In a contemporary cohort of 124,029 adult hemodialysis patients composed of three mutually exclusive racial/ethnic categories involving 16% Hispanics, 49% non-Hispanic Whites, and 35% African Americans, we found that African American and Hispanic patients had better survival than Whites even after controlling for such demographic variables as age, gender and diabetes. However, after additional multivariate adjustment for surrogates of nutrition and inflammation, together known as the MICS, African Americans had poorer survival than Hispanics or Whites. After removing the contribution of the nutritional status, higher hemoglobin concentrations were associated with lower survival in African Americans as compared to Whites. Hispanic hemodialysis patients showed a similar reduction of their survival advantage, compared to Whites, after controlling for the MICS, although Hispanic patients younger than 65 years maintained their better survival even after extensive multivariate adjustment.
These findings, if verified in additional studies, may have important clinical and public health implications, since they may indicate that a more favorable nutritional and inflammatory status is the main condition that confers survival benefit to these minorities in the hemodialysis patient populations.25–27
The incidence and prevalence of ESRD have been rising in the United States and in most countries in the world.28
Racial discrepancies in CKD have persisted for the past 20 years.3, 5, 29
The annual ESRD incidence for African Americans and Hispanics in 2006 reached 1,010 and 520 per million population, respectively, which is 3.6 and 1.5 times greater than the incidence in non-Hispanic Whites.28
The prevalence of ESRD continues to be highest for African Americans and Hispanics, at 5,004 and 2,326 per million population, respectively, as compared to 1,194 per million among Whites.28
In many maintenance dialysis clinics in inner-city areas, over one-half to two-thirds of dialysis patients are African American, whereas in many other dialysis centers, especially in California or Texas, Hispanics predominate. 28
As shown in , in our national cohort, over one-third of the dialysis patients were African Americans and 16% Hispanic, as compared to their proportions of 14% and 13% in the general U.S. population, respectively.28
About one out of every five American dialysis patients dies each year, and the 5-yr survival is only around 35%,5, 29
which is worse than survival for most cancers.5, 7, 29
At any given age group, mortality of dialysis patients is 10–100 times higher than that of non-dialyzed Medicare patients.4, 28, 30
Nearly half of the deaths are considered to be caused by cardiovascular disease.29, 31, 32
African American and Hispanic dialysis patients have higher survival than their non-Hispanic White counterparts, a phenomenon that has persisted over the past two decades.4, 5
The higher dialysis survival of these minorities is rather consistent and independent of demographic or residency status and also of the modality of dialysis treatment (thrice-weekly hemodialysis vs. daily peritoneal dialysis), the dialysis dose, and other factors related to dialysis treatment or techniques..28, 30
In the U.S. general population, disparities in income, education, and health have been implicated in the increased total mortality and shorter life expectancy of African Americans compared with Whites,33–35
even though as dialysis patients they have a much lower annual mortality rate (18%) than Whites (28%).29
A similar phenomenon is observed in preterm African American infants, who are more likely to survive than white infants born after pregnancies of comparable duration,36
even though within the ‘normal range’ of gestation/birth weight (≥37 weeks/≥2,500–3,000 g) African American infants are substantially more likely to die than white infants.36, 37
Similar results were found in Netherland, van den Beukel et al reported better survival in immigrant compare to native dialysis patients,38
and also in Israel, where Arab have higher end-stage renal disease but exhibit greater survival than Jewish Israelis.39
Our findings indicate that a more favorable nutritional and inflammatory profile, captured under the MICS adjustor, can explain the bulk of dialysis survival advantage of African Americans, in whom BMI and serum creatinine (an indicator of muscle mass as well as ingestion of skeletal muscle or meat).40
are substantially higher than in other groups (see ). Indeed, without this favorable nutritional profile, we found that African Americans had higher mortality than others. We also found that after nutritional-status adjustment, higher hemoglobin levels were associated with higher mortality in African Americans, as compared to white hemodialysis patients (). Similarly, some but not all previous studies have shown that hemoglobin levels above 13 g/dL are associated with increased mortality as compared to a Hb of 11.5 to 12 g/dL.41, 42
The survival superiority of African American hemodialysis patients has been treated as confounding that is to be adjusted away.43
Nonetheless, because race is determined long before nutritional status, the latter functions more as an intermediate rather than confounder, and thus can be considered an integral part of the effect of race.6
African American dialysis patients exhibit other differences from other racial/ethnic entities. In a 3-year contemporary cohort of 15,859 hemodialysis patients, African Americans were the only patients in whom a high serum LDL (>100 mg/ml) was associated with increase in cardiovascular death risk, whereas LDL-hypercholesterolemia was paradoxically protective in other races.44
A recent study in 9,303 incident hemodialysis patients, including 3,214 African Americans, suggested that therapy with active forms of vitamin D could explain the greater survival of African American hemodialysis patients. 45
Considering our current findings and the aforementioned studies together, there appear to be altered risk factor patterns in individuals from certain racial/ethnic backgrounds, but not from others, who have chronic health conditions that are associated with increased mortality.
