Obesity-Related Glomerulopathy: Body Mass Index and

Proteinuria
Wen-wen Shen, Hui-mei Chen, Hao Chen, Feng Xu, Lei-shi Li, and Zhi-hong Liu
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Background and objectives: Obesity-related glomerulopathy (ORG) is an increasing cause of end-stage renal disease, but
evidence concerning the effects of treatments is rather limited. This study was aimed at exploring the renoprotective effects
of weight loss on patients with ORG.
Design, setting, participants, & measurements: A total of 63 patients with renal biopsyproven ORG had food and exercise
intervention in the physician-supervised weight loss program and were divided into three groups on the basis of the
percentage of weight change from baseline to follow-up: significant weight loss (>3% reduction in body mass index [BMI]),
stable weight, or significant weight gain (>3% increase). Metabolic parameters and renal lesions were evaluated regularly for
2 years.
Results: After 6 months, 27 patients lost weight by 8.29 4.00%, with a mean decrease in proteinuria of 35.3%, whereas 24
months later, 27 patients achieved a 9.20 3.78% reduction in BMI and a 51.33% reduction in urine protein secretion. The
levels of serum triglyceride, serum uric acid, and BP were also decreased. Contrarily, in patients with increased BMI, urine
protein was increased by 28.78%. Correlation analysis showed proteinuria was associated with BMI, serum triglyceride, and
uric acid, and multivariate regression analysis indicated the changes in BMI were the only predictor of proteinuria (P < 0.01).
Conclusions: Weight loss intervention benefited remission of proteinuria in patients with ORG, whose function could not
be replaced by conventional pharmacotherapy.
Clin J Am Soc Nephrol 5: 14011409, 2010. doi: 10.2215/CJN.01370210
P
rofound lifestyle changes in modern China have re-
sulted in a remarkable increase in the population of
obesity (1). Sequelae of obesity include type 2 diabetes,
hypertension, cardiovascular diseases, and the progression of
renal diseases (2,3). Weight loss, either after bariatric surgery or
after lifestyle modification, normalizes blood glucose (4) and
decreases BP and plasma lipids (5,6) in obese patients. Simi-
larly, a significant reduction in urinary albumin excretion and
glomerular hyperfiltration has been reported in morbidly obese
patients with a dramatic decrease of body mass index (BMI)
(7,8). Moreover, even a small decrease in BMI is related to the
reduction of proteinuria in patients with diabetic nephropathy
and other chronic kidney diseases (911).
Obesity-related glomerulopathy (ORG) has been reported in
more and more obese patients without overt diabetes and pre-
existing renal diseases (12,13). It is a secondary form of focal
and segmental glomerulosclerosis (FSGS) manifested as pro-
teinuria and progressive renal dysfunction (14). The prognosis
for patients with ORG were significantly different from those
with diabetic nephropathy or with the primary form of FSGS
(15). However, the relationship between weight loss and the
outcome of ORG has not been clarified until now. Conclusions
from the studies of diabetic nephropathy (9) and unidentified
chronic kidney diseases (10,11,16) could be different from those
of histologic-proven ORG. And evidence from case reports
(17,18) concerning the aggressive treatment of ORG with bari-
atric surgery is unpersuasive because only a small population
was involved. In addition, the long-term effects of weight loss
in patients with ORG are not studied. So far, no well-designed
clinical research studies for histologic-proven ORG are avail-
able, especially those concerning the long-term effects of weight
loss and lifestyle modification.
In this regard, this study was designed to observe the rela-
tionship between body weight reduction and the changes in
proteinuria in patients with ORG. Patients who were diagnosed
with ORG by renal biopsy were included in the physician-
supervised weight loss program in our institute and followed
up for 2 years. It was the first study demonstrating that the
remission of ORG could be achieved in patients with weight
loss, but not in patients with increasing body weight.
Materials and Methods
Patient Selection
Patients with biopsy-proven ORG diagnosed in our institute from
February 2002 to August 2007 were recruited into this study. The
inclusion criteria included the following: (1) The presence of obesity
[BMI no less than 28 kg/m
2
according to the Working Group on
Obesity in China (19)]; (2) fasting blood glucose level 7.0 mmol/L and
postprandial glucose 11.1 mmol/L; (3) 24-hour urinary protein excre-
tion 0.4 g, without gross hematuria or evident microscopic hematuria;
(4) pathologic features included glomerulomegaly with or without focal
Received February 11, 2010. Accepted April 12, 2010.
Published online ahead of print. Publication date available at www.cjasn.org.
Correspondence: Prof. Zhi-hong Liu, 305 East Zhong Shan Road, Nanjing 210002,
China. Phone: 86 25 8086 0218; Fax: 86 25 8480 1992; E-mail: zhihong--liu@
hotmail.com
Copyright 2010 by the American Society of Nephrology ISSN: 1555-9041/5081401
segmental glomerular sclerosis, and pauci-immune complex deposition
with or without nonspecific or segmental C3 and IgM deposition; (5)
other underlying renal diseases such as IgA nephropathy, membranous
nephropathy, and diabetic nephropathy were excluded carefully. In-
formed signed consents were obtained for 63 patients, and this study
was approved by the Human Investigation Committee at Jinling Hos-
pital, Nanjing, China.
Study Design
Upon baseline investigation, patients were assigned to the physician-
supervised weight loss program in the Outpatient Center in our insti-
tute. A diet with an energy reduction of 500 kcal with respect to their
total caloric requirements was assigned to all of the patients, which
were calculated according to sex, height, and weight by the Harris-
Benedict formula as 135% of the basal metabolic rate. The diet con-
tained 55 to 65% carbohydrates, 20 to 30% fat, and 15% protein (20).
Patients were encouraged to do aerobic exercise for at least 60 minutes
at a frequency of at least 3 d/wk. The types of exercise were chosen by
patients according to their preference, mainly including walking, jog-
ging, and swimming. Anerobic exercise and anti-obesity medication
was avoided. The implementation of diet and exercise was carried out
at home. Patients were regularly interviewed every 3 months about the
implementation of the dietary and exercise intervention. Angiotensin-
converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker
(ARB) and rhein were given to the patients and lipid-lowering drugs
were used in patients with refractory dyslipidaemia. The patients were
assessed 6 and 24 months later at the same outpatient center. Evalua-
tion included the BMI, BP, 24-hour urine protein, estimated GFR
(eGFR), fasting blood glucose level, serum triglyceride (TG), serum
total cholesterol, HDL cholesterol (HDL), LDL cholesterol (LDL), and
serum uric acid (UA). BP was measured in the morning in duplicate at
each visit after 30 minutes of rest. On the basis of the changes in BMI,
patients were divided into three groups: increased BMI group (an
increase in BMI 3%), stable BMI group (the changes in BMI no greater
than 3%), and decreased BMI group (a decrease in BMI 3%).
Pathologic Features
Selected renal biopsy specimens were examined by two experienced
nephrologists blind to the study. Glomerular lesions, proximal tubular
atrophy, interstitial fibrosis, interstitial inflammatory cell infiltration,
and hyaline degeneration of small arteries were recorded. On the basis
of the percentage of area with proximal tubular atrophy, interstitial
fibrosis, and interstitial inflammatory cell infiltration in the renal cortex,
the severity was classified into mild (25%), intermediate (26% to
