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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Patients with diabetes mellitus &#40;DM&#41; have a substantially higher risk of developing end-stage chronic kidney disease &#40;ESCKD&#41; and cardiovascular disease&#44; with increased associated morbidity and mortality rates&#46;<span class="elsevierStyleSup">1-3</span> Kidney transplantation is the treatment of choice for these patients&#44; since it effectively reduces mortality as compared to diabetic and non-diabetic patients that remain on dialysis treatment&#46;<span class="elsevierStyleSup">4&#44;5</span></p><p class="elsevierStylePara">Approximately half of all patients with ESCKD have cardiovascular disease when they start dialysis treatment&#46;<span class="elsevierStyleSup">6</span> One third of all diabetics with ESCKD have coronary artery disease &#40;CAD&#41; that is clinically silent&#46;<span class="elsevierStyleSup">6</span> Despite kidney transplantation&#44; the percentage of deaths due to cardiovascular disease continues to be a source of concern in the initial post-transplant phase&#46;<span class="elsevierStyleSup">7-9</span></p><p class="elsevierStylePara">Although current guidelines suggest a selective conservative approach for the risk stratification of this population&#44; few specific tests exist for this sub-group of patients&#46;<span class="elsevierStyleSup">8</span> Several studies have evaluated the sensitivity of at-rest electrocardiograms and non-invasive procedures&#44; coming to the conclusion that these testing methods are not adequate in diabetic patients with ESCKD&#46;<span class="elsevierStyleSup">9-11</span> As a result&#44; there is still no consensus regarding what type of screening method is most appropriate for ruling out ischaemic pathologies in these patients and predicting post-transplant coronary complications&#46; Catheterisation involves substantial associated morbidity rates&#44; including contrast-induced nephropathy&#44; and can accelerate the need for starting dialysis&#46; However&#44; the benefits of coronary angiography outweigh the risks in patients with ESCKD&#46;<span class="elsevierStyleSup">12-15</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">PATIENTS AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Study population</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We carried out an observational&#44; descriptive&#44; retrospective study on the epidemiological and clinical aspects of diabetic patients with ESCKD&#46; We reviewed the clinical histories of asymptomatic diabetic patients with ESCKD who underwent pre-kidney transplant examinations in the Hospital General de Ciudad Real between January 2007 and October 2011&#46; The criteria for indicating CAD screening by cardiac catheterisation were&#58; age &#40;&#62;45 years&#41; and duration of diabetes &#40;&#62;15 years with type 1 DM&#44; &#62;10 years with type 2 DM and no other cardiovascular risk factors&#44; &#62;5 years with type 2 DM and other cardiovascular risk factors&#41;&#46; A total of 36 patients were identified with DM and no history of angina&#44; myocardial infarction&#44; or revascularisation with percutaneous or surgical coronary angioplasty&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Clinical and demographic data</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We measured the following clinical and demographic variables&#58; age &#40;years&#41;&#44; gender&#44; type of DM &#40;type 1 or 2&#41;&#44; duration of DM &#40;years&#41;&#44; family history of coronary disease&#44; arterial hypertension&#44; dyslipidaemia&#44; tobacco use &#40;including patients that quit using tobacco within the last 10 years&#41;&#44; obesity &#40;body mass index &#62;25kg&#47;m<span class="elsevierStyleSup">2</span>&#59; as such including overweight and obese patients&#41;&#44; pre-catheterisation treatment with statins&#44; oral anti-diabetic and&#47;or insulin treatment&#44; type of dialysis &#40;haemodialysis&#44; peritoneal dialysis&#41;&#44; glycosylated haemoglobin &#40;&#37;&#41;&#44; total cholesterol &#40;mg&#47;dl&#41;&#44; and low-density lipoprotein &#40;LDL&#41; cholesterol &#40;mg&#47;dl&#41;&#46;</p><p class="elsevierStylePara">The results of the cardiac catheterisation and the dates of the procedure were obtained from the haemodynamics department&#46; The percentage of stenosis required for diagnosing significant CAD