Critical Appraisal and Systematic Review of Studies on the Detection of Chronic Kidney Disease in Communities
Abstract
Background: Many studies have been developed and done in different countries around the world to detect the prevalence and incidence of chronic kidney disease and end-stage renal disease. Twelve studies were published to provide a basis for the estimation of the prevalence of chronic kidney disease in different communities by using different scientific methods, such as urinalysis and other techniques. These studies aim to increase awareness of the prevalence of the disease and to improve and develop appropriate treatment.
Methods: Twelve studies were evaluated namely the Third National Health and Nutrition Examination Survey (NHANES III), the Kidney Early Evaluation Program (KEEP), the Prevention of Renal and Vascular End-Stage Disease (PREVEND) in the Netherlands, the Iceland Study, the Bolivian study, the Zuni Kidney Project in Mexico, the Australian Diabetes, Obesity and Lifestyle Study (AusDiab Study), the Chinese study, the Screening for Hong Kong Asymptomatic Renal Population and Evaluation Program (SHARE), the Singaporean study, the Okinawa Screening Program, and the Chennai, India study. These studies were analyzed to examine and evaluate the prevalence and occurrence of CKD and ESRD in different communities around the world, and to assess the effectiveness and methodology of each study. Each study were analyzed by their study design, the socio-demographic parameters of the sample population studied, the representative sample population, and the CKD methods done in the study, such as the creatinine measurement methods, the methods used for estimation of the glomerular filtration rate, the methods used for albumin measurement, and dipstick measurements.
Results: The prevalence of chronic kidney disease and end-stage renal disease
In different populations produced different results in relation to their differences in considered parameters. In general, all of the studies were able to detect the prevalence of chronic kidney disease in different communities around the world. The studies arrived at the results by using different techniques or methods in detecting abnormalities in the urine of the sample population, and validating the results by using statistical tools. From the data gathered in all of the studies, it is suggested that diabetes, hypertension and kidney failure are the diseases related to the severity of chronic kidney disease and end-stage renal disease.
Conclusions: The twelve studies conducted in different communities have been successful in identifying individuals who are at high-risk of having the disease. These studies were also able to effectively use the available methods for analysis and evaluation to arrive at the possible result. They were able to provide awareness and information to the general public regarding the disease and somehow help to improve treatment of the persons inflicted by the disease.
Introduction
It has been reported that there has been a staggering rise in the number of people with chronic kidney disease (CKD), largely because of the ageing population and the growing global epidemic of type 2 diabetes (2006). Persons with CKD suffer a 10-100 times greater incidence of death from cardiovascular disease (CVD) compared to the general population, regardless of age, race or gender (2006). This incidence must be given attention for CKD is a progressive illness that has a silent, symptom-less onset and is characterized by declining renal function over years (2006). During the later stages of kidney disease, referred to as End Stage Renal Disease (ESRD), patients will require dialysis treatment of kidney transplantation (2006).
In the United States alone, there is a rising incidence and prevalence of kidney failure, as the number of patients enrolled in the ESRD Medicare-funded program has increased from approximately 10,000 beneficiaries in 1973 to 86,354 in 1983, and to 452,957 as of December 31, 2003 ( 2006). In addition, despite the magnitude of the resources committed to the treatment of ESRD and the substantial movements in the quality of dialysis therapy, these patients continue to experience significant mortality and morbidity, and a reduced quality of life ( 2006). It has been reported that in 2003, more than 82,000 ESRD patients died, and the survival probabilities for dialysis patients at 1, 2, 5 and 10 years are approximately 80, 67, 40 and 18 percent, respectively ( 2006). Moreover, 50% of dialysis patients have three or more comorbid conditions, the mean number of hospital days per year is approximately 14 per patient, and self-reported quality of life is far lower in dialysis patients than in the general population ( 2006). (2004) reports that, causes of CKD include diabetes mellitus, hypertension, ischemia, infection, obstruction, toxins, and autoimmune and infiltrative diseases (). The global increase in the incidence of obesity can also be attributed with the rise of CKD prevalence. In addition, the incidence and prevalence of the disease have doubled in the past decade, most likely because improved treatments for hypertension, diabetes mellitus, and coronary disease have increased longevity in affected patients and, therefore, their likelihood of developing CKD (2004).
Although the exact reasons for the growth of the ESRD program are unknown, it is postulated that changes in the demographics of the population, differences in disease burden among racial groups and under-recognition of earlier stages of CKD and of risk factors for CKD, may partially explain this growth ( 2006). Increasing evidence accumulated in the past decades indicates that earlier stages of CKD can be detected through laboratory testing and that therapeutic interventions implemented early in the course of CKD are effective in slowing or preventing the progression toward kidney failure and its associated complications ( 2006). In relation to the aim of communities to prevent further increase of the incidence of CKD and ESRD, many studies have been conducted to assess the existing conditions of many citizens around the world. The twelve studies from different countries serve as guides and evaluation of the prevalence and occurrence of CKD and ESRD in different communities.
Research Methodology (by the client)
Results
The NHANES III Study
The Third National Health and Nutrition Examination Survey was conducted between 1988 and 1994 in the United States ( 2003), which aims to provide a basis for estimating the prevalence and distribution of CKD (2003). The population of the study is 15,625 non-institutionalized adults, where non-Hispanic whites, African-Americans, and Mexican-Americans participated in the survey ( 2003). The study’s parameters include the age (20-39, 40-59, 90-69 or 70+ years old), gender (male or female), and race (non-Hispanic white, non-Hispanic black, Mexican American or other), diagnosed diabetes, and hypertension status, for the basis of the results and examination (2005). The populations having the age lower than 20 years old were not included. It has been reported that the blood pressure of the participants were measured, a random spot urine sample was obtained using a clean-catch technique and sterile containers, frozen non-hematuric specimens were analyzed (2005). In addition, urine albumin and creatinine concentrations were measured in the laboratory, where albumin was measured by solid-phase fluorescence immunoassay, and urine creatinine was measured by the modified kinetic method of Jaffe (2005). Serum creatinine was measured by the modified kinetic method of Jaffe using a Roche Hitachi 737 analyzer (2005). Furthermore, kidney function was assessed by estimating glomerular filtration rate with the simplified Modification of Diet in Renal Disease Study (MDRD) prediction equation (2005).
