chronic kidney disease ( ckd ) is a major global health burden due to its high prevalence and associated risk of end - stage renal disease ( esrd ) , cardiovascular disease ( cvd ) , and premature death ( 13 ) .
the global burden of disease study 2013 estimated 956,200 deaths worldwide were directly attributable to ckd in 2013 , which represents a 134.6% increase from 1990 ( 4 ) .
in addition , ckd was ranked as the 19 highest cause of years of life lost in 2013 ( 4 ) .
this number of deaths and years of life lost has almost certainly underestimated the disease burden of ckd , as it probably only captures deaths due to esrd .
it is well documented that cvd causes most of the deaths in patients with ckd ( 2,3 ) .
worldwide , an estimated 1.9 million esrd patients were on renal replacement therapy in 2010 ( 5 ) .
medical costs for the treatment of ckd and esrd are enormous and represent an immense financial burden to families and society as a whole .
for example , overall us medicare expenditures for ckd and renal replacement therapy in 2010 were 41.0 and 32.9 billion us dollars , respectively , accounting for 24% of the total medicare budget ( 6 ) .
diabetes and hypertension are the leading causes of ckd in all high - income countries and many low- and middle - income countries ( 1 ) .
the global epidemic of diabetes and hypertension could lead to a worldwide increase in prevalence and in the number of persons with ckd and its complications without effective interventions ( 7,8 ) . although the prevalence of ckd has been reported in individual countries , global estimates of ckd prevalence and absolute burden are not available .
accurate estimates of the worldwide prevalence of this condition are essential as a source of primary information and for rational planning of health services .
quantifying the global burden of ckd will allow public - health policy - makers around the world to assign sufficient priority and resources to its prevention and treatment .
we aimed to estimate the global prevalence and absolute burden of ckd in 2010 by pooling data from population - based studies worldwide .
a total of 35 reports from 33 studies conducted in 32 countries , which represent 48.6% of the global population 20 years old , were included in the analysis ( figure 1 ) ( 943 ) . among the included studies ,
16 were conducted in nationally representative samples and the rest were in multisite or regional samples ( table 1 ) .
the crude prevalence of ckd stages 15 varied from 4.5% in south korea to 25.7% in el salvador in men , and from 4.1% in saudi arabia to 16.0% in singapore in women ; stages 35 varied from 1.3% in china to 15.4% in nepal in men and from 1.7% in singapore to 21.3% in nepal in women .
the age - standardized global prevalence of ckd stages 15 among adults aged 20 years in 2010 was 10.4% in men ( 95% ci 9.3 to 11.9% ) and 11.8% in women ( 11.2 to 12.6% ) .
the age - standardized prevalence was 8.6% in men ( 7.3 to 9.8% ) and 9.6% in women ( 7.7 to 11.1% ) in high - income countries , and 10.6% in men ( 9.4 to 13.1% ) and 12.5% in women ( 11.8 to 14.0% ) in low- and middle - income countries ( table 2 ) .
the age - standardized global prevalence of ckd stages 35 among adults aged 20 years in 2010 was 4.7% in men ( 95% ci 3.4 to 6.7% ) and 5.8% in women ( 4.4 to 8.1% ) .
the age - standardized prevalence was 4.3% in men ( 3.5 to 5.2% ) and 5.7% in women ( 4.4 to 7.6% ) in high - income countries , and 4.6% in men ( 3.1 to 7.7% ) and 5.6% in women ( 3.9 to 9.2% ) in low- and middle - income countries .
the estimated total number of adults with any stage of ckd in 2010 was 225.7 million ( 205.7 to 257.4 million ) men and 271.8 million ( 258.0 to 293.7 million ) women worldwide .
the estimated total number of adults with any stage of ckd was 48.3 million ( 42.3 to 53.3 million ) men and 61.7 million ( 50.4 to 69.9 million ) women in high - income countries , and 177.4 million ( 162.9 to 209.0 million ) men and 210.1 million ( 200.8 to 231.7 million ) women in low- and middle - income countries ( table 2 ) .