was&#58; &#62;50&#37; in the left coronary artery &#40;LCA&#41; and the proximal segment of the left anterior descending &#40;LAD&#41; artery and &#62;70&#37; in all other segments&#46; The coronary disease distribution was described based on the affected vessel&#58; LCA&#44; LAD artery&#44; circumflex artery &#40;CX&#41;&#44; and right coronary &#40;RCA&#41; artery&#46; In addition&#44; left ventricular ejection fraction was measured using ventriculography &#40;&#37;&#41; and level of ventricular dysfunction &#40;mild&#58; 45&#37;-55&#37;&#44; moderate&#58; 30&#37;-45&#37;&#44; and severe&#58; &#62;30&#37;&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We evaluated continuous variables for normal distribution using the Kolmogorov-Smirnov test&#46; Continuous variables with a normal distribution were presented as mean &#177; standard deviation&#46; Discrete variables were presented as frequencies &#40;percentages&#41; and compared using chi-square tests&#46; We used Student&#8217;s t-tests for comparing continuous variables&#46; The relationship between pairs of qualitative variables was assessed using contingency tables and Pearson&#8217;s chi-square tests&#44; considering significant any <span class="elsevierStyleItalic">P</span>-value &#60;0&#46;05&#46;</p><p class="elsevierStylePara">We also performed a multivariate analysis using multiple logistic regression analyses to evaluate which factors were associated with significant CAD in diabetic ESCKD patients on the kidney transplant waiting list&#46; We considered the presence of significant coronary disease &#40;1&#58; yes&#59; 0&#58; no&#41; as the dependent variable&#46; The independent variables considered were&#58; dyslipidaemia &#40;1&#58; yes&#59; 0&#58; no&#41;&#44; tobacco use &#40;1&#58; yes&#44; 0&#58; no&#41;&#44; glycosylated haemoglobin &#40;&#37;&#41;&#44; and total cholesterol &#40;mg&#47;dl&#41;&#46; These variables were fed into a multiple logistic regression model&#59; using the Wald statistic&#44; and variables with a <span class="elsevierStyleItalic">P</span>&#8805;&#46;15 &#40;using a backwards selection procedure&#41; were eliminated from the model&#46; We used likelihood ratios to compare the final reduced model with the model containing all variables&#46;</p><p class="elsevierStylePara">The scale of the different continuous variables was evaluated using Box Tidwell tests&#46; We studied possible interactions between variables&#44; and variables with a significance level greater than 0&#46;05 were examined as possible confounding factors&#46; They were considered confounding factors if the change coefficients were &#62;15&#37;&#46; We used the Cook distance test in extreme cases&#46; We also used the Hosmer&#8211;Lemeshow test based on percentiles to evaluate the goodness of fit of the model&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The demographic and clinical characteristics of the sample were&#58; mean age was 52&#177;13 years &#40;range&#58; 32-72 years&#41;&#59; 66&#46;7&#37; were male&#44; 55&#46;6&#37; had type 1 DM&#44; mean time of DM was 16&#177;4&#46;8 years &#40;range&#58; 7-24 years&#41;&#59; 75&#37; were on haemodialysis&#44; 36&#37; had a family history of CAD&#44; 86&#46;1&#37; had hypertension&#44; 58&#46;3&#37; had dyslipidaemia&#44; 52&#46;8&#37; were smokers&#44; and 63&#46;9&#37; were obese&#46; As regards the pre-catheterisation treatment&#44; 41&#46;7&#37; of patients received statins&#44; 36&#46;1&#37; received oral anti-diabetics&#44; and 94&#46;4&#37; were on treatment with insulin&#46; The biochemical test results showed the following mean values&#58; glycosylated haemoglobin&#58; 6&#46;9&#37;&#177;0&#46;8&#37;&#59; total cholesterol&#58; 209&#46;46&#177;41&#46;05mg&#47;dl&#59; and LDL cholesterol&#58; 117&#46;58&#177;26&#46;34mg&#47;dl&#41;&#46;</p><p class="elsevierStylePara">The distribution of coronary vessels with significant damage &#40;&#62;50&#37; in proximal LAD and LCA&#59; &#62;70&#37; in all other segments&#41; is shown in Figure 1&#46; Of the 36 patients in the study&#44; 26 &#40;72&#46;2&#37;&#41; had significant CAD in one or more vessels&#46; According to the number of vessels&#44; we found that&#58; LCA disease and 1 vessel in 2 patients &#40;5&#46;6&#37;&#41;&#44; LCA and 2 vessels in 1 patient &#40;2&#46;8&#37;&#41;&#44; and LCA and 3 vessels in 2 patients &#40;5&#46;6&#37;&#41;&#46; Coronary disease different from LCA &#40;LAD&#44; RCA&#44; CX&#41; were as