Obesity and Survival on Dialysis In 3 sentences: This article examines studies on the relationship between body mass and survival in patients undergoing dialysis therapy. Several recent large studies have found that overweight and obese dialysis patients have lower mortality rates than normal weight patients, in what is known as the "dialysis-risk paradox". However, some studies have contradicted these findings or found no survival advantage with higher body mass, suggesting the relationship may differ based on factors like race, population characteristics, and length of follow-up.

1. Obesity and Survival on Dialysis
Abdulla K. Salahudeen, MD
● Several factors associated with greater cardiovascular mortality in the general population may show a paradoxi-
cal relationship in patients on dialysis therapy. This dialysis-risk paradox has been reported for high blood
pressure, serum lipid levels, and body mass, but the finding is more consistent and persuasive for obesity. This
article examines the literature on the association between body mass and dialysis survival and considers the
possible mechanistic and clinical implications. Am J Kidney Dis 41:925-932.
© 2003 by the National Kidney Foundation, Inc.
INDEX WORDS: Obesity; survival; body mass index (BMI); overweight; dialysis; hemodialysis (HD); peritoneal
dialysis (PD); risk factors; nutrition.
SEVERALRECENT STUDIES suggested that
factors associated with greater cardiovascu-
lar mortality in the general population may show
a paradoxical relationship in patients on dialysis
therapy. This paradox, variably described as di-
alysis-risk paradox1,2 or reverse epidemiology,3,4
has been reported for high blood pressure, serum
lipid levels, and body mass.1,5-14 However, the
finding is more consistent and persuasive for
obesity.8-11 This review examines the literature
on the association between body mass and dialy-
sis survival (summarized in Table 1) and dis-
cusses the possible mechanistic and clinical im-
plications.
The Diaphane collaborative study group15 in
France was one of the first to report in 1982 on
the paradoxical observation of a lack of mortality
increase with high body mass index (BMI; weight
for height squared) in dialysis patients. In this
study, Degoulet et al15 followed up the survival
of 1,453 patients undergoing dialysis between
1972 and 1978. Leavey et al,16 in 1998, while
assessing the influence of a number of com-
monly used clinical parameters on dialysis sur-
vival, confirmed the lack of association between
greater BMI values and increased mortality risk.
However, a study by the author’s group8 pub-
lished in 1999 identified for the first time a
significantly greater survival advantage in over-
weight and obese patients on hemodialysis
therapy. This study, in which survival was evalu-
ated prospectively for 12 months, was based on a
cohort of 1,300 patients undergoing outpatient
hemodialysis. The unexpected finding was that
overweight and obese (BMI ⱖ 27.5) patients had
significantly greater 12-month survival than nor-
mal-weight (BMI, 20 to 27.5) or underweight
(BMI ⬍ 20) patients. Further analysis of the data
using Cox proportional hazard models showed
that for every unit increase in BMI, the relative
risk (RR) for mortality was reduced by 10%. In
multivariate analyses, greater BMI remained a
significant factor for better survival, even after
adjustment for a number of variables commonly
linked to dialysis patients’ survival. In addition
to reduced mortality, overweight compared with
underweight patients had a significantly lower
rate of hospital admissions and shorter duration
of hospital stays. This unexpected and paradoxi-
cal finding of this article prompted an accompa-
nying editorial titled “Obesity and Mortality in
ESRD: Is It Good to Be Fat?”17 Although provoc-
ative, our study had a number of limitations, such
as the observational nature of the study and the
predominance of African Americans in the popu-
lation. However, a number of subsequent studies,
discussed next, supported the association be-
tween high BMI and better survival on hemodi-
alysis therapy.
In a study by Kopple et al,9 the influence of
nutritional and physical parameters on survival
was determined in 12,965 patients on hemodialy-
sis therapy. They reported a weight-for-height–
dependent decrement in mortality rate, with the
lowest mortality rates observed in overweight
patients. In another study by Wolfe et al18 on a
national US random sample from the US Renal
Data System (USRDS), body size in various
From the Department of Medicine, University of Missis-
sippi Medical Center, Jackson, MS.
Received October 4, 2002; accepted in revised form
December 17, 2002.
Address reprint requests to Abdulla K. Salahudeen, MD,
Department of Medicine, University of Mississippi Medical
Center, 2500 N State St, Jackson, MS 39216. E-mail:
asalahudeen@medicine.umsmed.edu
© 2003 by the National Kidney Foundation, Inc.
