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Contents lists available at ScienceDirect

Diabetes & Metabolic Syndrome: Clinical Research &

Reviews
journal homepage: www.elsevier.com/locate/dsx

Original article

Effect of weight loss on renal function in overweight and obese patients

with heart failure
Marjan Motiea,* , Lorraine S. Evangelistaa , Dawn Lombardob , Josiah Hoia ,
Tamara B. Horwichc , Michele Hamiltond, Gregg C. Fonarowe
a
Program in Nursing Science, University of California Irvine, Irvine, CA, United States
b
Clinical Heart Failure Program, Department of Medicine, University of California Irvine Medical Center, Irvine, CA, United States
c
Cardiology University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA, United States
d
Medicine/Cardiology UCLA, Heart Failure Program, Cedars-Sinai Heart Institute, Los Angeles, CA, United States
e
Ahmanson-UCLA Cardiomyopathy Center, Cardiology David Geffen School of Medicine, Los Angeles, CA, United States

A R T I C L E I N F O A B S T R A C T

Article history: Aims: The effect of intentional weight loss on glomerular filtration rate (GFR) in overweight and obese
Available online xxx patients with heart failure (HF), diabetes mellitus (DM) and/or metabolic syndrome (MS) has not been
studied. The purpose of the present study is to assess the short term effects of intentional weight loss on
renal function in this population.
Keywords: Materials and methods: Fifty nine patients were recruited to participate in a 3-month intensive behavioral
Heart failure
weight management intervention and received one of two standard structured energy-restricted meal
Renal function
plans (1200 or 1500 kcal/day) based on their computed calorie deficit. Weight and renal function (serum
Hyperfiltration
Obesity
creatinine, BUN and estimated glomerular filtration rate based on two formulas – Modification in Renal
Weight loss Disease Study (MDRD), and modified version of Cockcroft-Gault formula reported by Salazar Corcoran for
obese patients (absolute and relative formulas) – were evaluated at baseline and at 3 months.
Results: Participants had eGFR in the normal range at baseline and lost an average of 7.56  14.9 pounds
(p < 0.0001) over 3 months; however, there was no significant reduction in serum creatinine, BUN or
eGFR.
Conclusion: This study provides evidence that intentional weight loss in overweight and obese patients
with HF along with DM, and/or MS and normal baseline renal function does not adversely affect renal
function overtime.
ã 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

1. Introduction risk patients. Glomerular filtration rate (GFR) is used as the best
index of renal function by measuring the filtering capacity of the
With the obesity epidemic as a universal public health concern, kidneys [4,5]. Since using radiolabeled exogenous markers to
many studies are underway to design and test weight loss accurately measure GFR can be costly and time consuming, several
interventions that result in loss of body fat without any deleterious formulas have been used to provide estimated GFR (eGFR) based on
effects. Since obesity may lead to and be associated with chronic serum creatinine levels. Currently, renal function is assessed best
kidney disease (CKD) [1,2], the effect of dietary interventions on by eGFR, as serum creatinine is an unreliable marker of kidney
the potential risk of increased renal disease is of outmost concern. function [6,7]. The most widely used and validated formulas to
A systematic review of patients with existing CKD revealed that calculate eGFR are the Modification of Diet in Renal Disease
only a few randomized trials have examined the effect of weight (MDRD) [8] and a modified version of Cockcroft-Gault formula
loss on CKD and these have shown beneficial effects of weight loss reported by Salazar Corcoran. [9] The MDRD formula (which
on renal function but authors state the evidence is still sparse [3]. A incorporates age, gender, and serum creatinine) has been widely
major challenge in preventing CKD lies in early detection of high used in various investigations including a study of obese
individuals without overt kidney disease [10], in overweight and
obese Malaysian subjects [11], and in a weight management study
comparing very low vs. high carbohydrate diet [12]. However, the
* Corresponding author at: UCI Program in Nursing Science, Irvine, CA 92697,
validity of different measures of eGFR to assess CKD in obese
United States.
E-mail address: mmotie@uci.edu (M. Motie). patients has had conflicting reports [3,13,14]. A modification of the

http://dx.doi.org/10.1016/j.dsx.2016.06.026
1871-4021/ã 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: M. Motie, et al., Effect of weight loss on renal function in overweight and obese patients with heart failure,
Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.org/10.1016/j.dsx.2016.06.026
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2 M. Motie et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2016) xxx–xxx

