Yuan et al.

BMC Nephrology (2017) 18:23

DOI 10.1186/s12882-017-0441-9

RESEARCH ARTICLE Open Access

Prevalence and risk factors for

cardiovascular disease among chronic
kidney disease patients: results from the
Chinese cohort study of chronic kidney
disease (C-STRIDE)
Jun Yuan1,2, Xin-Rong Zou2, Si-Ping Han2, Hong Cheng2, Lan Wang1, Jin-Wei Wang3,4,5, Lu-Xia Zhang3,4,5,
Ming-Hui Zhao3,4,5, Xiao-Qin Wang2*, on behalf of the C-STRIDE study group

Abstract
Background: Although a high incidence of cardiovascular disease (CVD) is observed among chronic kidney disease
(CKD) patients in developed countries, limited information is available about CVD prevalence and risk factors in the
Chinese CKD population. The Chinese Cohort of Chronic Kidney Disease (C-STRIDE) was established to investigate
the prevalence and risk factors of CVD among Chinese CKD patients.
Methods: Participants with stage 1–4 CKD (18–74 years of age) were recruited at 39 clinical centers located in 28
cities from 22 provinces of China. At entry, the socio-demographic status, medical history, anthropometric
measurements and lifestyle behaviors were documented, and blood and urine samples were collected. Estimated
glomerular filtration rate (eGFR) was calculated by the CKD-EPI creatinine equation. CVD diagnosis was based on
patient self-report and review of medical records by trained staff. A multivariable logistic regression model was
used to estimate the association between risk factors and CVD.
Results: Three thousand four hundred fifty-nine Chinese patients with pre-stage 5 CKD were enrolled, and 3168
finished all required examinations and were included in the study. In total, 40.8% of the cohort was female, with a
mean age of 48.21 ± 13.70 years. The prevalence of CVD was 9.8%, and in 69.1% of the CVD cases cerebrovascular
disease was observed. Multivariable analysis showed that increasing age, lower eGFR, presence of hypertension,
abdominal aorta calcification and diabetes were associated with comorbid CVD among CKD patients. The odds
ratios and 95% confidence intervals for these risk factors were 3.78 (2.55–5.59) for age 45–64 years and 6.07 (3.89–9.
47) for age ≥65 years compared with age <45 years; 2.07 (1.28–3.34) for CKD stage 3a, 1.66 (1.00–2.62) for stage 3b,
and 2.74 (1.72–4.36) for stage 4 compared with stages 1 and 2; 2.57 (1.50–4.41) for hypertension, 1.82 (1.23–2.70) for
abdominal aorta calcification, and 1.70 (1.30–2.23) for diabetes, respectively.
Conclusions: We reported the CVD prevalence among a CKD patient cohort and found age, hypertension,
diabetes, abdominal aorta calcification and lower eGFR were independently associated with higher CVD prevalence.
Prospective follow-up and longitudinal evaluations of CVD risk among CKD patients are warranted.
Keywords: Cardiovascular Disease, Cerebrovascular Disease, Chronic Kidney Disease, Cohort Study, C-STRIDE,
Epidemiology, Hypertension, Risk Factors

* Correspondence: [email protected]
2
Renal Division, Department of Medicine, Hubei Provincial Hospital of
Traditional Chinese Medicine, The Affiliated Hospital of Hubei University of
Chinese Medicine, Wuhan 430061, China
Full list of author information is available at the end of the article

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Yuan et al. BMC Nephrology (2017) 18:23 Page 2 of 12

Background CKD stages were determined by the KDIGO classifica-

The prevalence of chronic kidney disease (CKD) has tion [9]. eGFR was determined with the CKD-EPI cre-
increased dramatically in economically developed atinine equation using serum creatinine (SCr) measured
countries as well as in developing countries. It is by the Roche enzymatic method [10]. For GN patients,
estimated that CKD has affected more than 100 the eGFR should be ≥15 ml/min/1.73 m2. For DN
million Chinese [1]. Many studies have showed a high patients, the defining eligibility is 15 ml/min/1.73 m2 ≤
incidence of cardiovascular disease (CVD) among CKD eGFR < 60 ml/min/1.73 m2 or eGFR ≥ 60 ml/min/
patients. The prevalence of CVD in CKD was 26.8%, 1.73 m2 with “nephrotic range” proteinuria, defined as
33.4%, 47.2%, and 39.1%, in CKD-ROUTE (Japan), CRIC 24-h urinary protein ≥3.5 g or urinary albumin creatin-
(US), CRISIS (UK) and MERENA (Spain), respectively ine ratio (UACR) ≥2 000 mg/g. For non-GN and non-
[2–5]. The mortality rate of end-stage renal disease DN patients, 15 ml/min/1.73 m2 ≤ eGFR < 60 ml/min/
(ESRD) was above 20% per year despite the use of 1.73 m2 was the cutoff for enrollment.
dialysis, and more than half of the death was related Clinical information and biological specimens for each
to CVD [6]. Lower estimated glomerular filtration patient were collected at entry. Their socio-demographic
rate (eGFR) has been recognized as a strong and in- status (age, gender, income, region, education), etiology
dependent risk factor for CVD [7]. Other predictive of kidney disease, health history (hypertension, diabetes,
factors contributing to higher prevalence of CVD in and cardiovascular disease), lifestyle (smoking, exercise)
CKD, including hypertension, diabetes mellitus (DM), and body mass index (BMI) were documented.
dyslipidemia, anemia (hemoglobin < 110 g/L), and al- Anthropometric measurements (weight, height, waist cir-
buminuria, have also been investigated substantively cumference, hip circumference, resting blood pressure,
in epidemiological studies [2–5]. Thus, early detection heart rate) were recorded. Electrocardiogram, abdominal
and treatment of these risk factors is a key strategy in aorta calcification (AAC) and 24-h urine protein were
the prevention of CVD in CKD. However, little is determined with standardized procedures at all centers.
known about the prevalence and risk factors for CVD Biochemical parameters including SCr, calcium, phos-
among the Chinese population with established CKD phorus, hemoglobin (Hb), fasting glucose, hemoglobin
whose genetic and economic heterogeneities are dif- A1C (HbA1c), triglyceride (TG), total cholesterol (TC),
ferent from those in developed countries. high density lipoprotein cholesterol (HDL-C), low density
Therefore, we have established the Chinese cohort lipoprotein cholesterol (LDL-C), intact parathyroid
study of chronic kidney disease (C-STRIDE), the first na- hormone (iPTH) and high-sensitivity C-reactive protein
tional prospective CKD cohort of Chinese population. It (hs-CRP) were measured in a central laboratory to avoid
was designed to explore risk factors for CKD progression testing variations among laboratories.
and adverse consequences, especially CVD events. The
purpose of the current study is to examine the baseline Definition of hypertension, diabetes, and cardiovascular
characteristics of this cohort and to identify risk factors disease events
for CVD in CKD patients. Hypertension at entry was defined as either systolic
blood pressure >140 mmHg, or diastolic blood pressure
Methods >90 mmHg (confirmed by at least three elevated
The design and methods of the C-STRIDE study were readings taken at least 1 week apart), or use of antihy-
published in details previously [8]. The study is an on- pertensive medications, or any self-reported history of
going multicenter prospective project involving 39 clin- hypertension. In addition, 24-hour ambulatory blood
ical centers located at 28 cities in 22 provinces of China pressure was measured for every participant. Diabetes
(Fig. 1). The enrollment was carried out between No- mellitus was defined as either a fasting glucose
vember 2011 and March 2016. Altogether, 3459 Chinese ≧7.0 mmol/L, or HbA1c ≧ 6.5%, or use of insulin or oral
patients with pre-stage 5 CKD were enrolled, and 3168 anti-diabetic medications, or any self-reported history of
of them finished all required examinations and are in- diabetes. CVD was defined as a history of myocardial
cluded in the study. infarction, hospitalization for congestive heart failure,
The Renal Institute of Peking University organized the serious cardiac arrhythmia incidents (resuscitated car-
C-STRIDE study and established a steering committee diac arrest, ventricular fibrillation, sustained ventricular
consisting of nephrologists, epidemiologists and statisti- tachycardia, paroxysmal ventricular tachycardia, atrial
cians to provide training course for the research staff fibrillation or flutter, severe bradycardia or heart block),
who performed the clinical procedures. A manual of peripheral arterial disease (PAD), or cerebrovascular
operation procedure (MOP) was drawn up to ensure all events (cerebral infarction, transient ischemic attack,
aspects of the study were carried out in a standard and cerebral hemorrhage or subarachnoid hemorrhage).
uniform manner. Reporting of CVD was based on both the patients’ self-
Yuan et al. BMC Nephrology (2017) 18:23 Page 3 of 12