approximately 50%), and severe (50%). On the basis of the percentage
of small arteries with hyaline degeneration in all interstitial small
arteries, the severity was divided into mild (25%), intermediate (26%
to approximately 50%), and severe (50%).
Other Definitions
On the basis of the outcome of proteinuria changes, the patients were
divided into four groups: complete remission group (proteinuria 0.4
g/24 h with stable renal function), partial remission group (a decrease
in proteinuria 50% of baseline value yet proteinuria 0.4 g/24 h),
stability group (a change in proteinuria 50% of baseline value), and
deterioration group (an increase in proteinuria 50% of the baseline
value). Smoking was defined as currently smoking or smoking within
1 year. Hypertension was defined as systolic pressure of 140 mmHg or
greater or diastolic pressure of 90 mmHg or greater or ongoing use of
anti-hypertensive medications. eGFR was calculated according to the
Modification of Diet in Renal Disease (MDRD) formula. New use of
drugs was defined as beginning to use the drug after or within 2 weeks
before enrollment.
Statistical Analyses
The quantitative data with normal distribution were expressed as
mean SD and those with abnormal distribution as median (mini-
mum, maximum). The qualitative data were presented as percentages.
ANOVA, U test, or
2
test was performed for comparisons among
groups. Paired t test was used for comparisons between data before and
after follow-up. Pearson, Spearman, or Kendall correlation analyses
were used to analyze the relationship among different parameters. A
value of P 0.05 was considered statistically significant. Univariate
linear regression was performed to screen the factors related to the
changes in proteinuria in which the factor with a value of P 0.05 was
further applied into stepwise multivariate regression analysis. The
statistical analysis was done with SPSS version 11.0.
Results
As shown in Table 1, 63 patients with pathologically con-
firmed ORG were recruited. The mean BMI was 30.83 2.86
kg/m
2
. Proteinuria was noted in all of the patients with a mean
24-hour urine protein excretion of 1.48 0.87 g. Among these
patients, three had heavy proteinuria (3.5 g/24 h) but without
hypoalbuminemia. The mean eGFR was 103.8 ml/min and
eight patients had an eGFR 60 ml/min. Significant glomeru-
lomegaly was present in all of the patients, whereas FSGS
lesions were found in 35 of them. Correlation analysis indicated
diastolic pressure was the only factor related to BMI.
Short-Term Effects of BMI Changes on Renal Injury and
Metabolic Disturbance
A total of 56 patients returned for the first assessment at the
sixth month. We divided them into increased BMI (n 8),
stable BMI (n 21), and decreased BMI (n 27) groups.
No significant difference in the parameters at baseline was
observed among these groups (Table 2). As shown in Table 3, in
the decreased BMI group, the mean proteinuria was decreased
from 1.57 0.99 to 1.10 0.92 g/24 h (P 0.05) with a mean
reduction of 35%. No profound changes in urine protein excre-
tion were found in the stable and the increased BMI group.
Figure 1a shows the distribution of the proteinuric outcome at
the sixth month. Remission was observed in 48.1% of the pa-
tients with decreased BMI, and nearly half of them were com-
pletely remitted. However, in the increased BMI group, only
one (12.5%) patient obtained remission and four patients (50%)
obtained deteriorated proteinuria (P 0.087). The TG/HDL
ratio in the decreased BMI group was markedly reduced, but
no difference of TG/HDL ratio changes was observed among
groups.
Long-Term Effects of BMI Changes on Renal Injury and
Metabolic Disturbance
Forty-eight patients completed the second assessment at the
24th month. On the basis of the changes in BMI, the patients
were re-divided into increased BMI (n 9), stable BMI (n 12),
and decreased BMI (n 27) groups (Table 3). The proteinuria
was reduced from 1.71 1.24 to 0.88 1.00 g/24 h with a mean
reduction of 51.3% in the decreased BMI group (P 0.01) and
1402 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 5: 14011409, 2010
increased by 28.78% in the increased BMI group (P 0.05). As
shown in Figure 1b, in the decreased BMI group, 25.8% of
patients obtained complete remission from proteinuria, and
partial remission was observed in 29.6%, which made an over-
all remission rate of 55.6%. Nevertheless, in the increased BMI
group, no patient was found to have complete remission in
proteiuria and even four (44.4%) of the patients had deterio-
rated proteinuria. A significant difference in the remission rate
of proteinuria was observed among these groups. But no dif-
ference was noted in renal function among these groups.
Profound changes in metabolic parameters were also ob-
served (Table 3). In the decreased BMI group, the TG/HDL
ratio and TG was decreased by 17.3 and 17.1%, respectively
(P 0.05), and UA was decreased from 421 127 to 388 74
mol/L (P 0.01). In addition, in the patients with decreased
BMI, the systolic pressure and diastolic pressure were signifi-
cantly decreased, with a mean reduction of 7.44 and 9.50%,
respectively.
Factors Related to the Outcome of Proteinuria Changes
As described above, weight control could confer short-term
and long-term protective effects against proteinuria in patients
with ORG. To explore the factors related to the outcome of
proteinuria changes, we ran univariate and stepwise multivar-
iate regression modeling analyses, using the changes in pro-
teinuria as a dependent variate. Besides weight changes, the
following covariates were examined in the analyses: gender,
age, baseline weight, both baseline and percentage change of
BP, serum glucose, cholesterols, triglycerides, uric acid, new
use of ACEI/ARB, rhein, and lipid-lowering drugs after 24
months. Results showed a strong relationship between de-
creased proteinuria and weight loss, decreased serum triglyc-
eride level, and reduced serum uric acid level (Figure 2). How-
ever, multivariate stepwise regression analysis indicated the
changes in body weight, but not the serum triglyceride level
and uric acid level, were the only factor related to the changes
in proteinuria (R
2
0.278; P 0.001).
Table 1. General information for 63 patients with ORG and the correlation with BMI
Correlation with BMI
Correlation Coefficient P
Gender (male) 42 (66.7%) 0.907
Age (year) 38.30 10.45 0.150 0.235
No. of smokers 15 (23.8%) 0.955
Kidney conditions
pathologic type (O-FSGS) 35 (55.6%) 0.838
eGFR(ml/min) 103.8 37.2 0.041 0.751
Urine protein excretion (g/24 h) 1.48 0.87 0.043 0.734
Proportion of large molecule (%) 19.39 6.61 0.019 0.884
Proportion of intermediate molecule (%) 75.11 8.47 0.006 0.964
Proportion of small molecule (%) 2.7 (0 to 28.9) 0.023 0.859
NAG (U/gCr) 17.53 12.67 0.062 0.624
16.5 U/gCr 42.9%
RBP (mg/L) 0.52 (0.01 to 7.82) 0.099 0.442
0.5 mg/L 49.2%
urinary osmolality 691.8 189.5 0.084 0.529
(mOsmol/kgH
2
O) 69.0%
800 mOsmol/kgH
2
O
Metabolic parameters
BMI (kg/m
2
) 30.83 2.86
Fasting blood glucose level (mmol/L) 4.90 0.80 0.087 0.492
triglyceride level (mmol/L) 2.49 1.06 0.089 0.503
total cholesterol level (mmol/L) 5.05 1.25 0.227 0.087
HDL (mmol/L) 1.16 0.40 0.084 0.566
LDL(mmol/L) 3.27 1.07 0.184 0.210
TG/HDL 2.14 1.09 0.028 0.856
uric acid level (mol/L) 420 81 0.067 0.622
serum albumin level (g/L) 41.4 3.8 0.081 0.556
systolic pressure (mmHg) 133.7 15.4 0.032 0.808
diastolic pressure (mmHg) 85.1 11.3 0.326 0.010
O-FSGS, obesity-related FSGS; eGFR, eGFR by MDRD equation; NAG, urinary N-acetyl--d-glucosaminidase; RBP, urinary
retinol binding protein; TG/HDL, ratio of TG to HDL.
Clin J Am Soc Nephrol 5: 14011409, 2010 Weight Loss in Patients with ORG 1403
T
a
b
l
e
2
.
G
e
n
e
r
a
l
i
n
f
o
r
m
a
t
i
o
n
f
o
r
t
h
e
p
a
t
i
e
n
t
s
a
t
b
a
s
e
l
i
n
e
6
t
h
M
o
n
t
h
2
4
t
h
M
o
n
t
h
I
n
c
r
e
a
s
e
d
B
M
I
(
n