0272-6386/03/4105-0002$30.00/0
PII: S0272-6386(03)00189-6
American Journal of Kidney Diseases, Vol 41, No 5 (May), 2003: pp 925-932 925

2. Table 1. Summary of References Related to Obesity and Survival on Dialysis Therapy
Reference
Dialysis
Type Patient Details
Body Mass
Measures
Effect of Body Mass
on Survival Comments
Degoulet et al15,
1982
HD 1,453 patients treated
in 33 French
dialysis centers,
5-y observation
BMI Greater mortality with
lower BMI; no
increased mortality
with higher BMI
First suggestion that higher
BMI might not be
associated with greater
mortality
Leavey et al16,
1998
HD Data on 3,607
USRDS patients,
5-y observation
BMI Greater mortality with
lower BMI; no
increase in
mortality with
higher BMI
Consistent with data from
Degoulet et al15
Kaizu et al20,
1998
HD 116 Japanese
Asians, 5-y
observation
BMI Greater mortality with
lower and higher
(BMI ⬎ 19) BMI
Asian population; longest
follow-up; first
suggestion that obesity
worsens dialysis survival
Fleischmann et
al8, 1999
HD 1,346 patients (Renal
Care Group, MS
cohort), mostly
African Americans;
1-y prospective
follow-up
BMI Greater mortality with
lower BMI, but
lower mortality,
fewer hospital
admissions, and
shorter stay with
greater BM; better
nutrition with
higher BMI
First report of a paradoxical
relationship of better
survival with overweight
and obesity
Kopple et al9,
1999
HD 12,965 patients, 1-y
observation
Body
weight,
weight
for
height
Lower mortality with
progressively
higher weight for
height; lowest
mortality rates in
overweight
patients
Supported the association
between overweight and
better survival in
hemodialysis
Wong et al22,
1999
HD 84,192 Asian
Americans and
Caucasians from
USRDS; 2-y
observation
BMI Lower mortality in
Asian Americans
than Caucasians;
higher mortality
with overweight
and obesity BMI
Lacked obesity-survival
paradox, ie, greater
mortality in obese
patients consistent with
the Asian data from
Kaizu et al20
Wolfe et al18,
2000
HD 9,165 USRDS
patients; 2-y
prospective
observation
Body
weight,
body
volume,
BMI
Close association
with body
measures and
dialysis survival
even in overweight
and obese patients
Supported the
obesity-survival paradox
in dialysis patients
Leavey et al10,
2001
HD 9,714 US and Europe
(DOPPS) patients,
variable follow-up
BMI Mortality risk
decreased with
increasing BMI,
even in obese
patients
Confirmed the presence of
obesity-survival paradox
in hemodialysis patients
and extended this to
European patients
Combe et al23,
2001
HD 1,610 patients in 20
French centers;
2.5-y observation
BMI No positive influence
of BMI on survival,
average BMI ⫽ 23
Contradicted the DOPPS
finding of better survival
with higher BMI; possibly
because of a population
with relatively lower BMI
Port et al11,
2002
HD Data on 45,967
patients from
HCFA billing
records
BMI The highest BMI
tertile had the
lowest mortality
risk
Confirmed the
obesity-survival paradox
Lowrie et al19,
2002
HD 43,334 patients;
Fresenius Medical
Care (North
America) clinical,
data system
Body
weight,
weight/
height,
BSA,
and BMI
Better survival with
large body mass
Confirmed the
obesity-survival paradox
Johnson et al28,
2000
PD 43 patients; 3-y
follow-up
BMI Better survival in
overweight PD
patients
Reported obesity-survival
paradox in PD patients
Aslam et al29,
2002
PD 104 patients; 2-y
observation
BMI No survival difference
between normal
and overweight
patients
Contradicted the Johnson
et al data, but found no
increased mortality with
obesity
Abbreviation: MS, Mississippi; HCFA, Health Care Financing Administration; BSA, body surface area; HD, hemodialysis.
ABDULLA K. SALAHUDEEN
926

3. forms of measurements, such as body weight,
body volume, and BMI, was shown to correlate
independently and significantly with better sur-
vival among patients who were overweight and
obese.
