Author Interviews, Diabetes, Kidney Disease / 17.04.2016 Interview with: Axel C. Carlsson, PhD Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University Uppsala Sweden What is the background for this study? Dr. Carlsson: Circulating endostatin levels has been shown to be associated with duration of hypertension and cardiovascular events. Moreover, endostatin levels were recently shown to parallel kidney function decline, and has been associated with increased mortality risk in different settings. However, less is known of circulating endostatin in patients with type 2 diabetes.  (more…)
Author Interviews, HPV, Kidney Disease, Transplantation, Vaccine Studies / 15.04.2016 Interview with: Dr. Delphine Robotham MD Division of Pediatric Nephrology Johns Hopkins University School of Medicine Baltimore, Maryland Medical Research: What is the background for this study? What are the main findings? Response: Cervical cancer is the second most common cancer in women worldwide and is almost entirely caused by high risk HPV genotypes.  Vaccines to high risk HPV genotypes have shown great success in protecting healthy women from the sequelae of infection, including cervical cancer and genital warts. Young women with a kidney transplant as well as those with chronic kidney disease have abnormal immune systems and as a result have a significantly increased burden of HPV-related disease making the potential health benefits of the HPV vaccine substantial in this particularly vulnerable population.  This study examined the immune response to the HPV vaccine among girls and young women with kidney disease. The goal of this research was to determine if girls and young women with chronic kidney disease (abnormal kidney function, on dialysis, or post kidney transplant) showed evidence of immune response to the quadrivalent HPV vaccine.  Immune response was determined by measuring the amount of antibody made by the patients against each of the 4 HPV genotypes included in the vaccine.  There are established thresholds of antibody above which patients are believed to have protection from infection.  We found that study participants with chronic kidney disease and those on dialysis had antibody levels above the threshold, indicating the vaccine should be effective in protecting them from HPV related disease.  A significant proportion of patients with kidney transplants showed evidence of inadequate antibody response.  This is important information as it means patients with a kidney transplant, whom we know are at increased risk of developing cervical cancer from HPV infection, may not be protected from HPV infections from the HPV genotypes included in the vaccine. (more…)
Author Interviews, Blood Pressure - Hypertension, Kidney Disease, Salt-Sodium / 31.03.2016 Interview with: Matthew Bailey PhD Faculty Principal Investigator British Heart Foundation Centre for Cardiovascular Science The University of Edinburgh, Edinburgh, United Kingdom. What is the background for this study? Dr. Bailey: This study started with our interest in salt homeostasis and long term blood pressure, so it’s firmly rooted in the cardiovascular/renal disease risk factor arena. We were interested in salt-sensitivity- why does blood pressure go up in some people when they eat salt but not in others. I’m a renal physiologist, so we had a number of papers looking at renal salt excretion and blood pressure. We initially used a gene targeting approach to remove a gene (Hsd11b2) which acts as a suppressor of the mineralocorticoid pathway. It’s mainly expressed in the kidney and when we deleted the gene  throughout the body we saw a number of renal abnormalities all associated with high mineralocorticoid activity. This was consistent with the “hypertension follows the kidney” theory of blood pressure control. There is a human disease called “Apparent Mineralocorticoid Excess”- there are people do not have the gene and are thought to have renal hypertension. Our study threw up some anomalies which we couldn’t easily interpret but suggested that the brain was involved. We moved to a more refined technology that allowed us to knockout a gene in one organ system but not another. We knew the gene was in the brain and localized to a very restricted subset of neurons linked to salt-appetite and blood pressure control. Previous studies had shown that these neurons were activated in salt-depleted rats (ie rats that needed to eat salt). We started there but didn’t anticipate that the effect on salt hunger and on blood pressure would be so large because renal function is -as far as we can tell- normal. (more…)
