MedicalResearch.com Interview with
Donal J. Sexton, MD, PhD
Department of Nephrology and Kidney Transplantation
Beaumont Hospital
Royal College of Surgeons in Ireland
Dublin, Ireland
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Patients who receive a kidney transplant as treatment for end stage kidney disease are at risk of malignancy due to immunosuppression. In contrast to
other solid organ transplant types, when kidney transplants fail it is possible for recipients to return to dialysis. Immunosuppression is usually reduced or completely stopped when the allograft fails due to the risk of infection on dialysis.
We decided to investigate what the trajectory of risk for non-melanoma skin cancer and invasive cancers overall (composite group) looked like for patients who have received multiple consecutive kidney transplants with intervening periods of graft failure. We compared cancer risk during periods of allograft failure and periods of functioning kidney transplants.
MedicalResearch.com Interview with:
Emily E. Groopman, B.A
Departments of Medicine
Hammer Health Sciences, and the Department of Epidemiology
Columbia University, New York
MedicalResearch.com: What is the background for this study? Response: Exome sequencing (ES), targeted capture of the protein-coding segments of the human genome, is quickly becoming a first-line diagnostic tool in clinical medicine, particularly for pediatric disorders and cancer. However, the utility of ES has not been investigated for the majority of constitutional disorders in adults, including for chronic kidney disease (CKD), which collectively affects more than 1 in 10 individuals worldwide.
Thus, we performed ES in 3,315 patients with CKD drawn from two independent cohorts, and evaluated the diagnostic yield and the clinical implications of genetic findings. The cohort was predominantly adult (91.6% of patients aged >21 years), ethnically diverse, and encompassed the major CKD subtypes, broadly reflective of the demographic and clinical features of United States CKD patient population.
MedicalResearch.com Interview with:
[caption id="attachment_46756" align="alignleft" width="142"] Dr. Rebholz[/caption]
Casey M. Rebholz, PhD, MS, MNSP, MPH, FAHA
Assistant Professor, Department of Epidemiology
Johns Hopkins Bloomberg School of Public Health
Core Faculty, Welch Center for Prevention, Epidemiology, and Clinical Research
Baltimore, MD 21287
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Individual beverages have been previously shown to influence risk of a wide range of cardiometabolic diseases. Less is known about beverage consumption and kidney disease risk.
In this study population, we found that one such beverage pattern consisted of soda, sugar-sweetened beverages, and water, and that higher adherence to the sugar-sweetened beverage pattern was associated with greater odds of developing incident kidney disease, even after accounting for demographic characteristics and established risk factors.
MedicalResearch.com Interview with:
[caption id="attachment_46606" align="alignleft" width="80"] Dr. Parikh[/caption]
Chirag R Parikh, M.B.B.S., Ph.D.
Director,Division of Nephrology
Professor of Medicine
School of Medicine, Johns Hopkins University
Baltimore, Maryland 21287MedicalResearch.com: What is the background for this study? Response: The initial study idea stemmed from our earlier cohort studies of predictors of delayed graft function after kidney transplantation. We previously found that kidneys from donors with Acute Kidney Injury (AKI) were more often discarded than kidneys from donors without AKI, and transplanted donor AKI kidneys were at increased risk for delayed graft function.
It was important to determine whether that increased risk for delayed graft function also translated into worse long-term outcomes for recipients of kidneys from donors with AKI.
Tetsuo Shoji, MD, PhD. Department of Vascular Medicine Osaka City University Graduate School of Medicine Osaka Japan
MedicalResearch.com: What is the
background for this study? What are the
main findings?
Response: Vitamin D is known to be associated with health and disease of various organs such as bone, heart, brain, and others. Vitamin D is activated by the liver and kidneys to a hormone called 1,25-dihydroxyvitamin D which binds to vitamin D receptor in cells to exert its functions.
Vitamin D activation is severely impaired in patients with kidney disease requiring hemodialysis therapy, leading to mineral and bone disorder(MBD). Therefore, active form of vitamin D is one of the standard choices of treatment for MBD caused by kidney function loss.
Previous observational cohort studies showed that the use of active vitamin D in hemodialysis patients was associated with lower likelihood of all-cause death, cardiovascular death, and incident cardiovascular disease.Potentially cardio-protective effects of active vitamin D were shown by basic studies using cultured cells and animal models. Then, many nephrologists began to believe that active vitamin D is a “longevity hormone” or a “panacea” for kidney patients requiring dialysis therapy, although there was no evidence by randomized clinical trials.