Fig. 1 The distribution of the 39 clinical sites of the C-STRIDE Study and population size of each province in China in 2013. a The distribution of
the clinical sites in China. The hollow triangles represent for the clinical sites in China. b The population size of each province in China in 2013

report and review of their medical records by trained ratios (aOR) with 95% confidence interval (CI) are pre-
staff on the same date of the baseline interview. sented. Covariates included in the multivariable logistic
regression models were gender, age (18–44 (as reference)
Statistical analysis vs 45–64 vs 65–74), smoking history (yes or no), exer-
The statistical analysis for C-STRIDE has been previ- cises more than 3.5 h per week (yes or no), hypertension
ously described [8]. Baseline values are presented as (yes or no), SBP > 130 mmHg (yes or no), diabetes (yes
mean ± standard deviation (SD) or medians and inter- or no), BMI≧24.0 kg/m2 (yes or no), CKD stages (stage
quartile ranges for continuous variables, and as numbers 1–2 (as reference) vs 3a vs 3b vs 4), Hb < 11 g/dl (yes or
and percentages for categorical data. Baseline character- no), serum calcium <8.4 mg/dl (yes or no), serum phos-
istics were compared between groups using analysis of phorus > 4.5 mg/dl (yes or no), iPTH > 65 pg/ml (yes or
variance (ANOVA), or chi-square tests, as appropriate. If no), LDL-C > 120 mg/dl (yes or no), HDL-C < 35 mg/dl
the distribution of the continuous variable did not satisfy (yes or no), TG > 150 mg/dl (yes or no), AAC (yes or
normal distribution, the Kruskal-Wallis rank sum test no).
was used. The cardiovascular risk factors were analyzed All P values are two-sided, and P < 0.05 was consid-
with covariates with multivariable logistic regression ered statistically significant. Analyses were conducted
models. The crude and multivariable adjusted odds with SAS software (version 9.4).
Yuan et al. BMC Nephrology (2017) 18:23 Page 4 of 12

Results school education, and 36.1% had annual income ≦RMB

Baseline demographic and clinical characteristics 30,000 Yuan. The 2015 per capita disposable income of
Anticipated and actual target distributions of CKD eti- urban residents in China is RMB 31,195 Yuan “(http://
ology and renal function are shown in Additional file 1: www.stats.gov.cn/tjsj/zxfb/201602/t20160229_1323991.h
Table S1. The actual percentage of participants with tml)”. The cohort is regionally diverse with 916 (28.9%)
glomerulonephritis (GN) was 60.6%, two times higher subjects from south of Yellow River and 2252 (71.1%)
than the targeted 30%. The percentages of diabetic ne- patients from the north. Mean BMI was 24.47 kg/m2,
phropathy (DN) and other causes were 13.9% and 25.6%, with 53.4% of all participants having a BMI ≧24 kg/m2.
much lower than the anticipated 30% and 40%, respect- 38.2% of the cohort participants were current smokers,
ively. Other causes include hypertensive renal damage, and almost half of the participants exercised less than
chronic pyelonephritis, hyperuricemic nephropathy, 3.5 h per week. Table 1 indicated that the CKD partici-
tubulointerstitial lesion and obstructive nephropathy. pants with CVD were more likely to be older, male, from
The proportions of participants with eGFR (ml/min/ the north, current smokers, and higher BMI than those
1.73 m2) < 45 and ≥45 were 53.5% and 46.5%, consistent without CVD (P < 0.005).
with the target of 40–60%. The proportions of partici-
pants in CKD stage 1 and 2, stage 3a, stage 3b and stage Baseline CVD prevalence in different stages of CKD
4 were 30.8%, 15.7%, 24.3%, and 29.3%, respectively. The baseline CVD prevalence in different stage of CKD is
The baseline demographic characteristics of the cohort shown in Table 2. The overall CVD prevalence of the co-
are shown in Table 1. The final enrolled cohort had a hort was 9.8%, in which the percentages of MI, CHF, cere-
mean age of 48.21 ± 13.7 years with 40.8% of women. brovascular disease and PAD were 20.6%,9.0%,69.1% and
Totally, 56.0% of the enrollments completed a high 16.1%, respectively. The prevalence of cerebrovascular

Table 1 Baseline demographic characteristics of participants of C-STRIDE Study (Nov 2011–Mar 2016)
Variable CVD P
Total Yes No Missing
value
(n = 3168) (n = 311) (n = 2857)
Age (yr) 48.21 ± 13.70 58.59 ± 10.51 47.08 ± 13.53 0 <0.001
Gender 0
Male 1876 (59.22) 215 (69.13) 1661 (58.14) <0.001
Female 1292 (40.78) 96 (30.87) 1196 (41.86)
Annual income 139
≤ 30 000 yuan 1092 (36.05) 119 (39.53) 973 (35.67) 0.18
> 30 000 yuan 1937 (63.95) 182 (60.47) 1755 (64.33)
Educational attainment 22
Junior high school degree or below 1384 (43.99) 150 (48.39) 1234 (43.51) 0.10
High school degree or above 1762 (56.01) 160 (51.61) 1602 (56.49)
Region 0
South 916 (28.91) 60 (19.29) 856 (29.96) <0.001
North 2252 (71.09) 251 (80.71) 2001 (70.04)
BMI (kg/m2) 24.47 ± 3.63 25.04 ± 3.35 24.41 ± 3.65 242 <0.001
BMI category (kg/m2) 242
< 24 1364 (46.62) 96 (35.29) 1268 (47.78) <0.001
≥ 24 1562 (53.38) 176 (64.71) 1386 (52.22)
Tobacco use 62
Yes 1185 (38.15) 156 (50.98) 1029 (36.75) <0.001
Exercise (hours/week) 758
≥ 3.5 1239 (51.41) 124 (52.99) 1115 (51.24) 0.61
< 3.5 1171 (48.59) 110 (47.01) 1061 (48.76)
eGFR (ml/min/1.73 m2) 50.72 ± 30.03 36.71 ± 18.87 52.25 ± 30.62 0 <0.001
Continuous variables are presented as mean ± SD. Categorical data are presented as numbers (n) of patients and percentages. BMI body mass index
Yuan et al. BMC Nephrology (2017) 18:23 Page 5 of 12