We observed that African American patients tended to have lower WBC and higher serum creatinine levels. Further studies are required to explore these differences. We found that African Americans had better survival than Whites even after controlling for case-mix variables. However, after additional multivariate adjustment for surrogates of nutrition and inflammation, African Americans had indeed even poorer survival than Whites similar to the general population. African-American patients have higher creatinine level () which is mainly correlated with muscle mass.46
Low serum creatinine is a potential marker for the protein-energy wasting (PEW) in maintenance hemodialsis patients.47
PEW is a strong predictor of mortality in this population.48
Additionally, African-American patients had lower WBC and higher percentage of lymphocytes representing the lowest level of inflammation. This profile suggests that PEW is less frequent in African Americans than in Whites.
We also examined survival features of Hispanic hemodialysis patients, the second largest and fastest growing US dialysis population. For the past two decades, evidence has accumulated of a tendency for U.S. Hispanics to have lower than average rates of most chronic illnesses, and better than expected health and mortality outcomes, despite the fact that many Hispanics live in relatively poor economic conditions.49–51
Proposed explanations include under-reporting of Hispanic deaths, ‘salmon bias’ (return of aged Hispanics to their homeland prior to death) and healthy-migrant effects52, 53
but may not fully account for this so-called “Hispanic Paradox”.6
Despite the decreased likelihood of Hispanics developing most chronic diseases, they are, nearly twice as likely to develop ESRD than non-Hispanic whites.54–56
This striking ‘paradox-within-a-paradox’ might be a function of the increased incidence and prevalence of diabetes mellitus, confirmed in our study (see ). Mexican Americans with type 2 diabetes mellitus are more likely to develop proteinuria,57
and six times more likely to progress to CKD-5,55
than non-Hispanic whites. Hispanic patients with CKD almost inevitably progress to CKD-5.55
The prevalence of type 2 diabetes mellitus is 2–5 times higher in Hispanics than in non-Hispanic whites.58–60
Mexican Americans, who are at highest risk of developing CKD, might share a common genetic background and ‘thrifty genotype’ with Native American Indians, themselves a group at high risk of developing diabetes mellitus and CKD.54, 61
When diabetic Mexican Americans undergo maintenance dialysis, however, they are more likely to survive than non-Hispanic whites;57, 62
which is yet another example of a paradox-within-a-paradox. In our current study we found that the survival advantage of Hispanic hemodialysis patients was mostly explainable by the MICS adjustor, which may indicate that, similar to African Americans, a more favorable nutritional/inflammatory status is also the potential biology behind the survival superiority of this ethnic group.
Our study is limited by the lack of detailed, up-to-date data of comorbid states or measurements of markers of inflammation such as C-reactive protein. However, as indicated previously, we believe that adjustment for the MICS, by including a number of indicators of malnutrition and inflammation, was adequately inclusive, as it could explain the preponderance of survival differences across the racial and ethnic groups. The strengths of this study include the recency of the patient data (from 2001–2006); uniformity in laboratory measurements (performed at a single facility); large sample size; use of time averaged Kt/V and laboratory data, with most values representing means of up to 3 monthly measurements; and analysis of 5-year survival.
In conclusion, in a large cohort of 124,029 adult hemodialysis patients, who were observed for up to 5 years during the first decade of the 21st century, African American and Hispanic patients had greater survival than Whites even after case-mix adjustment. After additional multivariate adjustment for surrogates of nutrition and inflammation, Hispanics had essentially the same mortality as White, whereas African Americans had a greater death risk compared to Hispanics or Whites. Our findings suggest that a healthier nutritional and inflammatory status is the main cause of the survival advantages of minorities who undergo hemodialysis treatment. Trials of nutritional and anti-inflammatory interventions are warranted to examine whether longevity can be improved in dialysis patients and other populations with chronic disease states and the wasting syndrome.