting the phase 2 clinical trial of baricitinib in the treatment of patients with diabetic kidney disease was initiated. (more…)
Author Interviews, Blood Pressure - Hypertension, Geriatrics, Kidney Disease / 24.05.2015

Enayet Karim Chowdhury, Research Fellow Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University The Alfred Centre Melbourne VIC 3004MedicalResearch.com Interview with: Enayet Karim Chowdhury, Research Fellow Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University The Alfred Centre Melbourne VIC 3004 Medical Research: What is the background for this study? What are the main findings? Dr. Chowdhury: The study was conducted on elderly treated hypertensive population. Australia is currently undergoing a demographic transition towards having increasing number of older people. As age advances quality of life becomes increasingly affected by a variety of chronic diseases including poor renal function. Therefore early detection and management of the risk associated with these chronic diseases is crucial. Managing hypertension, even though challenging, can significantly improve quality of life of a person by reducing risk of having cardiovascular events. The main finding of the study is that in elderly treated hypertensive people, a rapid decline in renal function was associated with a higher risk of having cardiovascular events irrespective of having chronic kidney disease or not. (more…)
Author Interviews, Heart Disease, Kidney Disease / 12.05.2015

MedicalResearch.com Interview with: Kirolos A. Jacob, MD, MSc PhD Candidate Division Vital Functions, Cardiothoracic Surgery and Intensive Care Medicine University Medical Center Utrecht Medical Research: What is the background for this study? What are the main findings? Dr. Jacob: Heart surgery carries many risks for a patient undergoing such a procedure. One of the most devastating complications following open heart surgery is kidney failure requiring dialysis. Most of these patients who develop kidney failure requiring dialysis after surgery have some form of chronic kidney disease before the operation, which placed them at especially high risk. Approximately one out of every 100 patients undergoing open heart surgery develops severe kidney failure. When such kidney failure occurs, the patient has more than 40% chance of dying. 1% sounds like a small percentage, however given the fact that each year, over half a million people undergo heart surgery in the USA alone, this means that an estimated 5,000 patients develop renal failure and of those about 2,500 die as a result of this complication. This figure is rising yearly as more and more patients are being operated due to the aging population. Also, this elderly population has often significant pre-existing kidney disease, further increasing the incidence of kidney failure after a heart operation. Thus, treatment strategies are needed for this relatively small yet very important and expanding group of patients. Heart surgery initiates an inflammatory reaction across the human body due to the surgical trauma and the heart-lung machine. This systemic immune system reaction is thought to play a vital role in the development of kidney injury after heart surgery. Our study investigated the effects of dexamethasone, a strong anti-inflammatory drug, on severe kidney injury after heart surgery. Severe kidney injury was defined as the use of dialysis during the hospital stay after surgery. We discovered that patients who receive the drug used 56% less frequently kidney dialysis, when compared to those receiving a placebo. Thus patients who did not receive the drug had about 2.5x higher risk for developing kidney failure when compared to those receiving dexamethasone. The beneficial effects of dexamethasone were particularly present in those who already had pre-existing kidney disease before heart surgery. This reinforces the fact that this drug could be of major importance for the increasing elderly population with pre-existing kidney disease undergoing a heart operation. (more…)
Author Interviews, End of Life Care, Heart Disease, JAMA, Kidney Disease / 27.04.2015

MedicalResearch.com Interview with: Susan P. Y. Wong, M.D. Acting Instructor & Senior Research Fellow Division of Nephrology University of Washington Medical Research: What is the background for this study? What are the main findings? Dr. Wong: There is a paucity of information on the use of cardiopulmonary resuscitation (CPR) and its outcomes among patients receiving maintenance dialysis. To address this knowledge gap, we performed a retrospective study to define contemporary trends in in-hospital CPR use and its outcomes among a nationally representative sample of 663,734 patients receiving maintenance dialysis between 2000 and 2011. We found that in-hospital CPR use among this cohort of patients was very high—nearly 20 times more common than that found in the general population. The rate of in-hospital CPR use has also been increasing among patients receiving maintenance dialysis despite evidence of poor long-term survival among these patients. Median survival after hospital discharge for members of this cohort was only 5 months, and this has not change substantially in the recent decade. We also found that a large proportion  of dialysis patients who died in hospital settings had received CPR during their terminal hospitalization. This proportion has also been steadily increasing over time, and in 2011, 1 in 5 dialysis patients who died in hospital had received CPR during their terminal hospitalization. (more…)
Author Interviews, Kidney Disease, UCLA / 07.04.2015