Table 2 Baseline prevalence rate of CVD in different stages of CKD in C-STRIDE Study (Nov 2011–Mar 2016)
Variable eGFR (ml/min/1.73 m2) P for
trend
Total >60 45–60 30–45 15–30
(n = 3168) (n = 975) (n = 497) (n = 769) (n = 927)
MI 64 (20.58) 6 (0.62) 9 (1.81) 22 (2.86) 27 (2.91) 0.001
CHF 28 (9.00) 3 (0.31) 5 (1.01) 9 (1.17) 11 (1.19) 0.14
Cerebrovascular disease 215 (69.13) 22 (2.26) 44 (8.85) 58 (7.54) 91 (9.82) <0.001
PAD 50 (10.08) 3 (0.31) 8 (1.61) 13 (1.69) 26 (2.81) <0.001
Total CVD 311 (9.82) 31 (3.18) 59 (11.87) 86 (11.18) 135 (14.56)
Categorical data are presented as numbers (n) of patients and percentages. MI myocardial infarction, CHF congestive heart failure, PAD peripheral arterial disease

events was significantly higher than that of other cardio- C and HDL-C were also different with and without CVD
vascular events. The participants with advanced CKD (P < 0.05). However, no significant difference was ob-
were more likely to have CVD. The prevalence of MI in- served in DBP (P = 0.83) or TG (P = 0.72).
creased with declining eGFR, with percentage of 0.6, 1.8, Lower lipid levels were observed in the CVD-CKD
2.9, 2.9%, respectively (P for trend = 0.001). The same pat- population compared to the non-CVD CKD population
tern was observed with cerebrovascular disease (P for (P < 0.001). The CVD population likely attracts more at-
trend < 0.001) and PAD (P for trend = 0.001). The propor- tention for hyperlipidemia and receives prescription
tions of MI, cerebrovascular disease and PAD were signifi- medications for lowering lipid levels, whereas the non-
cant higher in CKD stages 3b and 4 (eGFR < 45 ml/min/ CVD population is less likely to receive treatment. This
1.73 m2) (P < 0.001). The proportion of CHF presented a is confirmed by our finding that the proportion of statin
gradual increment with CKD progression, but no signifi- treatment was 37.9% in the CVD patients versus 17.0%
cant difference was observed through eGFR groups (P for in the non-CVD patients.
trend = 0.14).
Non-traditional CVD risk factors
Traditional CVD risk factors Table 4 shows the baseline characteristics of non-
Table 3 shows the baseline characteristics of the trad- traditional risk factors for CVD. The participants with
itional risk factors for CVD. Comparisons between pa- CVD had higher SCr than those without CVD (P < 0.001).
tients with and without CVD are presented. The iPTH and abdominal aorta calcification were significantly
participants with CVD were more likely to have hyper- different with and without CVD as well (P < 0.001). Sig-
tension and diabetes (P < 0.001). SBP, blood glucose and nificant difference was also found in hemoglobin and Hs-
HbA1C were significantly higher in CKD participants CRP (P < 0.05). There were no significant differences in
with CVD than without CVD (P < 0.001). The TC, LDL- UTP/24 h, serum calcium and phosphorus.

Table 3 Baseline characteristics of traditional risk factors characteristics for CVD in C-STRIDE Study (Nov 2011–Mar 2016)
Variable CVD P
Total Yes No Missing
value
(n = 3168) (n = 311) (n = 2857)
Hypertension 2106 (77.80) 232 (93.55) 1874 (76.21) 461 <0.001
SBP (mmHg) 129.29 ± 17.51 134.71 ± 17.25 128.74 ± 17.44 342 <0.001
DBP (mmHg) 80.93 ± 11.65 80.48 ± 10.98 80.98 ± 11.71 342 0.83
Diabetes 697 (22.27) 135 (43.41) 562 (19.94) 38 <0.001
Blood glucose (mg/dl) 94.32 ± 28.62 103.86 ± 30.78 93.24 ± 27 221 <0.001
G-Hb (%) 5.92 ± 1.24 6.58 ± 1.56 5.84 ± 1.17 1625 <0.001
TC (mg/dl) 231.63 ± 496.52 194.51 ± 95.90 235.89 ± 522.81 192 0.02
LDL-C (mg/dl) 108.66 ± 103.64 99.38 ± 39.06 109.82 ± 108.66 242 0.002
HDL-C (mg/dl) 44.86 ± 43.70 41.38 ± 13.92 45.24 ± 46.02 241 0.001
TG (mg/dl) 255.90 ± 1125.41 193.03 ± 128.39 262.98 ± 1185.9 193 0.72
Continuous variables are presented as mean ± SD. Categorical data are presented as numbers (n) of patients and percentages. SBP systolic blood pressure, DBP
diastolic blood pressure, G-Hb glycosylated hemoglobin, TC total cholesterol, LDL-C low density lipoprotein cholesterol, HDL-C high density lipoprotein cholesterol,
TG triglycerides
Yuan et al. BMC Nephrology (2017) 18:23 Page 6 of 12

Table 4 Baseline characteristics of non-traditional risk factors characteristics for CVD in C-STRIDE Study (Nov 2011–Mar 2016)
Variable CVD Missing P
value
Total Yes No
(n = 3168) (n = 311) (n = 2857)
eGFR (ml/min/1.73 m2) 50.72 ± 30.03 36.71 ± 18.87 52.25 ± 30.62 0 <0.001
Urine protein/24 h (g) 0.94 (0.34,2.30) 1.04 (0.24,2.84) 0.93 (0.35,2.26) 438 0.53
Serum calcium (mg/dl) 8.92 ± 0.76 9.00 ± 0.76 8.92 ± 0.76 160 0.34
Serum phosphorus (mg/dl) 3.66 (3.22,4.12) 3.66 (3.22,4.19) 3.66 (3.22,4.12) 163 0.55
Total iPTH (pg/mL) 46.66 (29.6,74.61) 55.85 (37.66,91.32) 45.79 (28.83,71.94) 578 <0.001
AAC (n) 2.62 ± 4.02 3.51 ± 4.25 2.52 ± 3.98 0 <0.001
Hemoglobin (g/dl) 12.76 ± 2.26 12.38 ± 2.16 12.80 ± 2.27 268 0.002
Hs-CRP (mg/L) 1.32 (0.53,3.20) 1.71 (0.64,4.46) 1.28 (0.51,3.10) 504 0.004
Continuous variables are presented as mean ± SD, or median with interquartile ranges. Categorical data are presented as numbers (n) of patients. SCr serum
creatinine, AAC abdominal aorta calcification, hs-CRP high-sensitivity C-reactive protein

