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hypertension or obesity&#44; predicts accelerated vascular damage and multiplies the associated risk<span class="elsevierStyleSup">2&#44;3</span>&#46;</p> <p class="elsevierStylePara">Furthermore&#44; the prevalence of CKD is growing worldwide due to the increase in related diseases as type 2 diabetes mellitus&#44; obesity&#44; hypertension or atherosclerosis<span class="elsevierStyleSup">7&#44;8</span>&#46; The asymptomatic nature of CKD makes its early detection more difficult&#44; which could be important as the treatment in early stages may prevent or delay its progression<span class="elsevierStyleSup">9</span>&#46; The knowledge of the prevalence of CKD might be useful to assess the level of its underdiagnosis and estimate the impact of potential screening policies&#46;</p> <p class="elsevierStylePara">The 2002 practice guideline of the Kidney Disease Outcomes Quality Initiative &#40;K&#47;DOQI&#41; of the National Kidney Foundation &#40;NKF&#41;<span class="elsevierStyleSup">10 </span>defined CKD as either kidney damage or glomerular filtration rate &#40;GFR&#41; 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with good performance among subgroups of age&#44; sex&#44; race&#44; diabetes or body mass index<span class="elsevierStyleSup">16&#44;17</span>&#46;</p> <p class="elsevierStylePara">In the last five years&#44; more than 25 epidemiological studies have investigated CKD prevalence worldwide<span class="elsevierStyleSup">14</span>&#44; leading to a median prevalence of 7&#46;2&#37; in persons aged 30 years or older&#44; and revealing ethnic-specific differences&#46; In our country&#44; the Spanish Society of Nephrology &#40;S&#46;E&#46;N&#46;&#41; has initiated a program to identify the true population at risk for CKD&#44; and to increase the preventive measures aimed at reducing the incidence of renal failure&#44; cardiovascular complications&#44; and progression to end stage renal failure<span class="elsevierStyleSup">18&#44;19</span>&#46;</p> <p class="elsevierStylePara">Within this program&#44; the &#171;Estudio Epidemi&#243;logico de la Insuficiencia Renal en Espa&#241;a&#187; &#40;EPIRCE&#41; is the first epidemiological study at a national level designed to describe the prevalence of CKD in the general Spanish population aged 20 years or older&#44; using the simplified MDRD equation&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">METHODS </span></p> <p class="elsevierStylePara">The EPIRCE was an epidemiologic&#44; general population-based&#44; cross-sectional study that included a randomly selected Spanish sample aged 20 years or older&#46; The exclusion criteria were residence outside the recruiting municipality&#44; or institutionalization at the time of the study&#46; The protocol was approved by an ethics committee&#44; and all enrolled patients provided informed consent&#46;</p> <p class="elsevierStylePara">The target sample were 13&#44;013 individuals&#44; stratified by age&#44; sex&#44; and habitat within each Spanish region&#44; according to the 2001 Census&#46; A total of 6&#44;464 out of the initial list of 13&#44;013 were finally contacted for the study&#46; Census errors were the most important reason for the impossibility to contact individuals&#46; The sample was recruited between January 2004 and January 2008 in 42 points &#40;municipalities&#41;&#46; The final completed interviews were 2&#44;746&#44; and the response rate was 42&#46;5&#37;&#46;</p> <p class="elsevierStylePara">Data were collected as follows&#46; First&#44; a letter describing the study was sent to each randomly selected individual&#46; Next&#44; a health professional contacted the potential respondents by phone to verify inclusion and exclusion criteria&#44; ask for participation&#44; and make appointments with those who volunteered&#46; A minimum of three negative answers were required to discard a selected individual&#46;</p> <p class="elsevierStylePara">The collected variables included anthropometric and sociodemographic data &#40;age&#44; gender&#44; ethnicity&#44; weight&#44; height&#44; body mass index&#41;&#44; blood pressure and clinical history at study inclusion &#40;obesity&#44; hypertension&#44; diabetes mellitus&#44; dyslipemia&#44; cardiovascular disease&#44; gout&#44; renal lithiasis&#44; CKD&#44; transplant&#41;&#46; Participants were also interviewed to determine their smoking and exercise habits&#44; alcohol consumption&#44; drug abuse and use of nephrotoxic drugs&#46; After informed consent was provided&#44; a blood sample was obtained from each individual for biochemical tests&#46; Serum creatinine concentration was determined in the same reference laboratory for all samples&#46; GFR was calculated as an indicator of renal function with the simplified MDRD formula<span class="elsevierStyleSup">20</span>&#44; and participants were classified according to the Kidney Disease Outcomes Quality Initiative guidelines<span class="elsevierStyleSup">10</span>&#46; Stage 3 was split into 3a &#40;GFR 45-59 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41; and 3b &#40;GFR 30-44 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&#46; Other analytical determinations included&#58; glucose&#44; urea&#44; total cholesterol &#40;C&#41;&#44; tryglicerydes &#40;Tg&#41;&#44; HDL-C&#44; LDL-C&#44; insulin resistance index &#40;HOMA&#41;&#44; haemoglobin &#40;Hb&#41;&#44; ferritin&#44; uric acid and urinary albumin to creatinine ratio&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical methods </span></p> <p class="elsevierStylePara">Adjustment weights were used to correct for non-response bias&#44; with the age&#44; gender and habitat distribution of survey respondents being equated to the population structure as determined from the 2001 census&#46; All prevalence and mean estimates were calculated with the weighted sample&#44; and asymptotic 95&#37; confidence intervals &#40;CI&#41; were obtained&#46; Univariate and multivariate logistic regression analyses&#44; also weighted for non-response bias&#44; were used to calculate the odds ratio &#40;OR&#41; and CIs for candidate CKD risk factors&#46; P values &#60;0&#46;05 were considered significant&#46; Since there were statistically significant differences in the response rate between participating municipalities &#40;data not shown&#41;&#44; a sensitivity analysis was performed comparing the results between highly responding centers &#40;&#62;60&#37; of response rate&#44; n &#61; 1&#44;098&#41; and the overall group&#44; to assess for a possible non-response bias&#46; All analyses were performed with SAS version 9&#46;1&#46;3 Service Pack 4 &#40;SAS Institute Inc&#46;&#44; Carey&#44; North caroline&#44; USA&#41;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS </span></p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Sociodemographic and clinical characteristics </span></p> <p class="elsevierStylePara">Table 1 and 2 show the characteristics of the 2&#44;746 respondents &#40;weighted estimates&#41;&#46; Mean age was 49&#46;5 years&#44; and about one quarter of individuals were older than 64 years &#40;25&#46;8&#37;&#41;&#46; As in the general Spanish population&#44; the ratio male&#58;female was 0&#46;9&#44; almost all were caucasian &#40;99&#46;1&#37;&#41;&#44; and the residence was urban in two thirds of cases &#40;66&#46;1&#37;&#41;&#46;</p> <p class="elsevierStylePara">Clinical history revealed an important prevalence of previously diagnosed dyslipemia &#40;29&#46;3&#37;&#41;&#44; obesity &#40;26&#46;1&#37;&#41;&#44; hypertension &#40;24&#46;1&#37;&#41; and diabetes &#40;9&#46;2&#37;&#41;&#46; Among cardiovascular events&#44; peripheral vascular episodes were the most frequent &#40;10&#46;8&#37;&#41;&#44; followed by ischaemic heart disease &#40;5&#46;1&#37;&#41; and cerebrovascular disease &#40;1&#46;7&#37;&#41;&#46; Current smoking habit and habitual alcohol intake were frequent &#40;25&#46;5&#37; and 45&#46;1&#37;&#44; respectively&#41;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">CKD prevalence </span></p> <p class="elsevierStylePara">The overall prevalence of CKD stages 3-5 &#40;eGFR &#60;60 ml&#47;min&#41; was 6&#46;83 &#37;&#44; with a 95&#37; CI of 5&#46;41 to 8&#46;25 &#40;3&#46;33&#37; for age 40&#173;64 years and 21&#46;42&#37; for age &#62;64 years&#41;&#46; When the albumin to creatinine ratio was added to the diagnostic criteria&#44; the prevalence rose to 9&#46;16&#37; &#40;95&#37; CI&#44; 7&#46;5 to 10&#46;8&#41;&#46; The prevalence estimates of CKD stages were&#58; 0&#46;99&#37; for stage 1&#59; 1&#46;3&#37; for stage 2&#59; 5&#46;4&#37; for stage 3a&#59; 1&#46;1&#37; for stage 3b&#59; 0&#46;27&#37; for stage 4&#59; and 0&#46;03&#37; for stage 5 &#40;table 2&#41;&#46; The prevalence of proteinuria &#40;ACR&#62;30 mg&#47;g&#41; in stage 3a was 5&#46;9&#37;&#44; in stage 3b&#44; 6&#46;8&#37;&#44; and in stage 4&#44; 36&#46;7&#37;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Risk factors for CKD </span></p> <p class="elsevierStylePara">Table 3 shows the unadjusted associations between sociodemographic and clinical characteristics of the patients and CKD&#46; The strongest predictor factor was age&#46; The observed odds ratios &#40;OR&#41; were 34&#46;4 for individuals between 40-64 years with respect to those between 20-39 years&#44; and 267&#46;5 for individuals above 64 years&#46; Other strong predictor factors were hypertension&#44; especially when previously diagnosed &#40;OR 5&#46;9&#41;&#44; pulse pressure above 60 mmHg &#40;OR 3&#46;8&#41;&#44; previous history of cardiovascular events &#40;ORs 4&#46;1 for ischaemic heart disease&#44; 3&#46;3 for cerebrovascular disease and 2&#46;1 for peripheral vascular disease&#41;&#44; overweight or obesity &#40;ORs of 2&#46;3 and 3&#46;5&#44; respectively&#41;&#44; diabetes &#40;OR 2&#46;4 for previously diagnosed patients&#41;&#44; dyslipemia &#40;OR 2&#46;1 for previously diagnosedpatients&#41; and gout &#40;OR 2&#46;2&#41;&#46;</p> <p class="elsevierStylePara">In the multivariate analysis&#44; the independent predictor factors that remained in the model were age&#44; obesity and previously diagnosed hypertension &#40;table 4&#41;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Sensitivity analyses </span></p> <p class="elsevierStylePara">Individuals recruited at highly responding centers &#40;&#62;60&#37; of response rate&#44; n &#61; 1&#44;098&#41; were healthier according to the following differences with respect to the overall sample&#58; they were less obese &#40;22&#46;9&#37; with BMI &#62;30 kg&#47;m<span class="elsevierStyleSup">2 </span>versus 26&#46;1&#37; in the total population&#41;&#44; less sedentary &#40;25&#46;4&#37; versus 28&#46;9&#37;&#41; and suffered less diabetes &#40;5&#46;2&#37; of non previously diagnosed diabetes versus 7&#46;0&#37;&#41;&#46; They also displayed more percentage of habitual alcohol consumption &#40;49&#46;7&#37; versus 45&#46;1&#37;&#41;&#46; Despite these findings&#44; the prevalence of CKD stages 3-5 in this subgroup was equivalent to that found in the overall sample&#58; 6&#46;65 &#40;95&#37; CI of 4&#46;66 to 8&#46;64&#41;&#46; The prevalence of proteinuria &#40;ACR &#62;30 mg&#47;g&#41; was slightly lower &#40;3&#46;6&#37;&#44; 95&#37; CI 1&#46;4 to 5&#46;8&#41;&#44; but not significantly different&#46; No differences were observed either in the prevalences within age&#44; gender or habitat categories&#44; nor in the risk factors associated to CKD &#40;data not shown&#41;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION </span></p> <p class="elsevierStylePara">The present study is the first epidemiological investigation of the prevalence of CKD in Spanish population aged 20 years or older at a national level&#46; The recruited sample is representative of all regions&#44; and has been adjusted to provide valid estimates of CKD prevalence in age&#44; gender and habitat subgroups&#44; according to the real distribution of Spanish population in 2001&#46;</p> <p class="elsevierStylePara">The prevalence of CKD found in our study &#40;6&#46;8&#37;&#41; is very similar to the median reported in a systematic review of 26 epidemiological studies around the world &#40;7&#46;2&#37;&#41;<span class="elsevierStyleSup">14</span>&#46; Since ethnic-specific differences have been reported<span class="elsevierStyleSup">14</span>&#44; the relevant comparisons with other European countries show that the prevalence in Spain remains within the range of previous studies that have used the MDRD equation &#40;4&#46;7-8&#46;1&#37; in studies from Italy<span class="elsevierStyleSup">21</span>&#44; Switzerland<span class="elsevierStyleSup">22</span>&#44; Norway<span class="elsevierStyleSup">23 </span>and Iceland<span class="elsevierStyleSup">24</span>&#41;&#46; These estimates are also similar to those from the US National Health and Nutrition Examination Surveys &#40;NHANES&#41; &#40;5&#46;6&#37; in 1988 through 1994 and 8&#46;05&#37; in 1999 through 2004&#41;<span class="elsevierStyleSup">25</span>&#44; despite the incidence of end stage renal disease &#40;ESRD&#41; in this country being much higher than in Europe<span class="elsevierStyleSup">26</span>&#46; The epidemiological study from Norway<span class="elsevierStyleSup">23 </span>investigated the progression rate from CKD stages 3 or 4 to ESRD in their cohort and found that the relative risk of progression in US caucasian patients was 2&#46;5 times higher than in Norwegian patients&#46; Among the possible explanations for these differences they postulate a later referral to nephrologist and a higher presence of obesity and diabetes in the US population&#46;</p> <p class="elsevierStylePara">The addition of the albumin&#47;creatinine ratio to the CKD diagnosis &#40;stages 1 and 2&#41; allowed to detect a further 2&#46;3&#37; of population at risk&#44; which substantially improves diagnostic accuracy without losing predictive power&#46; According to previous studies&#44; referral based on current stages 3 to 4 CKD identifies approximately only 70&#37; of all individuals that progress to ESRD<span class="elsevierStyleSup">27</span>&#46;</p> <p class="elsevierStylePara">We found a high prevalence of conventional risk factors&#44; overweight and obesity&#44; hypertension&#44; diabetes&#44; dyslipemia and smoking&#46; All of them were significantly associated to CKD&#44; which agrees with previous findings<span class="elsevierStyleSup">28&#44;29</span>&#46; With respect to smoking habit&#44; we did not find a significant association with current smoking&#44; but the ex-smoker status was related to a higher frequency of stage 4 CKD&#46; A possible explanation is that&#44; previous to the study entry&#44; these patients had already suffered other health problems that compelled them to discontinue tobacco&#46; Unexpectedly&#44; the habitual alcohol intake was inversely associated to CKD&#44; which partially agrees with the study of Kronborg et al&#46;&#44; who found that alcohol consumption in men predicted an increase in eGFR<span class="elsevierStyleSup">28&#44;29</span>&#46; Red wine has been shown to improve surrogate markers for cardiovascular disease&#44; such as nitric oxid release in the vessel wall&#46; It also possesses anti-inflammatory and anti-oxidative properties&#44; and inhibits platelet-derived growth factor-beta receptor phosphorylation<span class="elsevierStyleSup">30</span>&#46; However&#44; it would be very difficult to perform prospective&#44; randomized studies to demonstrate the benefits of moderate alcohol consumption&#44; as the important secondary harmful effects &#40;such as liver cirrhosis&#44; blood pressure elevation&#44; cancer or accidents&#41; should be taken into account&#46;</p> <p class="elsevierStylePara">The three independent predictor factors for CKD were increasing age&#44; obesity and history of hypertension&#44; which suggests that these conditions predispose to renal impairment through different mechanisms&#46;</p> <p class="elsevierStylePara">The decline in GFR with age has been repeatedly described<span class="elsevierStyleSup">14</span>&#46; The prevalence of CKD in patients above 64 years found in the EPIRCE study &#40;21&#46;4&#37;&#41; is comparable to that reported in other European countries &#40;15-25&#37;<span class="elsevierStyleSup">21-24</span>&#41;&#44; usually with higher prevalences in older