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NDT Advance Access originally published online on January 8, 2007
Nephrology Dialysis Transplantation 2007 22(4):1093-1099; doi:10.1093/ndt/gfl763
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Community-based screening for chronic kidney disease among populations older than 40 years in Beijing

LuXia Zhang1, Li Zuo1, GuoBin Xu2, Fang Wang1, Mei Wang1, ShuYu Wang3, JiCheng Lv1, LiSheng Liu3 and HaiYan Wang1

1Institute of Nephrology and Division of Nephrology and 2Department of Clinical Laboratory, Peking University First Hospital and 3Beijing Hypertension League Institute, Beijing China

Correspondence and offprint requests to: H. Y. Wang, MD, Division of Nephrology and Institute of Nephrology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, PR China. Email: why{at}bjmu.edu.cn



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. Chronic kidney disease (CKD) is a public health problem, while data from developing countries are limited. We sought to investigate the epidemiological features of kidney damage in metropolis-residing Chinese adults (>40 years old), and to determine the associated factors of CKD.

Methods. Two thousand three hundred and fifty-three residents in one district of Beijing were interviewed and tested for albuminuria, reduced renal function, haematuria and pyuria. The associations between demographic characteristics, health characteristics and indicators of kidney damage were examined.

Results. Albuminuria was detected in 6.2% of subjects; reduced renal function was found in 5.2% of subjects; haematuria was found in 0.8% and non-infective pyuria was found in 0.09%. Approximately, 11.3% (95% confidence interval: 10.0–12.8%) of subjects had at least one indicator of kidney damage. The awareness rate of CKD was only 7.2%. Systolic blood pressure and diabetes were independently associated with albuminuria. Age, diastolic blood pressure, hypercholesteraemia, hypertriglyceridaemia and hyperuricaemia were independently associated with reduced renal function.

Conclusions. This is the first report on the prevalence of CKD in a community-based population within a developing country, determined using protocols recommended by kidney disease improving global outcomes (KDIGO). The prevalence of CKD in our population was close to the levels observed in developed countries, and the spectrum of CKD and associated factors were similar to developed countries. Results from this study suggest that strategies aimed at an intervention of hypertension and other metabolic disorders might prove effective in controlling the pandemic of CKD in China, as well as other developing countries.

Keywords: albuminuria; China; chronic kidney disease; renal function; screening



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 References
 
Chronic kidney disease (CKD) is a major public health problem. While heart disease, cerebrovascular diseases and cancer remain the major causes of mortality resulting from chronic diseases, CKD has now assumed epidemic proportions and is among the leading causes of death in the industrialized world [1]. Reports from two metropolitan areas of China—Beijing and Shanghai—indicated that in 2002, the annual incidence of haemodialysis was 146.4 per million population and 148.1 per million population [2], respectively. These rates are almost double the reported incidence reported in 1999 [3]. The same trend has been noted in other developing countries [4,5].

CKD has few symptoms and is frequently unrecognized [6–11]. Several population-based screening programs were performed in developed countries [12–14]. However, studies to determine the prevalence and associated factors of individuals with kidney diseases in developing countries, especially in Chinese populations, are very limited. According to Chinese Dialysis and Transplantation Registration Report [3], the major cause of ESRD in Chinese adults was glomerulonephritis, while ESRD caused by diabetes and hypertension only accounted for 13.3% and 9.6%. But in the last 20 years, the prevalence of diabetes and hypertension in adults increased rapidly in China [15–17]. A similar trend has also been noted in other developing countries [4,18–20]. We wondered whether the changing epidemiology of diabetes and hypertension seen in Chinese adults directly affects the risk factors of CKD in the population. Thus, we initiated this study in middle-aged and senile populations in a metropolis, where the economic status as well as lifestyle has changed dramatically during the past few decades, with the intention to determine the prevalence, spectrum and associated risk factors of CKD in this population, with potential application to other developing countries.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 References
 
Study population
All residents, aged 40 years or older, who were served by a community hospital (Gucheng Hospital) located in an urban district of Beijing, were invited to participate in the study. Residents were contacted by telephone and notified of the screening protocol by the local general practitioner. Of the 5593 individuals who were eligible for inclusion in the study, 2353 (42.1%) volunteered to participate. All participants gave their informed consent.