Author Interviews, End of Life Care, Geriatrics, Kidney Disease / 24.03.2016 Interview with: Dr. Wouter R. Verberne Koekoekslaan 1 The Netherlands What is the background for this study? Dr. Verberne: The number of older patients with End Stage Renal Disease (ESRD) is increasing worldwide. When ESRD is approaching, patients need to be advised on the renal replacement therapy (RRT) necessary to remove toxic products and fluid from the body when their own kidneys are no longer able to do so. ESRD can be treated with kidney transplantation, hemodialysis or peritoneal dialysis. With increasing technical possibilities and with the widespread availability of dialysis treatment, age no longer limits dialysis treatment. It has been questioned whether older patients with ESRD, who often have multiple comorbidities, are likely to benefit from renal replacement therapy. Dialysis treatment comes with high treatment burden. Generally patients are treated in a dialysis facility 3 times per week, 3 to 4 hours per time. Patients with an anticipated poor prognosis on RRT may choose to forego dialysis and decide to be treated conservatively instead. Conservative management (CM) entails ongoing care with full medical treatment, including control of fluid and electrolyte balance and correcting anemia, and provision of appropriate palliative and end of life care. Shared decision making has been recommended to come to a joint decision on   renal replacement therapy by considering potential benefits and harms of all treatment options and the patient’s preferences. Data on outcomes, including survival and quality of life, are needed to foster the decision making. However, adequate survival data, specifically on older patients, are limited. A number of studies, predominantly from the United Kingdom, have determined survival of older patients managed conservatively compared with renal replacement therapy. In these studies, the numbers of recruited patients are generally small, the studies are performed in heterogeneous study populations, and there is significant variability in starting points used in survival analyses. We performed the first Dutch study in a large series of older patients slowly approaching ESRD, enabling the use of several starting points in survival analyses. The aims of the study were to compare survival in patients with ESRD ages ≥ 70 years old choosing either conservative management or renal replacement therapy and determine predictors of survival.  (more…)
Author Interviews, Johns Hopkins, Kidney Disease, Race/Ethnic Diversity, Transplantation / 26.02.2016 Interview with: Tanjala S. Purnell, PhD MPH Assistant Professor, Transplant Surgery and Epidemiology Johns Hopkins University School of Medicine  Medical Research: What is the background for this study? Dr. Purnell:  Kidney transplantation (KT) is the best treatment for most patients with end stage renal disease (ESRD), offering longer life expectancy and improved quality of life than dialysis treatment. Despite these benefits, previous reports suggest that black KT recipients experience poorer outcomes, such as higher kidney rejection and patient death, than white KT recipients. Our team wanted to examine whether this disparity has improved in recent decades. We hypothesized that advances in immunosuppression and post- kidney transplantation  management might differentially benefit black KT recipients, who were disproportionately burdened by immunological barriers, and contribute to reduced racial disparities in kidney transplantation outcomes. Medical Research: What are the main findings? Dr. Purnell: 
  1. From 1990 to 2012, 5-year failure rates of the transplanted kidney after Deceased Donor Kidney Transplantation (DDKT) decreased from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5-year failure after Living Donor Kidney Transplantation (LDKT) decreased from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites.
  2. Among DDKT recipients in the earliest group of patients, blacks were 39% more likely than whites to experience 5-year failure, but this disparity narrowed to 10% in the most recent group.
  3. Among LDKT recipients in the earliest group, blacks were 53% more likely than whites to experience 5-year failure, but this disparity narrowed to 37% in the most recent group.
  4. There were no statistically significant differences in 1-year or 3-year failure rates of transplanted kidneys after LDKT or DDKT in the most recent groups.
Author Interviews, Heart Disease, JAMA, Kidney Disease, Pharmacology / 24.02.2016 Interview with: Frederic T. Billings IV, MD, MSc Assistant Professor of Anesthesiology and Medicine Additional Specialty: Cardiothoracic Anesthesiology Vanderbilt University Medical Research: What is the background for this study? What are the main findings? Dr. Billings: Acute kidney injury (AKI) affects up to 30% of patients following cardiac surgery and is associated with long-term kidney function decline as well as a 5-fold increase in death during hospitalization following surgery. Statins affect several mechanisms of AKI following cardiac surgery including improvement of endothelial function and attenuation of oxidative stress, so we performed a clinical trial to test the hypothesis that high-dose atorvastatin (brand name Lipitor) use prior to and following surgery reduces AKI following cardiac surgery. In 615 patients who completed the study high-dose atorvastatin treatment, compared to placebo administration, did not reduce the risk of AKI overall, among patients naïve to statins, or patients already using a statin. In fact, among patients naïve to statins with baseline chronic kidney disease we found some evidence that atorvastatin may increase risk for kidney injury, although the number of patients was small in this subgroup. (more…)