the estimated total number of adults with ckd stages 35 in 2010 was 100.6 million ( 72.0 to 146.4 million ) men and 135.8 million ( 102.7 to 193.9 million ) women worldwide .
the estimated total number of adults with ckd stages 35 was 26.1 million ( 22.0 to 31.1 million ) men and 44.1 million ( 35.3 to 54.8 million ) women in high - income countries , and 74.5 million ( 50.3 to 123.5 million ) men and 91.7 million ( 66.7 to 143.1 million ) women in low- and middle - income countries .
the prevalence of ckd ( both stages 15 and stages 35 ) increased with age ( figure 2 ) .
subsequently , women had higher prevalences than men in middle - age groups , and this sex - difference became even greater in older age groups , especially for stages 35 .
the pattern of age - related increase in ckd prevalence in men and women was consistent in high - income and low- and middle - income countries ( table 2 ) .
in general , age - specific prevalences of ckd were higher in low- and middle - income countries compared to high - income countries , except in those aged 70 years , whose prevalence was higher in high - income countries for both men and women .
the absolute numbers of men and women with ckd were much greater in low- and middle - income countries compared to high - income countries .
approximately 78.6% of men and 77.3% of women with ckd stage 15 and 74.1% of men and 67.5% of women with ckd stage 35 were living in low- and middle - income countries .
our analysis indicated that over 497 million adults aged 20 years and older in the world had ckd stages 15 in 2010 . of them ,
236 million had moderate or severe decreases in kidney function , i.e. , ckd stages 35 .
the majority of individuals with ckd were living in low- and middle - income countries .
the age - adjusted prevalences of ckd were higher in low- and middle - income countries compared to high - income countries .
our results also suggest that women had a higher prevalence of ckd and that prevalences increased with age consistently in high - income and low- and middle - income countries .
however , the estimates in our analysis are limited by available data from published studies , including the use of only a single creatinine measurement to calculate estimated glomerular filtration rate ( egfr ) .
it has been suggested that creatinine - based equations might systematically underestimate the true gfr , particularly among individuals with higher gfr levels ( 60 ml / min per 1.73 m ) ( 44 ) .
in addition , the majority of population - based surveys did not follow patients for 3 months to confirm ckd .
eriksen and ingebretsen reported that among 6,863 individuals in the municipality of troms with an initial egfr of 3059 ml / min/1.73 m , 2,175 ( 31.7% ) had subsequent estimates 60 ml / min/1.73 m within 3 months ( 45 ) .
it is uncertain whether these findings are applicable to other populations with different races / ethnicities , geographic regions , and diets .
nevertheless , these data indicate that a single measure of egfr may substantially overestimate the prevalence of ckd due to false positives .
the high prevalence of ckd worldwide has led to an increased prevalence of esrd and mortality from cvd ( 13 ) .
it was estimated that more than 1.9 million esrd patients were on renal replacement therapy in 2010 ( 5 ) .
esrd causes reduced life expectancy and poor quality of life in patients and presents an enormous financial burden to families and society as a whole ( 1,6 ) .
cvd is the leading cause of death in the world , and ischemic heart disease and stroke collectively killed 12.9 million people in 2010 , which represents one in four deaths worldwide ( 4 ) .
both reduced gfr and albuminuria or proteinuria are associated with increased risk of esrd , cvd and premature death ( 2,3 ) .
therefore , the prevention , detection , and treatment of ckd should be an effective approach for reducing esrd , cvd , and total mortality in the world .
our study reported a high prevalence of ckd in the elderly , especially for ckd stages 35 .
this high prevalence of ckd is mirrored by an increased number of elderly on kidney dialysis ( 46 ) .
the national kidney foundation kidney disease outcomes quality initiative ( nkf kdoqi ) or the kidney disease : improving global outcomes ( kdigo ) clinical guidelines were used to define ckd in studies included in this analysis ( 47,48 ) .
the appropriateness of egfr < 60 ml / min/1/73 m as the cut - point for ckd in the elderly is debatable since older age is associated with a physiological decline in gfr , and moderately reduced gfr might have less risk predictive value for esrd , cvd , and total mortality in the elderly ( 44,49 ) .