Screening protocol and evaluation criteria
All subjects completed a questionnaire documenting their sociodemographic status (e.g. age, sex, income and education), personal and family health history (e.g. hypertension, diabetes and kidney disease) and lifestyle behaviour (e.g. smoking) under the assistance of general practitioners. A history of hepatitis and medications with renal side-effects (e.g. non-steroids, anti-inflammatory drugs and herbs containing aristolochic acid) were also investigated. Each participant underwent weight and height measurements, using a calibrated scale. The body mass index (BMI) was calculated as weight (in kilograms) divided by height squared (in square metres). Indicators of kidney damage and possible risk factors were then examined.

Albuminuria
Albumin and creatinine were measured on a morning spot urine sample. Albuminuria was measured by immunoturbidimetic methods (Audit Diagnostics, Cork, Ireland). Urinary creatinine was measured by means of enzymatic method on a Hitachi 7170 autoanalyzer (Hitachi, Tokyo, Japan). A urinary albumin–to–creatinine ratio (ACR, mg/g) was calculated. Microalbuminuria was defined as an ACR of 30 mg/g ≤ ACR ≤ 299 mg/g, and macroalbuminuria was defined as an ACR of >300 mg/g. The term ‘albuminuria’ is used to describe the presence of either microalbuminuria or macroalbuminuria.

Estimated glomerular filtration rate (eGFR). Blood was collected by venipuncture after an overnight fast of at least 10 h. Serum creatinine (Scr) was measured by enzymatic method. In addition, Scr of 52 fresh frozen serum samples were analysed by both enzymatic method and Jaffe's kinetic method on a Hitachi 7170 autoanalyzer (Hitachi, Tokyo, Japan) in our laboratory. A calibration equation was generated from the results (R2 = 0.999):


Formula

eGFR was calculated using a new estimating equation which was developed by modifying modification of diet in renal disease (MDRD) equation based on data from Chinese CKD patients [22], and reduced renal function was defined as an eGFR <60 ml/min/1.73 m2 (1.00 ml/s/1.73 m2):


Formula

Haematuria and pyuria
Dipstick testing (Roche Diagnositics, Mannheim, Germany) of morning spot urine samples was performed at the first screening visit. Subjects with haematuria of 1+ or greater were re-examined after 3 months by the urinary dipstick test and microscopic analysis. Three or more red blood cells by high power field were considered abnormal. Similarly, subjects with pyuria of 1+ or greater were re-examined, and those with more than five white blood cells per high power field were considered abnormal. Women during menstruation were excluded from the urine test. Subjects with confirmed haematuria and/or pyuria were interviewed by nephrologists to rule out cystitis.

Hypertension status
Blood pressures were measured according to the guidelines presented in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood pressure (JNC VII) [23]. Three readings were taken at 5 min intervals. Means of the three readings were calculated, unless the difference between the readings was >10 mmHg, in which case the mean of the two closest of the three measurements was used. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg, or use of anti-hypertensive medications irrespective of the BP.

Diabetes status
All participants, except those with a known diagnosis of diabetes, were given a standard 75 g oral glucose tolerance test after collection of a blood specimen after an overnight fast of at least 10 h. A second blood sample was taken after 2 h to determine plasma glucose. Plasma glucose levels were measured enzymatically with a glucose oxidase method using the Hitachi 7170 autoanalyzer (Hitachi, Tokyo, Japan). Standard World Health Organization criteria for the diagnosis of diabetes mellitus were used: fasting plasma glucose ≥7.0 mmol/l or 2 h plasma glucose ≥11.1 mmol/l [24].

Others
Serum total cholesterol, triglyceride and uric acid were measured by Hitachi 7170 autoanalyzer (Hitachi, Tokyo, Japan). HBsAg was also tested using enzyme-linked immunosorbent assay methods (Wantai Beijing, China).