To show evidence for it, we conducted a randomized clinical trial namedJ-DAVID in which 976 hemodialysis patients were randomly assigned to treatment with oral alfacalcidol or treatment without active vitamin D, and they were followed-up for new cardiovascular events during the four-year period. The risk of cardiovascular events was not significantly different between the two groups. The risk of all-cause death was not significantly different either.
To our surprise, the risk of cardiovascular event tended to be higher in the patients who continued treatment with active vitamin D than those who continued non-use of active vitamin D, although the difference was not statistically significant.
MedicalResearch.com Interview with:
[caption id="attachment_46253" align="alignleft" width="200"] Dr. Al-Aly[/caption]
Dr. Ziyad Al-Aly, MD
Associate Chief of Staff for Research and Education
Veterans Affairs St. Louis Health Care System
Institute for Public Health
Washington University, St. Louis MO
MedicalResearch.com: What is the background for this study? Response: A lot has changed in the US over the past 15 years including aging, population growth, and increased exposure to risk factors such as obesity, elevated blood pressure, etc. With all of these changes, we wondered, how did the burden of kidney disease change in the United States over the past 15 years.
MedicalResearch.com Interview with:
[caption id="attachment_46221" align="alignleft" width="174"] Dr. Milo Rasouly[/caption]
Hila Milo Rasouly, PhD
Postdoctoral research scientist
Ali Gharavi Lab
Columbia University
MedicalResearch.com: What is the background for this study? Response: Genome sequencing is increasingly used in clinical medicine to help make a clinical diagnosis and make predictions about potential future complications. The diagnostic yield and limitations for different indications are still being worked out. We are interested in studying the applications of genome sequencing for chronic kidney diseases. It is estimated that 10% of adults have chronic kidney disease (CKD), and amongst them, 10% are caused by single-gene (Mendelian) forms of disease.
The American College of Medical Genetics and Genomics developed guidelines on how to interpret genetic variants in order to make a genetic diagnosis. Our lab has been engaged in studying the yield and impact of genetic testing for CKD, and in the course of our research, we realized that a very large number of individuals have genetic variants that may be classified as pathogenic based on automated application of the guidelines. However, in majority of these cases, the genetic variant was much too frequent in the population to be plausibly disease-causing or did not match up well with the clinical diagnosis. This led us to wonder about the risk of false-positive genetic diagnosis. To analyze this risk for false-positive genetic diagnosis, we analyzed the genome sequence of 7,974 self-reported healthy adults.
MedicalResearch.com Interview with:
[caption id="attachment_45705" align="alignleft" width="125"] Dr. Verge[/caption]
Danilo Verge MD MBA
Vice President, CVRM Global Medical Affairs
AstraZeneca
MedicalResearch.com: What is the background for this study? Response: Dapagliflozin, an SGLT2 inhibitor (sodium-glucose co-transporter 2), has been shown to improve glycemic control by decreasing glucose reabsorption in the kidneys and inducing urinary glucose clearance. SGLT2 inhibitors have also been shown to be effective in lowering albuminuria and stabilizing eGFR (estimated glomerular filtration rate). The effect of dapagliflozin on UACR (urine albumin-to-creatinine ratio) has been shown to vary among patients.
The objective of this post-hoc analysis, based on the pooled data from 11 randomized, placebo-controlled clinical trials, was to assess baseline characteristics and concurrent changes in cardiovascular (CV) risk markers associated with UACR response to dapagliflozin.
MedicalResearch.com Interview with:
[caption id="attachment_45698" align="alignleft" width="125"] Dr. Agrawal[/caption]
Rahul Agrawal MD PhD
VP, Global Medicines Leader
AstraZeneca
MedicalResearch.com: What is the background for this study? About the study: HARMONIZE Global is a Phase III, randomized, multicenter, double-blind, placebo-controlled trial involving 267 patients with hyperkalemia (mean potassium levels greater than 5.0 mEq/L) in 47 study locations across the Asia Pacific region, which will support registration in Japan, Taiwan, Korea and Russia.