Overall CVD risk factors and 5% Hispanic participants living in the US. There are
The results of multiple logistic regression analysis of the many differences between Chinese and Western popula-
traditional and non-traditional risk factors for CVD tions, such as ethnicity, calorie intake, and body size
prevalence at enrollment are shown in Table 5. ORs [12]. These differences are apparent between the C-
were adjusted mutually for all potential risk factors listed STRIDE and CRIC cohorts, which also show differences
in the table. In multivariable analysis, the variables sig- in age, causes of CKD, prevalence of hypertension, dia-
nificantly associated with the presence of CVD were age, betes and CVD, BMI, and eGFR. Any of these differ-
hypertension, diabetes mellitus, CKD stage, and AAC. ences could affect the progression and treatment of
The risk factors of CVD with higher ORs were older age CKD. As shown in Table 6, the C-STRIDE participants
(OR: 3.78; 95% CI: 2.55–5.59) (P < 0.001) in age 45–64 were younger with a lower average BMI, and with a
years, (OR: 6.07; 95% CI: 3.89–9.47) (P < 0.001) in age lower prevalence of diabetes, hypertension and CVD.
65–74 years), followed by lower eGFR (OR: 2.07;95% The C-STRIDE baseline indicated that age is an inde-
CI:1.28–3.34) in CKD stage 3a (P = 0.003), (OR: 1.66; pendent and graded risk factor for CVD events in 45–74
95% CI: 1.00–2.62) in CKD stage 3b (P = 0.032), (OR: year old patients. China is a rapidly aging society in
2.73; 95% CI: 1.72–4.36) in CKD stage 4 (P < 0.001)), which more than one quarter of Chinese will be older
hypertension (OR: 2.57; 95% CI:1.50–4.41) (P < 0.001), than 65 years by 2050 [13]. The C-STRIDE study will
AAC (OR: 1.82; 95% CI: 1.23–2.70) (P = 0.003) and dia- help clarify the dimension of risks for ESRD and CVD
betes (OR: 1.70; 95%CI:1.30–2.23) (P < 0.001). among aging individuals with CKD. As summarized in
Tables 3, 4 and 5, the C-STRIDE cohort exhibits numer-
Discussion ous risk factors for CVD and several differences with the
C-STRIDE is a prospective observational multicenter CRIC cohort. The baseline prevalence of CVD was
study of the risk factors for CVD in stage 1–4 CKD. 33.4% in CRIC, more than three times the 9.8% preva-
Here we investigated the prevalence and risk factors of lence reported in C-STRIDE. The blood glucose control
CVD in CKD populations. We report that the overall in diabetic participants was also better in C-STRIDE
prevalence of CVD among 3168 participants was 9.8% at (mean A1C 6.0%) versus CRIC (mean A1C 7.7%). Fi-
enrollment. The percentage of different CVD subtypes nally, the mean BMI in C-STRIDE was 24.47 kg/m2,
among the subset of patients with CVD was MI 20.6%, considerably lower than that in CRIC (32.1 kg/m2). A
CHF 9.0%, cerebrovascular disease 69.1%, and PAD comparison of baseline characteristics between multiple
10.1%, respectively. Our results also show that age, dia- CKD cohort studies is shown in Table 6 [2–5].
betes, hypertension, abdominal aorta calcification and The overall CVD prevalence of 9.8% in CKD patients
stage 3 & 4 CKD are significantly associated with the is much lower than reported in developed countries in-
prevalence of CVD. cluding Japan, but much higher than the overall percent-
C-STRIDE was designed to establish a Chinese cohort age of 1.4% in the general Chinese population [14]. The
similar to the CRIC study [11], and to examine risk fac- significantly lower prevalence of baseline CVD observed
tors for CKD progression and CVD development in in our study compared to similar cohorts might be at-
CKD patients with an eGFR between 15–90 ml/min/ tributable to the higher average eGFR, lower prevalence
1.73 m2. C-STRIDE’s cohort consists of Chinese living in of diabetes and hypertension, and/or the younger age of
China, while CRIC is a mix of 45% White, 46% Black, subjects. These variables have been confirmed to be
Yuan et al. BMC Nephrology (2017) 18:23 Page 7 of 12

Table 5 Risk factors for the prevalence of CVD in C-STRIDE Study (Nov 2011 - Mar 2016)
Univariate P Age and sex adjusted P Multivariate adjusted P
OR (95% CI) OR (95% CI) OR (95% CI)a
Gender
Male 1.61 (1.25–2.07) <0.001 − − 1.36 (0.96─1.94) 0.09
Female (ref) 1 − 1
Age
18–44 (ref) 1 − 1
45–64 5.16 (3.56–7.48) <0.001 − − 3.78 (2.55–5.59) <0.001
65–74 10.25 (6.85–15.34) <0.001 − − 6.07 (3.89–9.47) <0.001
Tobacco use (yes/no) 1.79 (1.41–2.27) <0.001 1.46 (1.071–1.99) 0.017 1.31 (0.95–1.81) 0.10
Exercises < 3.5 h/week (yes/no) 1.07 (0.82–1.41) 0.61 0.81 (0.61–1.07) 0.14 0.80 (0.60–1.08) 0.14
Diabetic (yes/no) 3.08 (2.42–3.93) <0.001 1.93 (1.49–2.49) <.0001 1.70 (1.30–2.23) <0.001
Hypertension (yes/no) 4.53 (2.70–7.58) <0.001 3.37 (2.00–5.68) <.0001 2.57 (1.50–4.41) <0.001
HDL-C <35 mg/dl 1.40 (1.08–1.81) 0.01 1.26 (0.96–1.65) 0.09 1.14 (0.84–1.54) 0.41
LDL-C >120 mg/dl 0.76 (0.58–1.01) 0.05 0.74 (0.56–0.99) 0.04 0.81 (0.59–1.10) 0.17
TG >150 mg/dl 1.06 (0.84–1.35) 0.63 1.09 (0.85–1.40) 0.48 0.98 (0.75–1.28) 0.87
BMI
<24 (ref) 1 1 1
≥24 1.68 (1.29–2.18) <0.001 1.39 (1.06–1.81) 0.0174 1.30 (0.97–1.72) 0.08
CKD stages
1–2(ref) 1 1 1
3a 4.10 (2.62–6.43) <0.001 2.60 (1.64–4.13) <.0001 2.07 (1.28–3.34) <0.003
3b 3.83 (2.51–5.85) <0.001 2.22 (1.44–3.44) 0.0003 1.66 (1.00–2.62) 0.03
4 5.19 (3.47–7.76) <0.001 3.28 (2.16–4.97) <.0001 2.73 (1.72–4.36) <0.001
P >5 mg/dl 1.03 (0.72–1.45) 0.89 1.25 (0.87–1.795) 0.23 0.96 (0.66–1.42) 0.85
Ca <8.4 mg/dl 1 (0.74–1.35) 0.10 0.97 (0.71–1.33) 0.86 0.97 (0.69–1.36) 0.85
IPTH >65 pg/mL 1.62 (1.25–2.09) <0.001 1.42 (1.09–1.85) 0.01 1.03 (0.77–1.40) 0.83
AAC 3.71 (2.58–5.33) <0.001 2.18 (1.498–3.18) <.0001 1.82 (1.23–2.70) 0.003
Hb <11 g/dl 1.06 (0.78–1.43) 0.72 0.93 (0.68–1.27) 0.64 0.67 (0.47–0.95) 0.03
Note: aAll variables listed in the table were included in the multivariate adjusted analysis. OR odds ratio, CI confidence interval, LDL-C low density lipoprotein
cholesterol, HDL-C high density lipoprotein cholesterol, TG triglycerides, BMI body mass index, P serum phosphorus, Ca serum calcium, iPTH intact parathyroid
hormone, AAC abdominal aorta calcification, Hb hemoglobin