women<span class="elsevierStyleSup">22&#44;24</span>&#46; The reduction starts progressively in the third decade of life&#44; and becomes steeper after the age of 60&#44; although it has not been observed in all individuals<span class="elsevierStyleSup">31</span>&#46; There are several hypotheses to explain this phenomenon&#58; it can be related to pathologic processes &#40;cumulated immunologic&#44; infectious&#44; or toxic damage&#41;&#44; progressive ischemia due to vascular aging&#44; or cummulative changes in kidney structure due to hyperperfusion and hyperfiltration with resultant glomerulosclerosis<span class="elsevierStyleSup">32&#44;33</span>&#46;</p> <p class="elsevierStylePara">The contribution of sustained high blood pressure levels to renal function deterioration is well established&#58; systemic and glomerular hypertension results in increased urinary excretion of proteins and accelerates renal function deterioration&#46; Many studies have demonstrated that an adequate&#44; or even intensified blood pressure control &#40;less than 130&#47;80 mmHg&#41;&#44; can slow the progression of diabetic and non diabetic renal disease<span class="elsevierStyleSup">34</span>&#46; Moreover&#44; long-term studies indicate that the change in GFR may be minimal in well-controlled hypertensive patients&#44; and that patients with nonmalignant essential hypertension with early and good blood pressure control do not develop renal failure<span class="elsevierStyleSup">35</span>&#46; The relationship found in our cohort might be the result of inadequately controlled blood pressure levels in the individuals with current CKD&#46;</p> <p class="elsevierStylePara">The association between CKD and obesity was previously described in a prospective study of a large cohort<span class="elsevierStyleSup">36</span>&#46; The increase in body weight with time&#44; even within normal BMI values&#44; has also been independently associated with an increased risk for CKD<span class="elsevierStyleSup">37</span>&#46; One of the proposed mechanisms for the development of CKD in obese patients is the presence of an increased inflammation status&#46; This is supported by the study of Bavbek et al&#46;&#44; who found elevated serum C-reactive protein &#40;CRP&#41; levels in obese patients versus age-matched healthy controls&#44; and a negative correlation between CRP levels and GFR<span class="elsevierStyleSup">38</span>&#46; In morbidity obese patients who underwent very important weight reduction after biliopancreatic diversion all cardiovascular risk factors &#40;hypertension&#44; diabetes&#44; hyperlipidemia&#44; proteinuria &#41; improved during follow-up<span class="elsevierStyleSup">39</span>&#46;</p> <p class="elsevierStylePara">An early identification of CKD in primary care is very important&#44; as specialist referral at an appropriate timing may improve long-term outcomes&#46; It has been reported that&#44; in Spain&#44; late referral to nephrologist is common in chronic diseases such as diabetes or hypertension<span class="elsevierStyleSup">40</span>&#46; Our results indicate that almost ten percent of adult individuals may suffer some degree of renal impairment&#44; and therefore&#44; reveal the need for taking this disease into account&#46; In addition&#44; our findings suggest that the control of classical cardiovascular risk factors as obesity or hypertension in primary care setting might help preventing CKD development&#46;</p> <p class="elsevierStylePara">The main limitation of the study is its poor response rate&#46; The sensitivity analysis excluding the centers with low participation revealed some non-response bias&#44; which did not appear to introduce substantial bias into CKD and proteinuria prevalence estimates&#46; Another limitation is the indirect GFR estimation method&#44; based on a single creatinine measurement&#44; that should be used with caution<span class="elsevierStyleSup">41</span>&#46; Currently&#44; the benefit of performing extensive screening of unselected populations with the intention to reduce the subsequent risk of cardiovascular events or progression to end-stage-renal disease remains unproven<span class="elsevierStyleSup">42</span>&#46; Although the MDRD equation is the most commonly used in epidemiological studies<span class="elsevierStyleSup">14</span>&#44; it underestimates the GFR<span class="elsevierStyleSup">15</span>&#46; Moreover&#44; the cut-off value of 60 ml&#47;min per 1&#46;73 m<span class="elsevierStyleSup">2</span><span class="elsevierStyleSup">&#160;</span>for all ages leads to over diagnosis in elderly population&#46; A new equation recently developed seems to improve the GFR estimation<span class="elsevierStyleSup">43</span>&#46; Finally&#44; the cross-sectional design of the study does not allow inferring causal relationships between the risk factors and CKD&#46;</p> <p class="elsevierStylePara">Some strenghts of our study are its large sample size&#44; well representative of the different Spanish regions&#44; and the random selection of the participants&#46; The agreement with results from other European countries supports the external validity of our findings&#46;</p> <p class="elsevierStylePara">In conclusion&#44; we found a relatively high prevalence of assymptomatic CKD &#40;almost one of ten&#41; in apparently healthy general population from Spain&#44; especially in older&#44; obese and hypertensive patients&#46; Independently of age&#44; many of the risks factors for CKD are modifiable&#58; hypertension&#44; diabetes mellitus&#44; obesity&#44; dyslipemia and smoking&#46; Further studies should assess whether early detection of CKD in general population might avoid CKD progression and protect from associated cardiovascular risk factors&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Acknowledgements </span></p> <p class="elsevierStylePara">This study was supported in part by a grant from Amgen&#44; S&#46;A&#46; Writing assistance was supported by Amgen&#46;<br /><span class="elsevierStyleBold">Co-authors&#46; This study has been conducted by the above-signed authors&#44; Neus Valveny from Trial Form Support&#44; David Calbet from Saatchi&#38;Saatchi Healthcare&#44; and the EPIRCE study group&#46;<br /></span>The Coordinating investigators in each Authonomous Community were&#58; Andaluc&#237;a&#58; M&#46;A&#46; &#193;lvarez de Lara&#59; Asturias&#58; F&#46; Vega&#59; Arag&#243;n&#58; C&#46; Laviades&#44; P&#46;J&#46; Vives&#44; J&#46;M&#46; Pe&#241;a Porta&#59; Baleares&#58; J&#46; Marco&#44; A&#46; Sol&#237;s&#44; A&#46; Losada Gonz&#225;lez&#59; Cantabria&#58; G&#46; Fern&#225;ndez Fresnedo&#59; Canarias&#58; J&#46;F&#46; Navarro&#44; J&#46;A&#46; S&#225;nchez Joga&#59; Catalunya&#58; J&#46; Fort&#44; A&#46; Mart&#237;nez Castelao&#44; N&#46; Fonser&#233;&#59; Castilla-La Mancha&#58; F&#46; Tornero&#44; M&#46; Quintana&#59; Castilla-Le&#243;n&#58; J&#46; Grande Villoria&#44; A&#46; Molina&#44; M&#46;B&#46; Alaguero&#44; G&#46; Torres&#59; Ceuta y Melilla&#58; C&#46; Fern&#225;ndez Andrade&#59; Euskadi&#58; F&#46; Vidaur&#44; J&#46; Manrique&#44; M&#46; Rodr&#237;guez&#59; Extremadura&#58; F&#46; Caravaca&#44; B&#46; Cancho&#59; Galicia&#58; A&#46; Otero&#44; L&#46; Gonz&#225;lez&#59; La Rioja&#58; A&#46; S&#225;nchez Casaj&#250;s&#59; Madrid&#58; F&#46; Garc&#237;a&#44;&#160; M&#46; San Boixedau&#44; K&#46; L&#243;pez&#44; E&#46; Rubio&#44; C&#46; Bernis&#59; Murcia&#58; M&#46; Giron&#233;s&#59; Navarra&#58; J&#46;L&#46; As&#237;n&#59; Valencia&#58; J&#46; Hern&#225;ndez Jaras&#44; A&#46; Rius&#44; M&#46; Gonz&#225;lez Rico&#46;</p> <p class="elsevierStylePara"><a href="grande&#47;1011718078&#95;t2&#95;pag83&#46;jpg" class="elsevierStyleCrossRefs"><img src="1011718078_t2_pag83.jpg" alt="Prevalence of chronic kidney disease in the Spanish population aged 20 years or older based on the cohort collected in the EPIRCE study &#40;n &#61; 2&#44;746&#41;"/></a></p> <p class="elsevierStylePara">Table 2&#46; Prevalence of chronic kidney disease in the Spanish population aged 20 years or older based on the cohort collected in the EPIRCE study &#40;n &#61; 2&#44;746&#41;</p> <p class="elsevierStylePara"><a