Each participant underwent a series of examinations of tests, having four categories, including a physical examination, dental examination, specimen collection (for hematological and urinalysis), and personal interview (2003). To detect CKD, the urine samples were analyzed by computing the urinary albumin-to-creatinine ratio (2005). The use of the MDRD equation indicates that the urine samples were obtained only once for this equation can be used to estimate the glomerular filtration rate (GFR). Similarly, the Cockcroft-Gault equation can also be used to estimate GFR, and not requiring 24-hour urine sample collection for creatinine clearance (2004). All prevalence estimates and percentiles of the distribution of GFR by age were computed using sampling weights provided by National Center for Health Statistics, and computed in accordance with recommended procedures for NHANES including the delete 1 jackknife method (2005). Analyses were performed using SUDAAN software for the analysis of complex survey data (2005). Population estimates of the percentage affected by CKD were computed separately for each of four stages of CKD, defined in accordance with the National Kidney Foundation classification system and summed (2005). Albuminuria persistence rates were calculated using bootstrapping methods implemented in Stata (2005). The statistical methods used were able to help validate the data gathered from the sampling population.
Results of the study show a high but relatively stable prevalence of CKD among US adults, and suggest that decrease in kidney function is related to age-related declines (2005). This is mainly because with the increase in age, the deterioration of the proper functioning of the organs happens. The organs cannot function properly anymore, and cause complications and diseases such as CKD and ESRD. In addition, the prevalence of decreased kidney function was higher in women than in men, and non-Hispanic whites are more likely to have decreased kidney function than non-Hispanic blacks and Mexican Americans (2005). As expected, the prevalence of CKD was higher in hypertension, diabetes and older age, and the prevalence of moderately, and severely decreased kidney function is similar among blacks and non-Hispanic whites (2005). Both hypertension and a history of diabetes were associated with a high prevalence of decreased kidney function and albuminuria (2005). In the absence of these conditions, decreased kidney function and albuminuria were uncommon in the population as a whole (2005). The overall prevalence of albuminuria increased and was observed across gender, age and race or ethnicity groups ( 2005). The prevalence of macroalbuminuria was higher in non-Hispanic blacks compared with non-Hispanic whites, and individuals with a history of diabetes had a much higher prevalence of albuminuria (2005).
Being an effective study giving out proper estimates regarding the prevalence of CKD, NHANES studies are being repeated to continuously examine and evaluate the conditions of US citizens. The latest NHANES study suggests that the awareness of CKD is low and a disparity exists such that women are far less appropriate to be aware of having decreased kidney function (GFR < 60 ml/min per 1.73m2) than men (Coresh et al 2005). In addition, although the burden of CKD is high, it has not increased substantially in nearly a decade ( 2005). Moreover, whites and blacks share approximately the same prevalence of CKD overall despite the fourfold greater incidence of ESRD in blacks group, due to the poorer care directed at attenuating or interdicting the progression of CKD (2005). The result of this study show a high but relatively stable prevalence of CKD among U.S. adults and highlights the importance of using GFR estimating equations that incorporate age and gender as variables ( 2005). In addition, the greater increase in the incidence of ESRD may reflect increasing treatment rates, and a higher rate of progression of CKD to ESRD, and/or lesser rates of competing mortality, presumably as a result of less premature cardiovascular death (2005). However, the study is limited in its ability to assess disease burden cross sectionally in a national representative sample and limited in addressing disease risk and cause (2005). Moreover, the number of participants having kidney malfunction limits the power of subgroup comparisons (2005). Despite these, the authors conclude that the NHANES study is appropriate for increased awareness, diagnosis, and treatment, and reduce new cases of CKD and its complications, disability, death, and economic costs (2005), basing from the concept of (2003) as to conducting surveys after a year or so to reduce cost.
The KEEP Study
The Kidney Early Evaluation Program (2000-2001) was done in the U.S. and was designed to increase awareness of kidney disease and to improve clinical outcomes, through early detection among high-risk groups (2003). This study is a targeted cohort-screening program, targeting persons most at risk of CKD, such as those individuals with a personal or family history of diabetes or hypertension, or those who belong to a minority race or ethnic group (2003). In addition, screening should be carried out as a part of primary health care delivery, or alternatively through community-based screenings or health fairs, to include those less likely to receive regular health care provision (2003). It has been reported that eligible participants were men or women, at least 18 years old, with diabetes or hypertension, or with a family history of diabetes, hypertension, or kidney disease (2003). Some affiliates concentrated recruitment efforts in geographic areas with greater numbers of individuals from minority populations (2003). Participants were predominantly African American (43%), or Caucasian (36%); 68% were women (2003). Men participant age was 52 years and 24% of participants were 65 years or older (2003). Screening data were collected on participant socio-demographic characteristics, such as gender, age, and race or ethnicity, and medical history; medication history data were not obtained (2003). In addition, systolic and diastolic blood pressures were measured; blood and urine specimens were collected (2003). Blood specimens were processed for determination of glucose, creatinine, and hemoglobin, urine specimens were tested for albuminuria, hematuria, and pyuria, using dipstick analyses, and microalbuminuria will be measured directly in spot urine samples (2003). Estimated GFR, and indicator of kidney function, was calculated based on published formulas that used measured serum creatinine (2003). All screening results were made known to participants, and abnormal results were not considered diagnostic, but rather as indicative of increased risk (2003). Participants with abnormal results were advised to contact their health care providers for follow-up evaluation (2003).