independent risk factors for CVD among CKD patients men followed for 20 years [22]. The Japan Public Health
[15–19]. Deserving additional attention is the promin- Center-based prospective Study revealed 1,565 strokes
ence of cerebrovascular disease among C-STRIDE par- (2.7%) among 57,017 subjects in a Japanese population-
ticipants exhibiting CVD. This is similar to the findings based cohort [23].
of the ROUTE study (Japan) [20], but different from the Based on the results of previous similar cohorts in-
MERENA (Spain) [5] and CRIC (USA) [21] studies, in cluding the US CRIC [11] and the Japan CKD-JAC [24]
which heart disease and PAD constituted the majority of studies, we had anticipated that the distribution of CKD
CVD events. There are two possible explanations for the etiology in C-STRIDE would be 30% glomerulonephritis
high incidence of cerebrovascular disease. First, the C- (GN) and 30% diabetic nephropathy (DN) [8]. However,
STRIDE study excluded CKD patients with NYHA Class the actual distribution of CKD etiology was GN 60.6%
III or IV heart failure. Second, it appears that the (twice as high as the targeted 30%), DN 13.9% (less than
Chinese general population may have a higher CVA half of the targeted 30%) and other causes 25.6%. This is
prevalence than is observed in other countries. In a consistent with the data from the Chinese Renal Data
Chinese cohort study of ischemic cardiovascular disease, System, a national registry system for patients undergo-
45 cases (5.4%) of ischemic stroke and 24 cases (2.9%) of ing dialysis, which revealed that in China glomerular dis-
coronary heart disease were reported in 840 middle age ease was the most common cause of ESRD (57.4%),
Yuan et al. BMC Nephrology (2017) 18:23 Page 8 of 12

Table 6 Comparison of baseline characteristics of CKD cohort studies

C-STRIDE China ROUTE Japan CRIC US CRISIS UK MERENA Spain
n = 3168 n = 1138 n = 3612 n = 1325 n = 1129
Inclusion range of eGFR (ml/min/1.73 m2) 15–90 0–90 20–70 10–60 15–60
Age (years) 48.2 68 58.2 65.1 68
Male gender (%) 59.2 69.6 54 63.7 64
2
BMI (kg/m ) 24.5 23 32.1 28.4
Actual eGFR (ml/min/1.73 m2) 50.7 32.7 43.4 30.9 28
Diabetes (%) 21.7 37.1 47 32.4 40.8
Hypertension (%) 66.5 90.2 86 92.7
SBP (mmHg) 129.3 140 127.7 138.3 141
DBP (mmHg) 80.9 78 71.4 75.2 76
Hb (g/dl) 12.76 11.9 12.7 12.41 12.8
HDL-C (mg/dl) 44.86
LDL-C (mg/dl) 108.66 110 102.5 116
Ca (mg/dl) 8.9 9.1 9.2 9.14
P (mg/dl) 3.7 3.6 3.7 3.72 3.7
iPTH (pg/ml) 63.6 109 53 93.2 145
Proteinuria (mean) 2.16 g/24gCr 1.08 g/24 h 1.2 g/24 h
(median) 0.94 g/24 h 0.74 g/gCr 0.17 g/24 h
CVD prevalence (%) 9.8 26.8 33.44 47.2 39.1
eGFR estimated glomerular filtration rate, BMI body mass index, SBP systolic blood pressure, DBP diastolic blood pressure, Hb hemoglobin, HDL-C high density
lipoprotein cholesterol, LDL-C low density lipoprotein cholesterol, Ca calcium, P, phosphorus, iPTH intact parathyroid hormone, CVD cardiovascular disease, g/gCr
gram per gram creatinine

followed by DN (16.4%), hypertension (10.5%), and cystic the results found in Japan [20] and US [21], where in-
kidney disease (3.5%) [25]. Together, these data indicate creased proteinuria was associated with a higher CVD
that the etiological constituents of CKD in China are dif- prevalence.
ferent from those reported in developed countries, It is generally thought that albuminuria always pre-
where the leading cause of ESRD is DN [2–5]. Neverthe- cedes loss of renal function in diabetic kidney disease
less, China has the highest overall number of diabetic [33]. However, an increasing number of studies have cast
patients in the world, rising rapidly from 92.4 million in doubt on this classic paradigm. In a large number of
2007 to 113.9 million diabetic patients in 2013 [26]. recent studies, 20–39% of patients with diabetes and re-
Therefore, diabetes complications such as DN will likely duced eGFR had normal albuminuria [34–37]. In some
become the main cause of ESRD in the coming decades. clinical trials [38, 39], improvement in proteinuria did
Proteinuria is considered a risk factor for CVD and not translate into increased GFR or reduced end points
mortality in patients with CKD. Microalbuminuria, or such as the need for dialysis or death. Therefore, the role
even normal-range albuminuria, constitutes a risk for of proteinuria in representing renal function and in
CVD [27–32]. For instance, the AASK study of African predicting adverse outcomes of CKD warrants further
Americans, which investigated the cardiovascular and research. At baseline of our study, proteinuria was not
renal outcomes of 59,508 participants with stage 1–3 associated with CVD. Long-term follow-up will provide
CKD, indicated a significantly increased risk of CVD more information to help answer this question.
with higher urinary albumin excretion, despite relatively Over the past two decades the leading causes of mor-
low levels of baseline proteinuria [31]. Likewise, in a tality and morbidity have shifted from infectious diseases
population-based cohort study in Taiwan, elevated albu- to non-communicable disease such as vascular disease,
minuria was a key predictor of progression to CKD or renal disease and DM. These disorders have become
ESRD as well as indicating a higher risk of CVD and major public health problems in developed and develop-
mortality [32]. The amount of urinary protein in the C- ing countries alike, imposing heavy economic burdens
STRIDE patients (0.94 g/24 h) was higher compared [40, 41]. The relationship between DM and CVD has
with the CRIC cohort (0.17 g/24 h). In the Chinese co- been demonstrated in a series of studies [2–5, 42]. One
hort, urine protein was not significantly associated with recent study reported that the prevalence of DM among
CVD in CKD (P = 0.526) (Table 4). This is different from a representative sample of Chinese adults was 11.6%,
Yuan et al. BMC Nephrology (2017) 18:23 Page 9 of 12