href="grande&#47;1011718078&#95;t3&#95;pag84&#46;jpg" class="elsevierStyleCrossRefs"><img src="1011718078_t3_pag84.jpg" alt="Unadjusted associations between demographic or clinical characteristics and the presence of chronic kidney disease &#40;eGFR &#60;60 ml&#47;min per 1&#46;73 m2&#41;"/></a></p> <p class="elsevierStylePara">Table 3&#46; Unadjusted associations between demographic or clinical characteristics and the presence of chronic kidney disease &#40;eGFR <60 ml min per 1 73 m2</60></p> <p class="elsevierStylePara"><a href="grande&#47;1011718078&#95;t4&#95;pag85&#46;jpg" class="elsevierStyleCrossRefs"><img src="1011718078_t4_pag85.jpg" alt="Independent predictors of chronic kidney disease &#40;eGFR &#60;60 ml&#47;min per 1&#46;73 m2&#41; in the multivariate logistic regression model"/></a></p> <p class="elsevierStylePara">Table 4&#46; Independent predictors of chronic kidney disease &#40;eGFR <60 ml min per 1 73 m2 in the multivariate logistic regression model</60></p> <p class="elsevierStylePara"><a href="grande&#47;1011718078&#95;t1&#95;pag81&#95;copy1&#46;jpg" class="elsevierStyleCrossRefs"><img src="1011718078_t1_pag81_copy1.jpg" alt="Demographic and clinical characteristics of Spanish population aged 20 years or older based on the cohort collected in the EPIRCE study &#40;n &#61; 2&#44;746&#41;"/></a></p> <p class="elsevierStylePara">Table 1&#46; Demographic and clinical characteristics of Spanish population aged 20 years or older based on the cohort collected in the EPIRCE study &#40;n &#61; 2&#44;746&#41;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction&#58; </span>Chronic kidney disease &#40;CKD&#41; is an independent cardiovascular risk factor&#46; The knowledge of prevalence in general population may help to early detection of CKD and prevent or delay its progression&#46; <span class="elsevierStyleBold">Methods&#58; </span>Sociodemographic&#44; baseline characteristics&#44; and CKD prevalence &#40;measured by centralized serum creatinine and MDRD equation&#41; were evaluated in a randomly selected sample of general population aged 20 years or older&#44; collected in all Spanish regions and stratified by habitat&#44; age and sex according to 2001 census &#40;n &#61; 2&#44;746&#41;&#46; Univariate and multivariate logistic regression analyses were used to evaluate associations with CKD risk factors&#46; <span class="elsevierStyleBold">Results&#58; </span>Mean age was 49&#46;5 years&#46; The overall prevalence of Kidney Disease Outcomes Quality Initiative grades 3-5 CKD was 6&#46;8&#37;&#44; with a 95&#37; confidence interval &#40;CI&#41; of 5&#46;4 to 8&#46;2 &#40;3&#46;3&#37; for age 40-64 years and 21&#46;4&#37; for age &#62;64 years&#41;&#46; The prevalence estimates of CKD stages were&#58; 0&#46;99&#37; for stage 1 &#40;glomerular filtration rate &#91;GFR&#93; &#62;&#95;90 ml&#47;min per 1&#46;73 m<span class="elsevierStyleSup">2</span> with proteinuria&#41;&#59; 1&#46;3&#37; for stage 2 &#40;GFR 60-89&#41;&#59; 5&#46;4&#37; for stage 3a &#40;GFR 45-59&#41;&#59; 1&#46;1&#37; for stage 3b &#40;GFR 30-44&#41;&#59; 0&#46;27&#37; for stage 4 &#40;GFR 15-29&#41;&#59; and 0&#46;03&#37; for stage 5 &#40;GFR &#60;15&#41;&#46; An important prevalence of classical cardiovascular risk factors was observed&#58; dyslipemia &#40;29&#46;3&#37;&#41;&#44; obesity &#40;26&#46;1&#37;&#41;&#44; hypertension &#40;24&#46;1&#37;&#41;&#44; diabetes &#40;9&#46;2&#37;&#41; and current smoking &#40;25&#46;5&#37;&#41;&#46; The independent predictor factors for CKD were age&#44; obesity and previously diagnosed hypertension&#46; <span class="elsevierStyleBold">Conclusions&#58; </span>The prevalence of CKD at any stage in general population from Spain is relatively high&#44; especially in the elderly&#44; and similar to countries of the same geographical area&#46; Independently of age&#44; two modifiable risks factors&#44; hypertension and obesity&#44; are associated with an increased prevalence of CKD&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introducci&#243;n&#58; </span>La insuficiencia renal cr&#243;nica &#40;IRC&#41; constituye un factor de riesgo cardiovascular independiente&#46; El conocimiento de su prevalencia en la poblaci&#243;n general puede contribuir a la detecci&#243;n precoz de esta enfermedad y de prevenir o retrasar su evoluci&#243;n&#46; <span class="elsevierStyleBold">M&#233;todos&#58; </span>Se seleccion&#243; una muestra aleatoria de poblaci&#243;n general espa&#241;ola&#44; con edad igual o superior a 20 a&#241;os&#44; distribuida por todo el territorio nacional y estratificada por h&#225;bitat&#44; edad y sexo conforme al censo de 2001 &#40;n &#61; 2&#46;746&#41;&#46; Se recopilaron datos sociodemogr&#225;ficos y cl&#237;nicos&#44; y se evalu&#243; la prevalencia de IRC mediante determinaci&#243;n centralizada de creatinina s&#233;rica y aplicaci&#243;n de la ecuaci&#243;n MDRD&#46; Se llevaron a cabo an&#225;lisis univariantes y multivariantes para evaluar la asociaci&#243;n entre la IRC y diversos factores de riesgo&#46; <span class="elsevierStyleBold">Resultados&#58; </span>La edad media fue de 49&#44;5 a&#241;os&#46; La prevalencia global de IRC en estadios 3-5&#44; seg&#250;n la Kidney Disease Outcomes Quality Initiative&#44; fue del 6&#44;8&#37;&#44; con un intervalo de confianza del 95&#37; &#40;IC&#41; de 5&#44;4 a 8&#44;2 &#40;3&#44;3&#37; para edades 40-64 a&#241;os y 21&#44;4&#37; para edades &#62;64 a&#241;os&#41;&#46; Las prevalencias estimadas para cada uno de los estadios de IRC fueron&#58; 0&#44;99&#37; para estadio 1 &#40;tasa de filtrado glomerular &#91;TFG&#93; &#62;&#95;90 ml&#47;min por 1&#44;73 m<span class="elsevierStyleSup">2</span><span class="elsevierStyleSup">&#160;</span>con proteinuria&#41;&#59; 1&#44;3&#37; para estadio 2 &#40;TFG 60-89&#41;&#59; 5&#44;4&#37; para estadio 3a &#40;TFG 45-59&#41;&#59; 1&#44;1&#37; para estadio 3b &#40;TFG 30-44&#41;&#59; 0&#44;27&#37; para estadio 4 &#40;TFG 15-29&#41;&#44; y 0&#44;03&#37; para estadio 5 &#40;TFG &#60;15&#41;&#46; Se apreci&#243; una prevalencia considerable de factores de riesgo cardiovascular cl&#225;sicos&#58; dislipemia &#40;29&#44;3&#37;&#41;&#44; obesidad &#40;26&#44;1&#37;&#41;&#44; hipertensi&#243;n &#40;24&#44;1&#37;&#41;&#44; diabetes &#40;9&#44;2&#37;&#41; y tabaquismo activo &#40;25&#44;5&#37;&#41;&#46; Los factores predictores independientes de IRC fueron la edad&#44; la obesidad y la hipertensi&#243;n previamente diagnosticada&#46; <span class="elsevierStyleBold">Conclusiones&#58; </span>La prevalencia de IRC &#40;en cualquier estadio&#41; en la poblaci&#243;n general espa&#241;ola es relativamente elevada&#44; en especial en los individuos de edad avanzada&#44; y similar a la de otros pa&#237;ses del mismo entorno geogr&#225;fico&#46; Adem&#225;s de la edad&#44; dos factores de riesgo modificables&#44; la hipertensi&#243;n y la obesidad&#44; se asociaron con una mayor prevalencia de IRC&#46;</p>"
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Prevalence of chronic renal disease in Spain: Results of the EPIRCE study
on behalf of the EPIRCE Study Group, Alfonso Otero Gonzálezb, A.. de Franciscoc, P.. Gayosob, F.. Garcíad
b Nephrology Department and Research Unit, Ourense Hospital Complex, Orense, Spain,
c Nephrology Department, Hospital Marqués de Valdecilla, Santander, Spain,
