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chronic interstitial nephropathy &#40;42 patients&#41;&#44; renal polycystic disease &#40;19 patients&#41;&#44; ischaemic nephropathy &#40;24 patients&#41; and other kidney disease &#40;6 patients&#41;&#46;</p><p class="elsevierStylePara">The diagnosis of diabetic nephropathy was made according to clinical criteria in most cases &#40;suspected diagnosis&#41;&#46; In another 30 diabetic patients&#44; we observed that the cause of renal failure was due to reasons other than diabetic nephropathy&#59; in these cases&#44; it was diagnosed using more conclusive methods &#40;renal biopsy&#44; imaging diagnosis showing polycystic disease or ischaemic nephropathy&#44; etc&#46;&#41;&#46;</p><p class="elsevierStylePara">Comorbidity was very prevalent in this study group&#46; Upon classifying the patients according to the associated disease copresence index &#40;the comorbidity index described by Davies et al<span class="elsevierStyleSup">15</span> &#41;&#44; 134 showed no significant comorbidity&#44; 147 had a mild to moderate comorbidity and 50 had severe comorbidity&#46; Diabetes mellitus was the most frequent comorbidity &#40;in 98 patients&#41;&#44; followed by ischaemic disease of the central or peripheral nervous system &#40;77 patients&#41;&#44; heart failure &#40;66 patients&#41; and ischaemic heart disease &#40;48 patients&#41;&#46;</p><p class="elsevierStylePara">The most frequently-prescribed drugs in the study group were antihypertensives &#40;angiotensin-converting enzyme inhibitors&#44; angiotensin receptor blockers&#44; etc&#46;&#41;&#44; diuretics&#44; statins&#44; platelet antiaggregants and phosphorus binders&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Collection of clinical data and laboratory analysis</span></p><p class="elsevierStylePara">The clinical and analytical data were collected during the first visit&#44; which was recorded as the beginning of follow-up of patient evolution&#46; The information on the associated comorbid processes was obtained from the clinical history&#46; The diagnosis of ischaemic heart disease was considered if the patient presented one of the following&#58; previous myocardial infarction&#44; clinical signs of ischaemic heart disease&#44; or a positive angiogram&#44; stress test result or isotope scan&#46; Peripheral vascular disease was diagnosed in cases with clear clinical symptoms or signs&#44; or when there was shown to be significant stenosis &#40;&#62; 50&#37;&#41; in the distal aortic&#44; renal&#44; lower limb or carotid areas&#46; Patients with an aortic aneurism were also included in this group&#46;</p><p class="elsevierStylePara">A new CV episode was considered to be the development of acute severe ischaemic processes&#58; myocardial infarction&#44; unstable angina&#44; transient ischaemic attacks or cerebrovascular accidents&#44; or severe ischaemia of the lower limbs&#46; Sudden death by an undetermined cause was not considered to be a CV episode&#46;</p><p class="elsevierStylePara">After nocturnal fasting&#44; blood was drawn to analyse the following&#58; complete blood count&#44; urea&#44; creatinine&#44; calcium&#44; phosphorus&#44; albumin&#44; total cholesterol&#44; HDL-cholesterol and triglycerides &#40;Hitachi 917&#44; Roche Diagnostics&#44; Germany&#41;&#44; bicarbonate &#40;IL-1306 gas analyzer&#44; Instrumental Laboratory&#44; Milan&#44; Italy&#41; and C-reactive protein &#40;nephelometry&#44; N High Sensitivity CRP&#44; Behring&#44; Marburg&#44; Germany&#41;&#46; Levels of LDL cholesterol were estimated using the formula by Friedwald et al&#46;<span class="elsevierStyleSup">18</span> Glomerular filtration rate was estimated by the MDRD-4 method<span class="elsevierStyleSup">19</span> and proteinuria was measured in 24-hour urine samples using a benzethonium chloride turbidimetric assay &#40;U&#47;CSF protein&#44; Roche Diagnostics&#44; Germany&#41;&#46;</p><p class="elsevierStylePara">Measuring plasma levels of apolipoproteins A-I and B was done by immunonephelometry &#40;Behring Nephelometer BNII&#44; Marburg&#44; Germany&#41;&#44; with inter-assay coefficients of variation of 5&#37; for apolipoprotein A and 4&#37; for apolipoprotein B&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Study design and statistical methods</span></p><p class="elsevierStylePara">Death due to any cause and the development of new CV episodes&#44; whether or not they were fatal&#44; were the events for analysis&#46;</p><p class="elsevierStylePara">Patients were monitored following the initial evaluation with regular visits every 1 to 3 months while they continued in predialysis treatment&#44; or by indicating any change in evolution after beginning dialysis&#59; they were censored in cases of death due to any cause&#44; kidney transplant&#44; interrupted follow-up or upon reaching the end date for the study &#40;November 2008&#41;&#46;</p><p class="elsevierStylePara">To evaluate apo A and apo B&#191;s ability to predict mortality or the development of new CV events&#44; we performed a discrimination analysis by constructing ROC &#40;receiver operating characteristic&#41; curves and calculating the area under the curve&#46; According to the results of this analysis&#44; we chose the best predictor parameter&#40;s&#41; and examined the clinical and biochemical characteristics of patients in each tertile of distribution frequencies for that parameter in order to find confounding factors&#46; Continuous variables were compared between groups using analysis of variance &#40;ANOVA&#41; or the Kruskal-Wallis test&#44; according to the distribution characteristics of the variables&#46; The post hoc comparisons were made by using the Scheffe test&#46; To compare two continuous independent variables&#44; we used the Student-t test for unpaired samples or the non-parametric Mann-Whitney test according to the distribution characteristics of the variables&#46; The chisquare test was used to compare discrete variables&#46; The degree of relationship between two continuous parameters was analysed using Pearson&#191;s correlation coefficient&#46;</p><p class="elsevierStylePara">To establish whether or not there was an independent association between study variables &#40;apolipoproteins&#41; and mortality or the development of new CV episodes&#44; we used multivariate Cox proportional hazards models and we determined relative risks and 95&#37; confidence intervals&#46; These study variables were analysed both continuously and discretely &#40;tertiles&#41;&#46;</p><p class="elsevierStylePara">The models were adjusted upon introducing variables or risk factors with a potential influence on the final phases of the study &#40;age&#44; sex&#44; comorbidity index&#44; plasma albumin&#44; Creactive protein&#44; residual renal function&#44; proteinuria&#44; statins&#44; etc&#46;&#41;&#46; The choice of the variables best adjusted to the models was performed automatically by the progressive conditional