Prevalence of and risk factors for chronic kidney disease and diabetic kidney disease in a central Chinese urban population: a cross-sectional survey

This study was conducted to evaluate and update the current prevalence of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a China. Methods A total of 5231 participants were randomly recruited for this study. CKD and DKD were defined according to the combination of estimated glomerular filtration rate (eGFR), presence of albuminuria and diabetes. Participants completed a questionnaire assessing lifestyle and relevant medical history, and blood and urinary specimens were taken. Serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and urinary albumin were assessed. The age- and gender-adjusted prevalences of CKD and DKD were calculated, and risk factors associated with the presence of reduced eGFR, albuminuria, DKD, severity of albuminuria and progression of reduce renal function were analyzed by binary and ordinal logistic regression.


Conclusions
Our study shows the current prevalences of CKD and DKD in residents of Central China.
The high prevalence suggests an urgent need to implement interventions to relieve the high burden of CKD and DKD in China.

Background
Chronic kidney disease (CKD) is a common public health issue with an increasing incidence and prevalence in developing countries, such as China. The burden of CKD is not restricted to only the requirement of renal replacement therapy for end-stage renal disease (ESRD), but other serious complications, such as cardiovascular events and mortality are also highly influenced by kidney involvement [1,2].
In the past decade, CKD has been highly prevalent in China. The rapid increasing prevalence of relevant risk factors, such as diabetes and hypertension, plays an important role [3][4][5][6]. In 2010, Yang et al reported that the prevalences of diabetes and prediabetes were 9.7% and 15.5% in China, respectively [7]. In the same year, Ho and Hwang et al demonstrated that diabetic kidney disease (DKD) was responsible for 46.2% and 43.2% of ESRD cases in Hong Kong and Taiwan [8,9]. The inadequate awareness and control of diabetes and hypertension aggravated the health and socioeconomic burden of CKD and DKD in the Chinese population in several aspects, such as lower life expectancies, poor qualities of daily lives and overburdened cost of medical care [10][11][12][13]. Insufficient contract with health services, delayed health-seeking behavior and frequent use of the Chinese herb medicine are also contributed the high incidence and progression of CKD [14,15].
Previous studies have indicated that over 60% of CKD cases could be early detected from general screening [16][17][18]. Timely medical care is beneficial for improving the life qualities of CKD patients and reducing the morbidity and mortality caused by ESRD [18].
Nevertheless, studies reporting epidemiological features of CKD and DKD in Chinese population are still insufficient. Updating the epidemiological data and identifying the early risk factors is urgent and beneficial for developing effective strategies for the prevention of CKD, DKD and ESRD. Therefore, we conducted a cross-sectional study to provide current epidemiological data of CKD and DKD and to identify their risk factors in Central China.

Study subjects
From December 2017 to June 2018, the subjects were recruited from 3 communities in 3 districts of Zhengzhou: the Erqi, Zhongyuan and Jinshui districts. There are 12 administrative districts with a total population of approximately 10 million in Zhengzhou (data available on http://tjj.zhengzhou.gov.cn/). A multistage, stratified cluster sampling method was employed to select participants over 18 years old from the general population. In the first stage, 3 districts were randomly selected from 6 urban districts. In the second stage, one representative community in each district was selected according to the proportion of permanent residents. In the final stage, all permanent residents who satisfied the inclusion criteria and agreed to sign the informed consent were recruited in this study. Altogether, a total of 6000 subjects aged 18 years or older were selected from 3 communities, and 5231 subjects completed the survey and examination, with a response rate of 87.2%.