Results suggest that 29% of participants tested positive for microalbuminuria and 16% had calculated estimated GFR values (< 60 ml/min per 1.73m2) that indicated a moderate reduction in kidney function (2003). Five percent had elevated serum creatinine values (> 1.5 mg/dl in men, > 1.3 mg/dl in women) (2003). Only 3% of participants reported history of kidney disease at screening; 1712 participants with microalbuminuria, 839 participants with reduced eGFR, and 277 participants with elevated serum creatinine were identified as a result of screening (2003). Only 31% of participants with reduced eGFR and 27% of those with elevated serum creatinine were controlled to comorbidity specific blood pressure levels (2003). From the results of the study, it can be observed that most of the participants suffer from albuminuria, which is one indication of kidney malfunction. From this, it can be deduced that these individuals are more susceptible of having CKD and ESRD. The study mentioned of measuring the eGFR from the serum creatinine levels of the participants by using published formulas. From this statement, it can be deduced that the study may have used the MDRD study equation or the more precise Cockcroft-Gault equation, and the predictions can be made taking into account the patient’s age, race and body size (2004). No statistical method was used so the samples were taken several times for examination to arrive at the results of the study. Since urine samples were examined, the study should have used ROC curves to estimate ratio of albumin and creatinine present in the urine.
With this, the KEEP screening program identified significant numbers of persons with reduced kidney function, with previously undetected kidney disease risk factors, and with inadequate risk-factor control (2003). Regular screening for evidence in kidney disease and for conditions that contribute to kidney disease is critical so that appropriate interventions can be implemented (2003). However, preventing and managing kidney disease requires joint efforts on the part of health care providers and consumers (2003). Consumers need to embrace lifestyle behaviors that reduce their risk of disease including weight control, regular exercise, and adherence to medical recommendations regarding management of existing conditions (2003). In addition, to effectively promote healthy behaviors, health concepts and self-care management strategies must be delivered to the lay public in an understandable, accessible, and cost-effective manner (2003).
The PREVEND Study
It has been reported that in patients with type 1 and 2 diabetes mellitus, and the presence of urinary albumin excretion (UAE) > 30 mg/24 hour is highly predictive for later occurrence of cardiovascular disease (2005). The risk for cardiovascular events entailed by albuminuria seems at least partly independent from serum cholesterol and blood pressure, and these results indicate that in the general population, mass screening for the presence of abnormal urinary albumin excretion may be a useful strategy to identify people at high risk for cardiovascular events who may benefit from preventive strategies (2005). The Prevention of Renal and Vascular End-stage Disease study (1997-1998) is designed to prospectively investigate the natural course of increased levels of urinary albumin excretion and its relation to renal and cardiovascular disease in a large cohort drawn from the general population (2005). The population includes all inhabitants of the city of Groningen in the Netherlands, aged 28 to 75 years old, from which an early morning urine sample was collected, where urinary albumin (UAC) and creatinine concentration were measured (2005). This strategy aims to lessen costs and impracticality in mass screening and obtaining a 24-hour urine collection (2005). Subsequently, only those people with urinary albumin concentration (UAC) or albumin-creatinine ratio (ACR) above certain predefined value would be invited to collect a 24-hour urine (2005). The study includes the age, weight, gender and other socio-demographic parameters, and excludes subjects with type 1 diabetes mellitus and pregnant women, also when leukocythuria or erythrocythuria was present because this makes albumin measurement unreliable (2005). In addition, subjects with proteinuria and renal disease were excluded, thus, a study population of 2527 subjects was created that is a representative sample of the general population (2005). Aside from the Netherlands, the survey in Italy was also included.
The screening program consisted of two visits, where blood pressure, weight, and height were measured, blood was drawn in fasting condition, and subjects were asked to collect 24-hour urine on two consecutive days (2005). Oral and written instructions on how to collect 24-hour urine were given, and subjects were instructed to postpone urine collection in case of urinary tract infection or menstruation, and to refrain as far as possible from heavy exercise during the collection period (2005). In addition, urinary albumin excretion was determined by nephelometry, and was calculated as the average urinary albumin excretion in the two consecutive 24-hour urine collections (2005). Creatinine assessment in urine was determined by using an automatic enzymatic method called Kodak Ektachem dry chemistry in the USA, while urinary leukocyte and erythrocyte measurements were performed by Nephur-test and leuko-sticks in Boehringer, Germany (2005). For its statistical tools, the sensitivity and specificity were calculated to determine the diagnostic properties of ACR and UAC, which were measured in the spot morning urine collection, in predicting a UAE > 30 mg/24 hour (measured in 24-hour urine collections) (2005). In addition, determination of the confidence intervals for sensitivity and specificity was performed using the guidelines of Gardner and Altman, and ROC curves were calculated to compare the discriminative power of ACR and UAC (2005). The ROC curve analysis was also used to determine discriminator values for ACR and UAC (2005). Moreover, multiple regression analysis was performed with 24-hour urinary creatinine excretion as dependent variable, to test whether, and if so, which of these variables had a statistically significant impact on 24-hour urinary creatinine excretion in the study (2005). The independent variables tested were gender, age, weight, and race, and subsequently, it was analyzed whether these anthropometric variables influence the discriminator values of ACR and UAC (2005). Another statistical method used was the student t-test (or Welch t test in case standard deviations were statistically significantly different) was used to test differences of sensitivity or specificity of ACR versus UAC in predicting UAE > 30 mg/24 hour (2005). Calculations were performed using the statistical package SPSS, version 11.5, for Windows (2005).
Results of the study suggest that the prevalence of a UAE > 30 mg/24-hour was 6.1% and sensitivity for UAC in predicting UAE > 30 mg/24-hour does not differ significantly from the sensitivity for ACR, whereas the difference between the specificities of UAC and ACR is numerically small, but does reach statistical significance (2005). In addition, multiple regression analysis revealed that, in order of significance, gender, age, weight, and race were statistically significantly associated with urinary creatinine excretion (2005). Moreover, because diabetic subjects have a higher prevalence of elevated urinary albumin excretion, the study also calculated the diagnostic performance of UAC and ACR for diabetic and non-diabetic subjects separately, as sensitivity and specificity does not increase relevantly compared to the results in the overall study population (2005). With this data, the study reports that in the general population UAC and urinary ACR measured in a spot morning urine sample have satisfying and numerically similar power to predict which individuals will have a 24-hour UAE > 30 mg/24-hour in subsequent 24-hour urine collections (2005). In addition, the data suggest that applying traditionally used cut-off values for UAC and ACR results in low sensitivity and thus, in a relatively large percentage of false-negative test results for predicting microalbuminuria (2005). In relation to this, when urine is more concentrated, the concentration of albumin is higher and vice versa, therefore, a loss of specificity and sensitivity might be expected (2005). For this reason, the urinary albumin concentration can be divided by the urinary creatinine concentration (ACR ratio), thus correcting for variations in urinary volume (2005). The only disadvantage of the use of ACR is that additional measurement of urinary creatinine is needed at the expense of extra costs and additional variability, the amount depending on the creatinine measurement, per se, and on inter-individual differences in urinary creatinine excretion (2005). In turn, the authors conclude that in order to keep costs and the burden involved in mass screening for microalbuminuria as low as possible, it is proposed that prescreening should be done by measuring in a spot morning urine sample only urinary albumin concentration (2005). Those subjects with a urinary albumin concentration above a certain predefined level should be asked to collect 24-hour urines (2005). This screening program will not only help prevention of the epidemic of ESRD but at the same time, also lower cardiovascular morbidity and mortality (2005).