Study design: The trial design of HARMONIZE Global is similar to HARMONIZE (NCT02088073) but evaluated two doses of LOKELMATM (sodium zirconium cyclosilicate) instead of three, as well as patients in different geographical regions.
MedicalResearch.com Interview with:
Amal Trivedi, MD, MPH
Associate Professor of Health Services, Policy and Practice
Associate Professor of Medicine
Brown University
MedicalResearch.com: What is the background for this study? What are the main findings?Response: The Affordable Care Act Medicaid expansion gave states the option to expand coverage to low-income adults. Prior research has reported that these expansions have been associated with increased coverage, improved access to care, and in some studies better self-rated health. To date the impact of Medicaid expansion on mortality rates, particularly for persons with serious chronic illness, remains unknown.
Our study found an association between Medicaid expansion and lower death rates for patients with end-stage renal disease in the first year after initiating dialysis. Specifically, we found an absolute reduction in 1-year mortality in expansion states of -0.6 percentage points, which represents a 9% relative reduction in 1-year mortality.
MedicalResearch.com Interview with:
[caption id="attachment_45495" align="alignleft" width="200"] Dr. Ivarsson[/caption]
Dr Mattias Ivarsson PhDCEO, Inositec, co-author of data
MedicalResearch.com: What is the background for this study? Response: When control of factors in the blood that regulate mineral balance in the body is lost, the subsequent build-up of calcium deposits in the arterial walls and cardiac valves lead to an increase in cardiac events, particularly in patients with chronic kidney disease or diabetes, as well as all-cause mortality.
There is a significant unmet need for therapeutic agents capable of reducing pathological mineral accumulation regardless of their root cause. To date, there is no approved therapy for treating calcification-dependent cardiovascular disease.
MedicalResearch.com Interview with:
[caption id="attachment_45356" align="alignleft" width="200"] Dr. Shlipak[/caption]
Michael G. Shlipak, MD, MPH
Scientific Director , Kidney Health Research Collaborative (khrc.ucsf.edu)
Professor of Medicine, Epidemiology & Biostatistics
University of California, San Francisco
Associate Chief of Medicine for Research Development
San Francisco VA Medical Center
MedicalResearch.com: What is the background for this study?
Our study represents major advancements in our understanding of whether kidney tissue damage accompanies the diagnosis of chronic kidney disease during hypertension therapy.
The Systolic Blood Pressure Intervention Trial (SPRINT) was a landmark clinical trial that demonstrated that more intensive systolic blood pressure management (target <120 mmHg) reduced rates of major cardiovascular events and mortality compared with standard therapy (<140 mmHg). A recent announcement indicated that the lower systolic blood pressure target also slowed the rate of cognitive decline and dementia incidence.
The major concern with intensive blood pressure lowering in SPRINT is the 3-fold incidence of chronic kidney disease, as defined using the clinical standard of serum creatinine levels. This detrimental impact on the kidney was surprising because hypertension is a predominant risk factor for kidney disease, and hypertension therapy should reduce CKD risk.
Given the lower blood pressure targets in the recently-updated national hypertension guidelines, there has been substantial concern that guideline implementation of blood pressure targets could cause an epidemic of CKD and the attendant suffering from its downstream consequences of cardiovascular disease, heart failure, and kidney failure.
In our study, we compared SPRINT participants who developed CKD with matched controls, using a panel of validated urinary biomarkers of kidney damage. These urine tests can measure actual kidney damage, rather than relying on the creatinine which is an indirect reflection of the kidney’s filtering function.
In the group undergoing intensive blood pressure lowering in SPRINT, we found that the new cases of CKD had an overall lowering of the kidney damage biomarkers compared with the controls, contrary to what would have been expected if they were developing “real” CKD.
In contrast, the new CKD cases that developed in the standard treatment group did have overall elevations in the urinary biomarkers of kidney damage; 5 of the 9 biomarkers significantly increased relative to the CKD cases in the intensive treatment group.
MedicalResearch.com Interview with:
Elani Streja MPH PhD
Division of Nephrology and Hypertension
University of California, Irvine | UCI ·
Elvira O. Gosmanova, MD, FASN
Medicine/Nephrology
Albany Stratton VA Medical Center
Csaba P Kovesdy MD
Fred Hatch Professor of Medicine
Division of Nephrology, University of Tennessee Health Science Center
Nephrology Section Chief, Memphis VA Medical Center
Director, Clinical Outcomes and Clinical Trials Program
Memphis TN, 38163MedicalResearch.com: What is the background for this study? What are the main findings?Response: Cardiovascular disease (CVD) is one of the leading causes of mortality and morbidity in patients with chronic kidney disease (CKD).