d Clinical Epidemiology Unit, University Hospital Puerta de Hierro, Majadahonda, Madrid, Spain,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION </span></p> <p class="elsevierStylePara">Chronic kidney disease &#40;CKD&#41; is a major social health problem&#46; In the last decade&#44; it has been shown that early stages of CKD are asociated with an inflammatory state<span class="elsevierStyleSup">1 </span>that implies an increased cardiovascular morbidity and mortality risk at long term<span class="elsevierStyleSup">2&#44;3</span>&#44; higher than the risk of progression to end-stage renal disease<span class="elsevierStyleSup">2&#44;4</span>&#46; Cardiovascular events are the most common cause of death in these patients<span class="elsevierStyleSup">5</span>&#46; For this reason&#44; microalbuminuria and reduced glomerular filtration rate &#40;GFR&#41; &#40;&#60;60 ml&#47;min&#41; have been added to the list of non traditional cardiovascular risk factors<span class="elsevierStyleSup">6</span>&#46; In many patients&#44; the concurrence of these markers with classical factors as diabetes&#44; hypertension or obesity&#44; predicts accelerated vascular damage and multiplies the associated risk<span class="elsevierStyleSup">2&#44;3</span>&#46;</p> <p class="elsevierStylePara">Furthermore&#44; the prevalence of CKD is growing worldwide due to the increase in related diseases as type 2 diabetes mellitus&#44; obesity&#44; hypertension or atherosclerosis<span class="elsevierStyleSup">7&#44;8</span>&#46; The asymptomatic nature of CKD makes its early detection more difficult&#44; which could be important as the treatment in early stages may prevent or delay its progression<span class="elsevierStyleSup">9</span>&#46; The knowledge of the prevalence of CKD might be useful to assess the level of its underdiagnosis and estimate the impact of potential screening policies&#46;</p> <p class="elsevierStylePara">The 2002 practice guideline of the Kidney Disease Outcomes Quality Initiative &#40;K&#47;DOQI&#41; of the National Kidney Foundation &#40;NKF&#41;<span class="elsevierStyleSup">10 </span>defined CKD as either kidney damage or glomerular filtration rate &#40;GFR&#41; below 60 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> for three or more months&#46; GFR is usually estimated from serum creatinine using one of the following equations&#58; the Cockcroft-Gault &#40;CG&#41;<span class="elsevierStyleSup">11 </span>or the Modification of Diet in Renal Disease Study &#40;MDRD&#41;<span class="elsevierStyleSup">12 </span>equation&#46; These indirect methods are currently considered to be the easiest way to estimate GFR in epidemiologic studies conducted in adult individuals<span class="elsevierStyleSup">13</span>&#46; The MDRD equation is more commonly used<span class="elsevierStyleSup">14</span>&#44; but it leads to a certain underestimation of GFR &#40;6&#46;2&#37; in CKD patients and 29&#37; in healthy persons&#41;<span class="elsevierStyleSup">15</span>&#44; compared to the CG equation&#46; However&#44; it seems that the MDRD equation provides a more accurate estimation in patients with GFR below 60 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#44; with good performance among subgroups of age&#44; sex&#44; race&#44; diabetes or body mass index<span class="elsevierStyleSup">16&#44;17</span>&#46;</p> <p class="elsevierStylePara">In the last five years&#44; more than 25 epidemiological studies have investigated CKD prevalence worldwide<span class="elsevierStyleSup">14</span>&#44; leading to a median prevalence of 7&#46;2&#37; in persons aged 30 years or older&#44; and revealing ethnic-specific differences&#46; In our country&#44; the Spanish Society of Nephrology &#40;S&#46;E&#46;N&#46;&#41; has initiated a program to identify the true population at risk for CKD&#44; and to increase the preventive measures aimed at reducing the incidence of renal failure&#44; cardiovascular complications&#44; and progression to end stage renal failure<span class="elsevierStyleSup">18&#44;19</span>&#46;</p> <p class="elsevierStylePara">Within this program&#44; the &#171;Estudio Epidemi&#243;logico de la Insuficiencia Renal en Espa&#241;a&#187; &#40;EPIRCE&#41; is the first epidemiological study at a national level designed to describe the prevalence of CKD in the general Spanish population aged 20 years or older&#44; using the simplified MDRD equation&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">METHODS </span></p> <p class="elsevierStylePara">The EPIRCE was an epidemiologic&#44; general population-based&#44; cross-sectional study that included a randomly selected Spanish sample aged 20 years or older&#46; The exclusion criteria were residence outside the recruiting municipality&#44; or institutionalization at the time of the study&#46; The protocol was approved by an ethics committee&#44; and all enrolled patients provided informed consent&#46;</p> <p class="elsevierStylePara">The target sample were 13&#44;013 individuals&#44; stratified by age&#44; sex&#44; and habitat within each Spanish region&#44; according to the 2001 Census&#46; A total of 6&#44;464 out of the initial list of 13&#44;013 were finally contacted for the study&#46; Census errors were the most important reason for the impossibility to contact individuals&#46; The sample was recruited between January 2004 and January 2008 in 42 points &#40;municipalities&#41;&#46; The final completed interviews were 2&#44;746&#44; and the response rate was 42&#46;5&#37;&#46;</p> <p class="elsevierStylePara">Data were collected as follows&#46; First&#44; a letter describing the study was sent to each randomly selected individual&#46; Next&#44; a health professional contacted the potential respondents by phone to verify inclusion and exclusion criteria&#44; ask for participation&#44; and make appointments with those who volunteered&#46; A minimum of three negative answers were required to discard a selected individual&#46;</p> <p class="elsevierStylePara">The collected variables included anthropometric and sociodemographic data &#40;age&#44; gender&#44; ethnicity&#44; weight&#44; height&#44; body mass index&#41;&#44; blood pressure and clinical history at study inclusion &#40;obesity&#44; hypertension&#44; diabetes mellitus&#44; dyslipemia&#44; cardiovascular disease&#44; gout&#44; renal lithiasis&#44; CKD&#44; transplant&#41;&#46; Participants were also interviewed to determine their smoking and exercise habits&#44; alcohol consumption&#44; drug abuse and use of nephrotoxic drugs&#46; After informed consent was provided&#44; a blood sample was obtained from each individual for biochemical tests&#46; Serum creatinine concentration was determined in the same reference laboratory for all samples&#46; GFR was calculated as an indicator of renal function with the simplified MDRD formula<span class="elsevierStyleSup">20</span>&#44; and participants were classified according to the Kidney Disease Outcomes Quality Initiative guidelines<span class="elsevierStyleSup">10</span>&#46; Stage 3 was split into 3a &#40;GFR 45-59 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41; and 3b &#40;GFR 30-44 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&#46; Other analytical determinations included&#58; glucose&#44; urea&#44; total cholesterol &#40;C&#41;&#44; tryglicerydes &#40;Tg&#41;&#44; HDL-C&#44; LDL-C&#44; insulin resistance index &#40;HOMA&#41;&#44; haemoglobin &#40;Hb&#41;&#44; ferritin&#44; uric acid and urinary albumin to creatinine ratio&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical methods </span></p> <p class="elsevierStylePara">Adjustment weights were used to correct for non-response bias&#44; with the age&#44; gender and habitat distribution of survey respondents being equated to the population structure as determined from the 2001 census&#46; All prevalence and mean estimates were calculated with the weighted sample&#44; and asymptotic 95&#37; confidence intervals &#40;CI&#41; were obtained&#46; Univariate and multivariate logistic regression analyses&#44; also weighted for non-response bias&#44; were used to calculate the odds ratio &#40;OR&#41; and CIs for candidate CKD risk factors&#46; P values &#60;0&#46;05 were considered significant&#46; Since there were statistically significant differences in the response rate between participating municipalities &#40;data not shown&#41;&#44; a sensitivity analysis was performed comparing the results between highly responding centers &#40;&#62;60&#37; of response rate&#44; n &#61; 1&#44;098&#41; and the overall group&#44; to assess for a possible non-response bias&#46; All analyses were performed with SAS version 9&#46;1&#46;3 Service Pack 4 &#40;SAS Institute Inc&#46;&#44; Carey&#44; North caroline&#44; USA&#41;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS </span></p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Sociodemographic and clinical characteristics </span></p> <p class="elsevierStylePara">Table 1 and 2 show the characteristics of the 2&#44;746 respondents &#40;weighted estimates&#41;&#46; Mean age was 49&#46;5 years&#44; and about one quarter