follows&#58; disease in 1 vessel in 6 patients &#40;16&#46;7&#37;&#41;&#44; 2 vessels in 10 patients &#40;27&#46;8&#37;&#41;&#44; and 3 vessels in 5 patients &#40;13&#46;9&#37;&#41;&#46; The distribution of significant lesions by coronary artery was as follows&#58; significant LAD disease in 23 patients &#40;63&#46;9&#37;&#41;&#44; CX in 18 patients &#40;50&#37;&#41;&#44; and RCA in 10 patients &#40;27&#46;8&#37;&#41;&#46; Mean ventricular ejection fraction &#40;by ventriculography&#41; was 50&#46;28&#37;&#177;12&#46;12&#37; &#40;range&#58; 20-65&#41;&#44; and ventricular dysfunction was distributed in the following manner&#58; no ventricular dysfunction&#58; 20 patients &#40;55&#46;6&#37;&#41;&#59; mild dysfunction&#58; 8 patients &#40;22&#46;2&#37;&#41;&#44; moderate dysfunction&#58; 3 patients &#40;8&#46;3&#37;&#41;&#59; and severe dysfunction&#58; 5 patients &#40;13&#46;9&#37;&#41;&#46;</p><p class="elsevierStylePara">The summary results for the multiple logistic regression analysis are shown in the Table&#46; The univariate analysis of factors associated with significant CAD revealed that 65&#37; of patients with type 1 DM and 81&#46;3&#37; of patients with type 2 DM had significant coronary artery lesions&#44; with no significant difference between these two groups &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;279&#41;&#46; We did not observe a significant difference based on the following variables&#58; age &#40;odds ratio &#91;OR&#93; &#61;1&#46;042&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;182&#41;&#44; female sex &#40;OR&#61;0&#46;368&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;188&#41;&#44; family history of coronary disease &#40;OR&#61;2&#46;933&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;212&#41;&#44; arterial hypertension &#40;OR&#61;1&#46;917&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;511&#41;&#44; or LDL cholesterol levels &#40;OR&#61;1&#46;018&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;222&#41;&#46; The only variables that were significantly associated with significant coronary artery disease were&#58; dyslipidaemia &#40;OR&#61;10&#46;857&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;004&#41;&#44; tobacco use &#40;OR&#61;7&#46;778&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;009&#41;&#44; glycosylated haemoglobin &#40;OR&#61;9&#46;523&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;003&#41;&#44; and total cholesterol &#40;OR&#61;1&#46;040&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;01&#41;&#46; The latter variables were then included in the multiple logistic regression model&#46; Dyslipidaemia and total cholesterol were excluded from the model &#40;likelihood ratio &#61;1&#46;556&#44; degrees of freedom &#91;DF&#93; &#61;2&#41;&#46; All variables had a linear scale&#46; We evaluated all possible interactions which were not significant&#46; No patients had a Cook distance greater than 1&#46; The final result showed that the only variables significantly associated with CAD were&#58; tobacco use &#40;adjusted OR&#61;8&#46;341&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;048&#41; and percentage of glycosylated haemoglobin &#40;adjusted OR&#61;9&#46;535&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;006&#41;&#46; For every 1&#37; increase in the value of glycosylated haemoglobin&#44; the risk that an asymptomatic diabetic patient with ESCKD will develop significant CAD is 9&#46;525 times higher if all other variables are the same &#40;for a 95&#37; confidence interval&#44; this difference would be 1&#46;892-47&#46;944&#41;&#46; The ROC curve for this calculation is shown in Figure 2&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Ischaemic cardiopathy is a common cause of mortality and morbidity in patients with ESCKD&#46;<span class="elsevierStyleSup">15</span> The prevalence of asymptomatic CAD in diabetic patients with ESCKD was approximately 70&#37; in our study&#46; In addition&#44; these patients have a lower survival rate after an acute coronary event&#46;<span class="elsevierStyleSup">15</span> The diagnosis of CAD in patients with ESCKD&#44; especially in diabetics&#44; continues to be a substantial challenge&#46; Previous studies have shown that non-invasive methods for diagnosing CAD&#44; including clinical histories and at-rest&#47;stress electrocardiograms&#44; are not reliable for detecting coronary disease in diabetic patients with ESCKD&#46;<span