Introduction: Metabolic syndrome (MetS) and chronic kidney disease are both important risk factors for cardiovascular disease and are closely related to each other. We retrospectively investigated whether MetS or its components increase the risk of development of impaired kidney function in the Japanese general population. Methods: This is a retrospective cohort study which enrolled 14,917 participants who visited our hospital for physical checkups from 2008 to 2018 and had normal estimated glomerular filtration rate (eGFR ≥60 mL/min/1.73 m2) during the baseline examination. Participants were followed up for the median of 1,847 days until 2019 with the development of impaired kidney function (eGFR <60 mL/min/1.73 m2) as the endpoint. The definition of MetS was based on Japanese diagnostic criteria (2005). Results: Throughout the study, 2,150 participants (25.9 per 1,000 person-year) developed impaired kidney function after their baseline checkup. The incidence of impaired kidney function was more frequent in participants with MetS (39.3 per 1,000 person-year) than without (24.2 per 1,000 person-year, p < 0.001). Moreover, each MetS component was positively associated with the incidence of impaired kidney function, where the incidence of impaired kidney function increased with the number of MetS components at baseline (0, 1, 2, and ≥3 component(s); 17.3, 26.9, 32.9, and 39.7 per 1,000 person-year, respectively). Multivariate Cox hazard analysis revealed that MetS was an independent risk factor for impaired kidney function after adjusting for known risk factors (hazard ratio, 1.29; 95% confidence interval, 1.15–1.45). Conclusions: Testing for MetS and its components can help evaluate the risk of developing impaired kidney function in the general population.

Kidney is an organ of the silence because a symptom of kidney disease appears only in its end stage. However, kidney disease even in its early stage is a risk of cardiovascular events, a leading cause of death worldwide. It is extremely difficult to restore impaired kidney function. Early detection or primary prevention of kidney disease is quite important; thus, identifying individuals with increased risk of developing kidney disease is one of the most attractive approaches to reduce a burden of cardiovascular disease. Metabolic syndrome (MetS) is a condition that several metabolic disorders are clustered, and kidney disease often coexists with a component of metabolic disorders, such as increased blood pressure, impaired glucose tolerance, and dyslipidemia. The present study investigated whether MetS is a risk of kidney disease. A total of 14,917 subjects with normal kidney function were enrolled and followed up for 5 years with the endpoint of kidney disease. During the follow-up, 2,150 participants developed kidney disease and the occurrence of the disease was more frequent in individuals who had MetS at baseline than in those who did not. Moreover, each metabolic disorder was associated with future occurrence of kidney disease and the risk of kidney disease increased with increasing the number of metabolic disorders. Testing for MetS and its components can help identify individuals at increased risk of developing kidney disease.

1.
Galassi
A
,
Reynolds
K
,
He
J
.
Metabolic syndrome and risk of cardiovascular disease: a meta-analysis
.
Am J Med
.
2006
;
119
(
10
):
812
9
.
2.
Malik
S
,
Wong
ND
,
Franklin
SS
,
Kamath
TV
,
L’Italien
GJ
,
Pio
JR
, et al
.
Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults
.
Circulation
.
2004
;
110
(
10
):
1245
50
.
3.
Kokubo
Y
,
Okamura
T
,
Yoshimasa
Y
,
Miyamoto
Y
,
Kawanishi
K
,
Kotani
Y
, et al
.
Impact of metabolic syndrome components on the incidence of cardiovascular disease in a general urban Japanese population: the suita study
.
Hypertens Res
.
2008
;
31
(
11
):
2027
35
.
4.
Ministry of Health, Labour and Welfare
. The National Health and Nutrition Survey in Japan, 2019.
5.
Japanese Society of Nephrology
. Guideline on the Diagnosis and Treatment of CKD, 2012.
6.
The Japanese Society for Dialysis Therapy
. JSDT Renal Date Registry, 2021.
7.
Go
AS
,
Chertow
GM
,
Fan
D
,
McCulloch
CE
,
Hsu
C
.
Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization
.
N Engl J Med
.
2004
;
351
(
13
):
1296
305
.
8.
Perneger
TV
,
Brancati
FL
,
Whelton
PK
,
Klag
MJ
.
