Publication:
Author Interview: Akshay S. Desai, MD and Marc A. Pfeffer, MD, PhD
Association Between Cardiac Biomarkers and the Development of ESRD in Patients With Type 2 Diabetes Mellitus, Anemia, and CKD
Desai AS, Toto R, Jarolim P, Uno H, Eckardt K-U, Kewalramani R, Levey AS, Lewis EF, McMurray JJV, Parving H-H, Solomon SD, Pfeffer MA.
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA. Am J Kid Dis 2011.
What are the main findings of the study?
We studied the association between the cardiac-derived biomarkers troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and the development of end-stage renal disease (ESRD) in the first 1000 subjects with type 2 diabetes, chronic kidney disease, and anemia enrolled in TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy).
In this ambulatory CKD population, we found that levels of both cardiac biomarkers were frequently elevated; 45% had TnT levels detectable at greater than the usual reference limit for myocardial necrosis and 38% had NT-proBNP levels exceeding conservative thresholds for heart failure diagnosis.
Levels of both cardiac biomarkers were higher in patients with lower eGFR and also in those with greater baseline proteinuria. TnT and NT-proBNP levels were associated independently with the risk of ESRD and the composite of death or ESRD even after adjustment for eGFR, proteinuria, and other known predictors of CKD progression.
Were any of the findings unexpected?
Yes, several findings were unexpected.
First, the high prevalence of elevated cardiac biomarkers in this stable, ambulatory population with CKD was unanticipated.
While circulating levels of NT-proBNP are known to be influenced by renal function, the evidence for renal elimination of TnT is less compelling; accordingly, our data appear to provide evidence of subclinical cardiac injury in CKD.
Second, although others have noted higher levels of cardiac troponins and natriuretic peptides in CKD patients, our observation that levels of both biomarkers were higher in those with greater proteinuria even after adjusting for eGFR provides new insights into the cardio-renal connection.
Finally, while cardiac biomarker level elevations are associated with a higher risk of fatal and nonfatal cardiovascular events in TREAT as in other populations (see separate manuscript by McMurray JJV, et al. American Heart Journal 2011, in press), our observation that these biomarkers are also independently associated with the development of ESRD was suprising.
Although the mechanism underlying this association remains unclear, the observation that two biomarkers released from the heart are associated with progression of disease in the kidney provides evidence for a shared progression between cardiac and renal disease that requires further investigation.
What should clinicians and patients take away from this study?
Our observation that cardiac-derived biomarkers may enhance prediction of ESRD provides clinical support for experimental evidence of a link between cardiac injury and CKD progression.
As well, clinicians should take note of the high frequency of detectable TnT and elevated NT-proBNP in CKD patients, since this may have implications for interpretation of cardiac biomarker testing in this population.
In particular, these data regarding biomarker elevations in stable, ambulatory CKD subjects should be taken into account when defining thresholds for diagnosis of myocardial infarction and heart failure in CKD patients.
What recommendations do you have for nephrology health care providers as a result of your study?
Our data suggest that nephrologists should consider measurement of TnT and NT-proBNP in addition to eGFR, proteinuria, and other risk factors in assessing the risk for progression to ESRD amongst CKD patients.
Improved stratification of the risk for developing ESRD may facilitate early preparation for renal replacement therapy and even help to target future therapies designed to slow CKD progression.
Future analyses focused on validating these observations in the residual TREAT population and examining the additional prognostic impact of serial cardiac biomarker levels on the development of ESRD will help to further define the precise role of cardiac biomarker assessment in the management of CKD patients.
Abstract:
Abstract
BACKGROUND:
In patients with chronic kidney disease (CKD), as in other populations, elevations in cardiac biomarker levels predict increased risk of cardiovascular events. We examined the value of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in assessing the risk of developing end-stage renal disease (ESRD) in diabetic patients with CKD.
STUDY DESIGN:
Prospective cohort study nested within a randomized clinical trial.
SETTING & PARTICIPANTS:
Patients with type2diabetes, CKD (estimated glomerular filtration rate [eGFR], 20-60 mL/min/1.73 m(2)), and anemia enrolled in TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy).