elimination process&#46;</p><p class="elsevierStylePara">To confirm risk proportionality in all survival studies&#44; we examined graphs from correlating the logarithm &#40;-survival rate logarithm&#41; with the survival time logarithm&#44; and graphs of partial residues of each covariable compared with survival time&#46;</p><p class="elsevierStylePara">Data from this study was presented as means and standard deviations &#40;&#177; SD&#41;&#44; or as medians and interquartile ranges&#46; A value of p &#60; 0&#46;05 was considered to be statistically significant&#46; Statistical analysis was performed and graphics created using SPSS software version 15&#46;0 &#40;SPSS&#44; Chicago&#44; USA&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">The most important characteristics of the patients in the study are shown in table 1&#46; Note that the patients&#191; mean total cholesterol and lipoprotein levels are in an acceptable range&#44; and so are their apolipoproteins&#46;</p><p class="elsevierStylePara">Almost half of the patients were being treated with different statin drugs with widely varying doses&#46; There were no significant differences in total cholesterol&#44; HDL&#44; LDL&#44; apo A or apo B among the patients receiving and not receiving statins&#46; Patients treated with statins showed significantly higher triglyceride and VLDL levels &#40;165 &#177; 99 compared to 124 &#177; 85mg&#47;dl&#59; p &#60; 0&#46;0001&#59; 33 &#177; 25 compared to 22 &#177; 16mg&#47;dl&#59; p &#60; 0&#46;0001&#44; respectively&#44; Student-t test&#41;&#44; and lower C-reactive protein levels than in untreated patients&#44; with a difference in the statistical significance limit &#40;7&#46;5 &#177; 11&#46;9 compared to 12&#46;1 &#177; 21&#46;9mg&#47;l&#59; p &#61; 0&#46;06&#59; Mann-Whitney test&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Association between lipid&#44; lipoprotein and apolipoprotein levels and mortality&#47;new cardiovascular episodes</span></p><p class="elsevierStylePara">During the study period &#40;median follow-up length&#58; 985 days&#41;&#44; there were 105 deaths&#44; 54 new CV episodes&#44; 15 follow-up interruptions&#44; 185 starting dialysis and 37 receiving kidney transplants in the patient group&#46; The median follow-up length before starting dialysis &#40;predialysis period&#41; was 549 days&#46;</p><p class="elsevierStylePara">In the ROC curve analyses&#44; no significant associations were observed between total levels of cholesterol&#44; triglycerides or LDL and mortality&#46; HDL concentrations were negatively associated with mortality &#40;area below the curve 0&#46;416&#44; p &#61; 0&#46;014&#41;&#46; The apo A concentrations were also negatively associated with mortality&#44; but with a lower level of significance &#40;area below the curve 0&#46;372&#59; p &#60; 0&#46;0001&#41;&#46;</p><p class="elsevierStylePara">Concentrations of apo B were not related with mortality&#44; but the apo A&#47;apo B quotient was&#44; although not as strongly as apo A concentrations &#40;area below the curve 0&#46;403&#59; p &#61; 0&#46;005&#41;&#46;</p><p class="elsevierStylePara">The only parameter that was significantly associated with the development of new CV episodes was the concentration of apo A &#40;area below the curve 0&#46;410&#59; p &#61; 0&#46;035&#41;&#46;</p><p class="elsevierStylePara">Table 2 shows the characteristics for patients grouped by apo A tercile&#46; We observe significant differences for sex&#44; comorbidity index and levels of C-reactive protein among the three groups&#46; Women were predominant &#40;78&#37;&#41; in the patients grouped in the upper tertile for apo A&#44; which had a lower incidence rate of associated diseases and above all&#44; for diabetes mellitus &#40;19&#37; compared to 40&#37; in those grouped in the lowest tertile for apo A&#41;&#46; Patients grouped in the lowest tertile had significantly higher levels of C-reactive protein than the rest of the subgroups&#46; Patients with higher apo A concentrations also had higher levels of total cholesterol&#44; HDL and LDL&#46; No differences in the proportion of patients treated with statins were found among the three subgroups&#46;</p><p class="elsevierStylePara">An inverse linear correlation was observed between concentrations of apo A and C-reactive protein &#40;as a logarithm&#41; &#40;r &#61; -0&#46;30&#59; p &#60; 0&#46;0001&#41; &#40;figure 1&#41;&#44; but not with plasma albumin &#40;r &#61; -0&#46;021&#59; NS&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Apolipoprotein A concentrations&#44; apo A&#47;apo B quotient and survival or development of new cardiovascular episodes</span></p><p class="elsevierStylePara">In survival curves made using the Kaplan-Meier method without adjusting for other factors with a potential influence on mortality&#44; we observed significant differences among patients grouped according to apo A tertile &#40;log-rank &#61; 17&#46;05&#59; p &#60; 0&#46;0001&#41; &#40;figure 2&#41;&#46; We also observed differences in the statistical significance limit for survival with no new CV episodes&#59; it was more favourable in those patients grouped in the upper tertile for apo A &#40;log-rank &#61; 5&#46;76&#59; p &#61; 0&#46;056&#41;&#46;</p><p class="elsevierStylePara">In a multivariate Cox model adjusted by age&#44; sex&#44; body mass index&#44; comorbidity index&#44; serumalbumin&#44; C-reactive protein&#44; statin treatment and residual renal function&#44; the risk ratio &#40;RR&#41; for each 10mg&#47;dl of apo A was 0&#46;915&#44; with 95&#37; confidence intervals &#40;CI&#41; of 0&#46;844 and 0&#46;992 &#40;p &#61; 0&#46;031&#41; &#40;table 3&#41;&#46;</p><p class="elsevierStylePara">When the variable apo A is introduced in the multivariate model in the form of distribution frequency tertiles&#44; statistical significance was not reached &#40;RR &#61; 0&#46;784&#59; 95&#37; CI&#58; 0&#46;610-1&#46;009&#59; p &#61; 0&#46;059&#41;&#46;</p><p class="elsevierStylePara">The substitution of the variable apo A by HDL concentrations did not improve adjustment of the multivariate model &#40;table 3&#41;&#46; Substitution of apo A with the apo A&#47;apo B quotient in the multivariate model was not significant &#40;table 3&#41;&#46; Rather&#44; statistical significance was observed as a survival predictor when the variable was introduced in the form of apo a&#47;apo b tertiles or high levels &#40;upper tertile&#44; i&#46;e&#46; apo A&#47;apo B &#62; 1&#46;42&#41; &#40;table 3 and figure 3&#41;&#46;</p><p class="elsevierStylePara">The main factors determining the development of new CV episodes in the multivariate model were age &#40;RR for each additional 10 years&#58; 1&#46;39&#59; 95&#37; CI&#58; 1&#46;06-1&#46;72&#41;&#44; and the comorbidity index &#40;RR &#61; 4&#46;340&#59; 95&#37; CI&#58; 2&#46;819-6&#46;682&#41;&#46; No lipid parameters or statin treatment analysed in this study were significantly correlated with the development of new CV episodes