End-stage renal disease attributable to diabetes mellitus
.
Ann Intern Med
.
1994
;
121
(
12
):
912
8
.
9.
Atkins
RC
.
The epidemiology of chronic kidney disease
.
Kidney Int
.
2005
;
67
(
94
):
S14
18
.
10.
Coresh
J
,
Selvin
E
,
Stevens
LA
,
Manzi
J
,
Kusek
JW
,
Eggers
P
, et al
.
Prevalence of chronic kidney disease in the United States
.
JAMA
.
2007
;
298
(
17
):
2038
47
.
11.
Japan Nephrology Society
.
Special issue: clinical practice guidebook for diagnosis and treatment of chronic kidney disease 2012
.
Nihon Jinzo Gakkai Shi
.
2012
;
54
(
8
):
1034
191
.
12.
Definition and the diagnostic standard for metabolic syndrome–committee to evaluate diagnostic standards for metabolic syndrome
.
Nihon Naika Gakkai Zasshi
.
2005
;
94
(
4
):
794
809
.
13.
Matsuo
S
,
Imai
E
,
Horio
M
,
Yasuda
Y
,
Tomita
K
,
Nitta
K
, et al
.
Revised equations for estimated GFR from serum creatinine in Japan
.
Am J Kidney Dis
.
2009
;
53
(
6
):
982
92
.
14.
Obermayr
RP
,
Temml
C
,
Gutjahr
G
,
Knechtelsdorfer
M
,
Oberbauer
R
,
Klauser-Braun
R
.
Elevated uric acid increases the risk for kidney disease
.
J Am Soc Nephrol
.
2008
;
19
(
12
):
2407
13
.
15.
Iseki
K
,
Ikemiya
Y
,
Iseki
C
,
Takishita
S
.
Haematocrit and the risk of developing end-stage renal disease
.
Nephrol Dial Transpl
.
2003
;
18
(
5
):
899
905
.
16.
Bleyer
AJ
,
Shemanski
LR
,
Burke
GL
,
Hansen
KJ
,
Appel
RG
.
Tobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population
.
Kidney Int
.
2000
;
57
(
5
):
2072
9
.
17.
White
SL
,
Polkinghorne
KR
,
Cass
A
,
Shaw
JE
,
Atkins
RC
,
Chadban
SJ
.
Alcohol consumption and 5-year onset of chronic kidney disease: the AusDiab study
.
Nephrol Dial Transpl
.
2009
;
24
(
8
):
2464
72
.
18.
Chen
J
,
Muntner
P
,
Hamm
LL
,
Jones
DW
,
Batuman
V
,
Fonseca
V
, et al
.
The metabolic syndrome and chronic kidney disease in U.S. adults
.
Ann Intern Med
.
2004
;
140
(
3
):
167
74
.
19.
Thomas
G
,
Sehgal
AR
,
Kashyap
SR
,
Srinivas
TR
,
Kirwan
JP
,
Navaneethan
SD
.
Metabolic syndrome and kidney disease: a systematic review and meta-analysis
.
Clin J Am Soc Nephrol
.
2011
;
6
(
10
):
2364
73
.
20.
Sarathy
H
,
Henriquez
G
,
Abramowitz
MK
,
Kramer
H
,
Rosas
SE
,
Johns
T
, et al
.
Abdominal obesity, race, and chronic kidney disease in young adults: results from NHANES 1999-2010
.
PLoS One
.
2016
;
11
(
5
):
e0153588
.
21.
Fujiyoshi
A
,
Sekikawa
A
,
Shin
C
,
Masaki
K
,
David Curb
J
,
Ohkubo
T
, et al
.
A cross-sectional association of obesity with coronary calcium among Japanese, Koreans, Japanese Americans, and US Whites
.
Eur Heart J Cardiovasc Imaging
.
2013
;
14
(
9
):
921
7
.
22.
Watanabe
H
,
Obata
H
,
Watanabe
T
,
Sasaki
S
,
Nagai
K
,
Aizawa
Y
.
Metabolic syndrome and risk of development of chronic kidney disease: the Niigata preventive medicine study
.
Diabetes Metab Res Rev
.