class="elsevierStyleSup">16&#44;17</span> Studies of ischaemia using stress echocardiograms and radionuclide methods differ in terms of sensitivity and predictive power&#44; although in general they show a low negative predictive value&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">As regards risk factors&#44; it has been well established that diabetic patients with ESCKD have multiple associated cardiovascular risk factors&#46; Despite the high prevalence of CAD&#44; many diabetic patients with ESCKD do not show angina clinically as a consequence of the advanced diabetic nephropathy&#44; which could be explained by the high level of inactivity and reduced myocardial demand in these patients&#46; Additionally&#44; the constitutional symptoms associated with ESCKD may lead to an erroneous interpretation of symptoms&#46; These factors increase the complexity of the clinical evaluation of these patients prior to kidney transplantation&#46;<span class="elsevierStyleSup">19</span></p><p class="elsevierStylePara">Grupa et al&#46; evaluated the clinical factors associated with mortality following kidney transplants&#46; Their study revealed that this population is at high risk of cardiovascular events and has higher mortality and morbidity rates that other populations&#46;<span class="elsevierStyleSup">20</span></p><p class="elsevierStylePara">Cardiac catheterisation is the standard procedure for a diagnosis of CAD&#46; However&#44; this is a costly examination and may also cause progression of renal failure&#44; among other complications&#46; Despite this&#44; the benefits obtained from the diagnostic and therapeutic potential of this procedure outweigh the risks to the patient&#46; In many hospitals&#44; such as ours&#44; cardiac catheterisation is indicated in diabetic patients with ESCKD due to the low sensitivity of non-invasive cardiac tests&#46; Our study confirms the high prevalence of silent CAD in this population&#46; Silent CAD was found in 65&#37; of type 1 diabetics and 81&#46;3&#37; of type 2 diabetics&#46;</p><p class="elsevierStylePara">Tobacco use and high levels of glycosylated haemoglobin during the pre-transplantation evaluation are associated with CAD in these patients&#46; The univariate analysis also showed that obese patients&#44; patients with dyslipidaemia&#44; and those with high total cholesterol levels should be closely evaluated&#46;</p><p class="elsevierStylePara">Our study had several limitations&#46; Firstly&#44; we used a retrospective study design&#44; based on reviewing clinical histories and reports from cardiac catheterisations&#46; Secondly&#44; the small sample size greatly limited the statistical power of our tests&#44; the inclusion of variables&#44; and the analysis of these variables in the multiple logistic regression model&#46; Thirdly&#44; we did not include information regarding patient evolution and prognosis&#46; Finally&#44; all patients in our study underwent direct cardiac catheterisation&#46; While our study did not intend to validate non-invasive tests&#44; a comparative study would be useful for constructing an algorithm for the evaluation of coronary disease in diabetic patients&#46;</p><p class="elsevierStylePara">In conclusion&#44; we have demonstrated the high prevalence of significant CAD in asymptomatic diabetic patients with no history of ischaemic heart disease who are candidates for kidney transplants&#46; We identified a sub-population of greater risk&#58; patients with a history of tobacco use with high levels of glycosylated haemoglobin&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors affirm that they have no conflicts of interest related to the content of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11355&#95;16025&#95;33130&#95;en&#95;11355&#95;t14&#46;jpg" class="elsevierStyleCrossRefs"><img src="11355_16025_33130_en_11355_t14.jpg" alt="Factors associated with coronary disease in asymptomatic pre-kidney transplant diabetic patients"></img></a></p><p class="elsevierStylePara">Table 1&#46; Factors associated with coronary disease in asymptomatic pre-kidney transplant diabetic patients</p><p class="elsevierStylePara"><a href="grande&#47;11355&#95;16025&#95;33131&#95;en&#95;11355&#95;f13&#46;jpg" class="elsevierStyleCrossRefs"><img src="11355_16025_33131_en_11355_f13.jpg" alt="Percentage of vessels with significant disease"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Percentage of vessels with significant disease</p><p