therefore , use of a non - age - specific threshold for gfr to define ckd is most likely to substantially overestimate ckd prevalence in older age groups .
further studies are warranted to define an appropriate gfr threshold for ckd in the elderly .
our study also documented that women had a higher prevalence of ckd than men , and the gender difference was more pronounced in older age groups .
these findings are consistent with large , nationally - representative studies from the united states , finland , and china ( 12,29,33 )
. data from the us national health and nutrition examination survey ( nhanes ) showed that the higher prevalence of ckd in women compared to men was consistent when egfr was calculated based on the modification of diet in renal disease ( mdrd ) equation , chronic kidney disease epidemiology collaboration ( ckd - epi ) creatinine - based equation , and ckd - epi cystatin c - based equation ( 6 )
. however , the prevalence and incidence of esrd are significantly higher in men than in women ( 6 ) .
one possible explanation for this discrepancy is a faster progression of ckd to esrd in men compared to women ( 45 ) .
our findings indicated that ckd affected many more individuals in low- and middle - income countries than in high - income countries
. a higher prevalence of ckd and a much larger population resulted in a considerably greater absolute burden of ckd in low- and middle - income countries .
in fact , more than three quarters of patients with ckd were living in low- and middle - income countries in 2010 .
lifestyle changes due to rapid urbanization and globalization have led to the increased prevalence of ckd risk factors in low- and middle - income countries , while limited healthcare resources result in extremely low treatment and control rates of ckd risk factors in those countries ( 7,8 ) .
our study results call for global collaborative efforts to combat ckd in low- and middle - income countries .
the world health organization global action plan for the prevention and control of noncommunicable diseases 20132020 mentions kidney disease as a condition associated with two of its main diseases of interest , cvd and diabetes , but does not include ckd as a main priority ( 50 ) .
the worldwide epidemics of diabetes and hypertension have likely played a major role in the increased global burden of ckd ( 1,7,8 ) .
in addition , changes in lifestyle risk factors , environmental exposures , and the aging of the population have all likely contributed to the increased burden of ckd ( 1 ) .
these risk factors are also associated with an increased risk of esrd , cvd , and total mortality in patients with ckd . despite having an estimated prevalence similar to diabetes in many countries , much less attention and resources
have been allocated to ckd surveillance , prevention , and management compared with many other chronic diseases ( 51 ) . to reduce the global burden of ckd and related morbidities and mortalities
, a comprehensive approach is needed that focuses on several inter - related risks to health , including hypertension , high ldl cholesterol , tobacco use , obesity , physical inactivity , poor diet , and diabetes ( 1,47,48 ) . in conclusion ,
our findings indicate that ckd is an important global - health challenge , especially in low- and middle - income countries .
national and international efforts on the prevention , detection , and treatment of ckd are needed to reduce its morbidities and mortalities worldwide .
literature search , study selection , and data extraction were conducted independently and in duplicate by at least two investigators using a standardized protocol and data - collection form .
we searched medline using key words  prevalence  ,  cross - sectional study  ,  survey  ,  renal insufficiency 
,  renal disease  ,  chronic kidney disease  ,  kidney function  ,  glomerular filtration rate  ,  albuminuria  and  proteinuria  . the search was restricted to studies in humans published from january 1 , 1990 , to december 31 , 2014 . a manual search was performed using references cited in reviews and original research articles .
in addition , we searched projects awarded by the international society of nephrology global outreach program from 2005 , when the first clinical research program projects were funded , to 2014 .
eligibility criteria for inclusion were : ( 1 ) population - based original studies in which prevalence of ckd ( or data to calculate it ) was reported ; ( 2 ) sex- and age - specific prevalence of ckd was provided ; ( 3 ) ckd was defined according to the nkf kdoqi or kdigo guidelines ( 47,48 ) and ( 4 ) serum creatinine values were standardized .