Anemia, Author Interviews, Kidney Disease, Pharmacology / 22.02.2016 Interview with: Dr. Navdeep Tangri Attending physician and Assistant Professor in the Division of Nephrology Department of Medicine and the Department of Community Health Sciences University of Manitoba and Dr. David Collister  Seven Oaks General Hospital Renal Program Winnipeg, Manitoba Canada.  Medical Research: What is the background for this study? What are the main findings? Response: Anemia is common in chronic kidney disease (CKD) including dialysis and its treatment with erythopoetin stimulating agents (ESAs) reduces the need for blood transfusions and has varying effects on morbidity and mortality. The optimal hemoglobin (HGB) targets for treating anemia in CKD are controversial with safety concerns around the normalization of hemoglobin levels due to an increase in cardiovascular (CV) events. The effects of ESAs on health related quality of life (HRQOL) are unclear with individualization o fhemoglobin targets being controversial as clinicians and patients attempt to balance perceived HRQOL benefits with cardiovascular risk. We performed an updated meta-analysis of randomized controlled trials (RCTs) that evaluated the treatment of anemia in CKD with ESAs that targeted higher versus lower hemoglobin targets using validated HRQOL metrics including SF-36 and KDQ. We included 17 studies and found that higher hemoglobin targets compared to lower HGB targets did result in a statistically significant difference in HRQOL and thus did not improve HRQOL beyond a clinically meaningful threshold. Any change in HRQOL was further attenuated in dialysis subgroups. (more…)
Author Interviews, Genetic Research, Kidney Disease / 10.02.2016 Interview with: Prof. Hirofumi Kai Kumamoto University Japan MedicalResearch: What is the background for this study? Dr. Kai: Alport Syndrome (AS) is a hereditary progressive kidney disease that affects 1 in 5000-10000 individuals in the US. Depending on the specific subtype and genetic mutation, the onset, symptoms and progression vary among patients. Some have earlier onset and severe phenotypes while others have slow progression towards end-stage renal disease (ESRD). The gene affected in  Alport Syndrome is type 4 collagen, which codes for a protein component of the glomerular basement membrane (GBM). This mutation leads to the dysregulated proliferation (or dysplasia) of the GBM, which has an important role in urine filtration. The pathophysiological process of dysplasia indicates a dysfunction of protein/s that control cellular homeostasis. Because the tumor suppressor p53 is critically involved in modulating cell proliferation, we focused our attention on this protein. (more…)
Annals Internal Medicine, Author Interviews, Kidney Disease, Weight Research / 09.02.2016 Interview with: Yoosoo Chang MD PhD Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine Seoul, Korea Medical Research: What is the background for this study? What are the main findings? Response: There is substantial controversy and a lot of interest on the health implications of metabolically healthy obesity, that is, subjects who are obese but do not have metabolic abnormalities in spite of their high body mass index. The risk for chronic kidney disease (CKD) among obese patients without metabolic abnormalities is unknown. In this cohort study of South Korean men and women, metabolically healthy overweight and obese participants had increased incidence of Chronic Kidney Disease (CKD) compared with normal-weight participants. (more…)
Author Interviews, Kidney Disease / 12.01.2016 Interview with: Navdeep Tangri, MD, PhD FRCPC Department of Medicine Seven Oaks General Hospital University of Manitoba Winnipeg, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Tangri: Chronic kidney disease is common and its end stage of kidney failure requiring dialysis can be devastating for patients and families. While 26 million North Americans are affected by CKD, the vast majority of them will not experience kidney failure during their lifetime. Predicting the risk of kidney failure for an individual patient can help doctors plan treatment, improve shared decision making, and provide patients with piece of mind. In 2011, we developed equations that accurately predict the risk of dialysis in more than 8,000 Canadian patients with CKD. While these equations are widely used, global implementation has been limited due to a lack of validation in other countries/health systems. The current study addresses all of these concerns by comprehensively validating the risk equations in more than 700,000 participants spanning 30+ countries, and demonstrating its accuracy in predicting the risk of dialysis. (more…)
