点击显示 收起
Medical Service
Salt Lake VA Healthcare System
Salt Lake City, UT and
Division of Nephrology & Hypertension
University of Utah School of Medicine
85 North Medical Drive East, Room 201
Salt Lake City, UT 84112 E-mail: srinivasan.beddhu{at}hsc.utah.edu
Division of Nephrology & Hypertension
University of Utah School of Medicine
Salt Lake City, UT
Medical Service
Salt Lake VA Healthcare System
Salt Lake City, UT and
Division of Clinical Epidemiology
University of Utah School of Medicine
Salt Lake City, UT
Dear Sir:
With great interest, we read the recent review article by Kalantar-Zadeh et al (1) on the survival advantage of obesity in dialysis patients. We would like to respond to the fundamental assumptions of this review article and to the authors' comments on an earlier report of ours (2).
The paradoxical association of high body mass index (BMI) with better survival and of low BMI with worse survival in dialysis patients has been described by the authors as "reverse epidemiology" and interpreted as the survival advantage of obesity in dialysis patients. In addition, to explain the higher mortality associated with low BMI, the "malnutrition–inflammation complex syndrome" (MICS) theory suggested by the authors implies an association of low BMI with inflammation and cardiovascular disease in dialysis patients.
Kalantar-Zadeh et al suggest that obesity might be associated with low inflammation in dialysis patients, but all of the current evidence indicates that that is not the case. The actual paradox of what is called the BMI paradox in dialysis patients is the possible association of high BMI with inflammation and decreased mortality. Recent data suggest a cross-sectional association of high BMI or abdominal adiposity with inflammation in persons with moderate chronic kidney disease (CKD) and in the dialysis population (3). In dialysis patients, inflammation has been associated with coronary artery calcification (4), myocardial injury as shown by elevations in serum troponin T (5), and death (6). These data raise the question: if obesity is associated with inflammation in dialysis patients, how does obesity confer a survival advantage?
Furthermore, if MICS is the explanation for the association of low BMI with high mortality, then the most direct and valid demonstration of this hypothesis would be evidence of greater inflammation and progression of atherosclerosis in low-BMI dialysis patients. It is noteworthy that no study to date has shown the longitudinal association of low BMI with inflammation, incident atherosclerotic events, or progression of atherosclerosis in dialysis patients; this lack of association raises concerns about the validity of MICS as the explanation for high mortality associated with low BMI in dialysis patients. Indeed, in a large study of incident dialysis patients, we found no clear evidence of the association of low BMI with atherosclerotic events (7).
It is possible to explain the associations of high BMI with better survival and of low BMI with high mortality in dialysis patients (8) without invoking the reverse epidemiology and MICS theories. When the association of BMI with survival is examined, there might actually be 2 issues: the question of the effect of nutrition on survival and the question of the effect of adiposity on atherosclerotic events and cardiovascular events in dialysis patients. We hypothesize that, in dialysis patients, the effects of nutrition on survival are much stronger than are the effects of atherosclerotic events. We also hypothesize that undernutrition is not associated with inflammation or atherosclerosis but that it increases the hazard of death from concomitant cardiovascular and noncardiovascular events. On the other hand, better nutrition, as evidenced by greater muscle mass, decreases the hazard of death from concomitant cardiovascular and noncardiovascular events, which results in lower cardiovascular and noncardiovascular mortality than is seen in persons with low or moderate muscle mass. Compared with undernutrition, adiposity decreases the hazard of death from concomitant disease processes, but it is associated with inflammation, oxidative stress, and atherosclerotic events in dialysis patients just as in the general population, where there is no reverse epidemiology or MICS. The result of these associations is intermediate death rates; ie, those that are lower than rates in undernourished subjects but higher than those in well-nourished subjects with greater muscle mass. In other words, adiposity in dialysis patients confers a survival advantage over undernutrition but not over greater muscle mass.
We also want to respond to the comments of Kalantar-Zadeh et al about our earlier report (2). They stated that, in our study, residual renal function was a major confounder of the associations of body-composition groups with survival and that 24-h creatinine clearances reported in Form 2728 were calculated by using the Cockroft-Gault equation. However, when we used residual renal function as a stratification variable, the associations of body-composition groups with survival were not altered, which indicated that residual renal function was not a major confounder (9). Moreover, the correlation coefficient of the urinary creatinine value calculated by using the Cockroft-Gault equation with the urinary creatinine value calculated from the Form 2728 creatinine clearance was only 0.44, which indicates that the Form 2728 urinary creatinine values were not calculated by using the Cockcroft-Gault equation (9).
The authors also commented that our interpretation of the results was contradicted by our data. In another letter in the Journal, we (10) responded in detail to an article by Johansen et al (11) in which they raised concerns about our statement, in an earlier article, that "the survival advantage conferred by high BMI in dialysis patients is limited to patients with normal or high muscle mass" (2). We again showed and explained that, compared with normal-BMI incident dialysis patients who have "healthy" normal or high muscle mass, high-BMI dialysis patients have a survival advantage only if they have normal or high muscle mass, and they have higher mortality if their muscle mass is low. Whereas adiposity confers a survival advantage over undernutrition, higher muscle mass confers a survival advantage over adiposity, and, therefore, dialysis patients should be encouraged to gain muscle mass rather than fat mass. When a survival advantage of obesity in dialysis patients is claimed, as Kalantar-Zadeh et al have done, a false impression is given to the practicing nephrologists and dietitians that high body fat is as protective as high muscle mass in dialysis patients.
ACKNOWLEDGMENTS
The authors had no conflicts of interest
REFERENCES