8
)
S
t
a
b
l
e
B
M
I
(
n

2
1
)
D
e
c
r
e
a
s
e
d
B
M
I
(
n

2
7
)
P
I
n
c
r
e
a
s
e
d
B
M
I
(
n

9
)
S
t
a
b
l
e
B
M
I
(
n

1
2
)
D
e
c
r
e
a
s
e
d
B
M
I
(
n

2
7
)
P
G
e
n
d
e
r
(
m
a
l
e
)
5
(
6
2
.
5
%
)
1
6
(
7
6
.
2
%
)
1
7
(
6
3
.
0
%
)
0
.
5
8
6
7
(
7
7
.
8
%
)
9
(
7
5
.
0
%
)
1
6
(
5
9
.
3
%
)
0
.
4
6
3
A
g
e
(
y
e
a
r
s
)
4
0
.
1

1
0
.
9
3
8
.
3

1
2
.
3
4
0
.
2

9
.
3
0
.
8
1
6
3
9
.
9

1
1
.
2
4
0
.
4

1
0
.
6
3
9
.
7

1
0
.
6
0
.
9
8
0
N
o
.
o
f
s
m
o
k
e
r
s
2
(
2
5
.
0
%
)
4
(
1
9
.
0
%
)
7
(
2
5
.
9
%
)
0
.
8
4
8
3
(
3
3
.
3
%
)
3
(
2
5
%
)
5
(
1
8
.
5
%
)
0
.
6
4
5
K
i
d
n
e
y
c
o
n
d
i
t
i
o
n
s
p
a
t
h
o
l
o
g
i
c
t
y
p
e
(
O
-
F
S
G
S
)
4
(
5
7
.
1
%
)
1
1
(
5
6
.
5
%
)
1
5
(
5
3
.
8
%
)
0
.
8
1
7
4
(
4
4
.
4
%
)
8
(
6
6
.
7
%
)
1
5
(
5
5
.
6
%
)
0
.
5
9
3
e
G
F
R
(
m
l
/
m
i
n
)
1
0
2
.
3

4
2
.
7
1
1
0
.
5

4
1
.
1
9
8
.
6

3
4
.
7
0
.
5
6
5
1
0
6
.
5

2
6
.
3
9
7
.
9

3
2
.
1
9
8
.
8

3
8
.
5
0
.
8
2
4
u
r
i
n
e
p
r
o
t
e
i
n
(
g
/
2
4
h
)
1
.
0
5

0
.
6
2
1
.
4
3

1
.
1
5
1
.
5
7

0
.
9
9
0
.
6
2
2
1
.
1
3

0
.
6
3
1
.
2
6

0
.
7
0
1
.
7
1

1
.
2
4
0
.
2
5
5
p
r
o
p
o
r
t
i
o
n
o
f
l
a
r
g
e
m
o
l
e
c
u
l
e
(
%
)
1
9
.
2

5
.
2
1
8
.
5

6
.
1
2
1
.
5

7
.
2
0
.
2
7
7
1
8
.
0

9
.
0
1
9
.
6

6
.
9
1
9
.
0

6
.
5
0
.
8
6
2
p
r
o
p
o
r
t
i
o
n
o
f
i
n
t
e
r
m
e
d
i
a
t
e
m
o
l
e
c
u
l
e
(
%
)
7
0
.
4

1
4
.
9
7
3
.
9

7
.
4
7
4
.
4

9
.
1
0
.
6
0
8
7
2
.
9

8
.
6
3
7
6
.
5

6
.
8
7
6
.
1

8
.
6
0
.
5
3
1
p
r
o
p
o
r
t
i
o
n
o
f
s
m
a
l
l
m
o
l
e
c
u
l
e
(
%
)
4
.
0
(
0
t
o
1
4
.
3
)
4
.
5
(
0
t
o
2
6
.
2
)
0
(
0
t
o
2
8
.
9
)
0
.
2
8
6
6
.
1
(
0
t
o
2
8
.
9
)
1
.
2
(
0
t
o
1
4
.
2
)
4
.
3
(
0
t
o
2
3
.
7
)
0
.
5
3
6
N
A
G
(

1
6
.
5
U
/
g

C
r
)
3
(
3
7
.
5
%
)
6
(
2
8
.
6
%
)
1
7
(
6
3
.
0
%
)
0
.
1
2
0
4
(
4
4
.
4
%
)
5
(
4
1
.
7
%
)
1
4
(
5
1
.
9
%
)
0
.
8
8
9
R
B
P
(

0
.
5
m
g
/
L
)
4
(
5
0
.
0
%
)
1
0
(
4
7
.
6
%
)
1
5
(
5
5
.
5
%
)
0
.
8
4
7
5
(
5
5
.
6
%
)
5
(
4
1
.
7
%
)
1
5
(
5
5
.
6
%
)
0
.
7
8
8
u
r
i
n
a
r
y
o
s
m
o
l
a
l
i
t
y
(

8
0
0
m
O
s
m
o
l
/
k
g

H
2
O
)
5
(
6
2
.
5
%
)
1
5
(
7
1
.
4
%
)
1
4
(
5
1
.
9
%
)
0
.
3
8
4
7
(
7
7
.
8
%
)
8
(
6
6
.
7
%
)
1
6
(
5
9
.
3
%
)
0
.
5
9
3
M
e
t
a
b
o
l
i
c
p
a
r
a
m
e
t
e
r
s
B
M
I
(
k
g
/
m
2
)
2
9
.
6

2
.
2
3
0
.
2

2
.
2
3
1
.