Author Interviews, Duke, Heart Disease, Kidney Disease / 03.01.2016 Interview with: Renato D. Lopes MD, MHS, PhD Duke University Medical Center Duke Clinical Research Institute Durham, NC 27705   John P. Vavalle, MD, MHS Assistant Professor of Medicine Division of Cardiology UNC Center for Heart & Vascular Care Medical Research: What is the background for this study? What are the main findings?  Dr. Lopes: Patients with varying degrees of underlying renal failure who presented for primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI) were studied as part of the APEX-AMI trial. Baseline renal dysfunction portends a worse prognosis in patients undergoing PCI. However, the association between clinical outcomes and angiographic results with baseline renal function in this population of STEMI patients is not clearly defined.  We report the results of a trial population with a full spectrum of underlying renal function (normal to dialysis dependent) and developed a prediction model for the development of acute kidney injury following primary percutaneous coronary intervention. In summary, patients with worse underlying renal function had worse angiographic outcomes, higher mortality, and were less likely to be treated with evidence-based medications.  The rate of acute kidney injury (AKI) after PCI appears to increase with worsening underlying renal function, except for those with Class IV chronic kidney disease where the rate of AKI was lowest.  Our novel prediction model for the development of AKI found that the strongest predictors of AKI were age and presenting in Killip Class III or IV. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Heart Disease, JAMA, Kidney Disease, Surgical Research / 29.12.2015 Interview with: Azra Bihorac, MD, MS and Department of Anesthesiology Charles Hobson, MD, MHA Department of Surgery, Malcolm Randall Veterans Affairs Medical Center, Department of Health Services Research, Management, and Policy University of Florida Gainesville Florida  Medical Research: What is the background for this study? What are the main findings? Response:   Background is that as ICU clinicians we see acute kidney injury (AKI) and chronic kidney disease (CKD) frequently and have to deal with the consequences, and as AKI researchers we have shown that even mild and moderate AKI – even if there is complete resolution of the AKI by the time of hospital discharge – result in significantly increased morbidity and mortality for the surgical patient. Furthermore we are aware of the existing relationship between CKD and cardiovascular mortality, and we wanted to explore any relationship between AKI and cardiovascular mortality in the vascular surgery patients that we care for on a daily basis. The most important finding was the strong association between AKI and cardiovascular mortality in these patients – equal to the well-known association between CKD and cardiovascular mortality. (more…)
Author Interviews, Endocrinology, Kidney Disease, Transplantation, Vitamin K / 21.12.2015 Interview with: Josep M Cruzado, MD Head, Nephrology Department Hospital Universitari de Bellvitge  Medical Research: What is the background for this study? What are the main findings? Dr. Cruzado: Tertiary hyperparathyroidism is frequent after renal transplantation. Inappropriately high parathyroid hormone levels are associated with hypercalcemia, hyperphosphatemia, both allograft and vascular calcification and bone mineral density loss. Cinacalcet is highly effective to control hypercalcemia in this setting although there were no studies comparing cinacalcet with subtotal parathyroidectomy. Main findings are that subtotal parathyroidectomy is superior to cinacalcet in normalizing hypercalcemia amb iPTH, increased bone mineral density at femoral neck and is more cost effective (the cost of subtotal parathyroidectomy is equal to 14 months of cinacalcet and this drug should be maintained overtime). (more…)
Author Interviews, Duke, Heart Disease, JACC, Kidney Disease / 08.12.2015 Interview with: Daniel Friedman, MD Cardiology Fellow Duke University Hospital Durham, North Carolina MedicalResearch: What is the background for this study? What are the main findings? Dr. Friedman: Cardiac resynchronization therapy (CRT) has been demonstrated to reduce heart failure hospitalizations, heart failure symptoms, and mortality in randomized clinical trials. However, these well-known trials either formally excluded or did not report enrollment of patients with more advanced chronic kidney disease (CKD), which we defined as a glomerular filtration rate of <45ml/minute. Since advanced CKD has been associated with an increased risk of adverse outcomes among patients with a variety of pacemakers and defibrillators, many have questioned whether the risks of CRT may outweigh the benefits in this population. Furthermore, many have hypothesized that the competing causes of morbidity and mortality among advanced CKD patients who meet criteria for CRT may mitigate clinical response and net benefit. Our study assessed the comparative effectiveness of CRT with defibrillator (CRT-D) versus defibrillator alone in CRT eligible patients with a glomerular filtration rate of <60ml/minute (Stage III-V CKD, including those on dialysis). We demonstrated that CRT-D use was associated with a significant reduction in heart failure hospitalization or death in the overall population and across the spectrum of CKD. The lower rates of heart failure hospitalization or death was apparent in all subgroups we tested except for those without a left bundle branch block. Importantly, we also demonstrated that complication rates did not increase with increasing severity of CKD. (more…)
