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"cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "643" "paginaFinal" => "652" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efectos renoprotectores del propóleo sobre la toxicidad renal aguda inducida por gentamicina en ratones albinos suizos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1700 "Ancho" => 2500 "Tamanyo" => 576979 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Showing depositions of collagenous fibres in control (a), Gm (b and c), and GmP mice group.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Badr Abdullah Aldahmash, Doaa Mohamed El-Nagar, Khalid Elfakki Ibrahim" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Badr Abdullah" "apellidos" => "Aldahmash" ] 1 => array:2 [ "nombre" => "Doaa Mohamed" "apellidos" => "El-Nagar" ] 2 => array:2 [ "nombre" => "Khalid Elfakki" "apellidos" => "Ibrahim" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251416301274?idApp=UINPBA000064" "url" => "/20132514/0000003600000006/v1_201702210030/S2013251416301274/v1_201702210030/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Cystatin-C and TGF-β levels in patients with diabetic nephropathy" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "653" "paginaFinal" => "659" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Mumtaz Takir, Aslı Dogruk Unal, Osman Kostek, Nilufer Bayraktar, Nilgun Guvener Demirag" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Mumtaz" "apellidos" => "Takir" "email" => array:1 [ 0 => "mumtaztakir@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Aslı Dogruk" "apellidos" => "Unal" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Osman" "apellidos" => "Kostek" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Nilufer" "apellidos" => "Bayraktar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Nilgun Guvener" "apellidos" => "Demirag" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Division of Endocrinology and Metabolism, Department of Internal Medicine, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Division of Endocrinology and Metabolism, Department of Internal Medicine, Başkent University Hospital, İstanbul, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Internal Medicine, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Concentración de cistatina C y TGF-β en pacientes con nefropatía diabética" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1420 "Ancho" => 1649 "Tamanyo" => 129713 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Correlation of serum cystatin C with microalbuminuria in all four study groups.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Diabetic nephropathy (DN) is the leading cause of chronic kidney disease.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">1,2</span></a> Albumin excretion rate (AER) and glomerular filtration rate (GFR) are used to stage DN. However, these measurements are not sufficient in early diagnosis and monitoring the progression of DN. Therefore early markers should be devised for these purposes. Although microalbuminuria is accepted as a risk factor and marker for DN and progressive renal insufficiency,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a> some patients, especially type 2 diabetics, may have normoalbuminuric chronic kidney disease.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This shows that both normoalbuminuric and albuminuric pathways are at work.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">5</span></a> While some patients with MA present with normal kidney structure, some other normoalbuminuric diabetics have well-determined nephropathic lesion.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Cystatin C which is used for measurement of GFR, is produced in all nucleated cells and filtered freely from the glomerulus. It is reabsorbed totally and catabolised in the proximal tubules. Cystatin C is a suitable marker for GFR measurement owing to not being affected by age, weight, gender and protein intake.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">8–10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Transforming growth factor-beta (TGF-β1) is one of the growth factors which are implicated in DN pathogenesis. TGF-β1 causes mesangial extension by promoting renal cellular hypertrophy and by inducing the extracellular matrix expansion.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">11</span></a> Urinary TGF-β1 levels are increased as proportional to the severity of the nephropathy.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">12</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">We aimed to determine the value of serum Cystatin C and TGF-β1 in early detection of diabetic nephropathy in normoalbuminuric patients with type-2 diabetes mellitus.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">This was a cross-sectional study which was conducted at the Department of Endocrinology in Baskent University School of Medicine, Istanbul, Turkey, during 2009–2011, who agreed to participate in the study. Baskent University Ethical Committee approved the study protocol (Approval no: KA09/308). Patients with type 2 diabetes mellitus without known overt diabetic nephropathy were included in the study. Recruited patients were stratified into four groups, matched in terms of age, gender, microalbuminuria level and estimated GFR calculated with MDRD. We tried to exclude apparent causes of nondiabetic renal disease based on data obtained with urinary system ultrasonography, urine microscopy and urine culture. Patients who have history of nondiabetic renal disease, uncontrolled hypertension, liver disease, NYHA stage 3–4 heart failure, thyroid disease, malignity and steroid usage were excluded from the study. All participants were included in the study after signing informed consent forms.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Laboratory evaluation</span><p id="par0035" class="elsevierStylePara elsevierViewall">Following thorough medical history and detailed physical examination, blood samples were taken from all participants for measurement of fasting blood glucose, HbA1c, blood urea, creatinine and electrolytes, lipid profile, serum albumin, high sensitive C reactive protein (hsCRP). Freshly voided early morning urine samples were also collected for urinalysis. Patients also provided 24-h collected urine specimens for measurement of microalbumin.