The Iceland Study
Another study done in Europe is the Iceland Study, which is a population-based screening program aiming to estimate the prevalence of CKD in the general population. In addition, it also aims to examine lower prevalence of ESRD in Europe than in the United States, and whether this difference results from a lower prevalence or slower progression of chronic renal failure (CRF) in a European cohort (2002). The study includes a population of 18,912 subjects, with 9,773 women and 9,139 men, aged 33 to 81 years old and participated in the Reykjavik Study between 1967 and 1991 (2002). Urine samples were collected from the participants for serum creatinine measurements. It has been reported that subjects with serum creatinine (SCr) levels of 1.7 mg/dL (150 micromol/L) or greater were considered to have CRF, and its progression was defined as a decrease in estimated glomerular filtration rate greater than 1ml/min/1.73m2/y (2002). In addition, to estimate the glomerular filtration rate, the modified MDRD equation was used, while to examine creatinine clearance, the Cockcroft-Gault equation was used, and proteinuria were used to estimate the prevalence of CKD (Viktorsdottir et al 2005). Furthermore, the study used X-square and ANCOVA to compare the group with low estimated glomerular filtration rate to age-matched controls ( 2005).
Results of the study suggest that of 49 individual who had an SCr of 1.7 mg/dL (150 micromol/L) or greater at entry, 41 individuals (26 men, 15 women) had a persistent elevation in SCr levels (2002). Thirty-four individuals had mild CRF (SCr 1.7 to 2.5 mg/dL), 6 individual had moderate CRF (SCr 2.8 to 5.6 mg/dL), and 1 individual had ESRD (2002). Moreover, the crude prevalence of CRF was 0.22%, 0.15% among women and 0.28% among men, while the age-standardized prevalence was 0.23% for women and 0.42% for men (2002). Eighty-five percent of patients with CRF were 50 years or older, and 27 subjects had progressive renal failure, 17 of whom progressed to ESRD during a median of 7 years (2002). In addition, the proportion of subjects with estimated glomerular filtration rate < 60 ml/min/1.73m2 increased with advancing age, and an additional 2.39% men and 0.89% of women had proteinuria (2005). In conclusion, the prevalence of renal and cardiovascular risk factors including proteinuria, hypertension, lipid abnormalities and markers of inflammation was higher among those with low eGFR than age-matched controls (Viktorsdottir et al 2005). Furthermore, the prevalence of CRF is markedly lower in Iceland than in the United States, for 27% of the subjects did not show progression of their renal failure, and may explain in part the difference in ESRD prevalence between European countries and the United States (2002).
The Bolivia Study
It has been reported that much less is known about the prevalence and incidence of ESRD in middle-income and low-income countries, where the use of renal replacement therapy (RRT) is scarce or nonexistent (2005). Due to the long-term treatment, patients drop out of therapy in realizing that dialysis is not a cure, causing impoverishment of their families (2005). The Project for Renal Diseases in Bolivia was established and directed at education and prevention in the field of renal diseases, bearing in mind that Bolivia is a developing country, and that RRT, like dialysis and transplantation is only available for patients who earn over US 00 monthly, unlike most people who earns a monthly salary of less than US (2005). The study includes 14,082 healthy people with the mean age of 20.2 years (2005). A total of 6759 (48%) men and 7323 (52%) women participated in the study, and aims to demonstrate that polycythemia can be a risk factor for the development of proteinuria, and that pharmacologic intervention may help control high-packed cell volume and reduce urinary protein excretion, which eventually could translate to the prevention of renal disease progression (2005). Screening programs can be implemented with simple, cheap, and reliable tests, such as measurement of body weight, blood pressure, blood glucose, and dipstick urinalysis for protein (2005). Participants were instructed to void a clean urine specimen into a 200-ml vessel, where a dipstick test was performed on the unspun urine specimen by trained laboratory technicians (2005). The dipstick test is used frequently because it is rapid, inexpensive, and requires little technical expertise (‘Screening for Asymptomatic Bacteriuria’ 1996). The reagent strip is designed to react progressively, producing color changes, after given intervals of time (2005). The results were decided by careful visual comparison of the test strip with a color chart provided on the bottle label (2005). The urine was then prepared for microscopic analysis by centrifuging well-mixed samples and examining a drop of the resuspended sediment by subdued bright-field illumination under a light microscope (2005). Patients with positive urinalysis were enrolled in a follow-up program with subsequent laboratory and clinical checks, and complete urinalysis, biochemistry, and microbiology assays were performed during the follow-up (2005). Although the mass screening of this study is effective in collecting specimens, the difficulty emerged as for the rural population, traditional medicine is still widespread, so patients are not anymore concerned about following up with the researchers (2005). This is in line with the approach of the medicine man who visits the patients only once for diagnosis and treatment prescription (2005).
