Differences in nutritional and inflammatory status may be behind the survival advantage seen in African-American and Hispanic patients on hemodialysis, according to a new study published online ahead of print by the American Journal of Kidney Diseases.
“Nutritional markers are some of the most powerful predictors of outcomes in kidney disease patients,” said study author Csaba P. Kovesdy, MD, Chief of Nephrology at Salem VA Medical Center in Salem, VA. “If somebody has a marker that signals malnutrition or inflammation, those patients have a much higher mortality rate.
“What we found is that the crude mortality was lower in African-Americans, but once we adjusted for the fact that they had fewer known markers of inflammation, the adjusted mortality was the same or even worse than Caucasians with similar characteristics.”
Racial differences in hemodialysis survival had been revealed in previous observational studies.
“On the population level, we know that minorities and specifically African-Americans are at a general disadvantage in that they have a higher mortality rate, a higher cardiovascular disease [CVD] rate, and that's in general explained by complex issues,” Dr. Kovesdy said.
“On the other hand, in dialysis patients, there's a very surprising finding that African-Americans have a significantly better survival rate than Caucasians. Also, the number of African-Americans starting dialysis—that is, reaching end-stage renal disease—is now higher than one would expect based on their proportion in the general population.”
This study addressed a potential explanation for these differences.
“It's a complex question that involves a number of considerations, including how kidney disease behaves in a minority, how their survival translates into the numbers on dialysis, and how other things such as transplantation that have disparities in minorities have an effect on the numbers that we're seeing,” Dr. Kovesdy said.
Elani Streja, MPH, was the lead author of the study, and Kamyar Kalantar-Zadeh, MD, MPH, PhD, was the senior author. Ms. Streja and Dr. Kalantar-Zadeh are both affiliated with the Harold Simmons Center for Chronic Disease Research and Epidemiology in Torrance, CA, and the UCLA School of Public Health. Dr. Kalantar-Zadeh is also Associate Professor-in-Residence of Medicine, Pediatrics, and Epidemiology at the David Geffen School of Medicine at UCLA.
The study was supported by grants from the National Institute of Diabetes, Digestive, and Kidney Diseases of the National Institutes of Health; the American Heart Association; DaVita Clinical Research; and Mr. Harold Simmons.
The study included 124,029 adult hemodialysis patients, 16% of whom were Hispanic, 49% of whom were non-Hispanic whites, and 35% of whom were African-American. The association between race/ethnicity and five-year survival before and after adjustment for case-mix and surrogates of the malnutrition-inflammation complex syndrome was examined.
Like previous studies, this analysis showed that black and Hispanic dialysis patients had lower mortality than non-Hispanic white dialysis patients after traditional case-mix adjustment.
However, this survival advantage disappeared after adjustment for surrogates of the malnutrition-inflammation complex syndrome: Hispanic patients had similar mortality to non-Hispanic whites, and African-Americans had even higher mortality than whites, with a hazard ratio of 1.16 in a matched cohort.
Since this was an observational study, though, it can not prove that nutritional status and inflammation are causing death, Dr. Kovesdy noted.
“In order to prove a causal link, you would need to design an interventional study where you provide people with nutrients, where you treat their inflammation, and see that it's the better outcome,” he said
The study drew its conclusions from a sizable data set, noted Barry Freedman, MD, Professor of Urology and Nephrology at the Wake Forest University School of Medicine.
“The strengths of this study lie in its large database with longitudinal follow-up and superb investigative team,” Dr. Freedman said. “There are also some limitations. For example, several factors felt to reflect an individual's nutritional and inflammatory status reveal marked racial variation. These differences may relate more to intrinsic biologic variation between the races and therefore they may not reflect the effects of inflammation.”
Surrogates of the malnutrition-inflammation complex syndrome examined in the study include body mass index (BMI), serum albumin, total iron-binding capacity, ferritin, creatinine, phosphorus, calcium, bicarbonate, white blood cell count, lymphocyte percentage, hemoglobin, and protein intake.
Dr. Freedman referred to the biological differences by race for a few of these surrogates.
“In general, blacks have higher muscle mass, serum creatinine concentrations, and BMI relative to whites,” he said. “Blacks are also known to have generally lower white blood cell counts. These effects are common even in people who are not on dialysis.”
There is more work to be done, Dr. Freedman noted.
“We need to continue searching for inherited risk factors and effects of nonconventional cardiovascular disease risk factors that may contribute to racial differences in survival on dialysis,” he said. “Future research on this topic should consider genetic variation between race groups and how novel CVD risk factors contribute to atherosclerosis and dialytic survival.”
There are lingering questions, Dr. Kovesdy agreed.
“The questions that need answering here are: Why would African-Americans on dialysis have better nutrition?” he said. “Why would they have less inflammation? Is it something that relates to their medical care? Is it something that relates to some kind of biological characteristic of theirs?”
In order to improve outcomes in dialysis and end-stage renal disease, the focus should be on malnutrition and inflammation, noted Adriana Hung, MD, MPH, Assistant Professor of Medicine in the Division of Nephrology at Vanderbilt University School of Medicine.
“This report highlights that we need to intervene on those components,” she said. “I think that if we focus on treating inflammation, we'll hopefully be able to see some improvements in survival.”
Identifying factors responsible for the survival advantage in African-American and Hispanic dialysis patients could have major implications not just in kidney disease patients, but also in other populations with chronic disease and poor survival, the researchers wrote.
“For us, the implication is that we need now to move on with additional studies to identify the role of nutrition and inflammation in explaining outcome differences,” Dr. Kalantar-Zadeh added. “If that's the case, then the next step would be nutritional and anti-inflammatory interventions to improve survival.” •© 2011 Lippincott Williams & Wilkins, Inc.