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Serum glucose, creatinine, total cholesterol, HDL and LDL cholesterol, triglyceride were studied by enzymatic colorimetric; serum albumin; bromocresol green (BCG), ure; (BUN) urease, HbA1c; immune-examination (C4000, Abbott, USA), and hsCRP was studied with immunoturbidimetric methods (C8000, Abbott, USA). Microalbumin level in 24-h urine was determined with immunoturbidimetric method (C4000 system, Abbott, USA).</p><p id="par0045" class="elsevierStylePara elsevierViewall">Estimated GFR was calculated with 6 variable MDRD equation using age, race, gender, serum creatinine, blood urea nitrogen and albumin values.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">13</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The serums of patients were stored in −20<span class="elsevierStyleHsp" style=""></span>°C until laboratory analysis. Serum cystathionine C, serum TGF-β1 and urine TGF-β1 levels were determined with enzyme linked immunosorbent assay (ELISA) method. BioVendor (Czech Republic) ELISA kit and eBioscience (North America) ELISA were used for Cystatin C and TGF-β1 measurements, respectively.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">For statistical evaluation, NCSS (Number Cruncher Statistical System) 2007 and PASS (Power Analysis and Sample Size) 2008 Statistical Software (Utah, USA) programs were used. Oneway Anova test was used in intergroup comparison of the parameters showing normal distribution and Tukey HDS test was used in the determination of the group causing the difference. Kruskal–Wallis test was used in intergroup comparison of the parameters not showing normal distribution and Mann–Whitney <span class="elsevierStyleItalic">U</span> test was used in the group causing the difference. In comparison of the qualitative data, Chi-square test was used. The significance was accepted as <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">A total of 78 patients with type 2 DM were included in the study (mean age 57<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8. Four groups were described; patients with GFR value <60<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and MA <30<span class="elsevierStyleHsp" style=""></span>mg/day as group 1; patients with GFR value <60<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and MA between 30<span class="elsevierStyleHsp" style=""></span>mg and 300<span class="elsevierStyleHsp" style=""></span>mg/day as group 2; patients with GFR value >120<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and MA <30<span class="elsevierStyleHsp" style=""></span>mg/day as group 3, and patients with GFR value between 90 and 120<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and MA <30<span class="elsevierStyleHsp" style=""></span>mg/day as group 4. There were 10 men and 10 women in group 1 and 4 whereas 10 men and 11 women in group 2 and 15 men and 2 women in group 3. The laboratory parameters of the groups are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Significant difference was present among groups with regards to mean age, fasting blood glucose, HbA1c and serum creatinine level.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">No significant difference was found among groups in terms of the presence of HT which has a major role in DN pathogenesis. The evaluation of the groups in terms of micro and macrovascular complications of diabetes is depicted in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Highest rate of coronary artery disease (CAD) was seen Groups 1 and 2. No significance difference was evident among the groups regarding prevalence of retinopathy, diabetic foot and neuropathy (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Results of GFR, cystatin C, serum and urine TGF-β1, MA measurements are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. Significant difference was present among the groups in terms of cystatin C, serum and urine TGF-β1 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). Post Hoc Tukey HSD test which was performed to determine the intragroup significance, showed that cystatin C level of groups 1 and 2 was significantly higher compared with those of groups 3 and 4 (for Group 1; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001; for Group 2; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01). For the serum and urine TGF-β1, we found that the levels in group 2 were significantly higher than group 4 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.012; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.012). No significant association was determined between TGF-β1 and any of the studied variables.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Cystatin C showed a significant and positive correlation with age, duration of diabetes, and serum uric acid in group 2 (for age: <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.477, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.029; for duration of diabetes: <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.437, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.048; for serum uric acid: <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.465, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.039). As expected, serum cystatin C level was negatively associated with estimated GFR level (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.892, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001) only in group 2 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In group 3, only a negative significant correlation was present between LDL and cystatin C (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.72, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002). In group 4, cystatin C had a positive correlation with duration of diabetes (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.453, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.045) and a negative correlation with MA (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.520, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.019) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">When all the patients which are taken to the study are evaluated, statistically significant relation in negative direction and in % 72.6 level is detected (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.726, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001). Significant negative correlation is detected between GFR and creatinine (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.806, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001). Positive significant correlation is detected between age, hypertension and CAD and cystatin C levels (for age <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.534, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001; for hypertension <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.347, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002; for CAD <span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.382, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001, respectively).