in the adjusted models&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold"></span>The results of this study show that total serum cholesterol and triglyceride levels are not associated with mortality in CKD patients in pre-dialysis&#46; In addition&#44; levels of LDL cholesterol and apolipoprotein B &#40;apo B13&#41;&#44; which is theoretically the best indicator representing atherogenic lipid particles&#44; were not associated with a poorer survival rate&#46; Instead&#44; the lipid parameters with the strongest association with survival were apolipoprotein A &#40;apo A&#41; concentrations and the apo A&#47;apo B relationship&#46; This parameter&#191;s association with survival was not linear&#59; more favourable survival was only observed in patients with the highest levels &#40;upper tertile&#41;&#46; None of the lipid parameters under study was related to the development of new CV episodes during the follow-up period in an analysis adjusted by other risk factors&#46;</p><p class="elsevierStylePara">The results of the studies analysing the relationship between lipid alterations and mortality in CKD patients on dialysis conclude that there is no association&#44; or even that there is a paradoxical or contradictory association&#44; to that observed in the general population&#58; a lower survival rate in those cases with lower total cholesterol or LDL cholesterol levels&#46;<span class="elsevierStyleSup">6-9</span></p><p class="elsevierStylePara">An exception to these observations may be found among black CKD patients&#44; whose survival may be affected negatively by hypercholesterolaemia&#44; even in those undergoing dialysis&#46;<span class="elsevierStyleSup">20</span> The negative effect on the nutritional state caused by prolonged exposure to terminal uraemia&#44; dialysis procedures and the development of inflammation have been cited as a possible explanation for the inverse relationship between lipid alterations and mortality&#46;<span class="elsevierStyleSup">7&#44;9</span> The present study includes only patients with advanced CKD who have not yet begun dialysis so as to limit some of the confounding factors&#46; But even in predialysis states&#44; no relationship was observed between cholesterol levels&#44; LDL&#44; apo B or triglycerides and mortality or new CV episodes&#46; Unlike other studies of predialysis patients with CKD&#44;<span class="elsevierStyleSup">9</span> we found no negative relationship between total cholesterol or LDL levels and mortality in this study&#46; It is likely that the preserved nutritional state found in most of our patients would explain the differences between this study&#191;s findings and those of other studies&#46;</p><p class="elsevierStylePara">The mean concentration of apo A-I decreases proportionally to the decrease in glomerular filtration rate in CKD&#44;<span class="elsevierStyleSup">21</span> and this metabolic alteration is considered to be a CV risk factor&#44; although no studies have demonstrated a relationship between the levels of this protein and mortality in CKD&#46; The results from the present study show that high concentrations of apo A-I are associated with better survival&#46;</p><p class="elsevierStylePara">Some demographic&#44; clinical and biochemical characteristics of the patients grouped into tertiles according to the apo A level distribution frequency were significantly different&#46; The patients with the highest concentrations of apo A were younger&#44; predominantly female&#44; with a lower number of diabetics and lower overall comorbidity&#44; and a significantly lower mean level of C-reactive protein&#46; Furthermore&#44; we observed a significant correlation between apo A and Creactive protein levels&#46; This association between apo A levels and inflammation markers has already been described&#44;<span class="elsevierStyleSup">22&#44;23</span> and this apolipoprotein can be considered a negative acutephase reactant&#46; In this way&#44; it is difficult to determine whether the positive effect that high apo A levels have on CKD patient survival is due to the antiatherogenic mechanism&#44; or if it simply serves as an indirect inflammation marker&#44; or if both are true&#46; However&#44; we must point out that apo A levels added prognostic information about the survival of these patients when introduced in multivariate models including covariables such as age and the comorbidity index&#44; as well as albumin and C-reactive protein levels&#46;</p><p class="elsevierStylePara">Although a good correlation was made between the apo A and HDL levels&#44; it is possible that the predictive power of mortality for any reason was better with apo A than with HDL&#46; In the final phase of the study&#44; mortality was significantly associated with apo A levels&#44; but not HDL levels&#46;</p><p class="elsevierStylePara">The apo A&#47;apo B ratio was associated with survival&#44; but not as a monotonic function&#46; Only those patients with a high ratio had a higher survival rate&#46; It is likely that high levels of apo A&#47;apo B identify patients with a better vital prognosis and coincide with characteristics such as absence of inflammatory and malnutrition process&#44; along with controlled apo B levels &#40;whether or not by pharmacological means&#41; that are more similar to those providing contrasted survival benefits to the general population&#46;</p><p class="elsevierStylePara">This study has certain limitations&#46; The study had set covariables&#44; and did not consider variables that changed over time &#40;increases or decreases in lipid values in a certain follow-up time&#41;&#46; A large percentage of patients received treatment with statin drugs&#44; and although this covariable was taken into account for all survival analyses&#44; we cannot rule out the possibility of a certain degree of influence over the results due to medication and dose heterogeneity&#44; and due to maintaining the prescription over time&#46;</p><p class="elsevierStylePara">In addition to the apolipoproteins A-I and B&#44; there are others &#40;apo A-IV&#44; apo E&#44; apo&#91;a&#93;&#44; etc&#46;&#41; that may have a potential effect on the evolution of these patients&#44; and which were not analysed in this study&#46;</p><p class="elsevierStylePara">To conclude&#44; the total serum lipid and lipoprotein levels in predialysis patients with advanced CKD do not affect survival or the development of new CV episodes&#46; On the other hand&#44; high apo A levels and a high apo A&#47;apo B ratio were associated with a better vital prognosis in this patient group&#46;</p><p class="elsevierStylePara">Before we can recommend measuring these apolipoproteins as prognostic markers in CKD&#44; additional studies will be needed to determine their relationship with subclinical arteriosclerosis&#44; as well as effects that pharmacological modifications to plasma concentrations of these proteins may have on patient