Measurements and definitions
Data were collected by face-to-face interviews in examination centers at community health stations. All subjects completed a questionnaire that collected information about their sociodemographic status (e.g., age, gender, ethnicity, education, etc.), personal and family health history (e.g., diabetes, hypertension, hepatitis, etc.), lifestyle behaviors (e.g., smoking, alcohol consumption, physical activity, etc.) and awareness and control of chronic non-communicable disease (e.g., diabetes, hypertension, dyslipidemia, etc.) with assistance of trained practitioners, doctors and nurses. Anthropometric measurements, such as height, weight and blood pressure (BP), were obtained. Height and weight were measured while the participants were in light clothing without shoes, and body mass index (BMI, kg/m 2 ) was subsequently calculated. According to the Chinese "Criteria of weight for adults (No. WS/T 428-2013, available on http://www.nhfpc.gov.cn)", BMI was divided into four levels: underweight (< 18.5), healthy weight (18.5 -23.9), overweight (24 -27.9) and obesity (≥ 28). BP was measured using an electronic sphygmomanometer (Omron HEM-7071A, Japan) three times in one-minute intervals. The mean value of the three BP readings was used for statistical analysis unless the difference between the readings was higher than 10 mm Hg, in which case the mean value of the other two closest results was calculated. In addition to participants' self-reported use of antihypertension medications in the past 2 weeks, hypertension was defined as participants with an average systolic BP (SBP) ≥ 140 mm Hg and/or an average diastolic BP (DBP) ≥ 90 mm Hg [19]. Subjects with hypertension were considered to have controlled BP if SBP < 140 mm Hg and DBP < 90 mm Hg.
After at least 8 hours of overnight fasting, venous blood specimens were collected in vacuum tubes without an anticoagulant. Serum concentrations of creatinine, uric acid, total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein were measured using enzymatic colorimetry on a Cobas C 701 (Roche). The fasting plasma glucose (FPG) level was estimated by the glucose oxidative method (GOD-PAP). Urinary albumin and creatinine were measured from a fresh morning spot urine sample.
Albuminuria was measured with an immune-turbidimetric test. Urinary creatinine was evaluated by Jaffe's kinetic method. The urinary albumin to creatinine ratio (ACR, mg/g) was calculated automatically.
Indicators of renal damage were the presence of an eGFR less than 60 mL/min/1.73 m 2 or albuminuria. CKD was defined as the presence of one or two indicators of renal damage.
Diabetes was defined according to the 2009 American Diabetes Association (ADA) guidelines: 1. FPG ≥ 7.0 mmol/L; 2. Self-reported use of insulin or antidiabetic medications in the past 2 weeks; and 3. Self-reported previous diagnosis of diabetes by a physician.
Diabetic subjects with albuminuria and/or an eGFR less than 60 mL/min/1.73 m 2 were classified as having DKD. Control of diabetes defined as subjects with diabetes keep the FPG less than 7.0 mmol/L in past 7 days. Dyslipidemia was considered the presence of abnormal serum lipid concentrations according to the Chinese guidelines for the prevention and treatment of dyslipidemia in adults or the use of antidyslipidemia medications during the last 2 weeks [22]. Hyperuricemia was defined as a plasma uric acid concentration > 422 µmol/L for men and > 363 µmol/L for women.
Education was divided into 3 levels: 1. Primary school or lower; 2. Junior middle school; and 3. Senior high school or above. Diets rich in fruits and vegetables were considered as diets with daily average consumption of more than 500 g of fruits and vegetables. A highfat diet was defined as a diet with a daily average consumption of livestock and poultry of more than 75 g [23]. Physical activity was classified as low, moderate or high according to the international physical activity questionnaire (IPAQ 2001) [24].

Statistical analysis
Epidata software (version 3.1) was used for data entry and management. All statistical analyses were performed with SAS 9.1 (SAS Institute, Cary, NC, USA) and GraphPad Prism 6 (GraphPad Software, Inc., La Jolla, CA, USA) for Windows. A p-value < 0.05 was considered statistically significant. Data are expressed as the mean ± SD, median with range or frequency with percentage, as appropriate. Intergroup  guidelines, two models were used to calculate the data in the ordinal logistic regression.
In model 1, we analyzed data from subjects with an eGFR > 60 mL/min/1.73 m 2 and different levels of ACR (A1 -A3, n=5099) [21]. In model 2, data from all participants were divided into 5 groups as follows: low risk (no CKD); moderately increased risk; high risk; and very high risk [21]. The results of the tests of parallel lines indicated that the two models were statistically executable (both P values > 0.05).