3
.
0
0
.
2
0
3
3
0
.
6

2
.
5
3
0
.
3

2
.
5
3
0
.
2

1
.
7
0
.
8
9
6
f
a
s
t
i
n
g
b
l
o
o
d
g
l
u
c
o
s
e
(
m
m
o
l
/
L
)
4
.
5
4

0
.
6
9
4
.
8
4

0
.
7
7
5
.
0
9

0
.
8
2
0
.
2
5
5
4
.
6
7

0
.
7
8
4
.
7
7

0
.
8
5
4
.
9
5

0
.
9
0
0
.
7
0
0
t
o
t
a
l
c
h
o
l
e
s
t
e
r
o
l
(
m
m
o
l
/
L
)
4
.
3
9

0
.
7
3
5
.
0
2

1
.
2
6
5
.
2
5

1
.
0
2
0
.
1
5
7
5
.
2
3

0
.
9
6
4
.
4
8

0
.
9
0
5
.
3
7

1
.
4
2
0
.
1
3
0
t
r
i
g
l
y
c
e
r
i
d
e
(
m
m
o
l
/
L
)
2
.
1
0

1
.
6
1
2
.
5
3

0
.
8
8
2
.
3
3

1
.
1
1
0
.
6
4
5
3
.
0
7

1
.
9
1
2
.
3
1

1
.
0
8
2
.
6
9

1
.
2
2
0
.
5
4
4
H
D
L
(
m
m
o
l
/
L
)
1
.
0
2

0
.
1
9
1
.
3
2

0
.
5
5
1
.
2
7

0
.
4
0
0
.
3
8
5
1
.
2
4

0
.
1
9
1
.
0
4

0
.
2
2
1
.
2
8

0
.
5
2
0
.
3
6
0
L
D
L
(
m
m
o
l
/
L
)
2
.
8
5

0
.
9
6
3
.
6
1

1
.
1
6
3
.
4
0

1
.
2
5
0
.
3
9
9
2
.
5
8

0
.
9
0
2
.
8
3

1
.
0
1
3
.
3
6

0
.
9
7
0
.
1
9
1
T
G
/
H
D
L
1
.
9
8

0
.
5
9
2
.
4
8

1
.
5
2
1
.
9
6

0
.
8
2
0
.
3
5
2
2
.
2
9

1
.
4
9
2
.
4
7

1
.
4
4
2
.
0
8

0
.
8
5
0
.
6
6
3
s
e
r
u
m
u
r
i
c
a
c
i
d
(

m
o
l
/
L
)
4
3
5

1
1
1
4
1
8

6
6
4
4
4

7
9
0
.
6
0
9
4
0
5

8
5
4
1
4

8
4
4
2
1

1
2
7
0
.
9
5
1
s
e
r
u
m
a
l
b
u
m
i
n
(
g
/
L
)
4
3
.
4

3
.
3
4
2
.
7

2
.
4
4
1
.
0

4
.
3
0
.
1
6
7
4
4
.
3

4
.
6
4
3
.
1

3
.
2
4
1
.
2

3
.
8
0
.
1
1
7
s
y
s
t
o
l
i
c
p
r
e
s
s
u
r
e
(
m
m
H
g
)
1
3
3
.
7

1
3
.
3
1
3
1
.
1

1
7
.
3
1
3
6
.
8

1
4
.
4
0
.
4
7
7
1
3
6
.
2

1
8
.
1
1
3
3
.
2

1
8
.
4
1
3
4
.
5

1
2
.
3
0
.
8
9
1
d
i
a
s
t
o
l
i
c
p
r
e
s
s
u
r
e
(
m
m
H
g
)
8
3
.
6

1
3
.
3
8
5
.
7

1
1
.
2
8
4
.
8

1
0
.
6
0
.
9
2
0
8
7
.
3

1
0
.
2
8
3
.
7

1
1
.
3
8
4
.
8

1
0
.
9
0
.
7
7
9
T
r
e
a
t
m
e
n
t
r
e
g
i
m
e
n
d
u
r
i
n
g
f
o
l
l
o
w
-
u
p
p
e
r
i
o
d
A
C
E
I
/
A
R
B
s
8
(
1
0
0
%
)
2
1
(
1
0
0
%
)
2
6
(
9
6
.
3
%
)
0
.
5
7
9
9
(
1
0
0
%
)
1
2
(
1
0
0
%
)
2
7
(
1
0
0
%
)
1
.
0
n
e
w
u
s
e
o
f
A
C
E
I
/
A
R
B
s
7
(
8
7
.
5
%
)
1
6
(
7
6
.
2
%
)
2
2
(
8
1
.
5
%
)
0
.
7
7
4
7
(
7
7
.
8
%
)
9
(
7
5
.
0
%
)
2
1
(
7
7
.
8
%
)
0
.
9
8
1
r
h
e
i
n
7
(
8
7
.
5
%
)
2
0
(
9
5
.
2
%
)
2
7
(
1
0
0
%
)
0
.
2
3
0
9
(
1
0
0
%
)
1
2
(
1
0
0
%
)
2
4
(
8
8
.
9
%
)
0
.
2
8
8
n
e
w
u
s
e
o
f
r
h
e
i
n
6
(
8
7
.
5
%
)
1
7
(
8
1
.
0
)
%
2
3
(
8
5
.
2
%
)
0
.
7
9
1
7
(
7
7
.
8
%
)
7
(
5
8
.
3
%
)
2
0
(
7
4
.
0
%
)
0
.
5
3
4
L
L
D
1
(
1
2
.
5
%
)
2
(
9
.
5
%
)
3
(
1
1
.
1
%
)
0
.
9
6
9
2
(
2
2
.
2
%
)
3
(
2
5
%
)
1
(
3
.
7
%
)
0
.
1
1
1
n
e
w
u
s
e
o
f
L
L
D
0
(
0
%
)
0
(
0
%
)
3
(
1
1
.
1
%
)
0
.
1
8
2
0
(
0
%
)
2
(
1
6
.
7
%
)
1
(
3
.
7
%
)
0
.
2
1
0
G
r
o
u
p
i
n
g
w
a
s
d
o
n
e
a
c
c
o
r
d
i
n
g
t
o
t
h
e
p
e
r
c
e
n
t
a
g
e
o
f
B
M
I
c
h
a
n
g
e

3
%
f
r
o
m
b
a
s
e
l
i
n
e
t
o
f
o
l
l
o
w
-
u
p
a
t
t
h
e
6
t
h
a
n
d
2
4
t
h
m
o
n
t
h
,
r
e
s
p
e
c
t
i
v
e
l
y
.
O
-
F
S
G
S
,
o
b
e
s
i
t
y
-
r
e
l
a
t
e
d
F
S
G
S
;
e
G
F
R
,
e
G
F
R
b
y
M
D
R
D
e
q
u
a
t
i
o
n
;
N
A
G
,
u
r
i
n
a
r
y
N
-
a
c
e
t
y
l
-