Evidence for a clearer association between
greater BMI and better survival comes from the
recent work of Leavey et al.10 This study, based
on a large pool of prospective data from the
Dialysis Outcomes and Practice Patterns Study
(DOPPS) for nearly 10,000 hemodialysis pa-
tients in both Europe and the United States,
reported a significantly lower mortality RR in
overweight versus normal-weight patients, which
was readily apparent in both the US and Euro-
pean cohorts (Fig 1). The relationship between
high BMI and mortality was investigated further
by categorizing BMI for the entire study sample
into overweight and mild, moderate, and severe
obesity. Compared with a normal-BMI reference
group (BMI, 23 to 24.9), significantly lower RRs
were found for overweight (RR, 0.84; P ⫽ 0.008),
mild obesity (RR, 0.73; P ⫽ 0.0003), and moder-
ate obesity (RR, 0.76; P ⫽ 0.02), but not for
severe obesity (RR, 0.83; P ⫽ 0.331). In this
study, the BMI-survival relationship to over-
weight and mild to moderate obesity also was
demonstrable in a wide variety of subgroups of
patients on hemodialysis therapy irrespective of
differing baseline health status.
In another large hemodialysis population, Port
et al11 reaffirmed the association between BMI
and survival: patients with the lowest BMIs had a
42% greater mortality risk than patients in the
highest BMI tertile that included overweight and
obese patients. Latest in the series of positive
studies were the recently published data from
Lowrie et al.19 The study was on 43,334 patients
on hemodialysis therapy and the main-effect
models suggested improved survival with increas-
ing measures of body mass and dialysis dose.
Although the majority of studies found a posi-
tive association between body mass and survival
on dialysis therapy, a few studies have not. In a
study by Kaizu et al,20 of 116 patients without
diabetes from Japan followed up on hemodialy-
sis therapy for 12 years in the early 1980s,
patients with a BMI greater than 23.0 showed a
lowered survival rate compared with patients
with a BMI of 17.0 to 18.9. In this study, survival
on dialysis therapy also was associated with a
significant loss in BMI. A preliminary analysis
from our group suggests that loss of body mass,
even in obese patients, might portend greater
mortality.21 Although limited in number of pa-
tients, Kaizu et al20 provided one of the longest
follow-up periods. It is thus possible that obese
patients may have better survival in the short
term, but not necessarily in the long term. Further-
more, Japanese patients historically have had a
lower mortality rate on dialysis therapy com-
pared with European or US patients. Thus, race
may confound the effect of obesity on survival,
and unlike African Americans, in whom obesity
and higher survival on dialysis are strongly asso-
ciated, obesity may herald a detrimental effect on
Japanese patients.
The latter point is resonated by a larger study
in Asian Americans.22 Using the USRDS data-
base, Wong et al22 reported a significantly lower
Fig 1. RR for mortality against BMI in European and US dialysis patients. Reprinted with permission from Leavey
et al.10
OBESITY AND BETTER SURVIVAL ON DIALYSIS 927

4. mortality rate among Asian Americans compared
with Caucasian Americans and, more germane to
our discussion and consistent with Kaizu et al,20
an increase in mortality risk in Asian Americans
with greater BMIs (BMI ⬎ 25). In a recent study
from France, Combe et al23 did not find a posi-
tive influence of BMI on the 2-year survival of a
cohort of 1,610 hemodialysis patients. However,
this may not be surprising because mean BMI in
this population was 23, substantially less than
that reported in the US dialysis population or
DOPPS European population. Therefore, this
study might not have had the appropriate patient
population to test the hypothesis of whether
obesity is associated with better survival. The
Spanish Cooperative Study of Nutrition in Hemo-
dialysis24 is another study from Europe that as-
sessed survival and nutritional status. Malnutri-
tion was present in nearly 50% of their 761
hemodialysis patients, and many had protein-
calorie malnutrition and fat depletion. Not surpris-
ingly, an association was not found between
excess body mass and survival in this population.