Statins are lipid-lowering drugs that have a proven track record in reducing risk of CVD in patients with advanced CKD who did not yet reach its terminal stage or end-stage renal disease (ESRD). Paradoxically, new prescription of statins after ESRD onset failed to reduce CVD related outcomes in three large clinical trials. However, benefits of statin continuation at transition from advanced CKD to ESRD was never formally tested.
Therefore, we identified a cohort of 14,298 US Veterans who used statins for at least half of the year during 1 year before ESRD transition and evaluated mortality outcomes based on whether statins were continued or stopped after ESRD onset.
We found that ESRD patients who continue statins for at least 6 months after transition had 28% and 18% lower risk of death from any cause or cardiovascular causes, respectively, during 12-months of follow up, as compared with statin discontinuers.
MedicalResearch.com Interview with:
John W. Stanifer, MD MSc
Duke Health
MedicalResearch.com: What is the background for this study? What are the main findings?
Response:...
MedicalResearch.com Interview with:
[caption id="attachment_37320" align="alignleft" width="200"] Coffee Wikipedia image[/caption]
Miguel Bigotte Vieira MD
Nephrology and Renal Transplantation Department
Centro Hospitalar Lisboa Norte
Lisbon, Portugal
MedicalResearch.com: What is the background for this study? What are the main findings?Response: An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains unclear. We examined the association between varying levels of caffeine consumption and mortality among 4863 patients with CKD in a prospective nationwide cohort, using the continuous National Health and Nutrition Examination Survey (NHANES) 1999-2010.
Our study showed a protective effect of caffeine consumption among patients with chronic kidney disease. The reduction in mortality was present even after considering other important factors such as age, gender, race, smoking, other diseases, and diet.
MedicalResearch.com Interview with:
[caption id="attachment_43609" align="alignleft" width="125"] Dr. Madaio[/caption]
Michael P. Madaio, MD
Sydenstricker Professor and Chairman
Department of Medicine
Medical College of Georgia at
Augusta University
MedicalResearch.com: What is the background for this study? Response: Glomerulonephritis is a inflammatory disease of the kidney. Glomeruli are the filtering units in the kidney. This is most often immunologically mediated and are autoimmune.
Most therapies are directed at inhibiting the Immune/autoimmune process (immunotherapy) systemically.
MedicalResearch.com Interview with:
[caption id="attachment_43183" align="alignleft" width="140"] Dr. Eckman[/caption]
Mark H. Eckman, MD
Posey Professor of Clinical Medicine
Director, Division of General Internal Medicine
Director, Center for Clinical Effectiveness
University of Cincinnati Medical Center
Cincinnati, OHMedicalResearch.com: What is the background for this study? Response: People who are infected with hepatitis C virus and have kidney failure need a kidney transplant.
Recent studies have found that it is possible to transplant kidneys from donors who are infected with hepatitis C virus into patients who need a transplant and are already infected with the virus. In addition, drugs are available to cure most patients of hepatitis C virus, including those who have kidney failure. Infected patients who need a kidney transplant have 2 options. One option is to receive an infected kidney and then use drugs after the transplant to cure themselves and the transplanted kidney of the virus. Another option is to use the drugs first to get rid of the virus and then to receive a kidney from a donor who does not have hepatitis C virus infection.
For the more than 500,000 patients receiving dialysis for end-stage renal disease (ESRD), less than 4% receive kidney transplants. Because of the limited organ availability, hemodialysis is the final treatment for most patients with ESRD. Of the 10% or so of U.S. patients receiving dialysis who are infected with the hepatitis C virus (HCV), some are willing to accept HCV-infected kidneys, in part, because the wait times for such kidneys are shorter than those for HCV-uninfected kidneys. Because the yearly mortality rate for patients receiving hemodialysis is so high, between 4% and 16%, reducing the time to kidney transplant can have a dramatic effect on both survival and quality of life.
Because it may not be possible to do this type of research with actual people, we created a model that allowed us to estimate possible outcomes without using actual people.
