Nephrol Dial Transplant (2008) 23: 263–268
doi:10.1093/ndt/gfm511
Advance Access publication 31 October 2007
Original Article
A structured weight management programme can achieve improved
functional ability and significant weight loss in obese patients with
chronic kidney disease
Sharlene A. Cook1, Helen MacLaughlin2 and Iain C. Macdougall3
1
Department of Physiotherapy, 2Department of Dietetics and 3Department of Renal Medicine, King’s College Hospital,
London, UK
Abstract
Background. Kidney transplantation in obese patients
[body mass index (BMI) > 30 kg/m2] is associated with
a poorer outcome, and these patients are therefore
often excluded from transplant waiting lists.
Conventional weight loss strategies based on a high
fibre, low energy diet and exercise are often unsuitable
in the chronic kidney disease (CKD) population.
A comprehensive multidisciplinary weight management programme comprising a low fat, reduced energy
diet, individual exercise prescription and pharmacotherapy with orlistat 120 mg tds, was initiated to
determine whether obese patients with CKD could
reach an acceptable weight for transplantation.
Methods. Thirty-two patients who completed
12 months in the programme were monitored regularly
for weight and waist circumference measures as well
as exercise performance tests. Twenty-two patients
formed a contemporaneous control group. Exercise
performance tests included the 6 min timed walk test
(6MTWT), sit to stand transfers in 60 s (STS60), timed
up and go 3 m (TUAG) and the Duke’s activity status
index (DASI), a measure of functional ability.
Results. Friedman’s test analyses were performed to
assess differences between baseline and 12-month data.
Mean body weight reduced by 7.1% from 102.9 kg
to 95.7 kg (P < 0.001) This equates to a reduction
in BMI from 35.7 kg/m2 at baseline to 33.2 kg/m2 at
12 months. Waist circumference decreased by 12.9 cm
from 112.9 cm to 100.0 cm (P < 0.005) at 12 months.
The 6MTWT improved by 45% (P < 0.001), STS60 by
30% (P < 0.001), TUAG by 37% (P < 0.001) and
DASI by 50% (P < 0.001) after 12 months. To date,
two of the patients have received live-related renal
transplants and an additional seven patients have
now been successfully enrolled onto the transplant
waiting list.
Correspondence to: Sharlene Cook, Senior Renal Physiotherapist,
Department of Physiotherapy, King’s College Hospital, Denmark
Hill, London SE5 9RS, UK. Email: [email protected]
Conclusion. Preliminary experience from this
multidisciplinary programme combining diet, exercise
and orlistat suggests that significant weight loss
and improved physical functioning can be achieved
in obese CKD patients, potentially allowing them the
opportunity of kidney transplantation and the associated benefits of this compared with long-term
dialysis.
Keywords: anti-obesity agents; chronic kidney disease;
exercise training; orlistat; transplantation; weight
reduction
Introduction
Obesity has been associated with improved survival
in patients with end-stage renal disease (ESRD) in
a number of epidemiological studies. It is hypothesized
that a higher level of adiposity may provide a survival
advantage for patients with ESRD, a catabolic disease
state [1]. These findings do not correlate with associations found in the general population where obesity
is associated with poorer survival. High BMI is
associated with poor health status in the general
population [2], and it is not known whether the
association between BMI and quality of life follows
the expected or the paradoxical pattern in dialysis
patients. Nevertheless, the inability to make the
transition from dialysis to transplantation as a result
of obesity alone will increase the size of the ESRD
population and denies patients the long-term advantages of transplantation over dialysis.
Furthermore, kidney transplantation in obese
patients [body mass index (BMI) > 30 kg/m2] is associated with an increased risk in terms of higher rates
of wound infections, delayed graft function and
rejection [3].
A rise in obesity and hypertension is paralleled by
an increase in the incidence of CKD. The PREVEND
ß The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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264
study showed BMI to be independently associated
with urinary albumin excretion and increased glomerular filtration rate (GFR) [4], and BMI has been
identified as an independent predictor for end-stage
kidney disease after adjustment for baseline blood
pressure and diabetes mellitus [5].
Poor physical functioning among patients with
CKD has been documented repeatedly [6].
These patients are at increased risk of coronary
artery disease, and are typically able to participate in
only the most sedentary of activities. For several
reasons, CKD patients have only about half the
exercise capacity of normal sedentary individuals [7].
In dialysis patients, a reduced ability to exercise
has significance not only on quality of life but also
on morbidity and mortality [8].