Statistical analysis
Data entry and management were performed on Epidata software, version 3.1 (Epidata Association, Odense, Denmark). All analyses and calculations were performed by SPSS statistical package, version 10.0 (SPSS, Inc., Chicago, IL). Data were presented as the mean ± SD for continuous variables and as proportions for categorical variables. Descriptive analyses were used to characterize the participant population by sociodemographic data (e.g. age, sex and health insurance status) and health status (e.g. hypertension and diabetes). Prevalence and mean values of selected conditions by sex and age were examined using chi-square statistics for categorical variables and Wilcoxon's rank sum for continuous values. The unadjusted odds ratios (OR) between the exposure variables and indicators of kidney damage were determined by univariate logistic regression analysis. A multivariate logistic regression analysis was then performed to evaluate the simultaneous effects of the various exposure variables, with adjustment for any confounding variables. The exposure variables included age, gender, smoking, family history (diabetes, hypertension and CKD), medications, BMI, systolic BP, diastolic BP, diabetes, serum total cholesterol, serum triglyceride, serum uric acid and positive HBsAg.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 References
 
Complete information on the physical condition and indicators of kidney disease was available for 98.2% (n = 2310) of the participants examined. All subjects were Chinese. Sociodemographic characteristics are listed in Table 1. Age and gender distribution was similar between responders and non-responders. According to data released by the Beijing Municipal Bureau of Statistics (http://www.bjstats.gov.cn), our study population's demographic characteristics were similar to those of the Beijing population 40 years or older. For example, in the general population the sex ratio is 1.04 : 1 (male:female) vs 1 : 1.02 for our study; the average income is 2290 vs 2264.5 RMB/month and the percentage of people who have completed high school is 41.6 vs 41.3% in our study. The only difference between Beijing statistics and our study population was that the most common age categories of residents in Beijing are 40–49 years and 50–59 years (38.5 and 28.8%, respectively); these age groups are slightly younger than patients included in our study.


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  		Table 1. Sociodemographic and health care characteristics of screening population

 
Prevalence of indicators of kidney damage
Albuminuria
Microalbuminuria was detected in 5.3% (n = 123) of participants, and macroalbuminuria was detected in 0.9% (n = 21) of participants. The overall prevalence of albuminuria was 6.2% (n = 144; Table 2), with 93.1% of those cases occurring in participants without a reported history of kidney disease. The prevalence was similar in men and women (P = 0.606), and the increasing trend in prevalence of albuminuria with advancing age was only seen in women (P = 0.007 for women and P = 0.112 for men, respectively, across age groups). The prevalence of albuminuria was highest among subjects with diabetes and hypertension (18.2%), while in subjects without hypertension and diabetes; the incidence was only 1.9% (Figure 1A).


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  		Table 2. Prevalence of indicators of kidney damage

 

Figure 1
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  		Fig. 1. Prevalence of albuminuria (A) and reduced renal function (B) according to hypertension and diabetes. Data expressed as prevalence (95% CI for prevalence). eGFR defined as estimated GFR calculated by a new GFR-estimating equation which was developed by modifying MDRD equation based on data from Chinese CKD patients [22] <60 ml/min/1.73 m2 (1.00 ml/s/1.73 m2).

 
eGFR
Five percent of participants had eGFR values <60 ml/min/1.73 m2 (1.00 ml/s/1.73 m2, n = 119; Table 2), and 89.1% of subjects with reduced renal function did not report a history of kidney disease. The prevalence was similar in men and women (P = 0.851), and an increased incidence of an eGFR < 60 ml/min/1.73 m2 (1.00 ml/s/1.73 m2) with increasing age was seen in both men and women (P < 0.001 for trends across age groups). The prevalence of reduced renal function among hypertensive subjects with and without diabetes was similar (8.4 and 6.4%, P = 0.216; Figure 1B). The prevalence of reduced renal function in subjects without hypertension and without diabetes was 3.7%, which was similar to prevalence of reduced renal function in subjects without hypertension and with diabetes (2.6%, P = 0.568).

Haematuria and pyruia
Haematuria was detected on initial dipstick testing in 2.9% (n = 67) of participants. For those with haematuria but without pyuria (n = 47), haematuria was confirmed by repeated dipstick testing and urine sediment microscopy examination. We found that 0.8% (n = 18) of participants, with a female predominance (n = 14), had haematuria on re-examination. Pyuria was detected by initial dipstick testing in 437 participants. After confirmation by repeated dipstick testing and microscopy, 124 participants were still positive for pyuria. Brief interviews indicated that among these patients, pyuria in 122 participants was due to urinary tract infection (mostly older females, with symptoms of urinary tract infection, some with diabetes), with only two of them possibly related to long-term use of non-steroids anti-inflammatory drugs. Overall prevalence of haematuria and non-infective pyuria was 0.87%.