class="elsevierStylePara"><a href="grande&#47;11355&#95;16025&#95;33132&#95;en&#95;f2&#95;11355&#46;jpg" class="elsevierStyleCrossRefs"><img src="11355_16025_33132_en_f2_11355.jpg" alt="ROC curve"></img></a></p><p class="elsevierStylePara">Figure 2&#46; ROC curve</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introducci&#243;n y objetivos&#58;</span><span class="elsevierStyleBold">&#160;</span>La enfermedad arterial coronaria es una de las principales causas de morbilidad y mortalidad en pacientes diab&#233;ticos candidatos para trasplante renal&#46; La alta prevalencia de enfermedad coronaria en pacientes asintom&#225;ticos obliga a hacer despistaje de coronariopat&#237;a significativa&#46; Nuestro objetivo es conocer la prevalencia y los factores pron&#243;sticos asociados a enfermedad coronaria en este grupo de pacientes en nuestro medio&#46; <span class="elsevierStyleBold">M&#233;todos&#58;</span><span class="elsevierStyleBold">&#160;</span>Estudio observacional&#44; descriptivo y retrospectivo de los aspectos epidemiol&#243;gicos y cl&#237;nicos de los pacientes diab&#233;ticos con enfermedad renal cr&#243;nica candidatos a trasplante renal entre enero de 2007 y octubre de 2011&#46; <span class="elsevierStyleBold">Resultados&#58;</span>&#160;Se analiza una cohorte de 36 pacientes&#46; El 65&#37; &#40;13&#41; con diabetes mellitus tipo 1 y el 81&#44;3&#37; &#40;13&#41; con diabetes mellitus tipo 2 presentan enfermedad coronaria significativa&#46; En el an&#225;lisis multivariado de regresi&#243;n log&#237;stica&#44; se asociaron significativamente con enfermedad coronaria el tabaquismo &#40;<span class="elsevierStyleItalic">odds ratio </span>&#91;OR&#93; &#61; 8&#44;3&#44; p &#61; 0&#44;048&#41; y los niveles de hemoglobina glicosilada &#40;OR &#61; 9&#44;525&#44; p &#61; 0&#44;006&#41;&#46; Factores que no se asociaron significativamente a enfermedad coronaria incluyen&#58; edad&#44; sexo&#44; tipo de diabetes mellitus&#44; duraci&#243;n de diabetes mellitus &#40;a&#241;os&#41; e hipertensi&#243;n arterial&#46; <span class="elsevierStyleBold">Conclusi&#243;n&#58;</span>&#160;Los pacientes diab&#233;ticos sin cl&#237;nica anginosa con enfermedad renal cr&#243;nica candidatos a inclusi&#243;n en lista de trasplante renal presentan una alta prevalencia de enfermedad arterial coronaria significativa&#46; El tabaquismo y los niveles de hemoglobina glicosilada se asocian de forma independiente con la presencia de enfermedad arterial coronaria&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction and objectives&#58;</span>&#160;Coronary artery disease is a major cause of morbidity and mortality in diabetic kidney transplant candidates&#46; The high prevalence of coronary disease in asymptomatic patients creates the need for major coronary artery disease screening&#46; Our goal was to determine the prevalence and prognostic factors associated with coronary disease in this patient group&#46; <span class="elsevierStyleBold">Method&#58;</span>&#160;A retrospective study of a cohort of 36 asymptomatic patients with diabetes mellitus type 1 and 2 and chronic renal failure that were candidates for renal transplantation between January 2007 and October 2011&#46; <span class="elsevierStyleBold">Results&#58;</span>&#160;We followed a cohort of 36 patients&#46; Significant coronary disease was found in 65&#37; &#40;13&#41; of patients with type 1 diabetes mellitus and 81&#46;3&#37; &#40;13&#41; with type 2 diabetes mellitus&#46; In the multivariate logistic regression analysis&#44; smoking &#40;OR&#61;8&#46;3&#44; <span class="elsevierStyleItalic">P</span>&#61;&#46;048&#41; and glycosylated haemoglobin levels &#40;OR&#61;9&#46;525&#44; <span class="elsevierStyleItalic">P</span>&#61;&#46;006&#41; were significantly associated with coronary artery disease&#46; Factors not significantly associated with coronary artery disease included&#58; age&#44; sex&#44; type of diabetes mellitus&#44; duration of diabetes mellitus &#40;years&#41; and hypertension&#46; <span class="elsevierStyleBold">Conclusion&#58;</span>&#160;Diabetic patients without clinical angina and chronic renal failure who were candidates for inclusion in the kidney transplant waiting list have a high prevalence of significant coronary artery disease&#46; Smoking and glycosylated haemoglobin levels were independently associated with the presence of coronary artery disease&#46;</p>"
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