-
d
-
g
l
u
c
o
s
a
m
i
n
i
d
a
s
e
;
R
B
P
,
u
r
i
n
a
r
y
r
e
t
i
n
o
l
b
i
n
d
i
n
g
p
r
o
t
e
i
n
;
T
G
/
H
D
L
,
r
a
t
i
o
o
f
T
G
t
o
H
D
L
;
A
C
E
I
/
A
R
B
,
a
n
g
i
o
t
e
n
s
i
n
-
c
o
n
v
e
r
t
i
n
g
e
n
z
y
m
e
i
n
h
i
b
i
t
o
r
s
a
n
d
/
o
r
a
n
g
i
o
t
e
n
s
i
n
r
e
c
e
p
t
o
r
b
l
o
c
k
e
r
s
;
L
L
D
,
l
i
p
i
d
-
l
o
w
e
r
i
n
g
d
r
u
g
s
.
1404 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 5: 14011409, 2010
T
a
b
l
e
3
.
C
h
a
n
g
e
s
i
n
r
e
n
a
l
l
e
s
i
o
n
s
a
n
d
m
e
t
a
b
o
l
i
c
p
a
r
a
m
e
t
e
r
s
a
f
t
e
r
t
h
e
d
i
e
t
a
n
d
e
x
e
r
c
i
s
e
i
n
t
e
r
v
e
n
t
i
o
n
6
t
h
M
o
n
t
h
2
4
t
h
M
o
n
t
h
I
n
c
r
e
a
s
e
d
B
M
I
(
n

8
)
S
t
a
b
l
e
B
M
I
(
n

2
1
)
D
e
c
r
e
a
s
e
d
B
M
I
(
n

2
7
)
P
I
n
c
r
e
a
s
e
d
B
M
I
(
n

9
)
S
t
a
b
l
e
B
M
I
(
n

1
2
)
D
e
c
r
e
a
s
e
d
B
M
I
(
n

2
7
)
P
R
e
n
a
l
l
e
s
i
o
n
s
e
G
F
R
(
m
l
/
m
i
n
)
b
a
s
e
l
i
n
e
1
0
2
.
3

4
2
.
7
1
1
0
.
5

4
1
.
1
9
8
.
6

3
4
.
7
1
0
6
.
5

2
6
.
3
9
7
.
9

3
2
.
1
9
8
.
8

3
8
.
5
f
o
l
l
o
w
-
u
p
9
4
.
4

3
2
.
0
1
0
0
.
0

4
1
.
4
9
8
.
3

3
1
.
4
1
0
6
.
4

3
8
.
4
8
2
.
5

3
6
.
6
9
5
.
7

4
1
.
8

e
G
F
R
(
%
)

0
.
2

2
5
.
5
5
.
9

1
2
.
4
1
.
8

1
4
.
6
0
.
3
0
2

1
.
6

1
9
.
7

1
5
.
2

2
4
.
9

2
.
4

1
7
.
1
0
.
2
1
4
u
r
i
n
e
p
r
o
t
e
i
n
(
g
/
2
4
h
)
b
a
s
e
l
i
n
e
1
.
0
5

0
.
6
2
1
.
4
3

1
.
1
5
1
.
5
7

0
.
9
9
g
1
.
1
3

0
.
6
3
g
1
.
2
6

0
.
7
0
1
.
7
1

1
.
2
4
h
f
o
l
l
o
w
-
u
p
1
.
4
3

1
.
0
4
1
.
2
1

0
.
8
7
1
.
1
0

0
.
9
2
1
.
9
3

1
.
2
7
1
.
0
7

0
.
7
8
0
.
8
8

1
.
0
0

u
r
i
n
e
p
r
o
t
e
i
n
(
%
)
5
2
.
7
(

2
1
.
2
t
o
2
4
5
.
3
)

2
0
.
4
(

8
8
.
3
t
o
2
7
9
.
1
)

3
5
.
3
(

8
3
.
6
t
o
2
8
7
.
0
)
a
0
.
0
3
3
2
8
.
8
(

3
0
.
1
t
o
3
8
2
.
5
)

2
0
.
2
(

6
8
.
6
t
o
1
6
0
.
9
)
b

5
1
.
3
(

9
0
.
9
t
o
1
6
6
.
7
)
c
,
d
0
.
0
0
0
M
e
t
a
b
o
l
i
c
p
a
r
a
m
e
t
e
r
s
B
M
I
b
a
s
e
l
i
n
e
2
9
.
6
2

2
.
1
6
h
3
0
.
2
2

3
.
2
1
3
1
.
2
7

2
.
9
6
h
3
0
.
6
3

3
.
5
2
h
3
0
.
3
1

3
.
4
6
3
0
.
1
6

1
.
6
6
h
f
o
l
l
o
w
-
u
p
3
1
.
0
9

2
.
6
8
2
9
.
8
4

3
.
4
0
2
8
.
6
3

2
.
5
2
3
2
.
3
1

3
.
9
6
3
0
.
0
8

3
.
5
5
2
7
.
3
8

1
.
8
2
c
,
d

B
M
I
(
%
)
5
.
5
6

1
.
9
1

0
.
7
5

1
.
2
2
c

8
.
2
9

4
.
0
0
%
c
,
f
8
.
0
1

3
.
4
2

0
.
3
5

1
.
7
2
c

9
.
2
0

3
.
7
8
c
,
f
0
.
0
0
0
G
l
u
(
m
m
o
l
/
L
)
b
a
s
e
l
i
n
e
4
.
5
4

0
.
6
9
4
.
8
4

0
.
7
7
5
.
0
9

0
.
8
2
4
.
6
7

0
.
7
8
4
.
7
7

0
.
8
5
4
.
9
5

0
.
9
0
f
o
l
l
o
w
-
u
p
5
.
3
1

0
.
7
3
5
.
0
8

0
.
6
2
5
.
0
6

0
.
5
3
5
.
2
8

0
.
7
1
5
.
2
8

0
.
7
8
4
.
9
7

0
.
8
3

g
l
u
c
o
s
e
(
%
)
1
8
.
9

3
3
.
3
4
.
9

1
2
.
2
0
.
8

1
5
.
3
0
.
0
6
3
5
.
8

1
9
.
9
7
.
9

3
1
.
9
0
.
5

3
1
.
9
0
.
9
6
9
t
r
i
g
l
y
c
e
r
i
d
e
(
m
m
o
l
/
L
)
b
a
s
e
l
i
n
e
2
.
1
0

1
.
6
1
2
.
5
3

0
.
8
8
2
.
3
3

1
.
1
1
3
.
0
7

1
.
9
1
2
.
3
1

1
.
0
8
2
.
6
9

1
.
2
2
g
f
o
l
l
o
w
-
u
p
2
.
3
5

1
.
2
3
2
.
5
5

2
.
0
3
1
.
7
0

0
.
8
2
4
.
5
4

3
.
7
0
2
.
3
9

0
.
9
5
1
.
9
3

0
.
8
9

t
r
i
g
l
y
c
e
r
i
d
e
(
%
)