Orlistat (XenicalÕ , Hoffmann-La Roche, Basel,
Switzerland) is a non-systemically acting gastrointestinal lipase inhibitor that reduces the absorption
of dietary fat by about 30%. In randomized,
placebo-controlled trials of obese patients, orlistat in
conjunction with a mildly hypo-caloric diet was
associated with significantly greater weight loss than
diet alone [9].
The principal aim of this study was to establish
whether a structured, multidisciplinary programme
combining exercise, dietary intervention and orlistat
could achieve significant weight loss, decreased waist
circumference and improved functional ability in
patients with CKD. The main focus of this report
is the effect of this programme on a number
of exercise parameters [6 min timed walk test
(6MTWT), timed up and go 3 m (TUAG), sit to
stand 60 transfers (STS60) and Duke’s activity status
index (DASI)]. Baseline and 12-month data on BMI,
weight, waist circumference and kidney function
are also presented.
Subjects and methods
S. A. Cook et al
Table 1. Baseline characteristics (mean SD) of patients who
completed 12 months in the WMP and the control group.
Characteristic
Sex (no of subjects)
Female
Male
Race or ethnicity (no of subjects)
White
Black
Asian
Age (years)
Weight (kg)
Body mass index (kg/m2)
GFR (ml/min)
WMP
(n ¼ 32)
12
20
19
10
3
49.1
102.9
35.7
44.8
Control
(n ¼ 22)
9
13
(11.3)
(17.7)
(4.5)
(26)
7
11
4
49.2 (13.7)
101.68 (20.7)
34.1 (4.2)
38.8 (35.1)
around work, low motivation and non-compliance with the
treatment regime. One patient commenced dialysis during
the programme. No adverse events were recorded during the
programme; two patients died unrelated to the interventions
prescribed. Baseline characteristics for the 32 patients who
completed 12 months in the WMP, and for the 22 patients in
the control group are shown in Table 1.
CKD patients aged between 18 and 70 years with a BMI
of 30 kg/m2 or above, or 28 plus comorbidities, were
considered eligible for the programme. Exclusion criteria
included unstable angina, acute left ventricular failure (LVF),
a serious cardiac event in the preceding 6 weeks, uncontrolled
cardiac arrhythmias and uncontrolled hypertension.
Study design
This study utilized a prospective non-randomized design,
with a 24-month intervention. Data from the first 12 months
of the programme are reported here. Subjects were tested
at baseline, 3, 6, 9 and 12 months, and the results for body
weight, BMI, waist circumference and renal function
were compared with the contemporaneous observational
control group.
Patients
Intervention protocol
Sixty-six patients were initially referred to the Weight
Management Programme (WMP). Forty-four patients
under the care of the Renal Unit at King’s College
Hospital (27 M, 17 F) with CKD and stable or increasing
weight (BMI range 27.9–47.3 kg/m2) were recruited onto the
programme. The remaining 22 patients formed a contemporaneous observational control group (control) and
received standard care.
Of the patients in the WMP, eight patients were
undergoing peritoneal dialysis treatment, 14 were having
thrice-weekly haemodialysis, 19 were in stage 2–4 CKD,
and three had received kidney transplants. Priority was given
to pre-end-stage renal disease patients with a GFR of 50 ml/
min or less, particularly those otherwise suitable for
transplantation, along with potential living kidney donors
for such patients. Thirty-two patients out of the initial 44 in
the intervention group attended at least half of the clinic
appointments, giving a completion rate of 73%. Reasons
for non-completion were difficulty fitting in appointments
A multidisciplinary team consisting of a Consultant
Nephrologist, Exercise Physiotherapist and a team
of Dietitians delivered the programme, with the assistance
of the Pharmacist and Renal Transplant Coordinator as
required.
The patients were required to attend one clinic appointment each month for 6 months, and again at 9 and
12 months. They were seen by the Dietitian and
Physiotherapist at each appointment, and the Consultant
Nephrologist at the first visit (and as required). Data
were collected at the first visit (baseline), and at 3, 6, 9 and
12 months.
Patients were initially invited to attend a group information session, and were required to complete and return a
7-day food and activity diary before being accepted onto the
programme. The observational control group comprised
patients who were referred but did not enrol on the
programme. These patients were reviewed in renal outpatient clinics and their weight was recorded. Each patient
Weight management in obese CKD patients
on the programme was encouraged to comply with dietary,
exercise and pharmacotherapy treatment plans as prescribed.