As in hemodialysis, several studies in perito-
neal dialysis (PD), including the Canada-USA
study, have established that measures of lower
body mass and malnutrition are associated
strongly with increased mortality in PD pa-
tients.25-27 However, whether an association be-
tween greater body mass and better survival
exists in patients on PD therapy, as in those on
hemodialysis therapy, is not clear at the present
time. Studies by Johnson et al28 and Aslam et al29
specifically addressed this issue, but arrived at
dissimilar conclusions. In the former study, over-
weight PD patients had a significantly better
survival rate (71%) at 3 years compared with
normal-weight patients (31%), possibly because
of significantly higher nutrition among over-
weight patients. However, in the study by Aslam
et al,29 no survival advantage was reported in
overweight patients. As in the study by Johnson
et al,28 patients were divided into normal weight
(BMI, 20 to 27.5) or obese (BMI ⬎ 27.5).
During a 2-year period, obese patients on PD
therapy had fewer deaths compared with normal-
weight patients, which did not reach statistical
significance. Because this study included a rela-
tively small number of patients compared with
larger numbers of patients in hemodialysis stud-
ies, and the study by Johnson et al28 in PD
patients reported a survival advantage in over-
weight obese PD patients, it has been suggested
that a conclusion of lack of association in PD
patients based on the study byAslam et al29 alone
might be premature.30 Of note, all PD studies,
including the largeAdequacy of Peritoneal Dialy-
sis in Mexico trial,31 which was designed to test
the effect of peritoneal clearance on survival and
not to study the relationship between body mass
and survival, did not report an increased risk for
death in overweight and obese patients on PD
therapy.
Two additional and potentially confounding
issues, namely, dialysis dose and patient race,
need to be considered when one examines the
effect of body weight on dialysis patients’ sur-
vival. Several studies have shown that with a
standard prescription of dialysis, the delivered
dose of dialysis (urea reduction ratio or Kt/V) is
related inversely to body size (Fig 2),11,32,33 which
is not surprising given that V, the volume of
distribution of toxins, which in turn is a function
of body size, also is the denominator in Kt/V
calculation of dialysis dose. Thus, underweight
and overweight patients receive higher and lower
doses of dialysis, respectively (Fig 2).32,33 How-
ever, the mortality rate is greater in underweight
patients despite higher Kt/V and lower in over-
weight patients despite lower Kt/V.33 Thus, in
obese patients, a reverse association still exists
between obesity and survival despite lower Kt/
V.33 The best interpretation of this overriding
effect of body mass on Kt/V is that beyond a
Fig 2. Simple regression analysis of BMI and dialy-
sis dose in 1,151 patients on maintenance hemodialy-
sis therapy (r ⴝ 0.30; P < 0.0001). Reprinted with
permission from Salahudeen et al.33
ABDULLA K. SALAHUDEEN
928

5. certain dialysis dose, survival of dialysis patients
depends more on body mass. However, results of
recent studies from Salahudeen et al33 and Port et
al11 suggest that correcting for underdialysis based
on body weight in overweight patients might
further improve their survival.
The second issue is related to patient race and
survival on dialysis therapy. The correlation be-
tween dialysis dose and survival on dialysis
therapy is not simple34 and is influenced by race,
sex,35 body size,11,36 and possibly other factors.
The well-documented better survival of African-
American patients on dialysis therapy despite
lower delivered doses of dialysis defies a ready
explanation. That African-American patients in
general have a larger body mass than similar
groups of Caucasians might be one of the pos-
sible reasons for better survival (Fig 3).8,37,38
That better survival might not be race specific,
but might be a function of greater body mass and
nutrition, is suggested further by the DOPPS
finding that obese European dialysis patients,
which hardly included black individuals, also
had better survival (Fig 1). In this regard, Asians
or Asian Americans on dialysis therapy remain
an exception because they do not seem to show
the reverse epidemiological characteristics like
the rest, and as alluded to earlier, further studies
are required to clarify whether theAsian phenom-
enon of lack of obesity paradox is a race-specific
phenomenon.
Although there is a “U” curve relationship
between BMI and survival in the general popula-
tion,39 this may not be true for certain subgroups
of subjects. For example, a subgroup analysis of
a large population study showed a lack of upturn
in the mortality U curve in obese black sub-
jects.40 Similarly, a blunted upturn was observed
in obese subjects who were sick or smokers.40 In
another large population study that examined the
effect of age on mortality-BMI relationship, obe-
sity-related mortality risk (RR) did not increase
linearly with age because RR values did not
increase in obese patients of certain elderly age
groups.41 Thus, even in nondialysis subjects, the
relationship between overweight and mortality
appears not to be uniform. This is exemplified
further by reports in patients with congestive
cardiac failure. Obese patients with heart failure
had fewer clinical events, such that with every
unit increase in BMI, clinical events decreased
by 13%.42 However, although obese patients with
heart failure might have had fewer clinical events,
a recent report from the Framingham Heart Study
indicates that increased body mass in itself is an
independent risk factor for developing heart fail-
ure.43 Thus, obesity is unquestionably associated
with greater morbidity and mortality. However, a
reasonable supposition based on existing data
would be that once ill, excess body weight
through yet to be defined mechanisms might
confer survival advantage.