2010
;
26
(
1
):
26
32
.
23.
Tozawa
M
,
Iseki
C
,
Tokashiki
K
,
Chinen
S
,
Kohagura
K
,
Kinjo
K
, et al
.
Metabolic syndrome and risk of developing chronic kidney disease in Japanese adults
.
Hypertens Res
.
2007
;
30
(
10
):
937
43
.
24.
Ninomiya
T
,
Kiyohara
Y
,
Kubo
M
,
Yonemoto
K
,
Tanizaki
Y
,
Doi
Y
, et al
.
Metabolic syndrome and CKD in a general Japanese population: the Hisayama study
.
Am J Kidney Dis
.
2006
;
48
(
3
):
383
91
.
25.
Lee
CJ
,
Ryu
J
,
Kim
HC
,
Ryu
DR
,
Ihm
SH
,
Kim
YJ
, et al
.
Clinical benefit of treatment of stage-1, low-risk hypertension
.
Hypertension
.
2018
;
72
(
6
):
1285
93
.
26.
Ettehad
D
,
Emdin
CA
,
Kiran
A
,
Anderson
SG
,
Callender
T
,
Emberson
J
, et al
.
Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis
.
Lancet
.
2016
;
387
(
10022
):
957
67
.
27.
Chagnac
A
,
Herman
M
,
Zingerman
B
,
Erman
A
,
Rozen-Zvi
B
,
Hirsh
J
, et al
.
Obesity-induced glomerular hyperfiltration: its involvement in the pathogenesis of tubular sodium reabsorption
.
Nephrol Dial Transpl
.
2008
;
23
(
12
):
3946
52
.
28.
Oh
SW
,
Yang
JH
,
Kim
M-G
,
Cho
WY
,
Jo
SK
.
Renal hyperfiltration as a risk factor for chronic kidney disease: a health checkup cohort study
.
PLoS One
.
2020
;
15
(
9
):
e0238177
.
29.
Ruggenenti
P
,
Cravedi
P
,
Remuzzi
G
.
Mechanisms and treatment of CKD
.
J Am Soc Nephrol
.
2012
;
23
(
12
):
1917
28
.
30.
The GISEN Group
.
Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric non-diabetic nephropathy
.
Lancet
.
1997
;
349
(
9069
):
1857
63
.
31.
Ruggenenti
P
,
Perna
A
,
Gherardi
G
,
Gaspari
F
,
Benini
R
,
Remuzzi
G
.
Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy
.
Lancet
.
1998
;
352
(
9136
):
1252
6
.
32.
Ruggenenti
P
,
Perna
A
,
Gherardi
G
,
Garini
G
,
Zoccali
C
,
Salvadori
M
, et al
.
Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria
.
Lancet
.
1999
;
354
(
9176
):
359
64
.
33.
Ridker
PM
,
Buring
JE
,
Cook
NR
,
Rifai
N
.
C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women
.
Circulation
.
2003
;
107
(
3
):
391
7
.
34.
Ridker
PM
,
Rifai
N
,
Rose
L
,
Buring
JE
,
Cook
NR
.
Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events
.
N Engl J Med
.
2002
;
347
(
20
):
1557
65
.
35.
Bohle
A
,
Wehrmann
M
,
Bogenschütz
O
,
Batz
C
,
Müller
CA
,
Müller
GA
.
The pathogenesis of chronic renal failure in diabetic nephropathy: investigation of 488 cases of diabetic glomerulosclerosis
.
Path Res Pract
.
1991
;
187
(
2–3
):
251
9
.
36.
Antonopoulos
AS
,
Margaritis
M
,
Lee
R
,
Channon
K
,
Antoniades
C
.
Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials
.
Curr Pharm Des
.
2012
;
18
(
11
):
1519
30
.
37.
Lee
TM
,
Su
SF
,
Tsai
CH
.
Effect of pravastatin on proteinuria in patients with well-controlled hypertension
.
Hypertension
.
2002
;
40
(
1
):
67
73
.
38.
Schena
FP
,
Gesualdo
L
.
Pathogenetic mechanisms of diabetic nephropathy
.
J Am Soc Nephrol
.
2005
;
16
(
3_Suppl l
):
30
3
.
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