of individuals were older than 64 years &#40;25&#46;8&#37;&#41;&#46; As in the general Spanish population&#44; the ratio male&#58;female was 0&#46;9&#44; almost all were caucasian &#40;99&#46;1&#37;&#41;&#44; and the residence was urban in two thirds of cases &#40;66&#46;1&#37;&#41;&#46;</p> <p class="elsevierStylePara">Clinical history revealed an important prevalence of previously diagnosed dyslipemia &#40;29&#46;3&#37;&#41;&#44; obesity &#40;26&#46;1&#37;&#41;&#44; hypertension &#40;24&#46;1&#37;&#41; and diabetes &#40;9&#46;2&#37;&#41;&#46; Among cardiovascular events&#44; peripheral vascular episodes were the most frequent &#40;10&#46;8&#37;&#41;&#44; followed by ischaemic heart disease &#40;5&#46;1&#37;&#41; and cerebrovascular disease &#40;1&#46;7&#37;&#41;&#46; Current smoking habit and habitual alcohol intake were frequent &#40;25&#46;5&#37; and 45&#46;1&#37;&#44; respectively&#41;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">CKD prevalence </span></p> <p class="elsevierStylePara">The overall prevalence of CKD stages 3-5 &#40;eGFR &#60;60 ml&#47;min&#41; was 6&#46;83 &#37;&#44; with a 95&#37; CI of 5&#46;41 to 8&#46;25 &#40;3&#46;33&#37; for age 40&#173;64 years and 21&#46;42&#37; for age &#62;64 years&#41;&#46; When the albumin to creatinine ratio was added to the diagnostic criteria&#44; the prevalence rose to 9&#46;16&#37; &#40;95&#37; CI&#44; 7&#46;5 to 10&#46;8&#41;&#46; The prevalence estimates of CKD stages were&#58; 0&#46;99&#37; for stage 1&#59; 1&#46;3&#37; for stage 2&#59; 5&#46;4&#37; for stage 3a&#59; 1&#46;1&#37; for stage 3b&#59; 0&#46;27&#37; for stage 4&#59; and 0&#46;03&#37; for stage 5 &#40;table 2&#41;&#46; The prevalence of proteinuria &#40;ACR&#62;30 mg&#47;g&#41; in stage 3a was 5&#46;9&#37;&#44; in stage 3b&#44; 6&#46;8&#37;&#44; and in stage 4&#44; 36&#46;7&#37;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Risk factors for CKD </span></p> <p class="elsevierStylePara">Table 3 shows the unadjusted associations between sociodemographic and clinical characteristics of the patients and CKD&#46; The strongest predictor factor was age&#46; The observed odds ratios &#40;OR&#41; were 34&#46;4 for individuals between 40-64 years with respect to those between 20-39 years&#44; and 267&#46;5 for individuals above 64 years&#46; Other strong predictor factors were hypertension&#44; especially when previously diagnosed &#40;OR 5&#46;9&#41;&#44; pulse pressure above 60 mmHg &#40;OR 3&#46;8&#41;&#44; previous history of cardiovascular events &#40;ORs 4&#46;1 for ischaemic heart disease&#44; 3&#46;3 for cerebrovascular disease and 2&#46;1 for peripheral vascular disease&#41;&#44; overweight or obesity &#40;ORs of 2&#46;3 and 3&#46;5&#44; respectively&#41;&#44; diabetes &#40;OR 2&#46;4 for previously diagnosed patients&#41;&#44; dyslipemia &#40;OR 2&#46;1 for previously diagnosedpatients&#41; and gout &#40;OR 2&#46;2&#41;&#46;</p> <p class="elsevierStylePara">In the multivariate analysis&#44; the independent predictor factors that remained in the model were age&#44; obesity and previously diagnosed hypertension &#40;table 4&#41;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Sensitivity analyses </span></p> <p class="elsevierStylePara">Individuals recruited at highly responding centers &#40;&#62;60&#37; of response rate&#44; n &#61; 1&#44;098&#41; were healthier according to the following differences with respect to the overall sample&#58; they were less obese &#40;22&#46;9&#37; with BMI &#62;30 kg&#47;m<span class="elsevierStyleSup">2 </span>versus 26&#46;1&#37; in the total population&#41;&#44; less sedentary &#40;25&#46;4&#37; versus 28&#46;9&#37;&#41; and suffered less diabetes &#40;5&#46;2&#37; of non previously diagnosed diabetes versus 7&#46;0&#37;&#41;&#46; They also displayed more percentage of habitual alcohol consumption &#40;49&#46;7&#37; versus 45&#46;1&#37;&#41;&#46; Despite these findings&#44; the prevalence of CKD stages 3-5 in this subgroup was equivalent to that found in the overall sample&#58; 6&#46;65 &#40;95&#37; CI of 4&#46;66 to 8&#46;64&#41;&#46; The prevalence of proteinuria &#40;ACR &#62;30 mg&#47;g&#41; was slightly lower &#40;3&#46;6&#37;&#44; 95&#37; CI 1&#46;4 to 5&#46;8&#41;&#44; but not significantly different&#46; No differences were observed either in the prevalences within age&#44; gender or habitat categories&#44; nor in the risk factors associated to CKD &#40;data not shown&#41;&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION </span></p> <p class="elsevierStylePara">The present study is the first epidemiological investigation of the prevalence of CKD in Spanish population aged 20 years or older at a national level&#46; The recruited sample is representative of all regions&#44; and has been adjusted to provide valid estimates of CKD prevalence in age&#44; gender and habitat subgroups&#44; according to the real distribution of Spanish population in 2001&#46;</p> <p class="elsevierStylePara">The prevalence of CKD found in our study &#40;6&#46;8&#37;&#41; is very similar to the median reported in a systematic review of 26 epidemiological studies around the world &#40;7&#46;2&#37;&#41;<span class="elsevierStyleSup">14</span>&#46; Since ethnic-specific differences have been reported<span class="elsevierStyleSup">14</span>&#44; the relevant comparisons with other European countries show that the prevalence in Spain remains within the range of previous studies that have used the MDRD equation &#40;4&#46;7-8&#46;1&#37; in studies from Italy<span class="elsevierStyleSup">21</span>&#44; Switzerland<span class="elsevierStyleSup">22</span>&#44; Norway<span class="elsevierStyleSup">23 </span>and Iceland<span class="elsevierStyleSup">24</span>&#41;&#46; These estimates are also similar to those from the US National Health and Nutrition Examination Surveys &#40;NHANES&#41; &#40;5&#46;6&#37; in 1988 through 1994 and 8&#46;05&#37; in 1999 through 2004&#41;<span class="elsevierStyleSup">25</span>&#44; despite the incidence of end stage renal disease &#40;ESRD&#41; in this country being much higher than in Europe<span class="elsevierStyleSup">26</span>&#46; The epidemiological study from Norway<span class="elsevierStyleSup">23 </span>investigated the progression rate from CKD stages 3 or 4 to ESRD in their cohort and found that the relative risk of progression in US caucasian patients was 2&#46;5 times higher than in Norwegian patients&#46; Among the possible explanations for these differences they postulate a later referral to nephrologist and a higher presence of obesity and diabetes in the US population&#46;</p> <p class="elsevierStylePara">The addition of the albumin&#47;creatinine ratio to the CKD diagnosis &#40;stages 1 and 2&#41; allowed to detect a further 2&#46;3&#37; of population at risk&#44; which substantially improves diagnostic accuracy without losing predictive power&#46; According to previous studies&#44; referral based on current stages 3 to 4 CKD identifies approximately only 70&#37; of all individuals that progress to ESRD<span class="elsevierStyleSup">27</span>&#46;</p> <p class="elsevierStylePara">We found a high prevalence of conventional risk factors&#44; overweight and obesity&#44; hypertension&#44; diabetes&#44; dyslipemia and smoking&#46; All of them were significantly associated to CKD&#44; which agrees with previous findings<span class="elsevierStyleSup">28&#44;29</span>&#46; With respect to smoking habit&#44; we did not find a significant association with current smoking&#44; but the ex-smoker status was related to a higher frequency of stage 4 CKD&#46; A possible explanation is that&#44; previous to the study entry&#44; these patients had already suffered other health problems that compelled them to discontinue tobacco&#46; Unexpectedly&#44; the habitual alcohol intake was inversely associated to CKD&#44; which partially agrees with the study of Kronborg et al&#46;&#44; who found that alcohol consumption in men predicted an increase in eGFR<span class="elsevierStyleSup">28&#44;29</span>&#46; Red wine has been shown to improve surrogate markers for cardiovascular disease&#44; such as nitric oxid release in the vessel wall&#46; It also possesses anti-inflammatory and anti-oxidative