We addressed barriers to lifestyle change through the use
of Cognitive Behavioural Therapy—food and exercise
diary throughout, through process evaluation, costs and
benefits, and goal setting. We also used a motivational
interviewing approach to address patient ambivalence.
265
(6MTWT) [11], timed up and go 3m (TUAG), an agility
test [11] and the sit to stand 60 (STS60), a measure of the
number of sit to stand transfers achieved in 60 s [12]. Patients
were encouraged to exercise at a level of 13–15 (‘somewhat
hard’ to ‘hard’) on the Borg’s Rating of Perceived Exertion
(RPE) [13] for each test.
Functional ability
Exercise intervention
Individualized exercise programmes were developed for
each subject. The programme was adjusted to meet the
needs of the individual patient with differing functional
abilities due to the varying presentation of this chronic
illness. The programme was for independent home-based
exercise, and included cardiovascular exercise (primarily
walking with a pedometer, sit to stand exercises, swimming
and cycling) and resistance training in the form of
hand weights and therabandTM. A frequency of at least
3 days per week and duration of at least 20–30 min was
encouraged. Patients kept exercise diaries, which
were examined in the clinic every month. The exercise
programme was adjusted as required and increased to induce
a progressive training effect. Any problems (such as muscle
aching/pain) were addressed and encouragement for
continued participation was also given.
Dietary component
An individualized, low fat, calorie-reduced, renal-specific
diet was prescribed for each patient, based on current
patterns and food preferences. A calorie reduction of at
least 500 kcal per day from estimated requirements was
initiated at the first visit, and adjusted throughout the
intervention period as required. A minimum intake
of 1200 kcal per day was encouraged. Compliance with diet
was encouraged with the use of monthly food diaries.
This is described in more detail elsewhere [10].
Functional ability was assessed with the use of the Duke’s
activity status index (DASI), a questionnaire measuring
the ability to complete activities of daily living and sporting
activities [14].
Weight and waist circumference
Weight, BMI and waist circumference were measured at
each visit. Waist circumference was measured in a subgroup
of 13 patients since it was not always possible in dialysis
patients, particularly those receiving peritoneal dialysis.
Weight and BMI were recorded in the observational
control group at routine clinic visits.
Statistical analysis
All analyses were carried out using the statistical package
SPSS 13.0 for Windows. Standard descriptive statistics,
consisting of mean SD, were used to characterize
the subject population. Exercise data were not normally
distributed, and therefore Friedman’s test was used to
examine differences between the exercise testing scores at
baseline and 12 months. Body weight, BMI and waist
circumference were normally distributed, and therefore
Student’s paired t-test analyses were used to assess
differences at baseline and 12 months. An alpha level of
P < 0.05 was used to indicate statistical significance.
Results
Orlistat
Orlistat was prescribed to all patients at the recommended
dose of 120 mg tds. Compliance with this therapy
was assessed at each study visit, and side-effects and
tolerability monitored. Side-effects of orlistat therapy
included some faecal urgency diarrhoea in the first
2 months. The symptoms were, however, reduced
with dietary advice during clinic visits. Three patients
stopped taking orlistat prior to completion of the 12-month
programme.
Body weight, waist circumference and GFR
Changes in weight, BMI, waist circumference
and eGFR are displayed in Table 2. At 12 months, in
the WMP group, weight, BMI, waist circumference
and eGFR decreased significantly. In the control
group, there was no change in weight or BMI from
Table 2. Changes in body weight, waist circumference and eGFR
in the WMP group
Outcomes and assessments
The primary outcome measure was change in body
weight and BMI over time. Secondary outcomes included
measures of exercise capacity, functional ability, renal
function and waist circumference.
Exercise testing
Exercise testing was performed at baseline, 3, 6 and
12 months and included the 6 min timed walk test
Baseline
Weight (kg)
(n ¼ 32)
BMI (kg/m2)
(n ¼ 32)
Waist
circumference
(cm) (n ¼ 13)
eGFR (ml/min)
(n ¼ 12)
12 months
Difference P
102.9 (17.7) 95.7 (16.8)
6.9%
<0.001
35.7 (4.5)
33.2 (4.3)
6.9%
<0.001
112.9 (13.7)
100.0 (13.6) 11.4%
<0.005
44.8 (26)
35.5 (19.6)
<0.05
20.8%
266
S. A. Cook et al
Fig. 1. Mean percentage change in exercise performance measures: (A) 6 min timed walk test (6MTWT), (B) sit to stand 60 (STS 60),
(C) timed up and go (TUAG) and (D) Duke’s activity status index (DASI), from baseline to 12 months in obese CKD patients recruited
onto the WMP.
baseline to 12 months. The mean eGFR showed
a non-significant decline from 38.8 ml/min at baseline
to 33.6 ml/min at 12 months.