and the prevalence of pre-diabetes was 50.1% [26]. These better examine the function of eGFR, we employed the
statistics illustrate the importance of DM as a public staging of 3a and 3b instead of a single stage 3. Although
health problem in China and suggest that DM will be- a cohort study of Taiwan found no difference between
come the leading future cause of ESRD in China [43]. 3a and 3b in predicting CVD incidence [52], we ob-
Indeed, DN now accounts for 46.2% and 43.2% of ESRD served significant differences in the occurrence of MI,
cases in economically advanced regions such as Hong cerebrovascular disease and PAD between stages 3a and
Kong and Taiwan [25]. Unfortunately, despite recent im- 3b. A multitude of studies have clearly demonstrated
provements in glycemic and blood pressure control as that overt renal dysfunction is independently and signifi-
well as proteinuria reduction, DN remains the leading cantly associated with an increased risk of CVD events
cause of ESRD in developed countries [44]. Therefore, and mortality [53–55]. A study from Japan indicated that
there is an urgent need for development of novel thera- even after adjustment for other risk factors, the presence
peutic approaches that offer effective nephroprotection of CKD conferred a higher risk of cardiovascular death
and that block key pathogenic pathways leading to dia- with a hazard ratio of 1.20 [53]. A negative graded cor-
betic kidney disease. relation between eGFR and risk of cardiovascular death
Hypertension is a main cause of secondary CKD in was observed. The Framingham Heart Study suggested
China [45]. Numerous studies have demonstrated hyper- the same association [54]. The KORA Study demon-
tension as an important risk factor for CVD and all strated that CKD was strongly associated with an in-
causes of mortality [24, 46, 47]. With the 24-h ambula- creased risk of incident MI and CVD mortality,
tory blood pressure (ABP) monitoring, the baseline of independent from common cardiovascular risk factors in
C-STRIDE showed higher SBP and similar DBP in those men and women [55]. The MATISS Study suggested
with CVD. ABP was recently demonstrated to be more that in an elderly general population with low risk of
important than office blood pressure for predicting CVD CVD and low incidence of reduced renal function, even
and mortality [46]. Morning surge in blood pressure was a modest eGFR reduction was related to all-cause mor-
shown to be a predictor of stroke in elderly hyperten- tality and CVD incidence [56].
sives [47]. In the CKD-JAC study, where ABP was mea- The overall prevalence of AAC in the C-STRIDE study
sured at different times to distinguish the impacts of baseline was 32.9%, with statistically higher percentages
night and morning blood pressure, a higher morning in stages 3b and 4. Multiple regression analysis indicated
ABP surge was associated with CVD risk independently that AAC increases the risk for CVD in CKD. Another
[24]. In short, nearly all studies support the importance Chinese study [57] reported an AAC incidence of 54% in
of effective BP management in CKD as a public health the CKD patients, and also showed a strong association
priority. between the incidence of AAC and cardiovascular risks.
Internationally, a BMI of 25.0–29.9 kg/m2 is consid- Specifically, AAC was positively correlated with left
ered overweight and a BMI ≥30 kg/m2 is considered atrial anteroposterior diameter (LAD), pulmonary arter-
obese. Based on the BMI data of the Chinese population, ial systolic pressure (PASP) and carotid artery intima-
the Working Group on Obesity of the International Life media thickness (IMT), and negatively correlated with
Science Institute China Office recommended a BMI of ejection fraction (EF) and shortening fraction (SF) [57].
24 kg/m2 as the cut-off value for overweight and 28 kg/m2 A cohort study performed on adult Japanese patients
as the cut-off value for obesity for Chinese [48]. The C- with pre-dialysis CKD demonstrated 82% subjects had
STRIDE cohort and the ROUTE cohort (Japan) [2] AAC, and identified AAC as independent predictors for
had similar BMI, both lower than that in Western de novo cardiovascular events in CKD stages 4 and 5
studies [3–5]. Although some reports have suggested [58]. A US study [59] evaluated the association of AAC
higher BMI as an independent risk factor for advanced and CVD in 1974 randomly selected subjects (45 to
CKD and CVD [49], the link between BMI and CVD is 84 years old) with complete AAC and coronary artery
not clear cut. Our study does not support a correlation be- calcification (CAC) data from computerized tomo-
tween higher BMI and CVD. Several studies have shown graphic scans. It was found that AAC and CAC pre-
that higher BMI was actually associated with favorable dicted hard coronary heart disease and hard CVD events
outcomes. For instance, a BMI greater than 30 kg/m2 was independent of one another. Only AAC was independ-
associated with lower mortality among 920 patients with ently related to CVD mortality, and AAC showed a
advanced CKD in a Swedish study [50]. In the Athero- stronger association with total mortality than CAC.
sclerosis Risk in Communities (ARIC) cohort, a higher It is worth noting some limitations of our study. First,
body size was also associated with better overall survival we had a less-than-anticipated diabetes recruitment,
in stage 3 CKD [51]. which could cause a potential bias. The strict criteria for
Our results demonstrate declining GFR as a major risk DN screening may in part account for the lower diabetes
factor for CVD prevalence in the C-STRIDE cohort. To diagnosis in our cohort. The defining eligibility of DN
Yuan et al. BMC Nephrology (2017) 18:23 Page 10 of 12

was eGFR 15–59 ml/min/1.73 m2, or eGFR ≥ 60 ml/min/ protein; IMT: Intima-media thickness; iPTH: Intact parathyroid hormone;
1.73 m2 with “nephrotic range” proteinuria, which was KDIGO: Kidney Disease Improving Global Outcomes; LAD: Left atrial
anteroposterior diameter; LDL-C: Low density lipoprotein cholesterol;
defined as 24-h urinary protein ≥3.5 g or urinary MI: Myocardial infarction; MOP: Manual of operation procedure; NYHA: New
albumin creatinine ratio (UACR) ≥2 000 mg/g [8]. As a York Heart Association; PAD: Peripheral arterial disease; PASP: Pulmonary
result, early stage DN was not adequately screened for. arterial systolic pressure; ROUTE: Research and outcome in treatment and
epidemiology; SAS: Statistical analysis system; SBP: Systolic blood pressure;
Nevertheless, this design would ensure sufficient power SCr: Serum creatinine; SD: Standard deviation; SF: Shortening fraction;
to observe adverse consequences in the DN-subgroup TC: Total cholesterol; TG: Triglyceride; UACR: Urinary albumin creatinine ratio;
population, which will provide valuable information on UACR: Urinary albumin creatinine ratio

diabetes as a cause of CKD in China. Second, we used Acknowledgements

self-report and review of medical records to define CVD The authors thank every member of C-STRIDE Group for close and seamless
in this study. This may have missed a small group of cooperation. The detailed information on the members of the C-STRIDE Group
can be found in the published literature [8]. We thank Drs. Yuan Clare Zhang
participants with undiagnosed CVD, and therefore the and Parker B. Antin for critical reading of the manuscript and constructive
results of CVD-related morbidity may not be all- comments.
inclusive. Third, abdominal aorta calcification was deter-
Funding
mined by radiograph, which is less sensitive in detecting The study was supported by National Key Technology R&D Program of the
atherosclerotic lesions than newer modalities such as Ministry of Science and Technology (Project 2011BAI10B01) and Beijing Science
computerized tomography [60]. Therefore, early stage and Technology Committee (Project D131100004713007, “Establishment of
early diagnosis pathway and model for evaluating progression of chronic
vascular calcification may have been under reported. kidney disease”). We declare that the funding bodies didn’t take part in the
Computerized tomography was not available in this re- design of the study and collection, analysis, and interpretation of data and in
search due to the high costs. However, color Doppler writing the manuscript.
ultrasound has been used in the C-STRIDE cohort to
Availability of data and material
evaluate carotid artery calcification. This will improve The datasets during the current study are available from the corresponding
diagnostic sensitivity of cardiovascular calcification by author on reasonable request.
integration of radiographic and ultrasound techniques
Authors’ contributions
during follow-up. Study concept and design: XQW, JY; Acquisition of data: SPH, LW, XRZ;
Analysis and interpretation of data: JWW, LXZ; Drafting of the manuscript: JY,
HC, XQW; Critical revision of the manuscript for important content: JWW,
Conclusions
LXZ, MHZ; Statistical analysis: JWW, LXZ; Person in charge of study: XQW. All
In summary, the C-STRIDE baseline analysis has dem- authors read and approved the final manuscript.
onstrated that participants with progressive CKD have a
higher prevalence of CVD at entry than the general Competing interests
The authors declare that they have no competing interests.
Chinese population. Age, diabetes, hypertension, abdom-
inal aorta calcification and stage 3 & 4 CKD are signifi- Consent for publication
cantly associated with the prevalence of CVD. In the Not applicable.
next phase of the study, all subjects will be sampled an- Ethics approval and consent to participate
nually for at least 5 years. This Long-term follow-up of This study was approved by the ethics committee of Peking University First
participants will provide critical insight into the epidemi- Hospital. The institutional review boards of each participating hospitals
approved the study protocol and the study was conducted in accordance
ology of CVD in CKD, reveal the impact of individual with the ethical principles of the Declaration of Helsinki. The written
risk factors on adverse outcomes, and serve as a founda- informed consents were obtained from all study participants.
tion for future interventional investigations.
Author details
1
Hubei University of Chinese Medicine, Wuhan 430065, China. 2Renal
Additional file Division, Department of Medicine, Hubei Provincial Hospital of Traditional
Chinese Medicine, The Affiliated Hospital of Hubei University of Chinese
Additional file 1: Table S1. Anticipated and actual target distributions Medicine, Wuhan 430061, China. 3Renal Division, Department of Medicine,
of CKD etiology and renal function, C-STRIDE study (Nov 2011- Mar 2016). Peking University First Hospital, Beijing 100034, China. 4Institute of
(DOC 33 kb) Nephrology, Peking University, Beijing 100034, China. 5Key Laboratory of
Renal Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney
Disease Prevention and Treatment, Peking University, Ministry of Education,
Abbreviations Beijing 100034, China.
AAC: Abdominal aorta calcification; ABP: Ambulatory blood pressure;
ANOVA: Analysis of variance; aOR: Adjusted odds ratios; ARIC: Atherosclerosis Received: 12 July 2016 Accepted: 6 January 2017
risk in communities; BMI: Body mass index; CAC: Coronary artery calcification;
CI: Confidence interval; CKD: Chronic kidney disease; CRIC: Chronic renal
insufficiency cohort; C-STRIDE: Chinese Cohort Study of Chronic Kidney References
Disease; CVD: Cardiovascular disease; DBP: Diastolic blood pressure; 1. Zhang L, Wang F, Wang L, et al. Prevalence of chronic kidney disease in
DM: Diabetes mellitus; DN: Diabetic nephropathy; EF: Ejection fraction; China: a cross-sectional survey. Lancet. 2012;379(9818):815–22.
eGFR: Estimated glomerular filtration rate; ESRD: End-stage renal disease; 2. Iimori S, Naito S, Noda Y, et al. Anaemia management and mortality risk in
GN: Glomerulonephritis; Hb: Hemoglobin; HbA1c: Hemoglobin A1C; HDL- newly visiting patients with chronic kidney disease in Japan: The CKD-
C: High density lipoprotein cholesterol; hs-CRP: High-sensitivity C-reactive ROUTE study. Nephrology (Carlton). 2015;20(9):601–8.
Yuan et al. BMC Nephrology (2017) 18:23 Page 11 of 12