The model was a computer program that combined the best available information to approximate what might happen to participants in a real-world clinical trial.
MedicalResearch.com Interview with:
[caption id="attachment_42216" align="alignleft" width="150"] Dr. Ishida[/caption]
Dr. Julie H. Ishida MD
Department of Medicine, Division of Nephrology
University of California, San Francisco and
San Francisco Veterans Affairs Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Gabapentin and pregabalin are used for the management of symptoms such as neuropathic pain, itching, and restless leg syndrome in patients receiving hemodialysis. However, hemodialysis patients may be particularly vulnerable to adverse events related to these agents, which are cleared by the kidney, but there is limited data evaluating their risk in this population.
Gabapentin and pregabalin use were associated with risk for altered mental status, fall, and fracture, and in some cases, even at doses that would be considered safe for use in this population.
MedicalResearch.com Interview with:
Dr. William Clark
Lawson Health Research InstituteMedicalResearch.com: What is the background for this study? What are the main findings?Response: This study is about the use of increased water intake in people with chronic kidney disease (CKD).
Although there are a large number of benefits claimed most are not substantiated by evidence. However there is a growing body of evidence (animal and human observational studies) that increased hydration with the suppression of antidiuretic hormone preserves kidney function in CKD. This led to our current randomised clinical trial of 631 patients with stage 3 CKD and proteinuria to determine if drinking an extra 4-6 glasses of water per day for 1 year would slow their progressive loss of kidney function as measured by eGFR.
The main findings were that those coached to increase their water intake versus those coached to sustain their normal fluid intake suffered no ill effects from the intervention and on average were able to sustain an average increase of approximately 3 glasses of water per day. At the end of 1 year the increased hydration group had suppressed their antidiuretic hormone levels (copeptin) significantly but did not demonstrate a greater preservation in their eGFR.
MedicalResearch.com Interview with:
[caption id="attachment_40822" align="alignleft" width="132"] Dr. Foster[/caption]
Bethany J. Foster, MD MSCE
Montreal Children’s Hospital
Department of Pediatrics,
Department of Epidemiology, Biostatistics, and Occupational Health
McGill University, Montreal, QC, Canada
MedicalResearch.com: What is the background for this study? Response: Adolescent and young adult kidney transplant recipients have the highest risk of graft loss of any age group. One of the main reasons for this is not taking their anti-rejection medications as prescribed. Our study had the goal of testing an intervention to try to improve young patients' adherence to their strict medication schedule. The intervention included feedback of how well they were taking their medications (which was monitored electronically), text message reminders for medication doses, and individualized coaching to address their personal barriers to taking their medications.
MedicalResearch.com Interview with:
[caption id="attachment_40274" align="alignleft" width="143"] Dr. Alban[/caption]
Rodrigo F. Alban, MD FACS
Associate Director Performance Improvement
Associate Residency Program Director
NSQIP Surgeon Champion
Department of Surgery
Cedars-Sinai Medical CenterMedicalResearch.com: What is the background for this study? What are the main findings?Response: Continuous Renal Replacement Therapy (CRRT) is a modality of hemodialysis commonly used to manage renal failure in critically ill patients who have significant hemodynamic compromise. However, it is also resource-intensive and costly and its usage is highly variable and lacks standardization.
Our institution organized a multidisciplinary task force to target high value care in critically ill patients requiring CRRT by standardizing its process flow, promoting cross-disciplinary discussions with patients and family members, and increasing visibility/awareness of CRRT use. After our interventions, the mean duration of CRRT decreased by 11.3% from 7.43 to 6.59 days per patient. We also saw a 9.8% decrease in the mean direct cost of CRRT from $11642 to $10506 per patient. Finally, we also saw a decrease in the proportion of patients expiring on CRRT, and an increase in the proportion of patients transitioning to comfort care.
MedicalResearch.com Interview with:
[caption id="attachment_40249" align="alignleft" width="300"] L-R: Kerry Chen, Anita van Zwieten, Madeleine Didsbury, Germaine Wong[/caption]
Dr. Kerry Chen
Centre for Kidney Research, The Kids Research Institute
The Children’s Hospital at Westmead, Sydney School of Public Health,
The University of Sydney
Sydney, New South Wales, Australia
MedicalResearch.com: What is the background for this study? Response: Chronic kidney disease is a major public health issue, with end-stage disease often requiring a combination of complex medication regimens, dialysis and/or transplant surgery. In children, the major causes of CKD are genetic and congenital. The consequences of CKD in children can be long-term and debilitating especially as they transition into adulthood, affecting their physical, intellectual and emotional well-being.