the nkf kdoqi guidelines were selected because most nationally representative studies reporting ckd prevalence use these guidelines to define ckd . if a national study was available for a country , we used its data . if not , we used data from the largest and most recent multisite or regional study . if data from multiple regional studies within a country were available ( 15,16,30,31 )
, they were pooled to provide national estimates by weighting by age- and sex - specific sample size . if the most recent prevalence estimates were not published and if study datasets were available , age- and gender - specific prevalence estimates were calculated from the datasets .
we calculated age- and sex - specific prevalence of ckd stages 15 and stages 35 in the us population using data from nhanes 20072012 ( 29 ) and ckd stages 35 in argentina and uruguay using data from the study on the detection and follow - up of cardiovascular disease and risk factors in the southern cone of latin america ( cescas ) ( 30 ) .
if egfr from multiple equations was reported , we preferred the ckd - epi equation over the mdrd equation .
likewise , we preferred urinary albumin excretion 30 mg / day ( or albumin - to - creatinine ratio 30 mg / g ) over urinary protein excretion 300 mg / day or a positive dipstick test of 1 + or greater to define kidney damage if multiple markers were reported .
ckd stages 15 was defined as kidney damage or egfr < 60 ml / min/1.73 m , while ckd stages 35 was defined as egfr < 60 ml / min/1.73 m ( 47 ) .
countries were grouped into high - income countries and low- and middle - income countries using the world bank classification system updated in july 2013 ( 52 ) .
high - income countries are defined as those with a gross national income ( gni ) of $ 12,616 or more , and low - and middle - income countries are those with a gni less than $ 12,616 ( 52 ) . for countries without prevalence estimates meeting our inclusion criteria , we applied data from the country with the closest geographic proximity within the same geographical region defined using the world bank classification system ( 52 ) .
if more than one country with data neighbored a country with no data , the country with the most similar gni was used .
not all studies provided prevalence data for the full age range under consideration ( from 2029 years to 70 years ) .
incomplete age - specific prevalence was estimated using logistic regression to model the relationship between age and prevalence of ckd for each sex in high - income countries and low- and middle - income countries , separately .
median age and prevalence of ckd within each reported age group from available studies were used to create the predictive models .
goodness of fit was tested by cragg and uhler 's pseudo r - square , and all models were well fit in high - income countries ( r between 0.55 and 0.84 ) and had poorer fit in low- and middle - income countries ( r between 0.27 and 0.59 ) .
the prevalence and mean age in men and women from each study with missing age - specific prevalence were used to calibrate the predictive equation before it was used to estimate the age - specific prevalence for that country .
if studies did not provide age - specific data in the 10-year increments of interest ( i.e. , 2029 , 3039 , etc ) , we averaged the prevalence from the two closest 10-year age groups weighting by age - specific population size from the country to estimate the prevalence of ckd for the age ranges of interest . for countries that reported only the prevalence of ckd stages 35 ,
logistic regression was used to predict the age - specific prevalence of stages 15 in men and women for high - income countries and low- and middle - income countries , separately .
eight high - income countries ( 48 age - specific prevalence estimates ) and five low - income countries ( 30 age - specific prevalence estimates ) reported both prevalence of ckd stages 15 and stages 35 in men and women .
these data were used to generate the predictive models for ckd stages 15 prevalence estimates from the age - specific prevalence of ckd stages 35 . for studies that reported only the prevalence of ckd stages 15 ,
these models all had good fit assessed by cragg and uhler 's pseudo r - square ( r between 0.56 and 0.89 ) .
sex- and age - specific prevalences of ckd for each country were applied to the who sex- and age - specific population counts in 2010 to estimate the number of people with ckd in the country for each sex- and age - group ( 53 ) .
the total number of persons with ckd in high - income countries and low- and middle - income countries was summed separately to provide an estimate of the total number of persons with ckd for each income category by sex- and age - groups , and the number from each income category was added to obtain the worldwide count .
the sex- and age - specific prevalences of ckd for 2010 in high - income countries and low- and middle - income countries were calculated by dividing the total number of people with ckd in each income category by the number of people in that income category by sex- and age - groups .
worldwide prevalence was estimated by dividing the total number of persons with ckd by the total adult world population .
the prevalences of ckd in high - income countries and low- and middle - income countries were standardized by age to the 2010 world population separately for each sex and overall using the direct method .