PREDICTORS:
Serum levels of the cardiacbiomarkers TnT and NT-pro-BNP.
OUTCOMES:
Incidence of ESRD and the composite of death or ESRD.
MEASUREMENTS:
We measured TnT and NT-pro-BNP in baseline serum samples from the first 1,000 patients enrolled in TREAT. The relationship of these cardiac biomarker levels to the development of ESRD and death or ESRD was analyzed in multivariable regression models.
RESULTS:
Detectable TnT (≥0.01 ng/mL) was present in 45% of participants, and median NT-pro-BNP level was elevated at 605 pg/mL. Higher levels of both cardiacbiomarkers were associated independently with higher rates of ESRD, as well as death or ESRD, and remained prognostically important after adjustment for eGFR, proteinuria, and other known predictors of CKD progression. The addition of cardiacbiomarkers to a multivariable model for prediction of ESRD improved discrimination of those with and without an event by 16.9% (95% CI, 6.3%-27.4%).
LIMITATIONS:
Observational study in a clinical trial cohort; results require validation.
CONCLUSIONS:
In ambulatory patients with type2diabetes, anemia, and CKD, TnT and NT-pro-BNP levels frequently are elevated. These cardiac-derived biomarkers enhance prediction of ESRD beyond established risk factors. Measurement of TnT and NT-pro-BNP may improve the identification of patients with CKD who are likely to require renal replacement therapy, supporting a link between cardiac injury and the development of ESRD.
Home Dialysis Summit Recommends Policy Changes to Increase Home Dialysis Usage
WASHINGTON, April 25, 2012 /PRNewswire -- On the heels of the first National Summit on Home Dialysis Policy, Summit organizers released a report reflecting the views of the delegates -- leaders in the kidney disease patient, clinician, facility and industry communities -- on federal policy steps to improve utilization of home dialysis for patients who can benefit from this often advantageous form of treatment. Many of the organizers also announced they have formed a new alliance, called the Alliance for Home Dialysis, to advance the recommendations identified at the Summit.
The Summit's "Report of the Delegates" highlights key findings from a March 29th meeting in Washington, DC where experts probed why, despite widely accepted and well-documented benefits of home dialysis -- improved outcomes, enhanced patient satisfaction, improved quality of life, and lower costs-- fewer than ten percent of the more than 390,000 current U.S. dialysis patients receive treatment at home. Current rates of home dialysis utilization reflect a steep decline from the 1970s, when almost 40% of U.S. dialysis patients were treated in-home.
Specifically, delegates found that policymakers should work with stakeholders in the dialysis community to confront three areas:
Accessibility: Patients and clinicians face array of hurdles in education, training, and infrastructure that hinder equalized access to home dialysis.
Accountability: Utilization of home dialysis can be improved through measures within government programs that are designed to recognize and support excellence in the delivery of home dialysis services.
Aligning Incentives: Reimbursement policies, regulation of new technologies and other policy incentives can be realigned to better support federal policy goals of expanding access to home dialysis.
The Report includes 15 recommendations to serve these goals, including that federal policymakers should:
Maintain parity for home and in-center dialysis in Medicare reimbursement;
Support home dialysis mentoring programs, particularly those that use existing patients as mentors; and
Align federal and state regulatory requirements for home therapies, such as revising the Centers for Medicare and Medicaid Services Conditions for Coverage requirements, to reflect differences in home and in-center dialysis.
Summit supporters will begin work through the new Alliance to dialogue with federal policymakers and advance policy improvements in the three consensus areas that emerged at the Summit.
SOURCE National Summit on Home Dialysis Policy
National Kidney Foundation's Top 10 Things Every Dialysis Patient Should Know.
You have treatment choices. Options exist for how, where and when you dialyze. Dialysis can be done in a hospital, in a dialysis unit that is not part of a hospital, or at home. You and your doctor will decide which place is best, based on your medical condition and your wishes. There are different types of dialysis - peritoneal and hemodialysis. Work with your health care team to determine a treatment plan that makes you feel comfortable. Recent studies show that the majority of patients beginning in-center hemodialysis (HD) know very little, if anything, about the option to dialyze at home. Once informed, 40% or more of patients are interested in this treatment option, and yet less than 10% actually begin home dialysis. If you're dissatisfied with the type of dialysis treatment that you're receiving, ask your healthcare team if another type of dialysis treatment would be better.