Author Interviews, Biomarkers, Kidney Disease, University of Michigan / 07.12.2015 Interview with: Wenjun Ju, Ph.D., M.S. Research Assistant Professor, Internal Medicine Matthias Kretzler, M.D. Professor, Internal Medicine, Nephrology Research Professor, Computational Medicine and Biology University of Michigan Health System  Medical Research: What is the background for this study? What are the main findings? Response: Chronic kidney disease (CKD) is a global health issue that affects approximately 15% of the global population.. While not all patients with CKD will progress to end-stage kidney disease (ESKD), those that do tend to advance quickly and require dialysis or kidney transplant. They are also at an increased risk of death from cardiovascular disease. According to the International Society of Nephrology, treatment of CKD, including medical management, dialysis and kidney transplant, is very costly.  In the U.S. alone, therapy for CKD is likely to exceed $48 billion per year, and the ESKD program consumes 6.7 percent of the total Medicare budget to care for less than 1 percent of the covered population. In China, the disease will cost the economy the equivalent of $558 billion in the U.S. over the next decade. Early identification of patients that are more likely to experience end-stage kidney disease is an urgent, unmet clinical need. Currently, kidney biopsy is required to determine diagnosis and prognosis of kidney disease. This procedure is costly, carries a low, but significant health risk, and has limited ability to predict the future course of kidney disease. Together with the European Renal cDNA Bank and the Peking University Institute of Nephrology, the University of Michigan team identified epidermal growth factor (EGF) as a promising candidate for prediction of kidney function loss while analyzing transcriptomic data derived from kidney tissue biopsies of CKD patients across Europe and the U.S. We then validated the findings in urine samples from more than 940 patients in North America, Europe and China, and found that a decrease in urinary EGF protein concentration is an early sign of diminishing kidney function and pinpoints the at-risk patient population. (more…)
Author Interviews, Heart Disease, JAMA, Kidney Disease / 05.12.2015 Interview with: Girish N. Nadkarni, MD, MPH Division of Nephrology, Department of Medicine Icahn School of Medicine at Mount Sinai New York, New York What is the background for this study? What are the main findings? Dr. Nadkarni: Cardiovascular disease is one of the major causes of morbidity and mortality in patients with kidney disease. Moreover, there is a lack of good quality evidence in kidney disease patients. In addition, previous studies have shown that cardiovascular trials exclude patients with kidney disease. We wanted to analyze all of the clinical trials on acute myocardial infarctions and heart failure in the last decade and see if they continued excluding patients with kidney disease. We discovered that in 371 trials including close to six hundred thousand patients, the majority (57%) excluded patients with kidney disease. A large proportion of the trials excluded patients for non-specific reasons, rather than a prespecified threshold of kidney function and did not report kidney function at baseline. Finally, in trials that did include kidney patients and reported outcomes by kidney function, only 13% showed an interaction or suggestion of harm. (more…)
Author Interviews, Diabetes, Kidney Disease / 12.11.2015 Interview with: Charuhas Thakar, MD Director, Division of Nephrology and Hypertension Professor of Medicine University of Cincinnati Medical Research: What is the background for this study? What are the main findings? "Diabetes is the major contributor to the growing burden of end-stage renal disease,” says Charuhas Thakar, MD, professor and director of the Division of Nephrology and Hypertension at the UC College of Medicine. "Acute kidney injury is a common problem among diabetic patients who require admissions to hospitals. Approximately one-third of patients who develop AKI also have diabetes mellitus.” Dr. Thakar along with a team of researchers have looked at a cohort of about 3,700 patients with Type 2 diabetes longitudinally followed for a five-year period to determine AKI’s impact. AKI is a rapid loss of kidney function, which is common in hospitalized patients. It has many causes that include low blood volume, exposure to substances or interventions harmful to the kidney and obstruction of the urinary tract. (more…)
Author Interviews, Blood Pressure - Hypertension, Kidney Disease / 11.11.2015 Interview with: Dr Will Herrington MD, MRCP and Dr Natalie Staplin PhD Nuffield Department of Population Health, University of Oxford Oxford, UK Medical Research: What is the background for this study? What are the main findings? Response: These analyses use data from SHARP, a trial of 9000 patients with chronic kidney disease which established that lowering LDL-cholesterol with a statin-based regime (simvastatin 20mg/ezetimibe 10mg) safely reduced risk of a heart attack or stroke in kidney patients. We have now used the SHARP dataset to investigate the association between blood pressure and rate of renal progression among those with different levels of albumin in the urine. These observations show that higher systolic blood pressure is associated with faster rate of renal progression irrespective of the presence or absence of albumin in the urine. (more…)