Cockcroft-Gault formula has been developed by Salazar and Salazar-Corcoran formula were calculated by normalizing for body
Corcoran which has been validated in obese patients [9]. In the surface area (BSA) and expressing the eGFR as mL/min/1.73 m2
present study, we will compare the eGFR obtained at baseline where BSA (m2) = [weight (kg)]0.425  [height (cm)]0.725  0.007184.
using the MDRD and Salazar-Corcorian (absolute and relative) Data was analyzed using SPSS version 19.0 for Windows.
formulas to those estimated at 3 months following a weight loss Sociodemographic and clinical variables were computed using
regimen. This is a first report of eGFR in overweight and obese descriptive statistics (e.g., means and standard deviations for
patients with HF, DM, and/or MS with the primary aim to assess the continuous variables and Pearson x2 tests for categorical
short term effects of intentional weight loss on renal function variables). Changes in renal function, weight, waist circumference,
(serum creatinine, blood urea nitrogen [BUN] and eGFR). As a and body composition (e.g., lean mass, percent fat) from baseline to
secondary aim, we will examine the relationship between weight, 3 months were analyzed using independent two sample t-tests.
waist circumference, and body composition on eGFR by two The relationships between variables of interests were evaluated
methods described herein. using Pearson Moment Correlations and Spearman Rho depending
on level of measurement.
2. Materials and methods
3. Results
The enrollment criteria and study design have been described
elsewhere [15]. Briefly, 59 participants were recruited and 3.1. Participant characteristics
provided informed consent to participate in a randomized clinical
trial for overweight and obese patients with HF, DM, and/or MS Table 1 shows the sociodemographic and clinical characteristics
(Table 1). University of California Los Angeles and University of of the study sample. Participants ranged in age from 27 to 81 and
California Irvine Institutional Human Subjects Review Committees were on the average moderately obese (body mass index [BMI],
approved the study. Participants who met the inclusion exclusion 36.59  6.22 kg/m2). Participants’ baseline clinical characteristics
criteria [15] received a 3 month behavioral weight management including fasting blood glucose, cholesterol, BUN, creatinine and
intervention based on energy-restricted meal plans (1200 or blood pressure measurements are also shown in Table 1.
1500 kcal/day) which would provide a calorie deficit aimed at
500 kcal or more. They reported to the study centers at 2 weeks, 4 3.2. Changes in clinical status post intervention
weeks, 8 weeks and 12 weeks to meet with a nutrition counselor
and review goals and plans described in a “Participant Handbook”. Statistically significant changes in weight, waist circumference,
For the purpose of this descriptive study, weight, body and lean mass were noted from baseline to 3 months (Table 2, all
composition, physical and clinical characteristics were compared p’s < 0.005). However, the serum creatinine and BUN remained
at baseline vs. 3 month visits. Estimated GFR was derived by two unchanged over time. Likewise, serum creatinine driven formulas
formulas where age is measured in years, creatinine in mg/dL, of MDRD, and absolute and relative (normalized for body surface
weight and height (where needed) in kilograms and meters, area) Salazar-Corcoran formula did not change significantly over
respectively. time.
MDRD formula:
Estimated glomerular filtration rate (eGFR) (mL/min/ 3.3. Association between eGFR and weight and body composition
1.73 m2) = 186.3  (serum creatinine [mg/dL]) 1.154  (age) 0.203
 0.742 (if female). The correlation matrix for key variables is illustrated on Table 3.
Salazar-Corcoran formula: Data show that the eGFR by MDRD formula was significantly
For men: eGFR (mL/min) = (137 age)  [(0.285  weight) + correlated with BMI and total% body fat, and the eGFR by absolute
(12.1  height2)]/(51  serum creatinine) Salazar-Corcoran formula was significantly correlated with weight,
For women: eGFR (mL/min) = (146 age)  [(0.287  weight) + BMI, waist circumference and total% body fat. The relationships
(9.74  height2)]/(60  serum creatinine). Relative eGFR by the were not observed once a correction was made for body surface
area eGFR (Salazar-Corcoran, normalized); this finding is intuitive
Table 1 since this formula takes into account changes that would be
Sociodemographic and Clinical Characteristics (N = 59). expected secondary to changes in body weight.
Baseline
All Subjects 4. Discussion
Age, years (Mean  SD) 58.73 + 9.47
Male (%) 71.2% To our knowledge, this is the first study to explore the effect of
White (%) 49.2% intentional weight loss on renal function in overweight and obese
History of Diabetes 37.3%
patients with HF who also have DM and/or MS. Obesity is one of
History of Hypertension 50.8%
History of Smoking 47.5%
today’s most pressing health issues worldwide, and is believed to
History of Statin use 50.8% lead to health consequences including coronary heart disease,
NYHA class, N (%) hypertension, DM, dyslipidemia, sleep apnea, and certain cancers
Class 2 79.8% [16]. Furthermore, being overweight or obese and or having DM are
Class 3 18.6%
all risk factors for CKD [2,17–19].The present population of
Weight (lbs) 238.11 + 46.69
Fasting Glucose (mg/dl) 129.87 + 56.17 overweight and obese patients with HF, DM, and/or MS are
Total cholesterol 157.45 + 46.91 potentially vulnerable and at risk for renal damage.
LDL 90.47 + 35.83 In order to elucidate the effect of intentional weight loss on
HDL 40.93 + 12.07
changes in renal status, we enrolled overweight or obese patients
Triglycerides 148.11 + 72.02
BUN (mg/dL) 20.35 + 8.08
with normal kidney function (as evaluated by baseline creatinine
Creatinine (mg/dL) 1.088 + 0.28 levels). As an addition to the well-known MDRD equation for
SBP 119.80 + 19.90 estimating GFR, Salazar and Corcoran’s equation (which is a
DBP 72.56 + 11.76 modification of Cockcroft-Gault formula) [9], was utilized to
measure eGFR at baseline and 3 months. Our findings show that