</p><p id="par0085" class="elsevierStylePara elsevierViewall">When 60<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> is selected for GFR as the cut-off value, it is observed that the cystatin C levels are significantly different between the patients who have eGFR values over and below this cut-off point (GFR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>ml/min: 1548.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>613.8; GFR<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>ml/min mean: 816.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>310.8; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001). ROC analysis for cystatin C, in the cases where cystatin C is C<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>1064<span class="elsevierStyleHsp" style=""></span>mg/L, catch-up sensitivity of GFR in <60<span class="elsevierStyleHsp" style=""></span>ml/m was calculated as 80%, specificity as 86.21%; positive conjecture value as 66.67% and negative conjecture value is calculated as 92.59% (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The area under the curve in ROC analysis was found as 85.4% and standard error was calculated as 6%.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The albumin excretion rate (AER) which is used in staging of DN and GFR, is not sufficient for explaining the disease progress. While albumin excretion through urine is normal, GFR can decrease without any increase in AER. By considering that DN may have normoalbuminuric stage,<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">11</span></a> this situation is reported in type 1 diabetic patients who show typical specifications in favor of DN in renal biopsy.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">11</span></a> In our study, when detecting the early stage diabetic nephropathy, cystatin C levels are detected as higher in the groups which have normoalbuminuric eGFR <60<span class="elsevierStyleHsp" style=""></span>ml/m/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and as independent from eGFR serum and urine TGF-β1 level is detected as higher in microalbuminuria group.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In AER and GFR relation age is an important factor. GFR is type 2 diabetics over 70 years old, is approximately 60<span class="elsevierStyleHsp" style=""></span>ml/m/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>. In our study, eGFR was the lowest and the age was the oldest in normoalbuminuric group (average 62<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5 years).</p><p id="par0100" class="elsevierStylePara elsevierViewall">Today, GFR is accepted as the best index reflecting kidney function.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">13</span></a> GFR can be directly measured with the infusion of the exogenous markers such as inulin or <span class="elsevierStyleSup">51</span>Cr-EDTA. However these methods are not practical and not used in daily practice. Therefore, for the sake of practicality, American Diabetes Association (ADA) and National Kidney Foundation suggest the formula of Cockcroft-Gault (CG) and Modification of Diet in Renal Disease four-variable (MDRD) equations to estimate GFR.<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">14,15</span></a> Particularly MDRD equation is accepted as superior than CG owing to not depend on body weight measurement.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">13</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Serum creatinine concentration is an imperfect measure of GFR. In our study, the creatinine level in the patient groups whose GFR was <60<span class="elsevierStyleHsp" style=""></span>ml/m/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>, has not increased yet and the patients were normoalbuminuric. Since serum creatinine level is affected by muscle mass and diet, it is not an ideal marker for GFR calculation. Novel methods are needed for early and accurate detection of DN.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Cystatin C is an endogenic marker used for GFR determination because its serum level is dependent to almost whole of eGFR particularly it is seen more valuable in normal and mild decreased eGFR.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Laterza et al.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">5</span></a> have attributed cystatin C to be an important reagent in early stage kidney damage to its stabile production, muscle mass, not being dependent to age and gender or not showing reverse tendency to kidney secretion or blood circulation.</p><p id="par0120" class="elsevierStylePara elsevierViewall">In our study, the difference in cystatin C levels showed that even in normoalbuminuria stage, the diabetic renal disease can be identified.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In early diabetic kidney disease, there are contradictory results related to the role of cystatin C. As pursuant to our study, two studies show that cystatin C is not more sensitive than creatinine.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">16,17</span></a> Contrary to our results, in the study where cystatin C based equations and creatinine based equations like Schwartz, MDRD and CG formulas are compared and in a meta-analysis where 46 studies included, cystatin C is considered superior than creatinine in determination of decreased GFR.<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">18,19</span></a> Although a negative weak relation is detected in cystatin C and eGFR in our study, it was not statistically significant. We think that this situation might be due to the limited number of cases in the patient group. In the study where Mussap and colleagues have examined 52 type 2 diabetic patients,<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">20</span></a> eGFR has decreased from 120<span class="elsevierStyleHsp" style=""></span>ml/m/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> to 20<span class="elsevierStyleHsp" style=""></span>ml/m/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and cystatin C has increased more than the serum creatinine has. The association between Cystatin C and eGFR was detected stronger than the serum creatinine.