survival&#46; <br></br></p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;t1&#95;p543&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_t1_p543.jpg" alt="Clinical and biochemical characteristics of patients included in the study"></img></a></p><p class="elsevierStylePara">Table 1&#46; Clinical and biochemical characteristics of patients included in the study</p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;f1&#95;p543&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_f1_p543.jpg"></img></a></p><p class="elsevierStylePara">Figure 1&#46; </p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;t2&#95;p544&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_t2_p544.jpg" alt="Characteristics of patients grouped in tertiles according to the frequency distribution of apolipoprotein A level"></img></a></p><p class="elsevierStylePara">Table 2&#46; Characteristics of patients grouped in tertiles according to the frequency distribution of apolipoprotein A level</p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;f2&#95;p544&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_f2_p544.jpg"></img></a></p><p class="elsevierStylePara">Figure 2&#46; </p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;t3&#95;p545&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_t3_p545.jpg" alt="Prognostic value of the different study parameters for mortality&#44; in Cox regression models with or without adjustment for other covariables&#46;"></img></a></p><p class="elsevierStylePara">Table 3&#46; Prognostic value of the different study parameters for mortality&#44; in Cox regression models with or without adjustment for other covariables&#46;</p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;f3&#95;p545&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_f3_p545.jpg"></img></a></p><p class="elsevierStylePara">Figure 3&#46; </p>"
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        "resumen" => "Dyslipidaemia is a well-established risk factor for cardiovascular diseases in the general population&#46; However&#44; this association is not observed in chronic kidney disease &#40;CKD&#41; patients&#46; This study examines the association between lipid levels&#44; including apolipoproteins A-I and B concentrations&#44; and all-cause mortality or the development of new cardiovascular events in advanced CKD patients&#46; This observational prospective historical study included 331 patients with CKD stage 4 or 5 not yet on dialysis&#46; In addition to conventional clinical and biochemical data&#44; total cholesterol&#44; triglycerides&#44; HDL&#44; LDL&#44; apolipoprotein A-I &#40;apo A&#41; and B &#40;apo B&#41; plasma concentrations were measured&#46; Cox proportional hazard models were adjusted for age&#44; sex&#44; comorbidity index&#44; residual renal function&#44; serum albumin&#44; C-reactive protein levels&#44; and treatment with statins&#46; The median follow-up time was 985 days&#44; and during this period 105 patients died and 54 patients had a new cardiovascular event&#46; In fully-adjusted fixed-covariate Cox models&#44; the hazard ratio for each 10mg&#47;dl increase of apo A concentration was 0&#46;915 &#40;C&#46;I&#46; 95&#37; 0&#46;844 to 0&#46;992&#59; p &#61; 0&#44;031&#41;&#46; Patients with an apo A&#47;apo B ratio in the upper tertile &#40;i&#46;e&#46; &#62;1&#46;42&#41; had a better survival rate than the rest of the study patients &#40;hazard ratio &#61; 0&#46;592&#44; C&#46;I&#46; 95&#37; 0&#46;368 to 0&#46;953&#44; p &#60; 0&#46;05&#41;&#46; None of the study lipid parameters were associated with new cardiovascular events in the adjusted models&#46; In conclusion&#44; apo A concentrations and high apo A&#47;apo B ratios added independent predictive information about survival of CKD patients not yet on dialysis&#46;"
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        "resumen" => "<p class="elsevierStylePara">La dislipemia es un reconocido factor de riesgo cardiovascular en la poblaci&#243;n general&#44; pero no as&#237; en pacientes con enfermedad renal cr&#243;nica &#40;ERC&#41;&#46; Los objetivos del presente estudio han sido determinar si las alteraciones lip&#237;dicas m&#225;s comunes&#44; as&#237; como las concentraciones de apolipoprote&#237;na &#40;apo&#41; A y B&#44; son capaces de predecir la mortalidad y el desarrollo de nuevos episodios cardiovasculares &#40;CV&#41; en pacientes con ERC en estadios previos a la di&#225;lisis&#46; Se trata de un estudio de observaci&#243;n prospectivo hist&#243;rico en el que se incluyeron 331 pacientes con ERC en estadios 4-5 predi&#225;lisis&#46; Se determinaron los siguientes par&#225;metros lip&#237;dicos&#58; colesterol total&#44; triglic&#233;ridos&#44; HDL&#44; LDL&#44; apo A-I y apo B&#46; Se analiz&#243; la asociaci&#243;n de estas variables con la mortalidad global y con el desarrollo de episodios CV&#46; La mediana de seguimiento fue 985 d&#237;as&#44; y durante este per&#237;odo hubo 105 fallecimientos y 54 nuevos episodios CV&#46; En un modelo multivariable de Cox ajustado al resto de covariables de reconocida importancia pron&#243;stica&#44; la raz&#243;n de riesgo &#40;RR&#41; por cada 10 mg&#47;dl de apo A fue de 0&#44;915 &#40;IC 95&#37;&#58; 0&#44;844 a 0&#44;992&#59; p &#61; 0&#44;031&#41;&#46; Los pacientes con una relaci&#243;n apo A&#47;apo B elevada &#40;tercil superior&#44; &#62;1&#44;42&#41; tambi&#233;n tuvieron una supervivencia significativamente mejor que la del resto de los pacientes estudiados &#40;RR &#61; 0&#44;592&#44; IC 95&#37;&#58; 0&#44;3680-0&#44;953&#59; p &#60;0&#44;05&#41;&#46; No hubo relaci&#243;n significativa entre los par&#225;metros lip&#237;dicos y el desarrollo de episodios CV&#46; En conclusi&#243;n&#44; las concentraciones de apo A y una relaci&#243;n apo A&#47;apo B elevada se asocian con un mejor pron&#243;stico vital en pacientes con ERC predi&#225;lisis&#46;</p>"
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Prognostic value of apolipoproteins A and B in the evolution of patients with chronic kidney disease previous to dialysis
Valor pronóstico de las apolipoproteínas A y B en la evolución de los pacientes con enfermedad renal crónica avanzada prediálisis
Isis Cerezo Ariasa, N.. Fernándeza, B.. Romeroa, E.. Fernández-Carboneroa, R.. Hernández-Gallegoa, F.. Caravacaa