You can compare in-center dialysis facilities online. Information on over 5,600 US-based dialysis centers is available online through the Medicare website. To help you make choices about your care, you can compare different facilities side-by-side and evaluate each facility based upon clinic characteristics and quality measures. You can search for dialysis facilities by name or geographic proximity. After completing an initial facility comparison to determine which facilities best meet your needs - such as the number of hemodialysis stations at a particular location and whether there are evening shifts available - visit the facilities that you're most interested in. Talk to the staff and other patients, as well as your doctor to ensure that this dialysis facility is a good fit for you.
There are ways to prepare ahead for an emergency. Ask your dialysis facility about their emergency plan in case of a snow storm, fire, power outage or other natural disaster. As back up, make sure you have the names, locations and phone numbers of other dialysis units and hospitals in your area. Since regular community transportation services may not be working in an emergency, be prepared to make other arrangements for getting to dialysis. You may need to contact the police and Emergency Medical Services (EMS) for assistance. If you dialyze at home, make sure you have at least two weeks' worth of unexpired supplies on hand. If you have to miss a dialysis treatment, begin your emergency meal plan.
There is an easy way to transfer patient records between clinics. There is an easy, secure way for your health care team to transfer your treatment records online. In 2009, the Centers for Medicare and Medicaid Services (CMS) created a centralized web-based data collection system called CROWNWeb to help reduce and eliminate patient treatment interruptions. This central system helps to streamline patient care regardless of the reason for changing dialysis centers. For example, if you've been admitted to the hospital, or if you needed to relocate during an emergency evacuation, your doctors and health care team can access up-to-date information about your dialysis so that you continue to receive appropriate care no matter where you are.
You can travel while on dialysis.
Dialysis centers are located in every part of the United States and in many foreign countries. The treatment is standardized, but you need to plan ahead by making an appointment for dialysis at another center before you go. The staff at your center may help you make these appointments.
You can be your own best advocate. Know what key questions to ask your doctor or other healthcare professionals. Take notes so that you can refer back to them later. Partner with your doctor and decide on a treatment plan together. Advocate for yourself and share how you're feeling.
You have many rights. You as a patient have a great deal of control over your treatments. Patients have a bill of rights which includes receiving quality care, counseling about your medical information, and an expectation of privacy.
You also have responsibilities. Once you decide on a course of treatment, it's important to follow the recommendations of your health care team. If you decide to receive in-center dialysis, arrive at dialysis on time so that you can receive the full treatment without delays.
You can receive insurance coverage. If you have end stage renal failure, you are likely eligible for Medicare insurance coverage. Speak with your health care team and social worker for help filling out insurance paperwork.
You may need to follow a special diet. When your kidneys are not working properly, you may not be able to eat everything you like, and you may need to limit how much you drink. Your diet may vary according to the type of dialysis you receive. It is important to speak with a renal dietitian so that you are able to understand what you can and cannot eat based on your full health history.
Dialysis patients can work. Many dialysis patients can go back to work or school after they have gotten used to dialysis. After establishing a dialysis routine, many patients have more energy and find that they are able to time to work around this new schedule. Some patients even find creative ways to work remotely from dialysis with the use of a laptop or cell phone, depending on their field of expertise.
New Book to Help Educate Patients with Chronic Kidney Disease who may be facing Dialysis or Hemodialysis:
Help, I Need Dialysis! How to have a good future with kidney disease
By Dori Schatell, MS and Dr. John Agar
An internationally known nephrologist and life-long kidney patient educator explain how dialysis works, each of the ways to do it, and how your treatment choice may affect your diet, energy level, work, travel, sexuality and fertility, sleep, and survival. Comprehensive and fully referenced, this book is a must-read if you face the life-changing choices that come with kidney failure.
The information on hemodialysis is for informational purposes only and is not intended as specific medical advice or to be a substitute for medical advice from your physician or health care provider.
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