properties&#44; and inhibits platelet-derived growth factor-beta receptor phosphorylation<span class="elsevierStyleSup">30</span>&#46; However&#44; it would be very difficult to perform prospective&#44; randomized studies to demonstrate the benefits of moderate alcohol consumption&#44; as the important secondary harmful effects &#40;such as liver cirrhosis&#44; blood pressure elevation&#44; cancer or accidents&#41; should be taken into account&#46;</p> <p class="elsevierStylePara">The three independent predictor factors for CKD were increasing age&#44; obesity and history of hypertension&#44; which suggests that these conditions predispose to renal impairment through different mechanisms&#46;</p> <p class="elsevierStylePara">The decline in GFR with age has been repeatedly described<span class="elsevierStyleSup">14</span>&#46; The prevalence of CKD in patients above 64 years found in the EPIRCE study &#40;21&#46;4&#37;&#41; is comparable to that reported in other European countries &#40;15-25&#37;<span class="elsevierStyleSup">21-24</span>&#41;&#44; usually with higher prevalences in older women<span class="elsevierStyleSup">22&#44;24</span>&#46; The reduction starts progressively in the third decade of life&#44; and becomes steeper after the age of 60&#44; although it has not been observed in all individuals<span class="elsevierStyleSup">31</span>&#46; There are several hypotheses to explain this phenomenon&#58; it can be related to pathologic processes &#40;cumulated immunologic&#44; infectious&#44; or toxic damage&#41;&#44; progressive ischemia due to vascular aging&#44; or cummulative changes in kidney structure due to hyperperfusion and hyperfiltration with resultant glomerulosclerosis<span class="elsevierStyleSup">32&#44;33</span>&#46;</p> <p class="elsevierStylePara">The contribution of sustained high blood pressure levels to renal function deterioration is well established&#58; systemic and glomerular hypertension results in increased urinary excretion of proteins and accelerates renal function deterioration&#46; Many studies have demonstrated that an adequate&#44; or even intensified blood pressure control &#40;less than 130&#47;80 mmHg&#41;&#44; can slow the progression of diabetic and non diabetic renal disease<span class="elsevierStyleSup">34</span>&#46; Moreover&#44; long-term studies indicate that the change in GFR may be minimal in well-controlled hypertensive patients&#44; and that patients with nonmalignant essential hypertension with early and good blood pressure control do not develop renal failure<span class="elsevierStyleSup">35</span>&#46; The relationship found in our cohort might be the result of inadequately controlled blood pressure levels in the individuals with current CKD&#46;</p> <p class="elsevierStylePara">The association between CKD and obesity was previously described in a prospective study of a large cohort<span class="elsevierStyleSup">36</span>&#46; The increase in body weight with time&#44; even within normal BMI values&#44; has also been independently associated with an increased risk for CKD<span class="elsevierStyleSup">37</span>&#46; One of the proposed mechanisms for the development of CKD in obese patients is the presence of an increased inflammation status&#46; This is supported by the study of Bavbek et al&#46;&#44; who found elevated serum C-reactive protein &#40;CRP&#41; levels in obese patients versus age-matched healthy controls&#44; and a negative correlation between CRP levels and GFR<span class="elsevierStyleSup">38</span>&#46; In morbidity obese patients who underwent very important weight reduction after biliopancreatic diversion all cardiovascular risk factors &#40;hypertension&#44; diabetes&#44; hyperlipidemia&#44; proteinuria &#41; improved during follow-up<span class="elsevierStyleSup">39</span>&#46;</p> <p class="elsevierStylePara">An early identification of CKD in primary care is very important&#44; as specialist referral at an appropriate timing may improve long-term outcomes&#46; It has been reported that&#44; in Spain&#44; late referral to nephrologist is common in chronic diseases such as diabetes or hypertension<span class="elsevierStyleSup">40</span>&#46; Our results indicate that almost ten percent of adult individuals may suffer some degree of renal impairment&#44; and therefore&#44; reveal the need for taking this disease into account&#46; In addition&#44; our findings suggest that the control of classical cardiovascular risk factors as obesity or hypertension in primary care setting might help preventing CKD development&#46;</p> <p class="elsevierStylePara">The main limitation of the study is its poor response rate&#46; The sensitivity analysis excluding the centers with low participation revealed some non-response bias&#44; which did not appear to introduce substantial bias into CKD and proteinuria prevalence estimates&#46; Another limitation is the indirect GFR estimation method&#44; based on a single creatinine measurement&#44; that should be used with caution<span class="elsevierStyleSup">41</span>&#46; Currently&#44; the benefit of performing extensive screening of unselected populations with the intention to reduce the subsequent risk of cardiovascular events or progression to end-stage-renal disease remains unproven<span class="elsevierStyleSup">42</span>&#46; Although the MDRD equation is the most commonly used in epidemiological studies<span class="elsevierStyleSup">14</span>&#44; it underestimates the GFR<span class="elsevierStyleSup">15</span>&#46; Moreover&#44; the cut-off value of 60 ml&#47;min per 1&#46;73 m<span class="elsevierStyleSup">2</span><span class="elsevierStyleSup">&#160;</span>for all ages leads to over diagnosis in elderly population&#46; A new equation recently developed seems to improve the GFR estimation<span class="elsevierStyleSup">43</span>&#46; Finally&#44; the cross-sectional design of the study does not allow inferring causal relationships between the risk factors and CKD&#46;</p> <p class="elsevierStylePara">Some strenghts of our study are its large sample size&#44; well representative of the different Spanish regions&#44; and the random selection of the participants&#46; The agreement with results from other European countries supports the external validity of our findings&#46;</p> <p class="elsevierStylePara">In conclusion&#44; we found a relatively high prevalence of assymptomatic CKD &#40;almost one of ten&#41; in apparently healthy general population from Spain&#44; especially in older&#44; obese and hypertensive patients&#46; Independently of age&#44; many of the risks factors for CKD are modifiable&#58; hypertension&#44; diabetes mellitus&#44; obesity&#44; dyslipemia and smoking&#46; Further studies should assess whether early detection of CKD in general population might avoid CKD progression and protect from associated cardiovascular risk factors&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Acknowledgements </span></p> <p class="elsevierStylePara">This study was supported in part by a grant from Amgen&#44; S&#46;A&#46; Writing assistance was supported by Amgen&#46;<br /><span class="elsevierStyleBold">Co-authors&#46; This study has been conducted by the above-signed authors&#44; Neus Valveny from Trial Form Support&#44; David Calbet from Saatchi&#38;Saatchi Healthcare&#44; and the EPIRCE study group&#46;<br /></span>The Coordinating investigators in each Authonomous Community were&#58; Andaluc&#237;a&#58; M&#46;A&#46; &#193;lvarez de Lara&#59; Asturias&#58; F&#46; Vega&#59; Arag&#243;n&#58; C&#46; Laviades&#44; P&#46;J&#46; Vives&#44; J&#46;M&#46; Pe&#241;a Porta&#59; Baleares&#58; J&#46; Marco&#44; A&#46; Sol&#237;s&#44; A&#46; Losada Gonz&#225;lez&#59; Cantabria&#58; G&#46; Fern&#225;ndez Fresnedo&#59; Canarias&#58; J&#46;F&#46; Navarro&#44; J&#46;A&#46; S&#225;nchez Joga&#59; Catalunya&#58; J&#46; Fort&#44; A&#46; Mart&#237;nez Castelao&#44; N&#46; Fonser&#233;&#59; Castilla-La Mancha&#58; F&#46; Tornero&#44; M&#46; Quintana&#59; Castilla-Le&#243;n&#58; J&#46; Grande Villoria&#44; A&#46; Molina&#44; M&#46;B&#46; Alaguero&#44; G&#46; Torres&#59; Ceuta y Melilla&#58; C&#46; Fern&#225;ndez