Author Interviews, Depression, Diabetes, Kidney Disease / 10.11.2015 Interview with: Miklos Z Molnar, MD, PhD, FEBTM, FERA, FASN Associate Professor of Medicine Division of Nephrology, Department of Medicine University of Tennessee Health Science Center Memphis, TN, 38163  Medical Research: What is the background for this study? What are the main findings? Dr. Molnar: We examine the association between presence of depression and all-cause mortality; incident Coronary Heart Disease (CHD) (new onset AMI, CABG or PCI), incident ischemic stroke, slopes of eGFR (OLS, <-5 vs ≥-5 ml/min/1.73m2/yr) in 933,211 diabetic (based on ICD9, medication and HbA1c ≥ 6.5%) US Veterans with eGFR ≥ 60 ml/min/1.73m2 at baseline. We adjusted for independent covariates, collected from VA databases, such as age, gender, race, BMI, marital status, income, service connection, comorbid conditions (ICD9), baseline eGFR, serum albumin. Mean age was 64±11 years, 97% were male and 18% African-American. Depression was present in 340,806 (37%) patients at enrollment. During a median follow-up of 7.3 years, 180,343 patients (19%) developed Chronic Kidney Disease (CKD).AS (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: 1.20 (1.19-1.21)). Similarly, depression was associated with 35% higher risk of incident stroke (aHR and 95% CI: 1.35 (1.32-1.39), 24% higher risk of incident CHD (aHR and 95% CI: 1.24 (1.22-1.27) and 25% higher risk of all cause mortality (aHR and 95% CI: 1.25 (1.24-1.26) during the follow-up. (more…)
Author Interviews, Kidney Disease, Social Issues / 10.11.2015 Interview with: Dr. Rachael Morton, PhD Associate Professor Director of Health Economics, NHMRC Clinical Trials Centre The University of Sydney, Sydney Australia Medical Research: What is the background for this study? Dr. Morton: Household income was measured at baseline and study end among participants with moderate to severe chronic kidney disease (CKD), randomized into the Study of Heart and Renal Protection (SHARP).Household poverty was defined as <50% of the median household income for the participating country. (more…)
Author Interviews, Kidney Disease, Transplantation / 10.11.2015 Interview with: Sumit Mohan, MD, MPH Assistant Professor of Medicine & Epidemiology Director, Transplant Outcomes Research at CUMC Division of Nephrology, Department of Medicine Columbia University Medical Center   Medical Research: What is the background for this study? What are the main findings? Dr. Mohan: Kidney transplantation is the preferred treatment for End Stage Renal Disease but transplantation access is limited in part to the scarcity of organs in the United States. Despite this, currently 17% of all kidneys that are procured in the United States for transplant are discarded - a number that has been steadily increasing. The reasons for the discard of these kidneys is poorly understood and urgently needs to be studied. (more…)
Author Interviews, Heart Disease, Kidney Disease, Pharmacology / 08.11.2015 Interview with: Frederic T. (Josh) Billings IV, MD, Msc Assistant Professor of Anesthesiology and Critical Care Medicine Vanderbilt University Medical Center  Medical Research: What is the background for this study? What are the main findings? Dr. Billings: Acute kidney injury (AKI) following cardiac surgery is common (affects 20-30% of patients), and even mild forms of AKI are independently associated with a five-fold increase in death. Statins, commonly prescribed to reduce cholesterol concentrations and cardiovascular disease, affect several mechanisms underlying surgical AKI. Observational studies comparing rates of AKI between statin users and non-users have yielded inconsistent results and don’t assess the effect of statin use during the surgical period. In a double blind, placebo-controlled, randomized clinical trial of 653 cardiac surgery patients, we found that high-dose atorvastatin given prior to surgery, the day of surgery and daily postoperatively did not affect AKI. In fact, among statin-naïve patients with pre-existing kidney disease, rates of AKI were higher in those randomized to atorvastatin compared to those randomized to placebo. In patients who were using statins prior to the study, rates of AKI were similar between those randomized to atorvastatin and those randomized to placebo (short-term withdrawal), regardless of baseline kidney function. Safety markers of muscle and liver toxicity were not affected by statin treatment. (more…)
Author Interviews, Kidney Disease, Nature / 27.10.2015 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 12. 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 12 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 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 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, 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 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, 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…)