</p><p id="par0130" class="elsevierStylePara elsevierViewall">In the study of Surendar et al. in Indians who have glucose intolerance, it was determined that cystatin C levels have increased as comparative with glucose intolerance and the highest cystatin C levels were found in the group which had microalbuminuria and retinopathy.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">21</span></a> In our study, no difference was detected in terms of retinopathy among the groups and cystatin C levels were found highest in the normoalbuminuric group.</p><p id="par0135" class="elsevierStylePara elsevierViewall">In the previous study, ROC analysis made for identifying the diagnostic profile of serum cystatin C in predicting eGFR <60<span class="elsevierStyleHsp" style=""></span>ml/dk/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> in the type 2 diabetic patients and as similar to our study, cut-off value is detected as 1.06<span class="elsevierStyleHsp" style=""></span>mg/dl, the sensitivity of serum cystatin C level is 81% and the specificity is detected as.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">22</span></a> As pursuant to our study, serum cystatin C level of the normoalbuminuric is detected as significantly higher than the patients with GFR of ≤60<span class="elsevierStyleHsp" style=""></span>ml/dk/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>. This makes us think that cystatin C levels of serum and urine are related with the subclinical failure and may be the kidney uptake reagents which are measurable in the period earlier than the onset of albuminuria. In the study of Yang and friends, serum cystatin C level showed correlation with MA level.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">23</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">When we consider the relation between serum cystatin C and serum creatinine levels and MDRD in whole study population we determined that the predictive ability of serum creatinine for GFR was higher. This result, which is discordant with the majority of the literature, can be connected to the insufficiency of the cases in patient groups, selecting the case from the patients who have early period DN and formation of 25% of the total patient population by microalbuminuric patient group.</p><p id="par0145" class="elsevierStylePara elsevierViewall">In the microalbuminuric patient group and in the patient group with GFR <60<span class="elsevierStyleHsp" style=""></span>ml/m/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> or >60<span class="elsevierStyleHsp" style=""></span>ml/m/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>, negative and significant association was found. This patient group was the sole patient group with MA. This group was made up from older patients than normoalbuminuric and two other patient groups with GFR >90<span class="elsevierStyleHsp" style=""></span>ml/m/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>. It is known that the serum cystatin C level increases with advancing age. The presence of significant difference among the patient groups in terms of age, can be seen as another factor which limits our study.</p><p id="par0150" class="elsevierStylePara elsevierViewall">In both studies, high serum cystatin C level is associated with the previous coronary heart disease.<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">24,25</span></a> As similar to these studies, we have found positive significant correlation between CAD and serum cystatin C in the whole patient cohort.</p><p id="par0155" class="elsevierStylePara elsevierViewall">One of the cytokines which is responsible for DN initiation and progression is TGF-β. It is proven that TGF-β intervenes to all pathological changes which depend on the diabetic kidney disease.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">26</span></a> TGF-β causes kidney cell hypertrophy and excessive extracellular matrix production in interstitial fibroblasts, glomerular and tubular cells.</p><p id="par0160" class="elsevierStylePara elsevierViewall">In experimental DM, glomerular and tubule-interstitial compartments, expresses TGF-β or TGF-β type II receptor. Although the kidney of the non-diabetic subject removes TGF-β1 from the blood, kidney of a diabetic patient releases TGF-β1 protein into the circulation. TGF-β1 level which has increased in urine is associated with adverse clinical outcomes.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">27</span></a> In 3 patient groups which do not have MA in our study, we have found the serum and urine TGF-β1 levels were significantly higher in the groups with MA.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Increased kidney TGF-β1 production in the diabetic patients was examined and renal vein TGF-β1 concentration was found positive in diabetic patients and negative in non-diabetic patients.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">27</span></a> Urine TGF-β1 level in the diabetic patients increased fourfold than the non-diabetic patients and as contrary to our study, increased urine TGF-β1 excretion was present in all diabetic patients irrespective of MA status.</p><p id="par0170" class="elsevierStylePara elsevierViewall">There are some limitations of our study that need to be mentioned. The most important limitation of our study is the estimation of GFR measurements. All estimates of GFR based on serum creatinine will be affected from physiologic and/or pathologic limitations<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">28</span></a> and be far from ideal GFR. On the other hand, recent studies showed the CKD-EPI creatinine equation has similar GFR prediction in different patient population compared with the MDRD Study equation, even in the earlier CKD stages.<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">29,30</span></a> In addition, the CKD-EPI creatinine-cystatin C equation is more suitable compared with standard reference for cystatin C and creatinine based equations.