confidence intervals for all prevalence estimates were calculated using bootstrap methods ( 54 ) . for each prevalence estimate , we chose n studies , where n is the number of countries used to estimate that prevalence estimate , with replacement and calculated a mean prevalence .
then we repeated this process 10,000 times and choose the values at 2.5% and 97.5% of the distribution as our bootstrap 95% confidence intervals .
confidence intervals for all absolute burden estimates were calculated by multiplying the bootstrap 95% confidence intervals by the population for that prevalence estimate to get the 95% confidence intervals for the number of people with ckd .
all analyses were done using sas ( version 9.3 ) , r ( version 3.1.2 ) , and microsoft excel software .
we searched medline using key words  prevalence  ,  cross - sectional study  ,  survey  ,  renal insufficiency 
,  renal disease  ,  chronic kidney disease  ,  kidney function  ,  glomerular filtration rate  ,  albuminuria  and  proteinuria  .
the search was restricted to studies in humans published from january 1 , 1990 , to december 31 , 2014 .
in addition , we searched projects awarded by the international society of nephrology global outreach program from 2005 , when the first clinical research program projects were funded , to 2014 .
eligibility criteria for inclusion were : ( 1 ) population - based original studies in which prevalence of ckd ( or data to calculate it ) was reported ; ( 2 ) sex- and age - specific prevalence of ckd was provided ; ( 3 ) ckd was defined according to the nkf kdoqi or kdigo guidelines ( 47,48 ) and ( 4 ) serum creatinine values were standardized .
the nkf kdoqi guidelines were selected because most nationally representative studies reporting ckd prevalence use these guidelines to define ckd . if a national study was available for a country , we used its data . if not , we used data from the largest and most recent multisite or regional study . if data from multiple regional studies within a country were available ( 15,16,30,31 )
, they were pooled to provide national estimates by weighting by age- and sex - specific sample size . if the most recent prevalence estimates were not published and if study datasets were available , age- and gender - specific prevalence estimates were calculated from the datasets .
we calculated age- and sex - specific prevalence of ckd stages 15 and stages 35 in the us population using data from nhanes 20072012 ( 29 ) and ckd stages 35 in argentina and uruguay using data from the study on the detection and follow - up of cardiovascular disease and risk factors in the southern cone of latin america ( cescas ) ( 30 ) .
if egfr from multiple equations was reported , we preferred the ckd - epi equation over the mdrd equation .
likewise , we preferred urinary albumin excretion 30 mg / day ( or albumin - to - creatinine ratio 30 mg / g ) over urinary protein excretion 300 mg / day or a positive dipstick test of 1 + or greater to define kidney damage if multiple markers were reported .
ckd stages 15 was defined as kidney damage or egfr < 60 ml / min/1.73 m , while ckd stages 35 was defined as egfr < 60 ml / min/1.73 m ( 47 ) .
countries were grouped into high - income countries and low- and middle - income countries using the world bank classification system updated in july 2013 ( 52 ) .
high - income countries are defined as those with a gross national income ( gni ) of $ 12,616 or more , and low - and middle - income countries are those with a gni less than $ 12,616 ( 52 ) . for countries without prevalence estimates meeting our inclusion criteria , we applied data from the country with the closest geographic proximity within the same geographical region defined using the world bank classification system ( 52 ) .
if more than one country with data neighbored a country with no data , the country with the most similar gni was used .
not all studies provided prevalence data for the full age range under consideration ( from 2029 years to 70 years ) .
incomplete age - specific prevalence was estimated using logistic regression to model the relationship between age and prevalence of ckd for each sex in high - income countries and low- and middle - income countries , separately .
median age and prevalence of ckd within each reported age group from available studies were used to create the predictive models .
goodness of fit was tested by cragg and uhler 's pseudo r - square , and all models were well fit in high - income countries ( r between 0.55 and 0.84 ) and had poorer fit in low- and middle - income countries ( r between 0.27 and 0.59 ) .
the prevalence and mean age in men and women from each study with missing age - specific prevalence were used to calibrate the predictive equation before it was used to estimate the age - specific prevalence for that country .