MedicalResearch.com Interview with: Bryan B. Shapiro Harold Simmons Center for Kidney Disease Research and Epidemiology and Division of Nephrology and Hypertension Los Angeles Biomedical Research Institute Harbor–UCLA Medical Center Torrance, California Medical Research: What is the background for this study? What are the main findings? Response: The inverse relationship between body mass index (BMI) and mortality rates is well-documented in maintenance hemodialysis (MHD) patients. Virtually everyone has assumed that this relationship reflects the effect of body weight, and especially fat mass, on mortality in these patients. However, height is also a component of the BMI equation (BMI = body weight (kg)/height (m²)) and may be independently associated  with mortality in MHD patients. The results of this study, which examined 117, 644 MHD patients and was controlled for many demographic and laboratory variables, indicate that height, adjusted for body weight, is directly associated with mortality in a manner that is opposite to the weight-mortality relationship. Moreover, we found that the contribution of height to the inverse BMI-mortality relationship in dialysis is essentially as great as the contribution of weight. (more…)
Author Interviews, Kidney Disease, OBGYNE, Pharmacology / 01.04.2015

Dr. Mala Sachdeva MD North Shore University Hospital, Long Island Jewish Medical Center Assistant Professor, Nephrology, Internal Medicine Hofstra North Shore-LIJ School of MedicineMedicalResearch.com Interview with: Dr. Mala Sachdeva MD North Shore University Hospital, Long Island Jewish Medical Center Assistant Professor, Nephrology, Internal Medicine Hofstra North Shore-LIJ School of Medicine Medical Research: What is the background for this study? Dr. Sachdeva: The last study examining pregnancy and dialysis outcomes in the United States was performed more than 15 years ago. Our study was conducted to evaluate practice patterns and to trend maternal and fetal outcomes in the pregnant dialysis female over the past five years. We did a surveymonkey-based survey of American nephrologists on their knowledge of managing pregnancy patients on dialysis. Medical Research: What are the main findings? Dr. Sachdeva: Over the past five years, more than 59 pregnancies have been reported. During this time period, almost half of the American nephrologist respondents (43%) have cared for pregnant females on hemodialysis. Hence, we can see that more nephrologists are now faced with taking care of the pregnant dialysis patient. Although a good number of patients initiated dialysis during pregnancy (32%), the majority (58%) of pregnancies occurred within the first five years of being on maintenance dialysis. Pregnancy outcomes can improve. Of the reported pregnancies 23% did not result in live births. 50% of the pregnancies were complicated by preeclampsia. There were no maternal deaths. Most nephrologists prescribe 4 to 4.5 hours of hemodialysis. 64% of respondents provide dialysis for six days per week. Only 21% aimed for a target predialysis BUN of less than 20 mg/dL while 66% of nephrologists targeted a BUN less than 50mg/dL.  75% of respondents do not have access to fetal monitoring during dialysis for their pregnant patient. There are approximately 32% of American nephrologists who are somewhat to very uncomfortable caring for a pregnant woman on hemodialysis. 51% of American nephrologists or a member of their staff counsel their female dialysis patients about contraception. So in summary, while majority of the US based nephrologists are trying to dialyze pregnant ESRD patients with more intense prescriptions, there are still some gaps with comfort and knowledge. (more…)
Author Interviews, Gender Differences, Kidney Disease, Kidney Stones, Mayo Clinic / 30.03.2015

MedicalResearch.com Interview with: Majuran Perinpam, BsC Mayo Clinic Rochester, Minn MedicalResearch: What is the background for this study? Response: The four key urinary factors: Calcium, magnesium, oxalate and uric acid are all implicated in kidney stone formation. Age and sex are known to influence kidney stone risk and type (1). However the effects of demographics on excretion of the four key urinary factors are not clear. Since diet alters urinary excretions of the four factors, adjusting for this is important. During metabolic evaluation of kidney stone patients, these urinary factors are often measured in 24-hour urine samples. However, often a single adult reference range is used and the effect of demographics is rarely taken into account during the interpretation of results. MedicalResearch: What are the main findings? Response: From a cohort of 709 healthy individuals we found a substantial influence of age and sex on the excretion of urinary calcium. Adjusted models showed that urinary calcium, magnesium, oxalate and uric acid were all less in females, possibly explaining why kidney stones are more dominant in males (1). Also a positive association of urinary uric acid excretion with Cystatin C eGFR, but not eGFR calculated from creatinine, suggests cystatin C to possibly being involved in inflammation and hyperuricemia. But further studies are needed to investigate this. (more…)