To better understand these changes, the Kids Health and Wealth Study (KCAD) is the largest longitudinal cohort study of children and adolescents with CKD in Australia and New Zealand. Spread across 5 paediatric nephrology centres so far, the KCAD Study takes a life-course approach to collecting and analysing data pertaining to the interactions between reduced renal function and associated clinical, socio-economic, quality of life, psychological, cognitive and educational outcomes in children, especially as they progress in CKD stage and also as they transition into adulthood.
MedicalResearch.com Interview with:
[caption id="attachment_39968" align="alignleft" width="150"] Dr. Nowak[/caption]
Dr. Kristen L. Nowak PhD
Division of Renal Diseases and Hypertension
University of Colorado Anschutz Medical Campus
Aurora, CO 80045
MedicalResearch.com: What is the background for this study? Response: Subtle impairments in cognition are common with aging, even in the absence of clinically apparent dementia. Mild hyponatremia is a common finding in older adults; however, the association of lower serum sodium with cognition in older adults is currently uncertain.
We hypothesized that lower normal serum sodium would be associated with prevalent cognitive impairment and the risk of cognitive decline over time in asymptomatic, community-dwelling older men.
[caption id="attachment_38440" align="alignleft" width="400"] Normal rhythm tracing (top) Atrial fibrillation (bottom) Wikipedia[/caption]
Interview with:
Dr Xiaoxi Yao PhD
Assistant Professor
Researcher
Mayo Clinic
What is the background for this study? What are the main findings?
Response: Lifelong oral anticoagulation, either with warfarin or a non-vitamin K antagonist oral anticoagulant (NOAC), is indicated for stroke prevention in most patients with atrial fibrillation (AF). Emerging evidence suggests that NOACs may be associated with better renal outcomes than warfarin.
The study found renal function decline is common among patients with atrial fibrillation treated with oral anticoagulants. NOACs, particularly dabigatran and rivaroxaban, may be associated with lower risks of adverse renal outcomes than warfarin.
MedicalResearch.com Interview with:
[caption id="attachment_38095" align="alignleft" width="89"] Dr. Hedayati[/caption]
Dr. Susan Hedayati MD
Yin Quan-Yuen Distinguished Professorship in Nephrology
University of Texas Southwestern
Dallas, Texas
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We previously showed that Major Depression is associated with a significantly higher risk of death, dialysis initiation, and hospitalization among patients with Chronic Kidney Disease (CKD). Now we show that a common antidepressant medication, a selective serotonin reuptake inhibitors (SSRI), sertraline, does not improve depression in this patient population, a chronically ill group that is not only at significantly increased risk for developing depression but also its serious complications.
MedicalResearch.com Interview with:
Nilka Ríos Burrows, MPH, MT (ASCP)
Lead, Chronic Kidney Disease Initiative
CDC Division of Diabetes Translation.MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Kidney failure treated with dialysis or a kidney transplant is called end-stage renal disease (ESRD). ESRD is a costly and disabling condition often resulting in premature death.
During 2000–2014, kidney failure from diabetes among U.S. adults with diabetes decreased by 33%, and it declined significantly in most states, the District of Columbia, and Puerto Rico. No state experienced an increase in kidney failure from diabetes. Continued awareness and interventions to reduce risk factors for kidney failure, improve diabetes care, and prevent type 2 diabetes might sustain these positive trends.
MedicalResearch.com Interview with:
Vicente E. Torres, M.D., Ph.D.
Director of the Mayo Clinic Translational Polycystic Kidney Disease (PKD) Center
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Experimental work pioneered by Dr. Jared Grantham showed that cyclic AMP, an intracellular signaling molecule, promotes the development and growth of cysts. Vasopressin, a hormone produced by the pituitary gland, stimulates the production of cyclic AMP in the collecting ducts, from which most cysts derive in autosomal dominant polycystic kidney disease (ADPKD). While this effect of vasopressin is necessary for the kidneys to concentrate and reduce the volume of urine, it promotes the development and growth of cysts in patients with ADPKD. Dr. Vincent Gattone realized that inhibiting the action of vasopressin could be protective in polycystic kidney disease. Work in our and other laboratories confirmed that suppression of vasopressin production, release or action reduces cyst burden, protects kidney function, and prolongs survival in rodent models of the disease.