Please cite this article in press as: M. Motie, et al., Effect of weight loss on renal function in overweight and obese patients with heart failure,
Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.org/10.1016/j.dsx.2016.06.026
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Table 2
Changes in Weight and body composition and estimation of glomerular filtration rate after 3 months of behavioral weight management intervention (N = 59).

Baseline 3 Months p
Weight (Pounds) 238.11 + 46.69 230.55 + 45.00 0.000
BMI (kg/m2) 36.59 + 6.22 34.87 + 5.06 0.002
Waist Circumference (cm) 47.04 + 4.28 45.52 + 4.26 0.001
Lean Mass (kg) (DEXA)a 61.96 + 9.54 58.92 + 12.53 0.026
Total% Fat (DEXA)a 37.66 + 1.08 37.27 + 1.09 0.608
BUN (mg/dL) 20.35 + 8.08 21.067 + 9.02 0.140
Serum Creatinine 1.088 + 0.277 1.115 + 0.317 0.430
eGFR (MDRD) (ml/min/1.73m2)b 77.84 + 25.98 77.06 + 29.23 0.803
eGFR (Salazar-Corcoran)c 98.51 + 34.16 94.12 + 41.05 0.212
eGFR (Salazar-Corcoran) (mL/min/1.73 m2)d 81.71 + 30.38 77.63 + 77.63 0.479
a
DEXA (dual-energy X-ray absorptiometry).
b
eGFR (estimated by MRDR-Modification in Renal Disease Study) [8].
c
eGFR (estimated by Salazar-Corcoran formula) [9].
d
eGFR (Salazar-Corcoran formula normalized for body surface area BSA.

Table 3
Correlational Matrix of Key Variables of Interest at Baseline (N = 59).