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">31</span></a> However, the cost effectiveness of the CKD-EPI creatinine-cystatin C equation for clinical use should be considered. The second important limitation is the sample size of the study groups. But we wanted to be sure about patients with type 2 diabetes mellitus without known overt diabetic nephropathy. Larger new clinical trials are recommended to determine the role of serum cystatin C, serum and urine TGF-β1 level as an early biomarker of diabetic nephropathy. The third, diabetic foot ulcer with or without concomitant peripheral arterial disease is considered as two separate disease.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a> In our study, we did not exam the patients whether they have peripheral vascular disease.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusion</span><p id="par0175" class="elsevierStylePara elsevierViewall">Although urinary albumin excretion is suggested for detection of type 2 diabetic nephropathy, there is group of patients with decreased eGFR but without increased urinary albumin excretion, in which serum cystatin C level was indicated to be used as an early biomarker of diabetic nephropathy. In addition, despite that serum and urine TGF-β1 levels were also significantly higher in patients with MA, only increased urine TGF-β1 excretion was present in all diabetic patients irrespective of MA status.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres803807" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec802000" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres803808" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec801999" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Laboratory evaluation" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-09-10" "fechaAceptado" => "2016-06-25" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec802000" "palabras" => array:5 [ 0 => "Diabetic nephropathy" 1 => "Cystatin C" 2 => "TGF-β1" 3 => "Microalbuminuria" 4 => "Normoalbuminuria" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec801999" "palabras" => array:5 [ 0 => "Nefropatía diabética" 1 => "Cistatina C" 2 => "TGF-β1" 3 => "Microalbuminuria" 4 => "Normoalbuminuria" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate renal impairment in type 2 diabetic patients with normoalbuminuria or microalbuminuria by detection of serum cystatin C and serum and urinary TGF-β levels.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cross-sectional study conducted at the Department of Endocrinology in Baskent University School of Medicine. Patients with type 2 diabetes mellitus without known overt diabetic nephropathy were included in the study. Recruited patients were stratified into four groups, matched in terms of age, gender, microalbuminuria level and estimated GFR calculated with MDRD.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">78 patients were enrolled. They were categorized into four groups depending on their urinary albumin excretion and estimated glomerular filtration rate.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Macrovascular complication was found to be higher in patients with microalbuminuria than in other patients (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01), but there were no differences in terms of other diabetic complications. Serum cystatin C level was significantly higher in normoalbuminuric group one patients, while serum and urinary TGF-β1 levels were higher in microalbuminuric group two patients. The serum level of cystatin C was found to negatively correlate with eGFR in group two patients (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.892, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). Finally, there was a negative correlation between eGFR and cystatin C in all the patient groups (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.726, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Although urinary albumin excretion is recommended for the detection of type two diabetic nephropathy, there is a group of patients with decreased eGFR but without increased urinary albumin excretion, in which serum cystatin C level was indicated to be used as an early biomarker of diabetic nephropathy.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Evaluar la insuficiencia renal en pacientes con diabetes tipo 2 con normoalbuminuria o microalbuminuria mediante la detección de la concentración de cistatina C en suero y de TGF-β en suero y orina.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Estudio transversal realizado en el Departamento de Endocrinología de la Facultad de Medicina de la Universidad de Baskent. En el estudio, se incluyó a pacientes con diabetes mellitus tipo 2 sin nefropatía diabética manifiesta conocida. Los pacientes seleccionados se estratificaron en 4 grupos, agrupados en términos de edad, sexo, grado de microalbuminuria y filtración glomerular estimada (FGe) calculada mediante la fórmula MDRD.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se incluyó a 78 pacientes. Se clasificaron en 4 grupos dependiendo de la excreción urinaria de albúmina y de la FGe.</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se observó que la complicación macrovascular era mayor en los pacientes con microalbuminuria que en otros (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,01), pero no hubo diferencias con relación a otras complicaciones diabéticas. La concentración sérica de cistatina C fue significativamente mayor en los pacientes del grupo 1 con normoalbuminuria, mientras que las concentraciones de TGF-β1 en suero y orina fueron mayores en los pacientes del grupo 2 con microalbuminuria. Se observó una correlación negativa entre la concentración sérica de cistatina C y la FGe en los pacientes del grupo 2 (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0,892, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001). Por último, se observó una correlación negativa entre la FGe y la cistatina C en todos los grupos de pacientes (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0,726, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,001).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Aunque se recomienda la excreción urinaria de albúmina para la detección de la nefropatía diabética tipo 2, hay un grupo de pacientes con disminución de la FGe, pero sin aumento de la excreción urinaria de albúmina, en los que estaba indicado usar la concentración de cistatina C en suero como un biomarcador temprano de nefropatía diabética.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1336 "Ancho" => 1603 "Tamanyo" => 134361 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Correlation of serum cystatin C with eGFR in all four study groups.