Prevalence of CKD
Reduced eGFR was seen in 11.1% of participants with albuminuria, and the rest had eGFR > 60 ml/min/1.73 m2 (1.00 ml/s/1.73 m2). Of the participants with a reduced eGFR, 84.0% occurred without either albuminuria or haematuria; 13.4% also had albuminuria, and 2.5% also had haematuria. Eighty-five percent of the time haematuria occurred in the absence of other indicators of kidney damage, and 15.0% of the participants with haematuria also had a reduced eGFR. The prevalence of CKD according to the staging system proposed by the kidney disease outcomes quality initiative (K/DOQI) Working Group is listed in Table 2. The overall prevalence of CKD was 11.3% [95% confidence interval (CI): 10.0–12.8%]. The prevalence of CKD was the same in both genders (P = 0.325), and the increasing trend seen in the prevalence of CKD with increasing age was observed in both groups (P < 0.001, for trend across age groups). Before screening, only 7.2% of subjects with CKD reported a history of kidney disease. Age (P = 0.675), gender (P = 1.000), education (P = 0.133), health insurance coverage (P = 1.000), awareness of hypertension (P = 0.369) and diabetes (P = 1.000) were not different between subjects, either aware or unaware of CKD.

Associated risk factors of CKD
Table 3 presents the unadjusted and adjusted ORs for the presence of albuminuria. Systolic BP and diabetes were independently associated with albuminuria. Each progressive increase in category of systolic BP was associated with a progressively greater likelihood of albuminuria. Even at systolic BP levels between 130 and 139 mmHg, the OR increased by 85% (OR = 1.847, P = 0.016). Table 4 shows the unadjusted and adjusted ORs for presence of reduced renal function. Older age (increased by 10 years; OR = 2.833), diastolic blood pressure >90 mmHg (OR = 2.039), hypercholesteraemia (>6.18 mmol/l; OR 1.660), hypertriglyceridaemia (>1.7 mmol/l; OR = 1.661), hyperuricaemia (>7.0 mg/dl; OR = 3.724) were independently associated with reduced renal function.


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  		Table 3. Unadjusted and adjusted ORs for presence of albuminuria

 

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  		Table 4. Unadjusted and adjusted ORs for reduced renal functiona

 


   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
References
 
Protocols recommended by KDIGO [21] were used to examine the prevalence of CKD in a community-based population within a developing country. We demonstrated that among men and women of 40 years and older living in a metropolis of China, 11.3% have one or more indicators of CKD. The prevalence of CKD in the present study was close to that of the general population in developed countries. Factors associated with CKD in our study population were similar to those in developed countries, but no factors associated with glomerulonephritis and interstitial nephritis were found to be related to CKD in this study.

MDRD equation was recommended for estimating GFR in adults [11]. But ethnicity effects occurred when using MDRD equation [25], and Chinese were not included in the development of MDRD equations. A new GFR estimating equation, which was developed by modifying MDRD equation based on data from Chinese CKD patients offered significant advantages in different CKD stages, if used in Chinese population [22]. Especially underestimation of GFR in CKD stages 1–2 was significantly improved, resulting in a lower overestimation of prevalence of reduced renal function if used in Chinese population. By using this equation, the prevalence of reduced renal function in the present study was estimated to be 5.2%, which was comparatively lower than reports from the Third National Health and Nutrition Examination Survey (NHANES III, 10.8% in subjects older than 40 years) [14] and the Australian Diabetes, Obesity and Lifestyle Study (AusDiab, 11.2% in adults) [12]. In a study also from China [26], the prevalence of decreased renal function among subjects aged 35–74 years was 2.53%. The discrepancy might be due to a different age group, different geographic region and a different method for estimating glomerular filtration rate. The prevalence of albuminuria in our study was 6.2%, which was similar to results from a recent community-based study using the same methods and standards as the present study performed in another metropolitan area of China, in which the prevalence of albuminuria was 6.74% [27]. So the prevalence of albuminuria in Chinese metropolitan residents was lower than reports of albuminuria from developed countries [14]. Although the respective prevalence of indicators of kidney damage was comparatively lower, the overall prevalence of CKD in the present study was 11.3%, which was close to reports from developed countries [12,13], and perhaps due to less overlap between albuminuria and reduced renal function in the present study. The impact of burden of CKD revealed by the present study on the Chinese health care system is overwhelming. Based on the results from the present study, it is roughly predicted that there could be 48 million subjects older than 40 years suffering from CKD in China. If 1% of these patients progressed to ESRD, $6 billion would be needed to provide them all with renal replacement therapy. This is nearly 25 times the annual government health-care budget in 2004 in China. Therefore, programmes aimed at the early detection and intervention of CKD in China is critical.