Results suggest that 48.4% of the participants have urinary tract infection, 43.9% have isolated hematuria, 1.6% have chronic renal failure, 1.6% have renal tuberculosis, and 4.3% have other diagnoses, such as kidney stones (1.3%), diabetic nephropathy (1%), and polycystic kidney diseases (1.9%) (2005). The population includes patients of mixed Indian and European (mostly Spanish) ethnic origin, and born at altitudes of 3200 to 4000 meters (2005). Correlation with age and systolic and diastolic blood pressure levels were of borderline significance (2005). To validate the results, linear regression analysis was also performed, and found a positive and highly significant correlation between changes in packed cell volume and proteinuria at 6, 12, 18 and 24 months as compared with baseline (2005). In summary, this study can be taken as an example of how, by rationalizing resources and investing in research programs, renal disease progression and cardiovascular risk may eventually improve, which ultimately should translate into better quality of life for patients (2005). In addition, by reducing the need for dialysis and providing alternatives to costly RRT, an overall benefit would accrue to the national health system (2005).
The Zuni Kidney Project
The study done in Mexico aims to offer a unique opportunity to advance our understanding of the risk factors for the susceptibility and/or progression of renal disease (2003). The sample population is 10,228 adults from the general population, not specifying the ratio of men to women participants. The number of the population is too big for just one tribe only, but if these data were sufficient to produce most accurate and valid data, then it would be enough. Inclusion parameters include the age, gender, etiology of renal disease, tribe, education, and the prevalence of the co-existing conditions of the participants. Diabetes, hypertension, and CKD were evaluated using urine and blood tests, chemistry profile, serum creatinine, complete blood cell count, HbA1c, urine albumin and urine creatinine measurements (2003). These tests are sufficient for examination, because all aspects affecting the disease were evaluated, but only lack the use of statistical tools to completely evaluate the study. The results suggest that patients with diabetes are more susceptible to CKD, which leads to facilitating the development and implementation of primary and secondary prevention strategies (2003). The study concludes that case-control study such as this one, will allow the identification of vocational and environmental risk factors, suggesting the implementation of changes in the work place and home environments to reduce the risk of kidney disease (2003). This study was able to properly assess the prevalence of CKD in one tribe in Mexico, but must still conduct further studies regarding other tribes for a more effective prevention and treatment of the disease.
The AusDiab Study
The Australian Diabetes, Obesity and Lifestyle Study was a national population-based cross-sectional survey undertaken to determine the prevalence of diabetes mellitus, obesity and other cardiovascular disease risk factors in Australian adults (2003). Subjects of the study were predominantly Caucasian (92.9%), with a minority of Asian (5.7%), and Aboriginal and Torres Strait Islanders (0.8%), amounting to a total population of 11,247 (2003). Socio-demographic parameters include the age (25 to 44, 55 to 64, and 65 years old and older), gender, race, and risk factors for renal disease, such as diabetes mellitus and hypertension (2003). All subjects attended a local screening venue and completed a series of questionnaires, physical examinations, and specific laboratory tests examining diabetic status, cardiovascular risk factors, and kidney function (2003). Blood specimens collected were centrifuged on-site and transported daily with urine samples to the central laboratory (2003). In examining the incidence of proteinuria, urine protein and creatinine were measured on a morning spot urine sample, wherein urine protein was measured using pyrogallol red-molybdate by the Olympus AU600 auto-analyzer, and urine creatinine was measured by the modified kinetic Jaffe reaction using the Olympus AU600 auto-analyzer (2003). Hematuria was examined by dipstick testing of morning spot urine samples, and was transported to a central laboratory and examined by repeat dipstick and urine microscopy (2003). To examine the estimated GFR of the patient, blood was collected by venipuncture after an overnight fast, and serum creatinine was measured by the modified kinetic Jaffe reaction using the Olympus AU600 auto-analyzer (2003). In addition, the Cockcroft-Gault method was also used to estimate creatinine clearance, for renal impairment was defined as estimated GFR less than 60 ml/min per 1.73m2 (2003). The diabetes status of the patients were measured by collection of blood specimen after an overnight fast of at least 10-hours, and plasma glucose levels were measured enzymatically with a glucose oxidase method using the Olympus AU600 auto-analyzer (2003). Likewise, the hypertension status of patients were also analyzed by measuring the blood pressure levels repeatedly (2003). It has been reported that all analyses were conducted using Stata version 6.0 survey commands for analyzing complex survey data, and the prevalence rates of hematuria, proteinuria, and reduced GFR were calculated stratified by age, gender, and risk factors for renal disease, such as diabetes mellitus and hypertension (2003). Differences between subjects were tested by 2-tailed unpaired t test for continuous data and x2 test for categorical data (2003). The associations between age, gender, hypertension, and diabetes status, and indicators of kidney disease were determined by computing odds ratios and their respective 95% confidence intervals by logistic regression (2003).
Results of the AusDiab study suggest that with proteinuria, levels of urine protein to creatinine ratio of 0.2 mg/mg or greater were detected in 2.4% of participants (2003). Though similar in men and women, the increase in age leads to the increase in creatinine ratio, from 0.8% in the 25 to 44 years old to 6.6% in those 65 years old and over ( 2003). Hematuria was detected on initial dipstick testing in 5.2% and 4.6% of the participants by microscopy or repeat dipstick testing on a midstream sample of urine, and was more common in women than in men (2003). The increased risk of hematuria in women than in men was evident in the younger age groups, given the likelihood that urinary tract infection or menstrual contamination contributed to the higher prevalence, and leads to the exclusion of cases of isolated hematuria in women under the age of 50 and hematuria (2003). In renal impairment, an estimated GFR < 60 ml/min per 1.73 m2 was present in 11.2% of participants, including over half of those aged 65 years or older (2003). Old age, female gender, diabetes mellitus, and hypertension status were all predictive of renal impairment on univariate analysis, however, old age, gender, and hypertension status remained independently predictive on multivariate analysis (2003). In diabetes mellitus, the prevalence of proteinuria was fourfold higher compared with those without, while in hypertension, the prevalence of proteinuria was fivefold greater compared with those with normal blood pressure (2003). This study demonstrates that approximately 16% of Australian adults have one or more indicators of kidney damage and increased long-term risk of ESRD (2003).