9
.
2

2
9
.
3

4
.
7

3
8
.
2

1
5
.
3

4
8
.
7
0
.
7
2
8
5
5
.
3

8
1
.
5
7
.
3

4
7
.
0

1
7
.
1

3
6
.
1
b
0
.
0
0
5
T
G
/
H
D
L
b
a
s
e
l
i
n
e
1
.
9
8

0
.
5
9
2
.
4
8

1
.
5
2
1
.
9
6

0
.
8
2
g
2
.
2
9

1
.
4
9
2
.
4
7

1
.
4
4
2
.
0
8

0
.
8
5
g
f
o
l
l
o
w
-
u
p
1
.
9
0

0
.
9
5
2
.
5
5

2
.
0
1
1
.
4
0

0
.
7
7
3
.
9
8

2
.
7
3
2
.
3
0

1
.
2
7
1
.
7
9

1
.
0
8

T
G
/
H
D
L
(
%
)
0
.
6

4
2
.
7

6
.
4

3
7
.
6

2
1
.
1

3
2
.
7
0
.
4
1
6
7
3
.
0

1
1
6
.
6

1
0
.
1

4
3
.
8
a

1
7
.
3

3
7
.
3
a
0
.
0
3
1
s
e
r
u
m
U
A
(

m
o
l
/
L
)
b
a
s
e
l
i
n
e
4
3
5

1
1
1
4
1
8

6
6
4
4
4

7
9
4
0
5

8
5
4
1
4

8
4
4
2
1

1
2
7
h
f
o
l
l
o
w
-
u
p
4
0
7

3
0
4
1
8

6
4
3
7
8

6
7
3
9
7

7
3
4
2
1

1
1
6
3
8
8

7
4

u
r
i
c
a
c
i
d
(
%
)
6
.
5

2
2
.
7

3
.
3

1
8
.
8

9
.
8

1
4
.
2
0
.
1
1
6

0
.
9

9
.
9

1
.
8

9
.
7

4
.
9

1
0
.
7
0
.
2
6
5
s
y
s
t
o
l
i
c
p
r
e
s
s
u
r
e
b
a
s
e
l
i
n
e
1
3
3
.
7

1
3
.
3
1
3
1
.
1

1
7
.
3
1
3
6
.
8

1
4
.
4
1
3
6
.
2

1
8
.
1
1
3
3
.
2

1
8
.
4
1
3
4
.
5

1
2
.
3
h
f
o
l
l
o
w
-
u
p
1
3
1
.
8

1
2
.
7
1
3
0
.
8

1
2
.
9
1
3
4
.
5

1
3
.
0
1
4
3
.
9

1
8
.
1
1
3
9
.
2

1
5
.
8
1
2
5
.
4

8
.
5
7

s
y
s
t
o
l
i
c
p
r
e
s
s
u
r
e
(
%
)
4
.
6

1
7
.
0

1
.
6

1
4
.
5

0
.
2

1
0
.
2
0
.
6
3
6
8
.
1

1
8
.
7
5
.
6

1
5
.
1

7
.
4

8
.
4
b
,
d
0
.
0
0
5
d
i
a
s
t
o
l
i
c
p
r
e
s
s
u
r
e
b
a
s
e
l
i
n
e
8
3
.
6

1
3
.
3
8
5
.
7

1
1
.
2
8
4
.
8

1
0
.
6
8
7
.
3

1
0
.
2
8
3
.
7

1
1
.
3
8
4
.
8

1
0
.
9
h
f
o
l
l
o
w
-
u
p
7
8
.
7

4
.
0
7
9
.
7

1
0
.
4
8
5
.
0

1
1
.
0
8
9
.
0

1
5
.
0
9
0
.
2

1
2
.
6
7
7
.
1

8
.
2

d
i
a
s
t
o
l
i
c
p
r
e
s
s
u
r
e
(
%
)

1
.
7

1
5
.
2

1
.
9

1
8
.
6

2
.
1

1
5
.
2
0
.
9
9
9
5
.
0

1
4
.
8
7
.
3

1
3
.
4

9
.
5

9
.
1
a
,
e
0
.
0
0
1
e
G
F
R
,
e
G
F
R
b
y
M
D
R
D
e
q
u
a
t
i
o
n
;
G
l
u
,
f
a
s
t
i
n
g
p
l
a
s
m
a
g
l
u
c
o
s
e
;
T
G
/
H
D
L
,
r
a
t
i
o
o
f
T
G
t
o
H
D
L
;
U
A
,
u
r
i
c
a
c
i
d
.
a
P

