News & Research

    Medical Technology and Practice Patterns Institute, Bethesda, Maryland

Safe use of erythropoiesis-stimulating agents (ESAs) among diabetic patients undergoing dialysis

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Clinical Therapeutics/New Technology\Pharmacologic Treatment of Diabetes or its Complications, Diabetes Education, Epidemiology

Type of Grant: Clinical Translational Research

Project Start Date: January 1, 2011

Project End Date: December 31, 2013

Research Description

Anemia is a common and disabling co-morbidity for diabetic patients with renal failure. It can affect both quality of life and cause serious medical complications. Erythropoiesis stimulating agents (ESAs) have been approved to treat anemia.  Diabetes is the single most common cause of permanent renal disease in the US, accounting for 44% of new dialysis patients in 2006 (~180,000 persons) and nearly 40% of all diabetics have some form of kidney disease.  Studies have shown that people with diabetes and renal failure have more severe anemia and need larger doses of ESAs than those without diabetes.  However, a recent randomized trial -- the first to look at diabetic renal disease patients -- found that diabetics receiving ESA therapy had no survival benefit, had a higher risk of cardiovascular disease events, and higher diastolic blood pressure. In research performed by the proposed investigators, we found that diabetic dialysis patients had a higher risk of death and poorer outcomes with high ESA doses. Our study goal therefore is to examine the effect of different anemia management strategies for diabetic dialysis patients. Specifically, we want to examine whether diabetic patients should have a different goal (target hematocrit that measures the level of anemia) compared to other patients and perhaps cap the dose level to ensure safe and effective use of ESA therapy. This study could lead to improved patient outcomes, better product labeling, more cost-effective third-party payer policies, and improved clinical practice guidelines for diabetic patients with renal disease because currently, no such guidelines exist.

Research Profile

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes?

Anemia is a common and disabling co-morbidity for diabetic patients with renal failure. It can affect both quality of life and cause serious medical complications. Erythropoiesis stimulating agents (ESAs) have been approved to treat anemia.  Diabetes is the single most common cause of permanent renal disease in the US, accounting for 44% of new dialysis patients in 2006 (~180,000 persons) and nearly 40% of all diabetics have some form of kidney disease.  Studies have shown that people with diabetes and renal failure (RF) have more severe anemia than other RF patients and need larger ESA doses.  However, a recent randomized trial - the first to look at diabetic renal disease patients - found that diabetics receiving ESA therapy to improve their hematocrit levels had no survival benefit, had a higher risk of cardiovascular disease events, and higher diastolic blood pressure. In earlier research performed by the proposed investigators, we found that diabetic dialysis patients had a higher risk of death and poorer outcomes with high ESA doses. Our study goal therefore is to examine the effect of different anemia management strategies for diabetic dialysis patients. Specifically, we want to examine whether diabetic patients should have a different goal (target hematocrit that measures the level of anemia) compared to other patients and perhaps cap the dose level to ensure safe and effective use of ESA therapy. This study could lead to improved patient outcomes, better product labeling, more cost-effective third-party payer policies, and improved clinical practice guidelines for diabetic patients suffering from anemia and renal disease because currently, no such guidelines exist. 

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

Diabetes is the single most common cause of end-stage renal disease (ESRD) requiring a lifetime of dialysis treatment in the US, accounting for almost half of all new ESRD cases. In 2006 approximately 180,000 diabetic patients began continuous dialysis treatment and/or received a kidney transplant. Anemia is an almost universal co-morbidity of persons with both diabetes and renal failure. Compared with anemic renal failure patients without diabetes, patients with diabetes received higher doses of erythropoiesis-stimulating agents (ESA), also known as epoetin, but attain worse outcomes and have higher mortality and more cardiovascular events.  There are increasing concerns about the risks of ESA use in patients with diabetes and chronic kidney disease. 
Morbidity and mortality rates for persons with diabetes and ESRD in the US are unacceptably high. One area for improvement of patient survival is the management of anemia.  However, twenty years after the introduction of ESAs to treat anemia, there is still considerable uncertainty regarding the best treatment strategies, especially among complex dialysis patients with diabetes as a co-morbid condition. The aim of this project is to examine the effect of different anemia management strategies on diabetic patient outcomes who are also on dialysis.
Our study will contribute to controlling the risks among diabetic patients by: 1) highlighting patient safety issues including the adverse effects of epoetin therapy among an erstwhile unexamined cohort of diabetic patients undergoing dialysis; 2) extending this concern to the 27 million predialysis patients, most of whom have anemia; 39.6% of people with diagnosed and 41.7% with undiagnosed diabetes have renal disease; 3) focusing on the need for specific clinical guidelines for the treatment of anemia among diabetic patients with renal disease both before and after dialysis; and 4) facilitating the development of alternative anemia management strategies for a diabetic cohort that might not include epoetin therapy.

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts?

I have worked extensively in the area of health services research and patient outcomes over the last 18 years with a focus on chronic conditions including diabetes and renal failure. I have led numerous research projects, activities and publications including studying: association between antihypertensive drug use and hypoglycemia; anemia management strategies; access to kidney transplantation; clinical sequelae and costs of immunosuppressive therapy; and total direct and indirect costs of diabetes (a project sponsored by the ADA).  While working most recently in the area of renal failure, the contribution of diabetes to this condition is undeniable.  I have wanted for some time now to study diabetic patients with renal failure both before and after initiation of dialysis.  This is the first study that will allow me to examine anemia management strategies among a cohort of diabetic patients with permanent renal failure who are undergoing dialysis.  I hope this will be the first of many succeeding projects to improve the outcomes and well-being of persons who suffer from both diabetes and renal disease.

In what direction do you see the future of diabetes research going?

I see the future of diabetes research going in the same direction as the objectives proposed in this ADA grant.  That is, the study of diabetes in conjunction with other co-morbid conditions and the special requirements and/or treatment strategies required as a result of having two or more serious chronic medical conditions.  Diabetes can no longer be studied separately since the majority of diabetics suffer from multiple chronic and acute conditions.  Future outcomes studies must embrace the myriad other conditions suffered by diabetic patients.