This experimental work provided a strong rationale for clinical trials of tolvaptan, a vasopressin V2 receptor antagonist. Tolvaptan reduced the rate of kidney growth in the TEMPO 3:4 trial, in patients with early ADPKD. It also reduced the rate of decline in kidney function, measured by the estimated glomerular filtration rate (eGFR), from 10.1 to 6.8 mL/min/1.73 m2 over three years. The eGFR benefit was maintained during two additional years when all the patients were treated with tolvaptan in an open label extension of the TEMPO 3:4 trial (TEMPO 4:4). Safety laboratory tests performed every four months showed elevations of liver transaminases in blood in 4.4% of tolvaptan and 1% of placebo-treated patients. Three of 1,271 tolvaptan-treated patients during TEMPO 3:4 and TEMPO 4:4 had evidence of potentially serious drug-induced liver injury. These abnormalities occurred all within the first 18 months of exposure to tolvaptan.
Based on the TEMPO 3:4 results, tolvaptan was approved for the treatment of rapidly progressive ADPKD in Japan, Canada, European Union, Switzerland and South Korea. In the United States, the Food and Drug Administration requested additional data to further evaluate the efficacy and safety of this drug. The REPRISE trial was performed to determine the efficacy and safety of tolvaptan in patients with later stage ADPKD.
MedicalResearch.com Interview with:
Yue-Harn Ng,MD
University of New Mexico
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: African Americans (AA) have a higher incidence of end-stage renal disease but lower rates of kidney transplantation (KT) compared to whites (WH). Disparities persist after adjusting for medical factors. We assessed the relationship of non-medical (eg. cultural, psychosocial, knowledge) factors with kidney transplantation wait-listing (WL) within the context of racial differences.
In this longitudinal cohort study, we found that African American patients were less likely to be wait-listed compared to White patients. This difference was influenced by factors including age, comorbidities, socio-economic status, being on dialysis, having a living donor, transplant knowledge and social support.
MedicalResearch.com Interview with:
[caption id="attachment_37895" align="alignleft" width="116"] Dr. Shah[/caption]
Silvi Shah, MD, FACP, FASN|
Assistant Professor
Division of Nephrology
University of Cincinnati
Cincinnati, OH
MedicalResearch.com: What is the background for this study? What are the main findings?Response: Elderly represent the fastest growing segment of incident dialysis patients in Unites States. The annual mortality in end stage renal disease (ESRD) patients is very high ~ 20%.
Since most of the deaths occur in the first year of dialysis, it is possible that health conditions present prior to initiation of dialysis may impact long-term outcomes. In this study, we determined the impact of poor functional status at the time of dialysis initiation and pre-dialysis health status on type of dialysis modality, type of hemodialysis access and one-year mortality in elderly dialysis patients. We evaluated 49,645 adult incident dialysis patients (1/1/2008 to 12/31/2008) from the United Data Renal Data System (USRDS) with linked Medicare data for at least 2 years prior to dialysis initiation. Mean age of our study population was 72 years. At dialysis initiation, 18.7% reported poor functional status, 88.9% has pre-dialysis hospitalization, and 27.8% did not receive pre-dialysis nephrology care. Patients with poor functional status had higher odds of being initiated on hemodialysis than peritoneal dialysis, lower odds of using arteriovenous access as compared to central venous catheter for dialysis and higher risk of one-year mortality.
MedicalResearch.com Interview with:
Charat Thongprayoon, MD
Bassett Medical Center
Cooperstown, NY 13326
MedicalResearch.com: What is the background for this study? What are the main findings?Response: We conducted a meta-analysis including 5 observational studies with 536,902 patients to assess the risks of chronic kidney disease (CKD) and/or end-stage kidney disease (ESRD) in patients who are taking proton pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs).
We found a statistically significant association between the use of PPI and 1.3-fold increased risk of CKD or ESRD development. Compared with H2Ras, the use of proton pump inhibitors was significantly associated with 1.3-fold higher risk for CKD development.
Conversely, there was no significant association between the use of H2RAs and chronic kidney disease.
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