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1420 "Ancho" => 1649 "Tamanyo" => 129713 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Correlation of serum cystatin C with microalbuminuria in all four study groups.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1523 "Ancho" => 1504 "Tamanyo" => 60542 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">ROC curve which is obtained for cystatin C.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Body mass index (BMI), hemoglobin A1c (HbA1c), high density lipoprotein (HDL), low density lipoprotein (LDL), high sensitive c reactive protein (hsCRP).</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Mean (standard deviation).</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 1 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 2 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 3 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 4 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62.9 (5.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59.7 (6.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49.0 (8.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53.7 (8.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.001</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Duration of Diabetes Mellitus, months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">116.4 (100.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">127.4 (96.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96.0 (71.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">78.0 (45.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.243 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI, kg/m<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.6 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.0 (5.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.2 (6.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.6 (5.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.430 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glucose, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">118.8 (26.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">152.1 (62.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">143.9 (42.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">121.1 (32.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.043</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HbA1c, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.1 (0.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.9 (1.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.3 (1.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.7 (1.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.028</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.2 (0.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6 (0.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6 (0.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.001</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin, g/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.2 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.2 (0.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.3 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.3 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.559 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HDL-Cholesterol, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.2 (10.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.4 (7.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39.8 (10.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40.5 (5.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.774 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LDL-Cholesterol, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">102.6 (35.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">115.3 (34.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">129.6 (30.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">105.9 (29.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.079 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Triglyceride, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">148.3 (91.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">174.8 (79.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">175.9 (50.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">184.6 (68.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.074 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sedimentation rate, mm/hour \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.3 (14.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.1 (10.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.4 (5.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.2 (8.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.412 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">hsCRP, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.1 (4.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.0 (7.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.5 (5.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.6 (5.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.969 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1349395.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Laboratory parameters of the study groups.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 1 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 2 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 3 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 4 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Coronary Artery Disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (45%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (47.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (5.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2(10%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.003</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Retinopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (25%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (33.3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (11.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (20%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.454 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetic Foot \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (%0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (4.