The Chinese Study
The International Collaborative Study of Cardiovascular Disease in ASIA was a cross-sectional study of cardiovascular disease risk factors in a nationally representative sample of the general adult population in China (2005). This study is a four-stage stratified sampling method, which aims to estimate the prevalence and severity of CKD in the general adult population in China using serum creatinine-based equations to estimate level of kidney function (2005). The total of the population is 19,012 aged 35 to 74 years old, and distribution of CKD was examined by age, gender, and geographic region, as well as in rural versus urban areas ( 2005). Data were collected in examination centers, and during the visits, trained research staff administered a standard questionnaire to obtain information on demographic characteristics, including age, sex, education, occupation, and annual household income (2005). In addition, blood pressure and anthropometric measurements were also collected by trained and certified physicians or nurses using standard protocols and techniques, where blood pressure was measured three times with the participant in the seated position after five minutes of rest (2005). Body weight and height were measured twice during the examination in light indoor clothing without shoes (2005). Overnight fasting blood specimens were collected for measurement of serum creatinine, lipids and glucose, and serum creatinine was measured by the modified kinetic Jaffe reaction on a Hitachi 7060 Clinical Analyzer, using commercial reagents and reported using conventional units (2005). Moreover, a random sample of 60 serum specimens was sent to the Cleveland Clinic Laboratory for measurement of serum creatinine, where the Modification of Diet in Renal Disease Study measured serum creatinine levels (2005). In estimation of the glomerular filtration rate, the simplified equation developed using MDRD data was used, and for estimating the creatinine clearance (CCr) from the serum creatinine level, the Cockcroft-Gault formula was used (2005).
Results of the study indicate that the prevalence of persons with an estimate GFR < 60ml/min/1.73m2 is approximately 2.53%, which represents approximately 12 million persons with CKD in China (2005). In addition, the prevalence of CKD was higher with increased age in both men and women, and the age-standardized prevalence of CKD was higher in persons with diabetes or hypertension compared to those without, which were consistent among all age groups (2005). Moreover, older age was associated with greater prevalence of mildly, moderately, and severely decreased kidney function (2005). Although the prevalence of CKD in the Chinese population is lower than the US population due to the smaller range of ages, the burden of CKD is still high in the Chinese population because patients with proteinuria and normal or mildly decreased GFR were not included in the study’s prevalence estimates (2005). Therefore, the results of this study underscore the need to establish a national program for the detection, prevention, and treatment of CKD aimed at reducing morbidity and mortality from ESRD, cardiovascular disease, and premature death in China (2005).
The Hong Kong Study
End-stage renal disease (ESRD) is epidemic worldwide (2005). In Hong Kong, the annual incidence of ESRD has risen from 100 per million population, in 1996 to 140 per million population in 2003 (2005). The SHARE study or the Screening for Hong Kong Asymptomatic Renal Population and Evaluation Program is a population-based screening program aimed at identifying the prevalence of unrecognized renal disease in asymptomatic individuals, allowing further evaluation and disease-modifying interventions (2005). It has been reported that from November to December 2003, SHARE was conducted in several large residential communities in Hong Kong (2005). The screening tool included a questionnaire documenting demographics and history or family history of diabetes mellitus, hypertension, and chronic kidney disease, together with onsite measurements of blood pressure and urine dipstick for protein, blood, and glucose (2005).
Results of the study suggest that with the total of 1,811 participants, 1,201 subjects were entered into the final analysis (2005). Among the 1,201 who were apparently “healthy” or asymptomatic and without history of diabetes mellitus, hypertension, and chronic kidney disease, the prevalence of positive urine dipstick for protein was 3.2%, for glucose was 1.7%, for blood was 13.8%, for protein or blood was 16%, for any urine abnormality was 17.4%, and for hypertension was 8.7% respectively (2005). Thirty three percent of the age over 60 years old group had either hypertension or urine abnormalities, compared with 24.0% in the 41 to 60 year old group and 9.7% in the 20 to 40 years old group ( 2005). Having a family history of diabetes or hypertension increases the risk of having urine abnormalities, while a family history of hypertension also increases the risk of high blood pressure (2005). The study concludes that sub-clinical abnormalities in urinalysis or blood pressure readings are prevalent across all age groups in the adult population (2005). An effective screening program at the primary care level that identifies these subjects for further evaluation is warranted, and the public in Hong Kong should be educated toward the significance of such findings in order to have regular health check for asymptomatic renal diseases (2005).
The Singapore Study
It has been reported that the rising annual incidence of ESRD in many countries of the world, its profound effect on morbidity and mortality, and the escalating health care costs associated with it have promoted the development of strategies aimed at preventing the development and progression of CKD (2005). Proteinuria is a well recognized predictor of ESRD and all-cause mortality rates, as well as cardiovascular mortality rates (2002). Furthermore, Malay race, increasing age, both extremes of body mass index, self-reported family history of kidney disease, and higher systolic and diastolic blood pressure measurements were independently associated with dipstick-positive proteinuria (2002). Recent studies suggest that low grades of proteinuria or microalbuminuria might be associated with early renal disease even in the non-diabetic population (2002). Indeed, there has been increasing interest in the determination of risk factors for the development of proteinuria, because such studies might facilitate focused preventive and therapeutic efforts to delay the progression to significant renal damage (2002). The Singapore study is now aimed to identify the determinants of proteinuria for Chinese (2.1%), Malays (6.6%), and Asian Indians (1.7%) in Singapore, a country reported by the United States Renal Data System as having the third highest ESRD incidence rate in the world (2002). This study is part of the ongoing Prevention Program of the National Kidney Foundation Singapore (NKFS), the largest charitable organization in the country, which provides subsidized dialysis care to more than 60% of the total ESRD population in the country ( 2002). The Prevention Program, which was initiated in 1997, aims to reduce the incidence of ESRD in Singapore via a comprehensive strategy of screening, early intervention, research, and improved care of individuals at risk for the development of renal disease (2002). With this, the Singapore study is based on a nationwide screening program that seeks to identify adults who are at risk for renal disease and hypertension (2002).