a Servicio de Nefrología, Hospital Infanta Cristina, Badajoz, España,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">Cardiovascular disease is the leading cause of death and disability in developed countries&#46; The association between lipid alterations and increased cardiovascular mortality in the general population is a well-recognised fact&#46;<span class="elsevierStyleSup">1&#44;2</span></p><p class="elsevierStylePara">Patients with chronic kidney disease &#40;CKD&#41; are at a higher risk of developing cardiovascular diseases &#40;CV&#41; than the general population&#46;<span class="elsevierStyleSup">3-5</span></p><p class="elsevierStylePara">However&#44; in this patient group&#44; we do not observe a correlation between increased lipid concentration and mortality&#46;<span class="elsevierStyleSup">6&#44;7</span> On the contrary&#44; increased mortality associated with low total cholesterol levels has been shown in patients in advanced stages of CKD&#46;<span class="elsevierStyleSup">8</span> The deterioration of the nutritional state caused by prolonged exposure to uraemia and dialysis and the development of malnutritioninflammation-atherosclerosis &#40;MIA&#41; syndrome could explain this epidemiological peculiarity which goes against the general tendency&#46;<span class="elsevierStyleSup">7&#44;9</span></p><p class="elsevierStylePara">However&#44; CKD is associated with alterations in lipoprotein metabolism&#44; in both initial and late stages&#46; This can manifest itself independently from total plasma lipid concentrations&#44; and could potentially contribute to accelerating the development of atherosclerosis&#46;<span class="elsevierStyleSup">10-12</span></p><p class="elsevierStylePara">Apolipoproteins A &#40;apo A&#41; and B &#40;apo B&#41; are the structural proteins in HDL and LDL lipoproteins&#44; respectively&#46; Levels of apo B are better than LDL levels at reflecting the spectrum of proatherogenic lipid particles &#40;VLDL&#44; IDL and LDL&#41;&#46;<span class="elsevierStyleSup">13</span> The antiatherogenic role played by apo A also appears to be more important than that of HDL&#44; and this apolipoprotein is very much involved in the HDL particle maturation process mediated by lecithin-cholesterolacyltransferase&#44;<span class="elsevierStyleSup">14</span> as well as in various antioxidant processes&#46;<span class="elsevierStyleSup">15</span> Some epidemiological studies have shown that the relationship between apo A and apo B is a remarkable predictor of the development of ischaemic heart disease in the general population&#46;<span class="elsevierStyleSup">16&#44;17</span> The role these apolipoproteins play in predicting the evolution of CKD patients is not well understood&#46;</p><p class="elsevierStylePara">The objectives of the present study are to determine whether the most common lipid alterations&#44; as well as concentrations of apo A and apo B&#44; are capable of predicting mortality and the development of new CV episodes in patients with CKD in predialysis stages&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHODS</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Patients</span></p><p class="elsevierStylePara">This historical prospective observational study included all consecutive patients referred for a predialysis consult between June 2003 and June 2007&#46; The only inclusion criterion was having stage 3&#44; 4 or 5 chronic kidney disease previous to dialysis&#46;</p><p class="elsevierStylePara">The total number of patients under study was 331 &#40;156 women and 175 men&#41; with a mean age of 65 &#177; 15 years&#46; The average follow-up period was 985 days&#46; The renal failure aetiology was as follows&#58; unregistered &#40;116 patients&#41;&#44; primary glomerulonephritis &#40;58 patients&#41;&#44; diabetic nephropathy &#40;68 patients&#41;&#44; chronic interstitial nephropathy &#40;42 patients&#41;&#44; renal polycystic disease &#40;19 patients&#41;&#44; ischaemic nephropathy &#40;24 patients&#41; and other kidney disease &#40;6 patients&#41;&#46;</p><p class="elsevierStylePara">The diagnosis of diabetic nephropathy was made according to clinical criteria in most cases &#40;suspected diagnosis&#41;&#46; In another 30 diabetic patients&#44; we observed that the cause of renal failure was due to reasons other than diabetic nephropathy&#59; in these cases&#44; it was diagnosed using more conclusive methods &#40;renal biopsy&#44; imaging diagnosis showing polycystic disease or ischaemic nephropathy&#44; etc&#46;&#41;&#46;</p><p class="elsevierStylePara">Comorbidity was very prevalent in this study group&#46; Upon classifying the patients according to the associated disease copresence index &#40;the comorbidity index described by Davies et al<span class="elsevierStyleSup">15</span> &#41;&#44; 134 showed no significant comorbidity&#44; 147 had a mild to moderate comorbidity and 50 had severe comorbidity&#46; Diabetes mellitus was the most frequent comorbidity &#40;in 98 patients&#41;&#44; followed by ischaemic disease of the central or peripheral nervous system &#40;77 patients&#41;&#44; heart failure &#40;66 patients&#41; and ischaemic heart disease &#40;48 patients&#41;&#46;</p><p class="elsevierStylePara">The most frequently-prescribed drugs in the study group were antihypertensives &#40;angiotensin-converting enzyme inhibitors&#44; angiotensin receptor blockers&#44; etc&#46;&#41;&#44; diuretics&#44; statins&#44; platelet antiaggregants and phosphorus binders&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Collection of clinical data and laboratory analysis</span></p><p class="elsevierStylePara">The clinical and analytical data were collected during the first visit&#44; which was recorded as the beginning of follow-up of patient evolution&#46; The information on the associated comorbid processes was obtained from the clinical history&#46; The diagnosis of ischaemic heart disease was considered if the patient presented one of the following&#58; previous myocardial infarction&#44; clinical signs of ischaemic heart disease&#44; or a positive angiogram&#44; stress test result or isotope scan&#46; Peripheral vascular disease was diagnosed in cases with clear clinical symptoms or signs&#44; or when there was shown to be significant stenosis &#40;&#62; 50&#37;&#41; in the distal aortic&#44; renal&#44; lower limb or carotid areas&#46; Patients with an aortic aneurism were also included in this group&#46;</p><p class="elsevierStylePara">A new CV episode was considered to be the development of acute severe ischaemic processes&#58; myocardial infarction&#44; unstable angina&#44; transient ischaemic attacks or cerebrovascular accidents&#44; or severe ischaemia of the lower limbs&#46; Sudden death by an undetermined cause was not considered to be a CV episode&#46;</p><p class="elsevierStylePara">After nocturnal fasting&#44; blood was drawn to analyse the following&#58; complete blood count&#44; urea&#44; creatinine&#44; calcium&#44; phosphorus&#44; albumin&#44; total cholesterol&#44; HDL-cholesterol and triglycerides &#40;Hitachi 917&#44; Roche Diagnostics&#44; Germany&#41;&#44; bicarbonate &#40;IL-1306 gas analyzer&#44; Instrumental Laboratory&#44; Milan&#44; Italy&#41; and C-reactive protein &#40;nephelometry&#44; N High Sensitivity CRP&#44; Behring&#44; Marburg&#44; Germany&#41;&#46; Levels of LDL cholesterol were estimated using the formula by Friedwald et al&#46;<span class="elsevierStyleSup">18</span> Glomerular filtration rate was estimated by the MDRD-4 method<span class="elsevierStyleSup">19</span> and proteinuria was measured in 24-hour urine samples using a benzethonium chloride turbidimetric assay &#40;U&#47;CSF