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (%0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (%0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.432 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neuropathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (45%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (42.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (11.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (25%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.096 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1349396.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Evaluation of micro and macro vascular complications according to groups.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Estimated glomerular filtration rate (eGFR), serum transforming growth factor-beta 1 (sTGF-β1), urine transforming growth factor-beta 1 (uTGF-β1), microalbuminuria (MA).</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Mean (standard deviation).</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 1 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 2 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 3 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>17) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 4 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">eGFR, mL/m/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54.7 (7.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">78.2 (23.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">125.7 (6.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">106.1 (29.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.001</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cystatin C, mg/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.4 (0.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1 (0.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6 (0.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 (0.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.001</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">sTGF-β1, ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.7 (6.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.9 (3.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.1 (6.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.2 (6.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.022</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">uTGF-β1, pg/mg<span class="elsevierStyleHsp" style=""></span>cre \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">558.6 (23.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">633.2 (100.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">539.3 (204.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">442.2 (214.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.022</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MA, mg/24<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.0 (5.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89.8 (37.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.2 (8.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.3 (5.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><span class="elsevierStyleBold">0.001</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1349394.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Estimated GFR, cystatin C, serum and urine TGF-β1, and MA levels in study groups.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:32 [ 0 => array:3 [ "identificador" => "bib0165" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diabetic nephropathy: prevention and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.H. 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Year/Month | Html | Total | |
---|---|---|---|
2024 November | 2 | 0 | 2 |
2024 October | 48 | 51 | 99 |
2024 September | 43 | 26 | 69 |
2024 August | 59 | 59 | 118 |
2024 July | 48 | 15 | 63 |
2024 June | 70 | 52 | 122 |
2024 May | 81 | 32 | 113 |
2024 April | 61 | 40 | 101 |
2024 March | 51 | 17 | 68 |
2024 February | 37 | 33 | 70 |
2024 January | 42 | 24 | 66 |
2023 December | 27 | 19 | 46 |
2023 November | 41 | 26 | 67 |
2023 October | 59 | 29 | 88 |
2023 September | 37 | 28 | 65 |
2023 August | 54 | 19 | 73 |
2023 July | 53 | 23 | 76 |
2023 June | 43 | 24 | 67 |
2023 May | 58 | 27 | 85 |
2023 April | 38 | 12 | 50 |
2023 March | 88 | 15 | 103 |
2023 February | 52 | 16 | 68 |
2023 January | 43 | 14 | 57 |
2022 December | 95 | 31 | 126 |
2022 November | 85 | 25 | 110 |
2022 October | 66 | 36 | 102 |
2022 September | 59 | 26 | 85 |
2022 August | 51 | 42 | 93 |
2022 July | 44 | 43 | 87 |
2022 June | 62 | 31 | 93 |
2022 May | 39 | 26 | 65 |
2022 April | 53 | 42 | 95 |
2022 March | 54 | 43 | 97 |
2022 February | 62 | 41 | 103 |
2022 January | 64 | 35 | 99 |
2021 December | 50 | 53 | 103 |
2021 November | 58 | 36 | 94 |
2021 October | 118 | 62 | 180 |
2021 September | 65 | 43 | 108 |
2021 August | 67 | 37 | 104 |
2021 July | 87 | 48 | 135 |
2021 June | 73 | 34 | 107 |
2021 May | 74 | 41 | 115 |
2021 April | 180 | 124 | 304 |
2021 March | 105 | 43 | 148 |
2021 February | 78 | 25 | 103 |
2021 January | 73 | 36 | 109 |
2020 December | 59 | 15 | 74 |
2020 November | 53 | 18 | 71 |
2020 October | 58 | 33 | 91 |
2020 September | 77 | 20 | 97 |
2020 August | 65 | 23 | 88 |
2020 July | 72 | 10 | 82 |
2020 June | 60 | 17 | 77 |
2020 May | 52 | 13 | 65 |
2020 April | 49 | 16 | 65 |
2020 March | 59 | 11 | 70 |
2020 February | 56 | 34 | 90 |
2020 January | 79 | 28 | 107 |
2019 December | 81 | 29 | 110 |
2019 November | 85 | 15 | 100 |
2019 October | 53 | 13 | 66 |
2019 September | 47 | 22 | 69 |
2019 August | 82 | 14 | 96 |
2019 July | 126 | 26 | 152 |
2019 June | 34 | 17 | 51 |
2019 May | 39 | 17 | 56 |
2019 April | 127 | 39 | 166 |
2019 March | 77 | 25 | 102 |
2019 February | 46 | 27 | 73 |
2019 January | 53 | 21 | 74 |
2018 December | 200 | 40 | 240 |
2018 November | 329 | 25 | 354 |
2018 October | 258 | 22 | 280 |
2018 September | 91 | 19 | 110 |
2018 August | 60 | 31 | 91 |
2018 July | 41 | 17 | 58 |
2018 June | 35 | 18 | 53 |
2018 May | 72 | 21 | 93 |
2018 April | 122 | 12 | 134 |
2018 March | 89 | 18 | 107 |
2018 February | 105 | 5 | 110 |
2018 January | 112 | 11 | 123 |
2017 December | 139 | 6 | 145 |
2017 November | 105 | 12 | 117 |
2017 October | 31 | 18 | 49 |
2017 September | 59 | 13 | 72 |
2017 August | 81 | 9 | 90 |
2017 July | 55 | 8 | 63 |
2017 June | 81 | 10 | 91 |
2017 May | 66 | 11 | 77 |
2017 April | 47 | 7 | 54 |
2017 March | 32 | 5 | 37 |
2017 February | 23 | 8 | 31 |