0
.
0
5
v
s
.
i
n
c
r
e
a
s
e
d
B
M
I
g
r
o
u
p
.
b
P

0
.
0
1
v
s
.
i
n
c
r
e
a
s
e
d
B
M
I
g
r
o
u
p
.
c
P

0
.
0
0
1
v
s
.
i
n
c
r
e
a
s
e
d
B
M
I
g
r
o
u
p
.
d
P

0
.
0
5
.
v
s
.
s
t
a
b
l
e
B
M
I
g
r
o
u
p
.
e
P

0
.
0
1
v
s
.
s
t
a
b
l
e
B
M
I
g
r
o
u
p
.
f
P

0
.
0
0
1
v
s
.
s
t
a
b
l
e
B
M
I
g
r
o
u
p
.
g
P

0
.
0
5
f
o
l
l
o
w
-
u
p
v
s
.
b
a
s
e
l
i
n
e
.
h
P

0
.
0
1
f
o
l
l
o
w
-
u
p
v
s
.
b
a
s
e
l
i
n
e
.
Clin J Am Soc Nephrol 5: 14011409, 2010 Weight Loss in Patients with ORG 1405
Factors Related to the Outcome of Proteinuria and Renal
Function in Patients with Decreased BMI
Although patients with decreased BMI tended to have a
better outcome of proteinuria, there were still 12 (44.4%) pa-
tients who obtained no apparent remission. To explore the
factors causing the difference in the outcome of proteinuria
changes, these patients were subdivided into two groups: re-
mission group (complete and partial remission) and nonremis-
sion group (stable and deteriorated proteinuria). The laboratory
findings and pathologic features were compared between the
groups. Greater reduction in BMI in the remission group than
that in the nonremission group was found (10.76 3.72% versus
7.28 2.97%; P 0.05). Meanwhile, the reduction in TG
(35.68 16.96 versus 4.91 40.95%; P 0.01) and UA
(11.51 11.23 versus 2.08 8.60%; P 0.05) in the remis-
sion group was also greater. Figure 3 showed the patients could
be easily divided into two categories by the combination of
reduction in BMI, TG, and UA level. Although both groups had
similar reduction in BP, the BP level at the follow-up was not
consistent. The diastolic pressure level in the remission group
was lower than that in the nonremission group (73.8 5.7
versus 81.5 9.0 mmHg; P 0.05) and systolic pressure had the
same tendency (122.6 8.4 versus 129.1 7.7 mmHg; P 0.07).
Furthermore, no significant difference was noted between these
two groups in the drug use and pathologic features are noted in
Table 4.
Reduction of BMI and proteinuria did not benefit renal func-
tion in this study. During the 2 years of follow-up, only one
Figure 1. Relationship between changes in body weight and outcome of proteinuria at the (a) 6th month (short term) and (b) 24th
month (long term).
Figure 2. Results from univariate regression analysis, relating
change in proteinuria (dependent variable) at the 24th month.
Ch, serum cholesterol; Glu, fasting blood glucose; SBP, systolic
BP; DBP, diastolic BP; ACEI/ARB, new use of angiotensin-
converting enzyme inhibitors and/or angiotensin II receptor
blockers; rhein, new use of rhein; LLD, new use of lipid-
lowering drugs.
Figure 3. Relationships between the extent of reduction in BMI,
TG, UA, and outcome of proteinuria in 27 patients with de-
creased BMI after a 2-year follow-up. Solid spots represent
remission in proteinuria (complete remission and improvement
in proteinuria; n 15); hollow spots represent nonremission in
proteinuria (stable and deteriorated proteinuria; n 12).
1406 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 5: 14011409, 2010
patient, who had sustained moderate proteinuria, developed a
doubled serumcreatinine level. Areduction in eGFR 20%was
noted in 13 patients, among whom two (22.2%) had increased
BMI, four (33.3%) stable BMI, and seven (25.9%) decreased
BMI. To further explore the factors related to renal function, the
medication, laboratory findings, and pathologic features (Table
4) of the 27 patients with reduced BMI were analyzed. How-
ever, no significant factors were found to be correlated with
renal function decline, and the percentage of tubular atrophy
and renal interstitial fibrosis 25% would be suggested as a
best candidate for predicting the deterioration of renal function
with a P value at 0.084.
Discussion
Our study, for the first time, demonstrated that weight loss
reduced proteinuria in ORG patients. The renoprotective effect
of weight loss was independent of conventional medication.
With the decrease of BMI, diet and exercise intervention also
benefitted patients with ameliorated plasma lipids, uric acid,
and BP.
Weight loss by lifestyle modification decreased urinary pro-
tein by 35% after 6 months and by 51% after 24 months, respec-
tively. Previous reports about diabetic patients had suggested
an average of 30 to 50% reduction of proteinuria after signifi-
cant weight loss by hypocaloric diet in 1 or 5 months (9,10) and
a 50% reduction after a 12-month follow-up (21). It seemed
that the short-term effects of weight loss on patients with ORG
were comparable to those with diabetic nephropathy. Although
a longer term effect had not been observed previously, our
results showed that persistent weight loss helped to reduce
proteinuria in 2 years and weight gain increased the risk of
disease progression.
Weight loss alleviates glomerular hyperfiltration in obese
patients (7,8). If it saved renal function in patients with chronic
kidney diseases is still under debate. Reduced urinary protein
excretion by weight loss intervention is expected to stabilize
renal function (22). But unintentional weight loss is also re-
ported as being associated with the progression of renal dis-
eases (23), which might reflect nutritional deficit being related
to disease progression (24). In our study, we aimed to observe
the effect of weight loss intervention in the renal function of
patients with overt ORG, but failed to find a correlation be-
tween weight changes and changes in eGFR. It might be due to
the relatively short duration of follow-up (15,25). In fact, most
of our patients had stable renal function, and only one patient
doubled serum creatinine at the end of the follow-up. Longer
term follow-up would be needed to further clarify this ques-
tion. Nevertheless, we found that tubular atrophy and intersti-
tial fibrosis might be the best candidate predictors of renal
function (P 0.084), raising the importance of the pathologic
examination upon diagnosis. It should also be acknowledged
that eGFR calculated by the MDRD equation is not reliable in
obese patients, especially those with an eGFR 60 ml/min.
Therefore, further studies using iothalamate studies are war-
ranted.
Our observations suggested that metabolic factors other than
BMI had an effect on proteinuria, including plasma lipids, uric
acid, and BP. The decrease of TG/HDL ratio was an early
manifestation after weight loss. The TG/HDL ratio was not
only strongly related to BMI but also a sensitive indicator
reflecting the insulin resistance in nondiabetic patients with
obesity (26). Thus, the reduced TG/HDL ratio might imply the
improvement of insulin resistance in patients with decreased
BMI. Both the regression analyses and the factor analyses in
patients with weight loss showed that reduction of plasma TG
and UA is partly associated with the uric proteinlowering
effect of weight loss, which was consistent with previous re-
ports (5,6,27). Interestingly, although patients with weight loss
had significant decreased BP, the influence of BP on proteinuria
seemed to be more related to the absolute pressure, implicating
that there might be a threshold value of BP related to the
outcome of proteinuria.
ACEI/ARB was widely used in patients with renal diseases
because of its effect of reducing proteinuria (28). And all of our
Table 4. Relationship of pathologic features and medications with the outcome of renal lesions in 27 patients with
decreased BMI
n
Proteinuria eGFR Decline
Remission
(n 15)
Nonremission
(n 12)
20%
(n 20)
20%
(n 7)
Pathologic features
presence of O-FSGS lesions 15 10 (66.7%) 5 (41.7%) 10 (50.0%) 5 (71.4%)
tubular atrophy/renal interstitial fibrosis 25% 11 5 (33.3%) 6 (50%) 6 (30.0%) 5 (71.4%)
interstitial inflammatory cell infiltration 25% 11 6 (40.0%) 5 (41.7%) 7 (35.0%) 4 (57.1%)
hyaline degeneration of small arteries 25% 7 4 (26.7%) 3 (25.0%) 5 (25%) 2 (28.6%)
Medication
new use of ACEI/ARB 21 12 (80.0%) 9 (66.7%) 16 (80.0%) 5 (71.4%)
new use of rhein 20 10 (50.0%) 10 (50.0%) 14 (70.0%) 6 (85.7%)
new use of LLDs 1 0 (0%) 1 (8.3%) 1 (5.0%) 0 (0%)