Exercise testing
The exercise tests and functional ability scores
are presented in Figure 1. Exercise testing results are
presented for the 32 patients who had complete data at
12 months. The 6MTWT improved by 45%
(P < 0.001), STS60 by 30% (P < 0.001), TUAG by
37% (P < 0.001) and DASI by 50% (P < 0.001) after
12 months.
Discussion
This study sought to examine whether a structured,
multidisciplinary programme combining exercise,
dietary intervention and orlistat could impact on
weight loss and functional ability in patients with
CKD. The data presented here demonstrate significant
reductions in weight and waist circumference, along
with significant improvements in exercise capacity and
functional ability with this combined approach at
12 months.
There was a greater reduction in waist circumference
in this study compared with other studies using
diet and orlistat only, and this may be attributed to
the added individualized exercise programmes
prescribed for all the patients in the WMP [15].
This is consistent with results from a study by
You et al. [16] who demonstrated that the addition
of exercise training to dietary weight loss preferentially
reduces subcutaneous abdominal adipocyte size
in obese women.
This study also demonstrated significant improvements in exercise capacity and functional ability
after 12 months on the programme in patients who
followed the three-faceted approach of exercise
prescription, low fat, energy reduced diet and
orlistat. A study by Hollis et al. [17] evaluated the
effect of dietary advice and a general exercise
programme as part of a weight reduction programme
in peritoneal dialysis (PD) patients. This feasibility
study demonstrated significant weight loss with
this combined approach, but did not measure changes
in functional ability, nor the effect of an individualized
Weight management in obese CKD patients
exercise programme [17]. A number of studies in
the general population have evaluated the effect of diet
and orlistat as a combined approach, but to our
knowledge, this is the first study to assess the impact
of individualized exercise prescription on exercise
capacity and functional ability, as well as weight loss
and waist circumference in CKD. A handful of studies
that evaluated the effect of diet and orlistat as
an intervention advised participants to increase activity
by walking various distances [15], but this was
not formalized, nor was the effect evaluated as part
of the trials.
The mean improvements in exercise capacity and
functional ability of 11–50% in response to a
programme involving aerobic exercise are consistent
with a number of studies that evaluated the effect of
training programmes in dialysis patients [18–20].
Significant improvements ranged from 21 to 42% in
programmes lasting from 3 to 6 months. However,
these studies were not based on home exercise
programmes and only involved ESRD patients; thus
they cannot be directly compared. To our knowledge,
no studies have evaluated these exercise and functional
ability parameters as part of a structured weight loss
programme in patients with CKD.
Increased functional ability, as shown by the
significant increase in the DASI of 50% extrapolates
to patients being able to complete activities of
daily living with greater ease, and indeed some patients
were able to return to sporting activities. An adequate
level of physical capacity for ADLs is likely to improve
independence and employment potential of patients
with CKD.
To date, there have been two live-related transplants
and a further seven people listed for kidney transplantation as a direct result of the weight loss achieved
in our WMP.
The major limitation of this study is that it is nonrandomized, and the ‘control’ group comprised those
patients electing not to join the programme.
Our rationale for not randomizing the referred patients
to intervention and control groups was that the
programme was set up as a clinic and not as a clinical
trial. We also consider that it may have been unethical
not to offer the intervention to all patients since
a decrease in BMI may offer the only chance of them
becoming fit enough to be included on the transplant
waiting list.
These preliminary results from the first 12 months of
our WMP suggest that this multi-disciplinary programme can achieve meaningful reductions in weight
and waist circumference, along with improvements
in physical functioning in CKD patients, potentially
allowing them the opportunity of kidney transplantation and the associated benefits of this. In conclusion,
we believe this is the first study reporting changes
in weight, waist circumference and exercise testing in
obese CKD patients using exercise, diet and orlistat
therapy as a combined approach to encourage weight
loss and increased functional ability.
267
Further work is required to determine whether
these beneficial effects are maintained in the longer
term, and whether this can also impact on the high
cardiovascular risk inherent in this patient population.