Results
Of the 6000 participants involved in this study, 5231 had a complete data set and were entered into our statistical analysis. Their demographic and clinical characteristics are shown in Table 1. The prevalences of hypertension, dyslipidemia, hyperuricemia and diabetes were 34.6%, 14.6%, 11.5% and 7.6%, respectively. A total of 80.3% of the participants attended senior high school. The prevalences of current smokers and habitual drinkers were similar. The mean eGFR was 92.6 ± 21.5 mL/min/1.73 m 2 and the median ACR was 14.1 with an interquartile range of 8.8 to 23 mg/g. Generally, participants with reduced eGFR or albuminuria were older, less educated, performing heavy physical activity. They had a lower proportion of high fat diet and higher prevalences of cardiovascular disease, hypertension, dyslipidemia, hyperuricemia and diabetes than did those without indicators of renal damage.
According to the stratification of renal indicators, there were 132 subjects performed eGFR less than 60 mL/min/1.73m 2 and 858 individuals performed albuminuria (Table 2). Totally, 945 participants were suffering from CKD, in which 192 subjects were DKD patients. The adjusted prevalence of eGFR less than 60 mL/min/1.73m 2 was 2.8% (95% CI = 2.4 -3.3%) and that of albuminuria was 14.9% (95% CI = 13.9 -15.9%). The overall prevalence of CKD and DKD was 16.8% (95% CI = 15.8 -17.8%) and 3.5% (95% CI = 3.0 -4.0%), respectively. By disease stage, the prevalence was as follows: stage 1, 6.0%; stage 2, 7.8%; stage 3a, 2.4%; stage 3b, 0.2%; and stage 5, 0.1%. In subjects with normal eGFR, the number of stage A1 -A3 was 4286, 743 and 70, respectively. As shown in figure 1, comparing with men, prevalence of reduced eGFR was much higher in women subjects who aged over 40 years old and the overall prevalence was increased with age in both men and women. The prevalence of albuminuria increased with age and was higher in women than men in all age groups except for subjects who aged 60 -69 years old (24.7 versus 26.3%). Overall, the prevalences of CKD and DKD were increased with age in both men and women participants.
In all participants with diabetes (N = 400), comparing with those without renal damage, subjects with reduced eGFR were older, more likely to be women, insufficient consumption of meat, lack of physical activities, poor control of diabetes, higher proportion of hypertension and dyslipidemia, meanwhile, those with albuminuria performed lacking control of diabetes and higher proportion of dyslipidemia (Table 3). Twenty five subjects were classified as stage 3 -5 CKD and 181 subjects had albuminuria (Table 4) The prevalence of reduced eGFR was 6.3% (95% CI = 3.9 -8.6%) and that of albuminuria was 45.3% (95% CI = 40.4 -50.1%). The overall prevalence of CKD in participants with diabetes was 48.0% (95% CI = 43.1 -52.9%).
The prevalence of reduced eGFR was not significantly different among three tertiles of education and family income, while that of albuminuria was highest in subjects with lower tertile of education and upper tertile of family income ( Table 5). The overall adjusted prevalences of CKD were 33.5% (95% CI = 27.7 -39.3%) and 26.5% (95% CI = 22.4 -30.6%), respectively. Prevalences of hypertension and diabetes were lower in subjects with higher education condition while they were lowest in subjects with middle tertile of family income. The worst performance of controlling hypertension and diabetes was in subjects with upper tertile of education (6.9% and 29.9%) and middle tertile of family income (9.3% and 27.4%).
The results of the binary logistic regression are shown in Table 6. Older age, higher educated, and hypertension were all independently associated with a higher risk of reduced eGFR, while being a man performed the opposite. Factors independently associated with a higher risk of albuminuria were older age, being current smoker, a diet rich in fruits and vegetables, overweight, obesity, diabetes, hypertension and dyslipidemia. Better educated and more consumption of meat had lower ORs of developing albuminuria than the other factors. In addition, being an old man, having obesity, hypertension, dyslipidemia and hyperuricemia were significantly associated with an increased risk of DKD, while a diet rich in fruits and vegetables was related to a lower risk of developing renal damage in subjects with diabetes.
In the ordinal logistic regression, data were analyzed in two models (Table 7). In model one, aging, smoking, diet rich in fruits and vegetables, heavy physical activity, high BMIs, diabetes, hypertension, and dyslipidemia were positively associated with increased severities of albuminuria in subjects with normal eGFR values, while better educated and diet rich in meat were associated with reduced severities. Similarly, in model two, better educated and high-fat diet were also negatively related to an elevated risk of renal damage, while the factors including older age, current smoking, favoring fruits and vegetables diet, obesity, diabetes, hypertension and dyslipidemia showed a positive association.