protein&#44; Roche Diagnostics&#44; Germany&#41;&#46;</p><p class="elsevierStylePara">Measuring plasma levels of apolipoproteins A-I and B was done by immunonephelometry &#40;Behring Nephelometer BNII&#44; Marburg&#44; Germany&#41;&#44; with inter-assay coefficients of variation of 5&#37; for apolipoprotein A and 4&#37; for apolipoprotein B&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Study design and statistical methods</span></p><p class="elsevierStylePara">Death due to any cause and the development of new CV episodes&#44; whether or not they were fatal&#44; were the events for analysis&#46;</p><p class="elsevierStylePara">Patients were monitored following the initial evaluation with regular visits every 1 to 3 months while they continued in predialysis treatment&#44; or by indicating any change in evolution after beginning dialysis&#59; they were censored in cases of death due to any cause&#44; kidney transplant&#44; interrupted follow-up or upon reaching the end date for the study &#40;November 2008&#41;&#46;</p><p class="elsevierStylePara">To evaluate apo A and apo B&#191;s ability to predict mortality or the development of new CV events&#44; we performed a discrimination analysis by constructing ROC &#40;receiver operating characteristic&#41; curves and calculating the area under the curve&#46; According to the results of this analysis&#44; we chose the best predictor parameter&#40;s&#41; and examined the clinical and biochemical characteristics of patients in each tertile of distribution frequencies for that parameter in order to find confounding factors&#46; Continuous variables were compared between groups using analysis of variance &#40;ANOVA&#41; or the Kruskal-Wallis test&#44; according to the distribution characteristics of the variables&#46; The post hoc comparisons were made by using the Scheffe test&#46; To compare two continuous independent variables&#44; we used the Student-t test for unpaired samples or the non-parametric Mann-Whitney test according to the distribution characteristics of the variables&#46; The chisquare test was used to compare discrete variables&#46; The degree of relationship between two continuous parameters was analysed using Pearson&#191;s correlation coefficient&#46;</p><p class="elsevierStylePara">To establish whether or not there was an independent association between study variables &#40;apolipoproteins&#41; and mortality or the development of new CV episodes&#44; we used multivariate Cox proportional hazards models and we determined relative risks and 95&#37; confidence intervals&#46; These study variables were analysed both continuously and discretely &#40;tertiles&#41;&#46;</p><p class="elsevierStylePara">The models were adjusted upon introducing variables or risk factors with a potential influence on the final phases of the study &#40;age&#44; sex&#44; comorbidity index&#44; plasma albumin&#44; Creactive protein&#44; residual renal function&#44; proteinuria&#44; statins&#44; etc&#46;&#41;&#46; The choice of the variables best adjusted to the models was performed automatically by the progressive conditional elimination process&#46;</p><p class="elsevierStylePara">To confirm risk proportionality in all survival studies&#44; we examined graphs from correlating the logarithm &#40;-survival rate logarithm&#41; with the survival time logarithm&#44; and graphs of partial residues of each covariable compared with survival time&#46;</p><p class="elsevierStylePara">Data from this study was presented as means and standard deviations &#40;&#177; SD&#41;&#44; or as medians and interquartile ranges&#46; A value of p &#60; 0&#46;05 was considered to be statistically significant&#46; Statistical analysis was performed and graphics created using SPSS software version 15&#46;0 &#40;SPSS&#44; Chicago&#44; USA&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">The most important characteristics of the patients in the study are shown in table 1&#46; Note that the patients&#191; mean total cholesterol and lipoprotein levels are in an acceptable range&#44; and so are their apolipoproteins&#46;</p><p class="elsevierStylePara">Almost half of the patients were being treated with different statin drugs with widely varying doses&#46; There were no significant differences in total cholesterol&#44; HDL&#44; LDL&#44; apo A or apo B among the patients receiving and not receiving statins&#46; Patients treated with statins showed significantly higher triglyceride and VLDL levels &#40;165 &#177; 99 compared to 124 &#177; 85mg&#47;dl&#59; p &#60; 0&#46;0001&#59; 33 &#177; 25 compared to 22 &#177; 16mg&#47;dl&#59; p &#60; 0&#46;0001&#44; respectively&#44; Student-t test&#41;&#44; and lower C-reactive protein levels than in untreated patients&#44; with a difference in the statistical significance limit &#40;7&#46;5 &#177; 11&#46;9 compared to 12&#46;1 &#177; 21&#46;9mg&#47;l&#59; p &#61; 0&#46;06&#59; Mann-Whitney test&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Association between lipid&#44; lipoprotein and apolipoprotein levels and mortality&#47;new cardiovascular episodes</span></p><p class="elsevierStylePara">During the study period &#40;median follow-up length&#58; 985 days&#41;&#44; there were 105 deaths&#44; 54 new CV episodes&#44; 15 follow-up interruptions&#44; 185 starting dialysis and 37 receiving kidney transplants in the patient group&#46; The median follow-up length before starting dialysis &#40;predialysis period&#41; was 549 days&#46;</p><p class="elsevierStylePara">In the ROC curve analyses&#44; no significant associations were observed between total levels of cholesterol&#44; triglycerides or LDL and mortality&#46; HDL concentrations were negatively associated with mortality &#40;area below the curve 0&#46;416&#44; p &#61; 0&#46;014&#41;&#46; The apo A concentrations were also negatively associated with mortality&#44; but with a lower level of significance &#40;area below the curve 0&#46;372&#59; p &#60; 0&#46;0001&#41;&#46;</p><p class="elsevierStylePara">Concentrations of apo B were not related with mortality&#44; but the apo A&#47;apo B quotient was&#44; although not as strongly as apo A concentrations &#40;area below the curve 0&#46;403&#59; p &#61; 0&#46;005&#41;&#46;</p><p class="elsevierStylePara">The only parameter that was significantly associated with the development of new CV episodes was the concentration of apo A &#40;area below the curve 0&#46;410&#59; p &#61; 0&#46;035&#41;&#46;</p><p class="elsevierStylePara">Table 2 shows the characteristics for patients grouped by apo A tercile&#46; We observe significant differences for sex&#44; comorbidity index and levels of C-reactive protein among the three groups&#46; Women were predominant &#40;78&#37;&#41; in the patients grouped in the upper tertile for apo A&#44; which had a lower incidence rate of associated diseases and above all&#44; for diabetes mellitus &#40;19&#37; compared to 40&#37; in those grouped in the lowest tertile for apo A&#41;&#46; Patients grouped in the