Acknowledgements. The authors would like to thank the rest of
the Weight Management Programme team—Deepa Kariyawasam,
Marcelle Van Niekerk, Gemma Newell, Mandy De’Ath and Ellie
Woffenden- along with Dr Marisa Aguera and Xavier Serra for their
assistance with the statistical analysis.
Conflict of interest statement. This study was partially funded
by unrestricted educational grants from Roche Products Ltd (UK)
and Amgen UK. The manuscript was written entirely by the authors,
with no input from a ghostwriter or pharmaceutical company.
References
1. Johansen K, Kutner N, Young B, Kaysen G. Association
of body size with outcomes among patients beginning dialysis.
Am J Clin Nutr 2004; 80: 324–332
2. Byers T. Body weight and mortality. N Engl J Med 1995; 333:
723–724
3. Meier-Kreische HU, Arndorfer JA, Kaplan B. The impact
of body mass index on transplant outcomes: a significant
independent risk factor for graft failure and patient death.
Transplantation 2002; 73: 70–74
4. De Jong PE, Verhave JC, Pinto-Sietsma SJ, Hillege HL.
PREVEND study group. Obesity and target organ damage:
the kidney. Int J Obes Rel Metab Dis 2002; 26 [Suppl 4]: S21–S24
5. Hsu C, McCulloch C, Iribarren C, Darbinian J, Go A. Body
mass index and risk for end-stage renal disease. Ann Intern Med
2006; 144: 21–28
6. Naish P. Physical dysfunctioning – the case for rehabilitation.
Br J Renal Med 1999; 4: 6–8
7. Johansen K, Kutner N, Young B, Chertow G. Association of
body size with health staus in patients beginning dialysis. Am
J Clin Nutr 2006; 83: 543–549
8. Gutman RA, Stead WW, Robinson RR. Physical activity and
employment status of patients on maintenance dialysis. N Engl
J Med 1981; 304: 309–313
9. Davidson M, Hauptman J, DiGirolamo M et al. Weight control
and risk factor reduction in obese subjects treated for 2 years
with Orlistat. JAMA 1999; 281: 235–242
10. Maclaughlin H, Cook S, Macdougall IC et al. Beneficial
effects of a structured weight management programme involving
diet, exercise and orlistat in obese, diabetic patients with chronic
kidney disease. Diabetes Obesity Metab 2007(in press)
11. VanSwearingen JM, Brach JS. Making geriatric assessments work: selecting useful measures. Phys Ther 2001; 81:
1233–1252
12. Ritchie C, Trost SG, Brown W, Armit C. Reliability and validity
of physical fitness field tests for adults aged 55 to 70 years.
J Sci Med Sport 2005; 8: 61–70
13. Eston R, Thompson M. Use of ratings of perceived exertion
for predicting maximal work rate and prescribing exercise
intensity in patients taking atenelol. Br J Sport Med 1997; 31:
114–119
14. Hlatky MA, Boineau RE, Higginbotham MB et al. A brief
self-administered questionnaire to determine functional cpacity
(the Duke Activity Status Index). Am J Cardiol 1989; 64:
651–654
15. Broom I, Wilding J, Stott P, Myers N. UK multimorbidity study
group. Randomised trial of the effect of orlistat on body weight
and cardiovascular disease risk profile in obese patients. Int
J Clin Pract 2002; 56: 494–499
268
16. You T, Murphy K, Lyles M, Demons J, Lenchik L, Nicklas B.
Addition of aerobic exercise to dietary weight loss preferentially
reduces abdominal adipocyte size. Int J Obesity 2006; 30:
1211–1216
17. Hollis J, Corden E, Williams P. Longitudinal evaluation of
a weight reduction programme for patients on peritoneal
dialysis. Peritoneal Dial Int 2005; 25: S152–S154
18. Painter P. End stage renal disease. In: Skinner JS, ed. Exercise
Testing and Exercise Prescription for Special Cases. Theoretical
S. A. Cook et al
Basis and Clinical Application, Chapter 20, 2nd edn, Lipincott,
Williams & Wilkins, USA: 1993351–362,
19. Kouidi E, Albani M, Natsis K et al. The effect of exercise
training on muscle atrophy in haemodialysis patients. Nephrol
Dial Transplant 1998; 13: 685–699
20. Moore G, Parsons D, Stray-Gunderson J, Painter P,
Brinker K, Mitchell J. Uremic myopathy limits aerobic
capacity in haemodialysis patients. Am J Kidney Dis 1993;
22: 277–287
Received for publication: 14.12.06
Accepted in revised form: 3.7.07