if studies did not provide age - specific data in the 10-year increments of interest ( i.e. , 2029 , 3039 , etc ) , we averaged the prevalence from the two closest 10-year age groups weighting by age - specific population size from the country to estimate the prevalence of ckd for the age ranges of interest . for countries that reported only the prevalence of ckd stages 35 ,
logistic regression was used to predict the age - specific prevalence of stages 15 in men and women for high - income countries and low- and middle - income countries , separately .
eight high - income countries ( 48 age - specific prevalence estimates ) and five low - income countries ( 30 age - specific prevalence estimates ) reported both prevalence of ckd stages 15 and stages 35 in men and women .
these data were used to generate the predictive models for ckd stages 15 prevalence estimates from the age - specific prevalence of ckd stages 35 . for studies that reported only the prevalence of ckd stages 15 ,
these models all had good fit assessed by cragg and uhler 's pseudo r - square ( r between 0.56 and 0.89 ) .
sex- and age - specific prevalences of ckd for each country were applied to the who sex- and age - specific population counts in 2010 to estimate the number of people with ckd in the country for each sex- and age - group ( 53 ) .
the total number of persons with ckd in high - income countries and low- and middle - income countries was summed separately to provide an estimate of the total number of persons with ckd for each income category by sex- and age - groups , and the number from each income category was added to obtain the worldwide count .
the sex- and age - specific prevalences of ckd for 2010 in high - income countries and low- and middle - income countries were calculated by dividing the total number of people with ckd in each income category by the number of people in that income category by sex- and age - groups .
worldwide prevalence was estimated by dividing the total number of persons with ckd by the total adult world population .
the prevalences of ckd in high - income countries and low- and middle - income countries were standardized by age to the 2010 world population separately for each sex and overall using the direct method .
confidence intervals for all prevalence estimates were calculated using bootstrap methods ( 54 ) . for each prevalence estimate , we chose n studies , where n is the number of countries used to estimate that prevalence estimate , with replacement and calculated a mean prevalence .
then we repeated this process 10,000 times and choose the values at 2.5% and 97.5% of the distribution as our bootstrap 95% confidence intervals .
confidence intervals for all absolute burden estimates were calculated by multiplying the bootstrap 95% confidence intervals by the population for that prevalence estimate to get the 95% confidence intervals for the number of people with ckd .
all analyses were done using sas ( version 9.3 ) , r ( version 3.1.2 ) , and microsoft excel software .
 chronic kidney disease ( ckd ) is a major risk factor for end - stage renal disease , cardiovascular disease and premature death . 
 here we estimated the global prevalence and absolute burden of ckd in 2010 by pooling data from population - based studies . 
 we searched medline ( january 1990 to december 2014 ) , international society of nephrology global outreach program funded projects , and bibliographies of retrieved articles and selected 33 studies reporting gender- and age - specific prevalence of ckd in representative population samples . 
 the age standardized global prevalence of ckd stages 15 in adults aged 20 and older was 10.4% in men ( 95% confidence interval 9.311.9% ) and 11.8% in women ( 11.212.6% ) . 
 this consisted of 8.6% men ( 7.39.8% ) and 9.6% women ( 7.711.1% ) in high - income countries , and 10.6% men ( 9.413.1% ) and 12.5% women ( 11.814.0% ) in low- and middle - income countries . 
 the total number of adults with ckd was 225.7 million ( 205.7257.4 million ) men and 271.8 million ( 258.0293.7 million ) women . 
 this consisted of 48.3 million ( 42.353.3 million ) men and 61.7 million ( 50.469.9 million ) women in high - income countries , and 177.4 million ( 159.2215.9 million ) men and 210.1 million ( 200.8231.7 million ) women in low- and middle - income countries . 
 thus , ckd is an important global - health challenge , especially in low- and middle - income countries . 
 national and international efforts for prevention , detection , and treatment of ckd are needed to reduce its morbidity and mortality worldwide . 
Introduction
Results
Discussion
Methods
Data Sources and Searches
Study Selection
Data Extraction and Imputation
Data Synthesis and Analysis