lowest tertile had significantly higher levels of C-reactive protein than the rest of the subgroups&#46; Patients with higher apo A concentrations also had higher levels of total cholesterol&#44; HDL and LDL&#46; No differences in the proportion of patients treated with statins were found among the three subgroups&#46;</p><p class="elsevierStylePara">An inverse linear correlation was observed between concentrations of apo A and C-reactive protein &#40;as a logarithm&#41; &#40;r &#61; -0&#46;30&#59; p &#60; 0&#46;0001&#41; &#40;figure 1&#41;&#44; but not with plasma albumin &#40;r &#61; -0&#46;021&#59; NS&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Apolipoprotein A concentrations&#44; apo A&#47;apo B quotient and survival or development of new cardiovascular episodes</span></p><p class="elsevierStylePara">In survival curves made using the Kaplan-Meier method without adjusting for other factors with a potential influence on mortality&#44; we observed significant differences among patients grouped according to apo A tertile &#40;log-rank &#61; 17&#46;05&#59; p &#60; 0&#46;0001&#41; &#40;figure 2&#41;&#46; We also observed differences in the statistical significance limit for survival with no new CV episodes&#59; it was more favourable in those patients grouped in the upper tertile for apo A &#40;log-rank &#61; 5&#46;76&#59; p &#61; 0&#46;056&#41;&#46;</p><p class="elsevierStylePara">In a multivariate Cox model adjusted by age&#44; sex&#44; body mass index&#44; comorbidity index&#44; serumalbumin&#44; C-reactive protein&#44; statin treatment and residual renal function&#44; the risk ratio &#40;RR&#41; for each 10mg&#47;dl of apo A was 0&#46;915&#44; with 95&#37; confidence intervals &#40;CI&#41; of 0&#46;844 and 0&#46;992 &#40;p &#61; 0&#46;031&#41; &#40;table 3&#41;&#46;</p><p class="elsevierStylePara">When the variable apo A is introduced in the multivariate model in the form of distribution frequency tertiles&#44; statistical significance was not reached &#40;RR &#61; 0&#46;784&#59; 95&#37; CI&#58; 0&#46;610-1&#46;009&#59; p &#61; 0&#46;059&#41;&#46;</p><p class="elsevierStylePara">The substitution of the variable apo A by HDL concentrations did not improve adjustment of the multivariate model &#40;table 3&#41;&#46; Substitution of apo A with the apo A&#47;apo B quotient in the multivariate model was not significant &#40;table 3&#41;&#46; Rather&#44; statistical significance was observed as a survival predictor when the variable was introduced in the form of apo a&#47;apo b tertiles or high levels &#40;upper tertile&#44; i&#46;e&#46; apo A&#47;apo B &#62; 1&#46;42&#41; &#40;table 3 and figure 3&#41;&#46;</p><p class="elsevierStylePara">The main factors determining the development of new CV episodes in the multivariate model were age &#40;RR for each additional 10 years&#58; 1&#46;39&#59; 95&#37; CI&#58; 1&#46;06-1&#46;72&#41;&#44; and the comorbidity index &#40;RR &#61; 4&#46;340&#59; 95&#37; CI&#58; 2&#46;819-6&#46;682&#41;&#46; No lipid parameters or statin treatment analysed in this study were significantly correlated with the development of new CV episodes in the adjusted models&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold"></span>The results of this study show that total serum cholesterol and triglyceride levels are not associated with mortality in CKD patients in pre-dialysis&#46; In addition&#44; levels of LDL cholesterol and apolipoprotein B &#40;apo B13&#41;&#44; which is theoretically the best indicator representing atherogenic lipid particles&#44; were not associated with a poorer survival rate&#46; Instead&#44; the lipid parameters with the strongest association with survival were apolipoprotein A &#40;apo A&#41; concentrations and the apo A&#47;apo B relationship&#46; This parameter&#191;s association with survival was not linear&#59; more favourable survival was only observed in patients with the highest levels &#40;upper tertile&#41;&#46; None of the lipid parameters under study was related to the development of new CV episodes during the follow-up period in an analysis adjusted by other risk factors&#46;</p><p class="elsevierStylePara">The results of the studies analysing the relationship between lipid alterations and mortality in CKD patients on dialysis conclude that there is no association&#44; or even that there is a paradoxical or contradictory association&#44; to that observed in the general population&#58; a lower survival rate in those cases with lower total cholesterol or LDL cholesterol levels&#46;<span class="elsevierStyleSup">6-9</span></p><p class="elsevierStylePara">An exception to these observations may be found among black CKD patients&#44; whose survival may be affected negatively by hypercholesterolaemia&#44; even in those undergoing dialysis&#46;<span class="elsevierStyleSup">20</span> The negative effect on the nutritional state caused by prolonged exposure to terminal uraemia&#44; dialysis procedures and the development of inflammation have been cited as a possible explanation for the inverse relationship between lipid alterations and mortality&#46;<span class="elsevierStyleSup">7&#44;9</span> The present study includes only patients with advanced CKD who have not yet begun dialysis so as to limit some of the confounding factors&#46; But even in predialysis states&#44; no relationship was observed between cholesterol levels&#44; LDL&#44; apo B or triglycerides and mortality or new CV episodes&#46; Unlike other studies of predialysis patients with CKD&#44;<span class="elsevierStyleSup">9</span> we found no negative relationship between total cholesterol or LDL levels and mortality in this study&#46; It is likely that the preserved nutritional state found in most of our patients would explain the differences between this study&#191;s findings and those of other studies&#46;</p><p class="elsevierStylePara">The mean concentration of apo A-I decreases proportionally to the decrease in glomerular filtration rate in CKD&#44;<span class="elsevierStyleSup">21</span> and this metabolic alteration is considered to be a CV risk factor&#44; although no studies have demonstrated a relationship between the levels of this protein and mortality in CKD&#46; The results from the present study show that high concentrations of apo A-I are associated with better survival&#46;</p><p class="elsevierStylePara">Some demographic&#44; clinical and biochemical characteristics of the patients grouped into tertiles according to the apo A level distribution frequency were significantly different&#46; The patients with the highest concentrations of apo A were younger&#44; predominantly female&#44; with a lower number of diabetics and lower overall comorbidity&#44; and a significantly lower mean level of C-reactive protein&#46; Furthermore&#44; we observed a significant correlation between apo A and Creactive protein levels&#46; This association between apo A levels and inflammation markers has already been described&#44;<span class="elsevierStyleSup">22&#44;23</span> and