3. Shah R, Matthews GJ, Shah RY, et al. Serum Fractalkine (CX3CL1) and 27. Culleton BF, Larson MG, Parfrey PS, Kannel WB, Levy D. Proteinuria as a risk
Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal factor for cardiovascular disease and mortality in older people: a
Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;66(2):266–73. prospective study. Am J Med. 2000;109(1):1–8.
4. Ritchie J, Rainone F, Green D, et al. Extreme Elevations in Blood Pressure 28. Hillege HL, Fidler V, Diercks GF, et al. Urinary albumin excretion predicts
and All-Cause Mortality in a Referred CKD Population: Results from the cardiovascular and noncardiovascular mortality in general population.
CRISIS Study. Int J Hypertens. 2013;2013:597906. Circulation. 2002;106(14):1777–82.
5. Martinez-Castelao A, Gorriz JL, Portoles JM, et al. Baseline characteristics of 29. Xu J, Knowler WC, Devereux RB, et al. Albuminuria within the “normal”
patients with chronic kidney disease stage 3 and stage 4 in Spain: the range and risk of cardiovascular disease and death in American Indians: the
MERENA observational cohort study. BMC Nephrol. 2011;12:53. Strong Heart Study. Am J Kidney Dis. 2007;49(2):208–16.
6. Collins AJ, Foley RN, Chavers B, et al. United States Renal Data System 2011 30. Wright Jr JT, Bakris G, Greene T, et al. Effect of blood pressure lowering and
Annual Data Report: Atlas of chronic kidney disease & end-stage renal antihypertensive drug class on progression of hypertensive kidney disease:
disease in the United States. Am J Kidney Dis. 2012;A7:e1–420. results from the AASK trial. JAMA. 2002;288(19):2421–31.
7. Drury PL, Ting R, Zannino D, et al. Estimated glomerular filtration rate 31. Brantsma AH, Bakker SJ, Hillege HL, De Zeeuw D, De Jong PE, Gansevoort
and albuminuria are independent predictors of cardiovascular events RT. Cardiovascular and renal outcome in subjects with K/DOQI stage 1–3
and death in type 2 diabetes mellitus: the Fenofibrate Intervention chronic kidney disease: the importance of urinary albumin excretion.
and Event Lowering in Diabetes (FIELD) study. Diabetologia. 2011; Nephrol Dial Transplant. 2008;23(12):3851–8.
54(1):32–43. 32. Liao LN, Liu CS, Li CI, et al. Three-year incidence of elevated albuminuria
8. Gao B, Zhang L, Wang H, Zhao M. Chinese cohort study of chronic kidney and associated factors in a population-based cohort: The Taichung
disease: design and methods. Chin Med J (Engl). 2014;127(11):2180–5. Community Health Study. Eur J Prev Cardiol. 2015;22(6):788–97.
9. Kidney Disease: Improving GlobalOutcomes (KDIGO) CKD Work Group. 33. Fernandez-Fernandez B, Ortiz A, Gomez-Guerrero C, Egido J. Therapeutic
KDIGO 2012 Clinical Practice Guideline for theEvaluation and Management approaches to diabetic nephropathy–beyond the RAS. Nat Rev Nephrol.
of Chronic Kidney Disease. Kidney inter. 2013;3:1–150. 2014;10(6):325–46.
10. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate 34. Molitch ME, Steffes M, Sun W, et al. Development and progression of renal
glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12. insufficiency with and without albuminuria in adults with type 1 diabetes in
11. Lash JP, Go AS, Appel LJ, et al. Chronic Renal Insufficiency Cohort (CRIC) the diabetes control and complications trial and the epidemiology of
Study: baseline characteristics and associations with kidney function. Clin J diabetes interventions and complications study. Diabetes Care. 2010;33(7):
Am Soc Nephrol. 2009;4(8):1302–11. 1536–43.
12. Le ML, Wilkens LR, Kolonel LN, Hankin JH, Lyu LC. Associations of sedentary 35. Kramer HJ, Nguyen QD, Curhan G, Hsu CY. Renal insufficiency in the
lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of absence of albuminuria and retinopathy among adults with type 2 diabetes
colorectal cancer. Cancer Res. 1997;57(21):4787–94. mellitus. JAMA. 2003;289(24):3273–7.
13. Feng Z, Liu C, Guan X, Mor V. China’s rapidly aging population creates 36. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR. Risk factors for renal
policy challenges in shaping a viable long-term care system. Health Aff dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes.
(Millwood). 2012;31(12):2764–73. 2006;55(6):1832–9.
14. Yang ZJ, Liu J, Ge JP, Chen L, Zhao ZG, Yang WY. Prevalence of 37. Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM. Albuminuria and renal
cardiovascular disease risk factor in the Chinese population: the 2007–2008 insufficiency prevalence guides population screening: results from the
China National Diabetes and Metabolic Disorders Study. Eur Heart J. 2012; NHANES III. Kidney Int. 2002;61(6):2165–75.
33(2):213–20. 38. Haller H, Ito S, Izzo JL, et al. Olmesartan for the delay or prevention of
15. Ohno M, Deguchi F, Izumi K, et al. Correlation between renal function and microalbuminuria in type 2 diabetes. N Engl J Med. 2011;364(10):907–17.
common risk factors for chronic kidney disease in a healthy middle-aged 39. Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with
population: a prospective observational 2-year study. PLoS ONE. 2014;9(11), telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET
e113263. study): a multicentre, randomised, double-blind, controlled trial. Lancet.
16. Yamagata K, Ishida K, Sairenchi T, et al. Risk factors for chronic kidney 2008;372(9638):547–53.
disease in a community-based population: a 10-year follow-up study. 40. Beaglehole R, Yach D. Globalisation and the prevention and control of non-
Kidney Int. 2007;71(2):159–66. communicable disease: the neglected chronic diseases of adults. Lancet.
17. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease 2003;362(9387):903–8.
and the risks of death, cardiovascular events, and hospitalization. N Engl J 41. Atkins RC. The epidemiology of chronic kidney disease. Kidney Int Suppl.
Med. 2004;351(13):1296–305. 2005;94:S14–8.
18. Ryan TP, Fisher SG, Elder JL, et al. Increased cardiovascular risk associated 42. Levin A, Djurdjev O, Barrett B, et al. Cardiovascular disease in patients with
with reduced kidney function. Am J Nephrol. 2009;29(6):620–5. chronic kidney disease: getting to the heart of the matter. Am J Kidney Dis.
19. Ninomiya T, Kiyohara Y, Kubo M, et al. Chronic kidney disease and 2001;38(6):1398–407.
cardiovascular disease in a general Japanese population: the Hisayama 43. Zhang L, Long J, Jiang W, et al. Trends in Chronic Kidney Disease in China.
Study. Kidney Int. 2005;68(1):228–36. N Engl J Med. 2016;375(9):905–6.
20. Iimori S, Noda Y, Okado T, et al. Baseline characteristics and prevalence of 44. Fernández FB, Elewa U, Sánchez-Niño MD, et al. 2012 update on diabetic
cardiovascular disease in newly visiting or referred chronic kidney disease kidney disease: the expanding spectrum, novel pathogenic insights and
patients to nephrology centers in Japan: a prospective cohort study. BMC recent clinical trials. Minerva Med. 2012;103(4):219–34.
Nephrol. 2013;14:152. 45. Wang C, Deng WJ, Gong WY, et al. High prevalence of isolated nocturnal
21. Rahman M, Xie D, Feldman HI, et al. Association between chronic kidney hypertension in Chinese patients with chronic kidney disease. J Am Heart
disease progression and cardiovascular disease: results from the CRIC Study. Assoc. 2015;4(6), e002025.
Am J Nephrol. 2014;40(5):399–407. 46. Ohkubo T, Imai Y, Tsuji I, et al. Prediction of mortality by ambulatory blood
22. Jin X, Zhou J, Zhou J, Pan X, Chen H, Ge J. Role of novel risk factors in predicting pressure monitoring versus screening blood pressure measurements: a pilot
risk of ischemic cardiovascular diseases in middle aged men in twenty years in study in Ohasama. J Hypertens. 1997;15(4):357–64.
Shanghai. Zhonghua Liu Xing Bing Xue Za Zhi. 2016;37(3):335–8. 47. Kario K, Pickering TG, Umeda Y, et al. Morning surge in blood pressure as a
23. Svensson T, Inoue M, Sawada N, et al. Coping strategies and risk of predictor of silent and clinical cerebrovascular disease in elderly
cardiovascular disease incidence and mortality: the Japan Public Health hypertensives: a prospective study. Circulation. 2003;107(10):1401–6.
Center-based prospective Study. Eur Heart J. 2016;37(11):890–9. 48. Wu YF, Ma GS, Hu YH, et al. The current prevalence status of body
24. Imai E, Matsuo S, Makino H, et al. Chronic Kidney Disease Japan Cohort overweight and obesity in China: data from the China National
study: baseline characteristics and factors associated with causative diseases Nutrition and Health Survey. Zhonghua Yu Fang Yi Xue Za Zhi. 2005;
and renal function. Clin Exp Nephrol. 2010;14(6):558–70. 39(5):316–20.
25. Liu ZH. Nephrology in china. Nat Rev Nephrol. 2013;9(9):523–8. 49. Kramer H, Luke A, Bidani A, Cao G, Cooper R, McGee D. Obesity and
26. Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese prevalent and incident CKD: the Hypertension Detection and Follow-Up
adults. JAMA. 2013;310(9):948–59. Program. Am J Kidney Dis. 2005;46(4):587–94.
Yuan et al. BMC Nephrology (2017) 18:23 Page 12 of 12