One of the proposed mechanisms for better
survival in obese patients is through better nutri-
tion. In our study, biochemical markers of better
nutrition aggregated with greater BMI.8 How-
ever, in the same study, greater BMI retained its
positive influence on survival even after adjust-
Fig 3. Frequency distribution of BMI in Caucasian and African-American patients on hemodialysis therapy.
Reprinted with permission from Fleischmann et al.8
OBESITY AND BETTER SURVIVAL ON DIALYSIS 929

6. ing for parameters of better nutrition, implying
that in uremic patients with a greater BMI, mecha-
nisms beyond better nutrition may offset part of
the toxic effects of uremia. Consistent with the
view that all the survival advantage of greater
BMI may not be caused by nutrition is the
finding of Leavey et al10 in DOPPS patients that
although a trend existed, overweight and obese
patients did not have significantly greater bio-
chemical markers of better nutrition.
Although not a perfect correlate, overweight
patients have increased adipose tissue and there-
fore are less likely to experience energy deficits.
Arguably for this reason, underweight patients
on hemodialysis therapy might be more likely to
fall ill or tend to recover more slowly from
illness than normal-weight or overweight pa-
tients, as shown in our study.8 Occasionally,
greater BMI could be caused by greater muscle
mass or increased water content. Statistical anal-
ysis with adjustment for indirect measures of
muscle mass and water content did not change
the BMI-mortality relationship.10 One sugges-
tion is that overweight and obese patients with
increased energy and nutritional reserves may be
able to withstand uremia- and dialysis-related
stresses in various forms, mainly infection, in-
flammation, and episodes of inadequate protein-
calorie intakes.
An alternate suggestion is that an ability to
maintain body weight, especially in the over-
weight and obesity range, is merely the demarcat-
ing feature of a noninflamed, relatively healthy,
likely-to-survive patient. In contrast to better
survival with obesity, loss of body weight corre-
lated closely with protein-energy malnutrition
and inflammation. The latter is suggested to be
cytokine-mediated and believed to be triggered
in response to a variety of dialysis-related stimuli,
particularly infection. This state of inflammation,
in turn, is believed to set up a vicious cycle
leading to more malnutrition and inflamma-
tion.44-46 If malnourished patients were to be
susceptible to an inflammatory state, it is plau-
sible that overweight patients might be resistant
to dialysis-related inflammatory syndrome. How-
ever, there are few data on the extent of inflam-
matory syndrome in overweight and obese pa-
tients on dialysis therapy.
The studies cited that support an association
between overweight and better survival in a
dialysis population are observational in nature. It
is unlikely that an interventional study that in-
duces a gain in overweight in dialysis patients
will be performed to test whether a causal rela-
tionship exists between obesity and improved
survival. In the absence of such studies, the
linkage between obesity and survival could be
argued as an association in that a beneficial effect
of obesity in dialysis patients could be caused by
other unappreciated survival factors cosegregat-
ing with overweight and obesity. Historically,
protein-energy malnutrition and not obesity has
been the main nutritional illness facing dialysis
patients. However, recent data from US regional
and national databases indicate that in parallel
with the increasing overweight and obesity in
the general population, there is a greater pro-
portion of patients with overweight and obe-
sity in the dialysis population, as well as in the
kidney transplant recipient pool. Ill effects of
obesity are well known, and the finding that
greater BMI in dialysis patients is associated
with lower mortality should not lighten the
concern over obesity as a significant risk factor
for renal allograft failure.47-49 In this juncture,
a pragmatic approach to the management of
dialysis patients with regard to body weight
would be to: (1) monitor serial BMI; (2) be
concerned about progressive loss of BMI, even
in overweight patients (to attempt to delineate
the cause and, if possible, treat effectively);
and (3) aim to maintain high-normal BMI, if
necessary, with the liberal use of high-caloric
supplements.
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