1 2 3 4 5 6 7 8
1. Weight
2. BMI 0.813**
3. Waist Circumference 0.798** 0.732**
4. Lean Mass 0.521** 0.189 0.405**
5. Percent Body Fat 0.153 0.561** 0.327** 0.482**
6. eGFR (MDRD) 0.209 0.346** 0.177 0.111 0.348**
7. eGFR (Salazar) 0.573** 0.556** 0.380** 0.162 0.277* 0.876**
8. eGFR (Salazar-Normalized to BSA) 0.102 0.072 0.057 0.126 0.021 0.129 0.086
**
Correlation is significant at the 0.01 level (2-tailed).
*
Correlation is significant at the 0.05 level (2-tailed).

serum creatinine, BUN, and eGFR (estimated using both methods) research particularly in obese individuals and are especially
did not change over 3 months despite a change in weight and BMI. flawed with respect to weight loss due to alterations in body
The present results are in agreement with previous studies of short composition [24]. Furthermore, a very recent study showed that
term weight loss interventions (24 or 52 weeks) that reported no the association between weight change and renal function
differences in serum creatinine and eGFR (estimated by MDRD) in reflected a wide variation based on the method of assessment
overweight or obese participants with or without type-2 DM [25]. The effect of increased weight with increase in systemic
[12,20,21].It is important to note that in all these studies (present arterial pressure and increase renal plasma flow and eGFR are well
one included), participants were selected based on the absence of documented [26,27] such that a reduction in weight is anticipated
any preexisting renal insufficiencies (indicated by low eGFR of to result in a decrease in absolute eGFR or a reduction in obesity
>60 mL/min/1.73 m2 defined by the Kidney Disease Outcome related glomerular hyperfiltration [28].
Quality Initiative Guidelines) [22]. Thus, the lack of any effect of The present report shows a trend toward decreasing values for
short term weight loss on renal function is only valid in those with eGFR (absolute or relative to BSA) but the changes were not
preserved renal function; the effect of weight loss on overweight or statistically significant. Since the study was only 12 weeks in
obese HF patients with compromised kidney function warrants length, it is possible that the changes may approach significance
further investigation. over longer period of time and with possible further changes in
Our findings indicate that absolute values of eGFR (by MDRD weight. There was not a randomized concurrent control group not
and Salazar methods) were significantly correlated with BMI and exposed to the intentional weight loss intervention. Another
percent body fat; however, these relationships were not observed limitation of the current study is the small sample size. The eGFR
in the Salazar equation modified for BSA. Since serum creatinine is data for those that did not complete the study and the average
produced by muscle tissue, changes in muscle mass can affect eGFR results for a larger sample of overweight and obese patients with
and confound the conclusions regarding renal function. Our results HF, DM and/or MS are needed to better delineate the effect of
reflected a significant reduction in average lean mass. Correcting intentional weight loss on renal function.
for BSA was important to clearly indicate a lack of change in eGFR
with intentional weight loss. In clinical settings, BSA has been 5. Conclusion
described as a better indicator of metabolic mass than body weight
because it is less influenced by changes in mass of fatty tissue [23]. The results of this study provide evidence that intentional
The mean values of eGFR estimated by both methods (MDRD and weight loss in overweight and obese patients with HF along with
Salazar absolute or relative) were in the normal range (defined by DM, and/or MS and normal baseline renal function does not
National Kidney Foundation of >60 mL/min/1.73 m2). However, adversely affect renal function over a 3 month behavioral weight
whether the eGFR were accurate can only be verified by in vivo management program. Future studies are warranted to examine
isotopic renal clearance methods which are cumbersome and the effect of macro and micro nutrients on the changes in risks
expensive. Estimated GFR relying on formulas based on serum associated with renal function over short and long term durations
creatinine and/or cystatin C remain controversial in clinical in this highly vulnerable population.

Please cite this article in press as: M. Motie, et al., Effect of weight loss on renal function in overweight and obese patients with heart failure,
Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.org/10.1016/j.dsx.2016.06.026
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Please cite this article in press as: M. Motie, et al., Effect of weight loss on renal function in overweight and obese patients with heart failure,
Diab Met Syndr: Clin Res Rev (2016), http://dx.doi.org/10.1016/j.dsx.2016.06.026