50. Evans M, Fryzek JP, Elinder CG, et al. The natural history of chronic renal
failure: results from an unselected, population-based, inception cohort in
Sweden. Am J Kidney Dis. 2005;46(5):863–70.
51. Kwan BC, Murtaugh MA, Beddhu S. Associations of body size with
metabolic syndrome and mortality in moderate chronic kidney disease. Clin
J Am Soc Nephrol. 2007;2(5):992–8.
52. Chen YC, Su YC, Lee CC, Huang YS, Hwang SJ. Chronic kidney disease itself
is a causal risk factor for stroke beyond traditional cardiovascular risk factors:
a nationwide cohort study in Taiwan. PLoS ONE. 2012;7(4), e36332.
53. Nakamura K, Okamura T, Hayakawa T, et al. Chronic kidney disease is a risk
factor for cardiovascular death in a community-based population in Japan:
NIPPON DATA90. Circ J. 2006;70(8):954–9.
54. Parikh NI, Hwang SJ, Larson MG, Levy D, Fox CS. Chronic kidney disease as a
predictor of cardiovascular disease (from the Framingham Heart Study). Am
J Cardiol. 2008;102(1):47–53.
55. Meisinger C, Doring A, Lowel H. Chronic kidney disease and risk of incident
myocardial infarction and all-cause and cardiovascular disease mortality in
middle-aged men and women from the general population. Eur Heart J.
2006;27(10):1245–50.
56. Donfrancesco C, Palleschi S, Palmieri L, et al. Estimated glomerular filtration
rate, all-cause mortality and cardiovascular diseases incidence in a low risk
population: the MATISS study. PLoS ONE. 2013;8(10), e78475.
57. Bao HD, Sheng XH, Wang NS, et al. Analysis the Occurrence and Risk
Factors of Abdominal Aorta Calcification in Advanced CKD Patients. CJITWN.
2014;11:957–60.
58. Hanada S, Ando R, Naito S, et al. Assessment and significance of abdominal
aortic calcification in chronic kidney disease. Nephrol Dial Transplant. 2010;
25(6):1888–95.
59. Criqui MH, Denenberg JO, McClelland RL, et al. Abdominal aortic calcium,
coronary artery calcium, and cardiovascular morbidity and mortality in the
Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2014;
34(7):1574–9.
60. Wilson PW, Kauppila LI, O’Donnell CJ, et al. Abdominal aortic calcific
deposits are an important predictor of vascular morbidity and mortality.
Circulation. 2001;103(11):1529–34.

Submit your next manuscript to BioMed Central

and we will help you at every step:
• We accept pre-submission inquiries
• Our selector tool helps you to find the most relevant journal
• We provide round the clock customer support
• Convenient online submission
• Thorough peer review
• Inclusion in PubMed and all major indexing services
• Maximum visibility for your research

Submit your manuscript at

www.biomedcentral.com/submit