O-FSGS, obesity-related FSGS; O-GM, glomerulomegaly alone; ACEI/ARB, angiotensin-converting enzyme inhibitors or/
and angiotensin II receptor blockers; LLDs, lipid-lowering drugs.
Clin J Am Soc Nephrol 5: 14011409, 2010 Weight Loss in Patients with ORG 1407
patients were given the medication except for those having
contraindications. Meanwhile, rhein was used in most of the
Chinese patients with diabetic nephropathy. It was demon-
strated to reverse the cellular hypertrophy, fibronectin synthe-
sis, and excessive glucose uptake of the diabetic mesangial
cells, by inhibiting the hexosamine pathway (29). Therefore, the
use of two drugs may have additional benefits for patients with
ORG. No profound correlation was found between new use of
ACEI/ARB and proteinuria, possibly implicating the occur-
rence of aldosterone escape. However, it is difficult to assess the
effects of these drugs because they were widely used in our
patients. A multicentered, randomized, double-blind, placebo-
controlled phase III clinical trial of rhein is now being under-
taken in China in patients with diabetic nephropathy, which
will help us to further investigate its effect.
Compliance with the diet and exercise treatment is a crucial
issue in assessment of therapeutic effectiveness. According to
our observation, there were 15 out of 63 patients that were
poorly adherent and lost in the 2-year follow-up, which might
suggest poor compliance in a small group of patients. However,
most patients had good compliance with the therapy. In 27
patients who lost weight at the 6th month, 23 of them showed
a continuous decreased BMI at the 24th month. Although life-
style adjustment is difficult for obese patients to stick to, the
report of favorable outcome of weight control in a relatively
short period (6 months) may be very encouraging and enhance
their adherence with the therapy. A frequent follow-up and
education may also help physicians to discover existing prob-
lems and improve the effects of lifestyle modification in ORG.
Acknowledgments
This work was supported by the National Natural Science Founda-
tion of China (Grant 30800546) and the Doctoral Foundation of Educa-
tion, Ministry of China (Grant 200802841008).
Disclosures
None.
References
1. Yang J, Lu F, Zhang C, Liu Z, Zhao Y, Gao F, Sun S, Zhang
Y: Prevalence of prehypertension and hypertension in a
Chinese rural area from 1991 to 2007. Hypertens Res 33:
331337, 2010
2. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS:
Body mass index and risk for end-stage renal disease. Ann
Intern Med 144: 2128, 2006
3. Tozawa M, Iseki K, Iseki C, Oshiro S, Ikemiya Y, Takishita
S: Influence of smoking and obesity on the development of
proteinuria. Kidney Int 62: 956962, 2002
4. Jacobs M, Bisland W, Gomez E, Plasencia G, Mederos R,
Celaya C, Fogel R: Laparoscopic sleeve gastrectomy: A
retrospective review of 1- and 2-year results. Surg Endosc
24: 781785, 2010
5. Monteiro Jr FC, Silva Jr WS, Salgado Filho N, Ferreira PA,
Araujo GF, Mandarino NR, Barbosa JB, Lages JS, Lima Jde
R, Monteiro CC: Effects of weight loss induced by bariatric
surgery on the prevalence of metabolic syndrome. Arq Bras
Cardiol 92: 418422, 435439, 452456, 2009
6. Welty FK, Nasca MM, Lew NS, Gregoire S, Ruan Y: Effect
of onsite dietitian counseling on weight loss and lipid
levels in an outpatient physician office. Am J Cardiol 100:
7375, 2007
7. Chagnac A, Weinstein T, Herman M, Hirsh J, Gafter U, Ori
Y: The effects of weight loss on renal function in patients
with severe obesity. J Am Soc Nephrol 14: 14801486, 2003
8. Agrawal V, Krause KR, Chengelis DL, Zalesin KC,
Rocher LL, McCullough PA: Relation between degree of
weight loss after bariatric surgery and reduction in al-
buminuria and C-reactive protein. Surg Obes Relat Dis 5:
2026, 2009
9. Saiki A, Nagayama D, Ohhira M, Endoh K, Ohtsuka M,
Koide N, Oyama T, Miyashita Y, Shirai K: Effect of weight
loss using formula diet on renal function in obese patients
with diabetic nephropathy. Int J Obes (London) 29: 1115
1120, 2005
10. Morales E, Valero MA, Leon M, Hernandez E, Praga M:
Beneficial effects of weight loss in overweight patients with
chronic proteinuric nephropathies. Am J Kidney Dis 41:
319327, 2003
11. Ishizaka Y, Ishizaka N, Tani M, Toda A, Toda E, Koike K,
Nagai R, Yamakado M: Association between changes in
obesity parameters and incidence of chronic kidney dis-
ease in Japanese individuals. Kidney Blood Press Res 32:
141149, 2009
12. Praga M: Obesitya neglected culprit in renal disease.
Nephrol Dial Transplant 17: 11571159, 2002
13. Chen HM, Li SJ, Chen HP, Wang QW, Li LS, Liu ZH:
Obesity-related glomerulopathy in China: A case series of
90 patients. Am J Kidney Dis 52: 5865, 2008
14. Chen HM, Liu ZH, Zeng CH, Li SJ, Wang QW, Li LS:
Podocyte lesions in patients with obesity-related glomeru-
lopathy. Am J Kidney Dis 48: 772779, 2006
15. Kambham N, Markowitz GS, Valeri AM, Lin J, DAgati
VD: Obesity-related glomerulopathy: An emerging epi-
demic. Kidney Int 59: 14981509, 2001
16. Navarro-Diaz M, Serra A, Romero R, Bonet J, Bayes B,
Homs M, Perez N, Bonal J: Effect of drastic weight loss
after bariatric surgery on renal parameters in extremely
obese patients: Long-term follow-up. J Am Soc Nephrol 17:
S213S217, 2006
17. Tran HA: Reversible obesity-related glomerulopathy fol-
lowing weight reduction. Med J Aust 184: 367, 2006
18. Fowler SM, Kon V, Ma L, Richards WO, Fogo AB, Hunley
TE: Obesity-related focal and segmental glomerulosclero-
sis: Normalization of proteinuria in an adolescent after
bariatric surgery. Pediatr Nephrol 24: 851855, 2009
19. Zhou BF: Predictive values of body mass index and waist
circumference for risk factors of certain related diseases in
Chinese adultsstudy on optimal cut-off points of body
mass index and waist circumference in Chinese adults.
Biomed Environ Sci 15: 8396, 2002
20. Tighe AP, Allison DB, Kral JG, Heymsfiel SB: Nutrition
support of obese patients. In Clinical Nutrition: Parenteral
Nutrition, 2nd ed., edited by Rombeau JL, Caldwell MD,
Philadelphia, Saunders, 1993, pp 649666
21. Solerte SB, Fioravanti M, Schifino N, Ferrari E: Effects of
diet-therapy on urinary protein excretion albuminuria and
renal haemodynamic function in obese diabetic patients
with overt nephropathy. Int J Obes 13: 203211, 1989
22. Navaneethan SD, Yehnert H, Moustarah F, Schreiber MJ,
1408 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 5: 14011409, 2010
Schauer PR, Beddhu S: Weight loss interventions in
chronic kidney disease: A systematic review and meta-
analysis. Clin J Am Soc Nephrol 4: 15651574, 2009
23. Tokashiki K, Tozawa M, Iseki C, Kohagura K, Kinjo K,
Takishita S, Iseki K: Decreased body mass index as an
independent risk factor for developing chronic kidney dis-
ease. Clin Exp Nephrol 13: 5560, 2009
24. Harrington M, Gibson S, Cottrell RC: A review and meta-
analysis of the effect of weight loss on all-cause mortality
risk. Nutr Res Rev 22: 93108, 2009
25. Othman M, Kawar B, El Nahas AM: Influence of obesity on
progression of non-diabetic chronic kidney disease: a ret-
rospective cohort study. Nephron Clin Pract 113: c16c23,
2009
26. Brehm A, Pfeiler G, Pacini G, Vierhapper H, Roden M:
Relationship between serum lipoprotein ratios and insulin
resistance in obesity. Clin Chem 50: 23162322, 2004
27. Noakes M, Keogh JB, Foster PR, Clifton PM: Effect of an
energy-restricted, high-protein, low-fat diet relative to a
conventional high-carbohydrate, low-fat diet on weight
loss, body composition, nutritional status, and markers of
cardiovascular health in obese women. Am J Clin Nutr 81:
12981306, 2005
28. Ferrari P, Marti HP, Pfister M, Frey FJ: Additive antipro-
teinuric effect of combined ACE inhibition and angiotensin
II receptor blockade. J Hypertens 20: 125130, 2002
29. Zheng JM, Zhu JM, Li LS, Liu ZH: Rhein reverses the
diabetic phenotype of mesangial cells over-expressing the
glucose transporter (GLUT1) by inhibiting the hexosamine
pathway. Br J Pharmacol 153: 14561464, 2008
Access to UpToDate on-line is available for additional clinical information
at http://www.cjasn.org/
Clin J Am Soc Nephrol 5: 14011409, 2010 Weight Loss in Patients with ORG 1409