Discussion
Henan Province is one of the largest provinces in China, and its population accounts for an estimated 8% of the entire country according to the China Population Census in 2009. The city of Zhengzhou has a population of nearly 10 million people and is one of the representative urban centers in Central China. To the best of our knowledge, the present study was the first study performed with a large representative sample of an urban population in Central China to evaluate the current epidemiological features of both vital indicators of renal damage, eGFR and albuminuria, and DKD. In this study, the prevalence of CKD was 16.8% and that of DKD was 3.5%, corresponding to over 3 million adults in Henan Province. Generally, older age, sex, education, smoking, unhealthy BMIs, diabetes, hypertension, dyslipidemia and hyperuricemia were significantly associated with a higher risk for and elevated severities of reduced renal function. Compared with previous studies, these findings indicated that the prevalence of CKD was higher in the urban population in Central China than in the urban populations in South China (12.1%) and North China (13.0%) and that the prevalence of CKD increased by 6% since 2009 (10.5%) [11,25,26].
In 2012, Zhang et al conducted a national survey using a multistage stratified sampling method and reported that the prevalence of CKD in Chinese urban residents was 8.9%, out of which 2.3% subjects had reduced eGFR and 7.0% subjects had albuminuria [27].
Compared with our current study, the number of people with CKD increased in the past six years. Older age was shown to be independently associated with a higher risk of reduced renal function, which was further supported by our present study [11,[28][29][30][31][32]. Aging has become a highlighted social problem in China. According to the data from the China Population Census in 2009, the proportion of residents aged over 50 and 60 years was 24.0% and 12.7% in Henan Province, respectively. In this study, the mean age of the subjects without renal damage was 40.3 years, while the mean ages of those with reduced eGFR, albuminuria and DKD were 63.0, 51.5 and 57.9 years, respectively. The age distribution partly contributed to the higher prevalence of CKD in this study population.
Diabetes and hypertension are reported to be significantly related to the high prevalence and incidence of CKD [3,[33][34][35]. In the past twenty years, a noteworthy increase in the prevalence of diabetes and hypertension in the Chinese population occurred. Xiang et al conducted a national survey in China and demonstrated that the prevalence of impaired glucose tolerance and diabetes mellitus was 3.2% and 4.8%, respectively [36]. In 2004, the Fourth National Health and Nutrition Examination Survey of China (NHANES) reported that the prevalence of diabetes had increased to 6.4% [37]. Even though the growth rate decelerated in the past 10 years, the results from the 2016 Global Burden of Disease study suggested that 6.6% of all-age Chinese individuals had diabetes [5]. In 2002, a national survey by Gu et al suggested that the overall prevalence of hypertension was 13.6% in residents aged over 15 years [38]. Ten years later, the results of the International Collaborative Study of Cardiovascular Disease in Asia indicated that 27.2% of middle-aged Chinese adults had hypertension [39]. were associated with CKD. In our study, we found that a larger proportion of subjects with both hypertension and diabetes had reduced eGFR and albuminuria than those without them. Results of the logistic regression also showed that hypertension was independently associated with a higher risk of reduced eGFR with ORs of 1.81 and both diabetes and hypertension were associated with higher risk of albuminuria with ORs of 2.71 and 2.79, respectively. Therefore, the higher prevalence of CKD in our study population could be caused by the high proportion of subjects with diabetes (7.6%) and hypertension (34.6%).
Dyslipidemia tends to develop along with kidney function decline in patients with CKD, even in the early stages. Dyslipidemia is also associated with a higher risk of cardiovascular disease, which is the main cause of death in patients with CKD and ESRD

Ethics approval and consent to participate
This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No. KY-2018-LW-66). All participants provided written informed consent before data collection. The present study was performed in accordance with the Declaration of Helsinki.

Consent for publication
Not applicable.

Availability of data and material
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.    Note: Albuminuria was defined as urinary albumin to creatinine ratio ≥ 30mg/g creatinine. CKD was defined as an eGFR less adjusted for synthesized weights.
Abbreviations: eGFR, estimated glomerular filtration rate.  Abbreviations: eGFR, estimated glomerular filtration rate. Note: Albuminuria was defined as urinary albumin to creatinine ratio ≥ 30mg/g creatinine. CKD was defined as an eGFR less adjusted for synthesized weights.
* P trend was calculated by Cochran-Armitage test   Figure 1 Adjusted prevalence of indicators of renal damage, DKD and CKD, stratified by sex and age. Adjusted prevalences of eGFR less than 60 mL/min/1.73m2 (eGFR < 60), albuminuria (ALB), diabetic kidney disease (DKD) and chronic kidney disease (CKD). Data expresses as prevalence and bars are 95% CIs. Figure 2