Screenings for urinary abnormalities and hypertension are major components of the program, and targets four discrete population, as follows: the working population (screening is performed at work sites), the general adult population (screening is performed at housing estates, at community centers, and through the use of mobile screening buses), the pediatric population (screening is performed at school sites), and the taxi driver population (an occupational cohort for which screening is performed at taxi repair offices) (2002). This study includes only data for the working population, for which screening was performed at work sites, and individuals who underwent screening through the community-based school-based, and taxi driver-focused programs were excluded from these analyses because subjects from the community-based and taxi driver-focused programs were still being enrolled at the time of manuscript preparation (2002). In addition, screening was conducted during an 8-hour period each day, and 16 teams composed of four staff nurses and three coordinators, all of whom were employees of the NKFS, performed health screening (2002). Work site screening was performed on every working day of the year (2002). A total of 213,873 subjects participated in the work site screening program during the period of January 1999 to December 2000, and this period was selected because data on race were collected beginning in the year 1999 (2002). Of the total number of subjects who participated in the screening program, 19,542 women (9.1%) were excluded because they were undergoing menstruation ate the time of the screening, and 5,214 (2.4%) were excluded because of missing data (2002).
Moreover, each subject completed a self-administered questionnaire regarding demographic information, medical history of renal disease, diabetes mellitus, or hypertension, and the NKFS coordinator ensured completeness of the questionnaire responses ( 2002). Each subject underwent weight and height measurements, using a calibrated scale and the body mass index or BMI was calculated as weight divided by height squared (2002). The subject was then asked to collect a clean-catch, midstream, random urine specimen, which was subjected to dipstick analysis of protein, blood, and glucose according to the instructions provided by the dipstick manufacturer (2002). After the subject rested for 5 minutes, blood pressure was measured twice with an automated sphygmomanometer and an average of the two readings was calculated ( 2002). A third measurement was performed using a mercury sphygmomanometer (2002). All survey forms and health screening results were entered into a database by a data management company, using a double-entry system, and for its evaluation of the consistency of the data entry process, correlational analyses were performed (2002). In addition, data analyses and calculations were performed by using the SPSS statistical package, version 10.1 (2002). The crude or unadjusted relationships between the exposure variables and the presence or absence of proteinuria were examined in univariate logistic regression analyses, while multivariate logistic regression analysis was then performed to evaluate the simultaneous effects of the various exposure variables, with adjustments for the potential confounding effects of other factors (2002).
Results of the Singapore study suggest that increasing age, both extremes of BMI, and higher systolic and diastolic blood pressure measurements are associated with the presence of proteinuria ( 2002). Gender was not observed to be significantly associated with proteinuria in this Asian population (2002). In addition, the Malay race was significantly associated with proteinuria, compared with the Chinese race (2002). Age is a recognized risk factor for renal disease, and is attributed partly to glomerular obsolescence and decreased renal vascular flow (2002). These findings persisted even after adjustment for the confounding effects of other variables, as well as preexisting diabetes mellitus, hypertension or renal disease (2002). This study is significant because the determination of factors associated with proteinuria in this population could guide the design of a more focused screening strategy, by identifying individuals at higher risk for abnormalities ( 2002). Such a targeted prevention strategy could potentially result in the reduction of ESRD in the population, at highest risk for its development (2002).
The Okinawa Study
The Okinawa study is a community-based screening program aimed for CKD screening and early detection for prevention of ESRD, cardiovascular disease and premature death (2003). It has been reported that since 1971, all chronic dialysis patients treated in Okinawa from the start of therapy have been entered into a registry, and the ESRD trends over the past 30 years have recently been published (2003). With this, for geographic and cultural reasons, ESRC patients in Okinawa tend not to move away, thus providing a good population in which to study the outcomes of ESRD and cardiovascular disease, and understanding the process of disease progression for ESRD prevention (2003). The total population of the screening program participants was 107,192, approximately 13.7% of the population of all individuals over 18 years of age in Okinawa (2003). In men, the estimated proportion of the general population in each age group who participated was as follows: 7.2% in those aged 18 to 29 years, 13.3% in those aged 30 to 39 years, 15.4% in those aged 40 to 49 years, 16.8% in those aged 50 to 59 years, 22.1% in those aged 60 to 69 years, 22.2% in those aged 70 to 70 years, and 14.2% in those aged 80 years and older (2003). In women, it was 5.7% in those aged 18 to 29 years, 10.4% in those aged 30 to 39 years, 15.1% in those aged 40 to 49 years, 20.3% in those aged 50 to 59 years, 25.55 in those aged 60 to 69 years, 23.8% in those aged 70 to 79 years, and 11.6% in those aged 80 years and older ( 2003). In addition, the age, occupation, lifestyle, and residence of the participants, and detection of hypertension, diabetes, proteinuria, hematuira and cardiovascular diseases were also included as parameters.
The Okinawa General Health Maintenance Association (OGHMA) is a non-profit organization founded in 1972 (2003). The OGHMA screening program is a large, community-based health examination, which is conducted annually, and once each year, the doctors, nurses, and staff of the association visit sites throughout Okinawa where people reside or are employed (2003). They provide medical examinations, inform the participants of the results, and when necessary, recommend further examination (2003). The screening includes an interview regarding general health status, a physical examination, a urine test, and blood tests (2003). It has been reported that a nurse of a doctor measures blood pressure using a standard mercury sphygmomanometer, and dipstick urinalysis is performed in spontaneously voided fresh urine (2003). Moreover, participants responded to a questionnaire pertaining to lifestyle issues including smoking, alcohol consumption, and exercise habits, and also provided information regarding medical history and current medications (2003). Body mass index or BMI was calculated as body weight in kilograms divided by height squared in meters, while hypertension and diabetes mellitus was also diagnosed (2003). All subjects fasted overnight before blood sampling, and questionnaire responses were discussed during the physical examination, and a physician further interviews the subject (2003). Participants who were already on chronic dialysis were excluded from the study (2003). For the statistical analysis, the cumulative incidence of ESRD was calculated as the ratio of the number of dialysis patients to the number of participants at risk of ESRD (2003). All relative risks of ESRD were adjusted for age, blood pressure, proteinuria and hematuria, using the SAS model (2003).