Andrade&#59; Euskadi&#58; F&#46; Vidaur&#44; J&#46; Manrique&#44; M&#46; Rodr&#237;guez&#59; Extremadura&#58; F&#46; Caravaca&#44; B&#46; Cancho&#59; Galicia&#58; A&#46; Otero&#44; L&#46; Gonz&#225;lez&#59; La Rioja&#58; A&#46; S&#225;nchez Casaj&#250;s&#59; Madrid&#58; F&#46; Garc&#237;a&#44;&#160; M&#46; San Boixedau&#44; K&#46; L&#243;pez&#44; E&#46; Rubio&#44; C&#46; Bernis&#59; Murcia&#58; M&#46; Giron&#233;s&#59; Navarra&#58; J&#46;L&#46; As&#237;n&#59; Valencia&#58; J&#46; Hern&#225;ndez Jaras&#44; A&#46; Rius&#44; M&#46; Gonz&#225;lez Rico&#46;</p> <p class="elsevierStylePara"><a href="grande&#47;1011718078&#95;t2&#95;pag83&#46;jpg" class="elsevierStyleCrossRefs"><img src="1011718078_t2_pag83.jpg" alt="Prevalence of chronic kidney disease in the Spanish population aged 20 years or older based on the cohort collected in the EPIRCE study &#40;n &#61; 2&#44;746&#41;"/></a></p> <p class="elsevierStylePara">Table 2&#46; Prevalence of chronic kidney disease in the Spanish population aged 20 years or older based on the cohort collected in the EPIRCE study &#40;n &#61; 2&#44;746&#41;</p> <p class="elsevierStylePara"><a href="grande&#47;1011718078&#95;t3&#95;pag84&#46;jpg" class="elsevierStyleCrossRefs"><img src="1011718078_t3_pag84.jpg" alt="Unadjusted associations between demographic or clinical characteristics and the presence of chronic kidney disease &#40;eGFR &#60;60 ml&#47;min per 1&#46;73 m2&#41;"/></a></p> <p class="elsevierStylePara">Table 3&#46; Unadjusted associations between demographic or clinical characteristics and the presence of chronic kidney disease &#40;eGFR <60 ml min per 1 73 m2</60></p> <p class="elsevierStylePara"><a href="grande&#47;1011718078&#95;t4&#95;pag85&#46;jpg" class="elsevierStyleCrossRefs"><img src="1011718078_t4_pag85.jpg" alt="Independent predictors of chronic kidney disease &#40;eGFR &#60;60 ml&#47;min per 1&#46;73 m2&#41; in the multivariate logistic regression model"/></a></p> <p class="elsevierStylePara">Table 4&#46; Independent predictors of chronic kidney disease &#40;eGFR <60 ml min per 1 73 m2 in the multivariate logistic regression model</60></p> <p class="elsevierStylePara"><a href="grande&#47;1011718078&#95;t1&#95;pag81&#95;copy1&#46;jpg" class="elsevierStyleCrossRefs"><img src="1011718078_t1_pag81_copy1.jpg" alt="Demographic and clinical characteristics of Spanish population aged 20 years or older based on the cohort collected in the EPIRCE study &#40;n &#61; 2&#44;746&#41;"/></a></p> <p class="elsevierStylePara">Table 1&#46; Demographic and clinical characteristics of Spanish population aged 20 years or older based on the cohort collected in the EPIRCE study &#40;n &#61; 2&#44;746&#41;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction&#58; </span>Chronic kidney disease &#40;CKD&#41; is an independent cardiovascular risk factor&#46; The knowledge of prevalence in general population may help to early detection of CKD and prevent or delay its progression&#46; <span class="elsevierStyleBold">Methods&#58; </span>Sociodemographic&#44; baseline characteristics&#44; and CKD prevalence &#40;measured by centralized serum creatinine and MDRD equation&#41; were evaluated in a randomly selected sample of general population aged 20 years or older&#44; collected in all Spanish regions and stratified by habitat&#44; age and sex according to 2001 census &#40;n &#61; 2&#44;746&#41;&#46; Univariate and multivariate logistic regression analyses were used to evaluate associations with CKD risk factors&#46; <span class="elsevierStyleBold">Results&#58; </span>Mean age was 49&#46;5 years&#46; The overall prevalence of Kidney Disease Outcomes Quality Initiative grades 3-5 CKD was 6&#46;8&#37;&#44; with a 95&#37; confidence interval &#40;CI&#41; of 5&#46;4 to 8&#46;2 &#40;3&#46;3&#37; for age 40-64 years and 21&#46;4&#37; for age &#62;64 years&#41;&#46; The prevalence estimates of CKD stages were&#58; 0&#46;99&#37; for stage 1 &#40;glomerular filtration rate &#91;GFR&#93; &#62;&#95;90 ml&#47;min per 1&#46;73 m<span class="elsevierStyleSup">2</span> with proteinuria&#41;&#59; 1&#46;3&#37; for stage 2 &#40;GFR 60-89&#41;&#59; 5&#46;4&#37; for stage 3a &#40;GFR 45-59&#41;&#59; 1&#46;1&#37; for stage 3b &#40;GFR 30-44&#41;&#59; 0&#46;27&#37; for stage 4 &#40;GFR 15-29&#41;&#59; and 0&#46;03&#37; for stage 5 &#40;GFR &#60;15&#41;&#46; An important prevalence of classical cardiovascular risk factors was observed&#58; dyslipemia &#40;29&#46;3&#37;&#41;&#44; obesity &#40;26&#46;1&#37;&#41;&#44; hypertension &#40;24&#46;1&#37;&#41;&#44; diabetes &#40;9&#46;2&#37;&#41; and current smoking &#40;25&#46;5&#37;&#41;&#46; The independent predictor factors for CKD were age&#44; obesity and previously diagnosed hypertension&#46; <span class="elsevierStyleBold">Conclusions&#58; </span>The prevalence of CKD at any stage in general population from Spain is relatively high&#44; especially in the elderly&#44; and similar to countries of the same geographical area&#46; Independently of age&#44; two modifiable risks factors&#44; hypertension and obesity&#44; are associated with an increased prevalence of CKD&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introducci&#243;n&#58; </span>La insuficiencia renal cr&#243;nica &#40;IRC&#41; constituye un factor de riesgo cardiovascular independiente&#46; El conocimiento de su prevalencia en la poblaci&#243;n general puede contribuir a la detecci&#243;n precoz de esta enfermedad y de prevenir o retrasar su evoluci&#243;n&#46; <span class="elsevierStyleBold">M&#233;todos&#58; </span>Se seleccion&#243; una muestra aleatoria de poblaci&#243;n general espa&#241;ola&#44; con edad igual o superior a 20 a&#241;os&#44; distribuida por todo el territorio nacional y estratificada por h&#225;bitat&#44; edad y sexo conforme al censo de 2001 &#40;n &#61; 2&#46;746&#41;&#46; Se recopilaron datos sociodemogr&#225;ficos y cl&#237;nicos&#44; y se evalu&#243; la prevalencia de IRC mediante determinaci&#243;n centralizada de creatinina s&#233;rica y aplicaci&#243;n de la ecuaci&#243;n MDRD&#46; Se llevaron a cabo an&#225;lisis univariantes y multivariantes para evaluar la asociaci&#243;n entre la IRC y diversos factores de riesgo&#46; <span class="elsevierStyleBold">Resultados&#58; </span>La edad media fue de 49&#44;5 a&#241;os&#46; La prevalencia global de IRC en estadios 3-5&#44; seg&#250;n la Kidney Disease Outcomes Quality Initiative&#44; fue del 6&#44;8&#37;&#44; con un intervalo de confianza del 95&#37; &#40;IC&#41; de 5&#44;4 a 8&#44;2 &#40;3&#44;3&#37; para edades 40-64 a&#241;os y 21&#44;4&#37; para edades &#62;64 a&#241;os&#41;&#46; Las prevalencias estimadas para cada uno de los estadios de IRC fueron&#58; 0&#44;99&#37; para estadio 1 &#40;tasa de filtrado glomerular &#91;TFG&#93; &#62;&#95;90 ml&#47;min por 1&#44;73 m<span class="elsevierStyleSup">2</span><span class="elsevierStyleSup">&#160;</span>con proteinuria&#41;&#59; 1&#44;3&#37; para estadio 2 &#40;TFG 60-89&#41;&#59; 5&#44;4&#37; para estadio 3a &#40;TFG 45-59&#41;&#59; 1&#44;1&#37; para estadio 3b &#40;TFG 30-44&#41;&#59; 0&#44;27&#37; para estadio 4 &#40;TFG 15-29&#41;&#44; y 0&#44;03&#37; para estadio 5 &#40;TFG &#60;15&#41;&#46; Se apreci&#243; una prevalencia considerable de factores de riesgo cardiovascular cl&#225;sicos&#58; dislipemia &#40;29&#44;3&#37;&#41;&#44; obesidad &#40;26&#44;1&#37;&#41;&#44; hipertensi&#243;n &#40;24&#44;1&#37;&#41;&#44; diabetes &#40;9&#44;2&#37;&#41; y tabaquismo activo &#40;25&#44;5&#37;&#41;&#46; Los factores predictores independientes de IRC fueron la edad&#44; la obesidad y la hipertensi&#243;n previamente diagnosticada&#46; <span class="elsevierStyleBold">Conclusiones&#58; </span>La prevalencia de IRC &#40;en cualquier estadio&#41; en la poblaci&#243;n general espa&#241;ola es relativamente elevada&#44; en especial en los individuos de edad avanzada&#44; y similar a la de otros pa&#237;ses del mismo entorno geogr&#225;fico&#46; Adem&#225;s de la edad&#44; dos factores de riesgo modificables&#44; la hipertensi&#243;n y la obesidad&#44; se asociaron con una mayor prevalencia de IRC&#46;</p>"
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Article information
ISSN: 20132514
Original language: English
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Idiomas
Nefrología (English Edition)