In 1999, the Chinese Dialysis and Transplantation Registration Report indicated that glomerulonephritis accounted for 49.9% of ESRD [3], a value that is similar to other developing countries [5,28]. In addition, interstitial nephritis attributed to inadvertent use of medications, which increased rapidly over the last 10 years in China [29]. As a result, it is justifiable to include these indicators in CKD screening. But, the prevalence of haematuria and non-infective pyuria seen in the present study was very low, and none of the factors related to glomerulonephritis or interstitial nephritis were found to be associated with CKD. The factors related to CKD in the present study include BP, diabetes, dyslipidaemia, aging and hyperuricaemia, which are similar to those of developed countries [12,13,30,31]. The disparity between our results and the Chinese Dialysis and Transplantation Registration Report in 1999 [3] might be related to the rapidly increasing prevalence of diabetes and hypertension in the population. A nationwide screening of diabetes in 1996 included 42 751 people from 11 provinces and indicated that the prevalence of diabetes and impaired glucose tolerance were 3.21 and 4.76%, respectively [32]. In the 1990s, the prevalence of hypertension was 11.26%, increasing by 25% in about 10 years [33]. Results from the Fourth National Health and Nutrition Examination Survey of China [15], which was finished in 2004, demonstrated that at the beginning of the 21st century, the prevalence of diabetes and hypertension climbed to 6.4 and 18.0%, respectively, and the prevalence of dyslipidaemia was 18.6% [15]. It is reasonable to assume that the increasing tendency in hypertension and metabolic disorders might lead to a similar increase in the prevalence of CKD.

This study revealed a critical opportunity to restrain the increasing tendency of CKD in China. Reports from the United States indicate that the incidence of ESRD caused by diabetes decreased during 1997–2002 among females and whites aged <65 years, and stopped increasing among males and blacks aged 65–74 years, perhaps partly due to an integrated intervention of diabetes [34]. Hoy et al. [35] showed a reduction in natural death and renal failure from a systematic screening and an integrated treatment programme of CKD in an Australian aboriginal community. Another preliminary report from India showed the effectiveness of treating patients with hypertension or diabetes within limited public health resources [36], and then indirectly indicated the possibility of controlling the increasing tendency of CKD in developing countries.

Our study has certain limits and constraints. First, the age-shift towards an older age group compared to the general population may introduce a bias in the evaluation of the prevalence of CKD and its risk factors. Second, except for haematuria and pyuria, indicators of kidney damage were defined based on a single measurement. In K/DOQI guidelines [11], the definition of CKD needs persistency of kidney damage for at least 3 months, which means that in order to define CKD, indicators of kidney damage should be re-evaluated at least once after 3 month. And reports from NHANES III indicated that in repeated measurement, only 63.2% of those with albuminuria would have positive results [12]. So the single measurement of indicators of CKD in the present study might overestimate the prevalence of CKD; while in most cross-sectional studies of CKD [12,13,30,31,37], the measurements of kidney damage were just once, perhaps due to pragmatic and economic reasons. The cost-effectiveness of repeated measurements in CKD screening needs to be further validated. Our study revealed potentially momentous challenges facing health providers and medical professionals of China, along with opportunities to control the pandemic of CKD effectively. These same challenges could soon emerge in other developing countries undergoing rapid economic development, and our results may be important in evoking establishing effective prevention and intervention of CKD to control the pandemic of CKD.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 18.10.06
Accepted in revised form: 22.11.06


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Metabolic Syndrome and Chronic Kidney Disease in a Chinese Population Aged 40 Years and Older
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