this apolipoprotein can be considered a negative acutephase reactant&#46; In this way&#44; it is difficult to determine whether the positive effect that high apo A levels have on CKD patient survival is due to the antiatherogenic mechanism&#44; or if it simply serves as an indirect inflammation marker&#44; or if both are true&#46; However&#44; we must point out that apo A levels added prognostic information about the survival of these patients when introduced in multivariate models including covariables such as age and the comorbidity index&#44; as well as albumin and C-reactive protein levels&#46;</p><p class="elsevierStylePara">Although a good correlation was made between the apo A and HDL levels&#44; it is possible that the predictive power of mortality for any reason was better with apo A than with HDL&#46; In the final phase of the study&#44; mortality was significantly associated with apo A levels&#44; but not HDL levels&#46;</p><p class="elsevierStylePara">The apo A&#47;apo B ratio was associated with survival&#44; but not as a monotonic function&#46; Only those patients with a high ratio had a higher survival rate&#46; It is likely that high levels of apo A&#47;apo B identify patients with a better vital prognosis and coincide with characteristics such as absence of inflammatory and malnutrition process&#44; along with controlled apo B levels &#40;whether or not by pharmacological means&#41; that are more similar to those providing contrasted survival benefits to the general population&#46;</p><p class="elsevierStylePara">This study has certain limitations&#46; The study had set covariables&#44; and did not consider variables that changed over time &#40;increases or decreases in lipid values in a certain follow-up time&#41;&#46; A large percentage of patients received treatment with statin drugs&#44; and although this covariable was taken into account for all survival analyses&#44; we cannot rule out the possibility of a certain degree of influence over the results due to medication and dose heterogeneity&#44; and due to maintaining the prescription over time&#46;</p><p class="elsevierStylePara">In addition to the apolipoproteins A-I and B&#44; there are others &#40;apo A-IV&#44; apo E&#44; apo&#91;a&#93;&#44; etc&#46;&#41; that may have a potential effect on the evolution of these patients&#44; and which were not analysed in this study&#46;</p><p class="elsevierStylePara">To conclude&#44; the total serum lipid and lipoprotein levels in predialysis patients with advanced CKD do not affect survival or the development of new CV episodes&#46; On the other hand&#44; high apo A levels and a high apo A&#47;apo B ratio were associated with a better vital prognosis in this patient group&#46;</p><p class="elsevierStylePara">Before we can recommend measuring these apolipoproteins as prognostic markers in CKD&#44; additional studies will be needed to determine their relationship with subclinical arteriosclerosis&#44; as well as effects that pharmacological modifications to plasma concentrations of these proteins may have on patient survival&#46; <br></br></p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;t1&#95;p543&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_t1_p543.jpg" alt="Clinical and biochemical characteristics of patients included in the study"></img></a></p><p class="elsevierStylePara">Table 1&#46; Clinical and biochemical characteristics of patients included in the study</p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;f1&#95;p543&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_f1_p543.jpg"></img></a></p><p class="elsevierStylePara">Figure 1&#46; </p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;t2&#95;p544&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_t2_p544.jpg" alt="Characteristics of patients grouped in tertiles according to the frequency distribution of apolipoprotein A level"></img></a></p><p class="elsevierStylePara">Table 2&#46; Characteristics of patients grouped in tertiles according to the frequency distribution of apolipoprotein A level</p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;f2&#95;p544&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_f2_p544.jpg"></img></a></p><p class="elsevierStylePara">Figure 2&#46; </p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;t3&#95;p545&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_t3_p545.jpg" alt="Prognostic value of the different study parameters for mortality&#44; in Cox regression models with or without adjustment for other covariables&#46;"></img></a></p><p class="elsevierStylePara">Table 3&#46; Prognostic value of the different study parameters for mortality&#44; in Cox regression models with or without adjustment for other covariables&#46;</p><p class="elsevierStylePara"><a href="grande&#47;44718078&#95;f3&#95;p545&#46;jpg" class="elsevierStyleCrossRefs"><img src="44718078_f3_p545.jpg"></img></a></p><p class="elsevierStylePara">Figure 3&#46; </p>"
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        "resumen" => "Dyslipidaemia is a well-established risk factor for cardiovascular diseases in the general population&#46; However&#44; this association is not observed in chronic kidney disease &#40;CKD&#41; patients&#46; This study examines the association between lipid levels&#44; including apolipoproteins A-I and B concentrations&#44; and all-cause mortality or the development of new cardiovascular events in advanced CKD patients&#46; This observational prospective historical study included 331 patients with CKD stage 4 or 5 not yet on dialysis&#46; In addition to conventional clinical and biochemical data&#44; total cholesterol&#44; triglycerides&#44; HDL&#44; LDL&#44; apolipoprotein A-I &#40;apo A&#41; and B &#40;apo B&#41; plasma concentrations were measured&#46; Cox proportional hazard models were adjusted for age&#44; sex&#44; comorbidity index&#44; residual renal function&#44; serum albumin&#44; C-reactive protein levels&#44; and treatment with statins&#46; The median follow-up time was 985 days&#44; and during this period 105 patients died and 54 patients had a new cardiovascular event&#46; In fully-adjusted fixed-covariate Cox models&#44; the hazard ratio for each 10mg&#47;dl increase of apo A concentration was 0&#46;915 &#40;C&#46;I&#46; 95&#37; 0&#46;844 to 0&#46;992&#59; p &#61; 0&#44;031&#41;&#46; Patients with an apo A&#47;apo B ratio in the upper tertile &#40;i&#46;e&#46; &#62;1&#46;42&#41; had a better survival rate than the rest of the study patients &#40;hazard ratio &#61; 0&#46;592&#44; C&#46;I&#46; 95&#37; 0&#46;368 to 0&#46;953&#44; p &#60; 0&#46;05&#41;&#46; None of the study lipid parameters were associated with new cardiovascular events in the adjusted models&#46; In conclusion&#44; apo A concentrations and high apo A&#47;apo B ratios added independent predictive information about survival of CKD patients not yet on dialysis&#46;"
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Nefrología (English Edition)