Results of the study suggest that the incidence of hematuria increased linearly with age in men from 0.9% at age 18 to 29 years to 8.2% at 80 years and older (2003). This trend was also observed in women; the incidence of hematuria increased with age from 7.3% at 18 to 29 years to 15.3% at age 80 years and older (2003). Similarly, the incidence of proteinuria increased linearly with age in men, from 4% at 18 to 29 years to 6% at 80 years and older, and women, from 3% incidence at 18 to 29 years to 7% at 80 years and older (2003). The incidence of proteinuria and hematuria combined was less that 2% in all age groups for both genders (2003). The prevalence of hypertension was 35.8%, while the prevalence of elevated serum creatinine for both genders remained around 0.2% from 1983 to 1993, despite the large changes in the sample number (2003). The incidence of obesity was 11.3% in men and 17.1% in women (2003). Early detection of renal dysfunction and identification of risk factors for ESRD may encourage otherwise healthy individuals to modify their lifestyle and improve treatment follow-through, therefore, the increasing risk of the population from ESRD, leads to more public education regarding its risks in Okinawa’s need to reduce the number of ESRD patients (2003).
The Chennai Study
The study conducted in Chennai, India is a population-based screening program, which aims to prevent and treat CKD with the use of the cheapest available drugs for the country cannot afford renal replacement therapy (RRT) for the treatment of ESRD (2005). The sample population of the study is 21,496, having the sex ratio of 0.97 and the mean family size of 4.1 (2005). The participants were randomly chosen from the community, with inclusion parameters of age, gender, lifestyle, economic status, and education. In addition, the literacy rate of the participants was 35% overall, 42% in males and 30% in females, and 43% of the population was economically dependent on the rest (2005). It has been reported that approximately 50% of chronic renal failure in India is due to diabetic nephropathy, hypertensive nephropathy, or chronic pyelonephritis, and can be prevented from going into the end stage by good control of diabetes and hypertension from the outset, and by finding the cause of urinary infection early and tackling it effectively (2005). With this crisis, the Kidney Help Trust took up the task of preventing chronic renal failure at the community level with a comprehensive yet cheap screening program, and treatment with low-cost medicines, such as hydrochlorothiazide, reserpine, and hydralazine for hypertension, and glibenclamide and metformin for diabetes (2005). The initial survey places a greater workload on the Preventive and Social Health Workers, and seeks to minimize the program by using girls who had finished their higher secondary school education, and who were awaiting entrance to the university (2005). The survey was conducted during their summer vacation, and the girls were given three days of intensive training, and adding a procedure of random checking of their findings to make sure there were no errors (2005). The girls were from the villages that are trained and work from their homes, and visit the patients in their own homes (2005). A simple questionnaire is distributed, urine is examined for protein by sulphosalicylic acid, and for glucose by Benedict’s reagent, and blood pressure is recorded in all people over the age of five (2005). The sulphosalicylic acid test for protein and the Benedict’s reagent test for glucose serve as preliminary tests, and anyone who test positive were examined by doctors, to estimate glucose, urea, creatinine and albumin (2005).
It has been reported that details of the demographic data have not been worked out for this population as yet, but it is expected to be similar to the original population (2005). Glomerular filtration rate (GFR) has been calculated by the MDRD formula using age, sex, urea, creatinine, and albumin, and the results for the two groups have been compared (2005). In addition, the study examined the number of people with GFR below 80ml/min in the two groups, and compared them with a chi-square test using Epi info release 6 (2005). Results of the study suggest that GFR was found to be below 80ml/min in the old area in 8.6 per 1000 population, and in the new area in 13.9 per 1000 population, and suggest that the study may have prevented or delayed the onset of renal failure in 5.3 subjects per 1000 population (2005). Moreover, the model of prevention of chronic renal failure is well worth emulating in other parts of the country, and of the world (2005). There may be other benefits, which the program have not specifically looked for, in prevention of cerebral, coronary, and peripheral arterial disease, since control of hypertension has been excellent, and control of diabetes is fairly good (2005). From this, it can be deduced that the Chennai study provides an effective method for prevention of chronic renal failure at the community level (2005), but must continue to do surveys, detect all diseases, and allocate treatment and cheap medicines to the entire population to prevent CKD. Due to this problem, the government of India can also seek help from different world organizations to fund them in the prevention of CKD and other diseases, and help them provide treatment such as renal replacement therapy or RRT.
Conclusion
All the twelve studies were able to address the issue and the problem regarding the prevalence of CKD. Based on the results of the studies, factors such as age, gender, and the existence of diabetes, proteinuria, hematuria, renal failure and hypertension were the leading causes of CKD. From the findings of the studies, the detection of the prevalence of CKD and other kidney-related diseases in the communities will be easier, to administer the best prevention and cure. All the studies were effective in estimating the occurrence and prevalence of kidney-related diseases in different communities, whether low-income or developing countries and all studies have concrete plans on how to solve this problem. These studies were able to give awareness to the citizens all over the world to improve their lifestyles, especially in relation to their age and existing diseases.
In my opinion, the most reliable study is the Bolivian study. This study was able to administer the detection of proteinuria and other kidney-related diseases by using cost-effective processes. This study will be very useful to other low-income countries as well, so that prevention will be properly implemented and decrease CKD incidence. In addition, this study produced reliable data, in relation to its population.
The least reliable study is the Chennai study. Although the processes used were simple and cost-effective, they could be good sources of error and confusion of data, most especially in dealing with large numbers of participants. With the lack of manpower and resources, it would be hard for the researchers to examine the entire population. The reliability and effectiveness of a community study do not only depend on the sophisticated processes used, but on the sample size of the population and their participation as well.
To make the data of prevalence and incidence of CKD more accurate, more studies must be done in other countries to examine and evaluate the conditions of other citizens around the world. Aside from these countries, other low-income countries and middle-income countries must also fund projects and researches to detect the prevalence of CKD and ESRD. This will not only be helpful to the diagnosis of the disease but also in increasing the awareness of many people regarding its increasing incidence. This also would help many hospitals in its improvement in facilities in aiming for data accuracy and validity. The conduction of studies in different countries should also give information and education to many citizens regarding chronic kidney disease and end-stage renal disease, including the diseases associated with them.
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