Baseline characteristics of the study patients.

<p>Baseline characteristics of the study patients.</p

Renal Outcomes of Pioglitazone Compared with Acarbose in Diabetic Patients: A Randomized Controlled Study

<div><p>Objective</p><p>To assess the effect of pioglitazone on renal outcome, including urinary albumin excretion and estimated glomerular filtration rate (eGFR), in diabetic patients.</p><p>Design</p><p>A prospective, randomized, open-labeled, controlled study.</p><p>Setting</p><p>Taipei Veterans General Hospital.</p><p>Patients</p><p>Sixty type 2 diabetic patients treated with sulfonylureas and metformin, whose glycated hemoglobin (HbA1c) levels were between 7% and 10% and eGFR was between 45 and 125 mL/min/1.73 m².</p><p>Intervention</p><p>The patients were randomized to receive acarbose or pioglitazone and followed up for 6 months. Thirty patients were randomly assigned to receive acarbose, and 30 patients were assigned to receive pioglitazone.</p><p>Measurements</p><p>The primary study endpoint was the changes in the urinary albumin-to-creatinine ratio (UACR). The secondary endpoint was the changes in eGFR and other parameters.</p><p>Results</p><p>After 6 months of treatment, the mean changes in UACR were −18 ± 104 and 12 ± 85 (<i>p</i> = 0.25, between groups) for the acarbose and pioglitazone groups, respectively. The mean changes in eGFR were 0 ± 14 and −7 ± 16 mL/min/1.73 m² (<i>p</i> = 0.09, between groups) for the acarbose and pioglitazone groups, respectively. The reductions in HbA1c were similar in both groups. Fasting blood glucose was lower in the pioglitazone group than in the acarbose group. Significant body weight gain was observed in the pioglitazone group as compared with the acarbose group (1.3 ± 2.8 vs. −0.6 ± 1.5 kg, <i>p</i> = 0.002).</p><p>Conclusion</p><p>In type 2 diabetic patients who were treated with sulfonylureas and metformin and possessed HbA1c levels between 7% and 10%, additional acarbose or pioglitazone for 6 months provided similar glycemic control and eGFR and UACR changes. In the pioglitazone group, the patients exhibited significant body weight gain.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01175486" target="_blank">NCT01175486</a></p></div

Within-group changes before and after 6 months of intervention.

<p>Within-group changes before and after 6 months of intervention.</p

Volume status for predicting mortality.

<p>The receiver operating characteristic (ROC) curve for prediction of all-cause mortality constructed using the ratio of extracellular water to total body water (ECW/TBW) at baseline (A). The optimal cutoff point for ECW/TBW is listed in the attached table, along with the sensitivity, specificity and accuracy for predicting mortality at the end of the follow-up period. The area under ROC curve is significantly larger than 0.5. Kaplan-Meier analysis curve for all-cause mortality in relation to the ECW/TBW at baseline, stratified by the cutoff point among hemodialysis patients (B).</p

Baseline characteristics of the study participants by categories of ECW/TBW and plasma aldosterone.

<p>For abbreviations see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057511#pone-0057511-t001" target="_blank">Table 1</a>.</p>a<p>Comparisons among three groups in patients with ECW/TBW ≤48% and >48%, respectively. Statistical analysis by one-way ANOVA test, Pearson <i>x</i>² test, and Kruskal-Wallis test as appropriate.</p>b<p>P<0.05 versus patients with plasma aldosterone of <140 pg/mL.</p>c<p>P<0.05 versus patients with plasma aldosterone of 140–280 pg/mL.</p><p>Prior CVD category consisted of congestive heart failure, coronary artery disease, cerebrovascular disease, and peripheral arterial disease.</p

Kaplan-Meier mortality curves according to aldosterone tertile.

<p>All-cause mortality in relation to plasma aldosterone levels at baseline among hemodialysis patients.</p

Baseline characteristics of the study participants by categories of ECW/TBW.

<p>Abbreviations: BMI denotes body mass index; BP, blood pressure; CVD, cardiovascular disease; ECW, extracellular water; ECW/TBW, ratio of extracellular water to total body water; EPO, erythropoietin; HD, hemodialysis; hs-CRP, high-sensitivity C-reactive protein; IL-6, inerleukin-6; RAAS, renin-angiotensin-aldosterone system; TBW, total body water; UF, ultrafiltration.</p>a<p>Comparison between two groups of patients with ECW/TBW ≤48% and >48%.</p><p>Statistical analysis by ^bStudent <i>t</i>-test, ^cPearson <i>x</i>² test, and ^dMann-Whitney U test.</p><p>Prior CVD category consisted of congestive heart failure, coronary artery disease, cerebrovascular disease, and peripheral arterial disease.</p

Kaplan-Meier mortality curves according to aldosterone tertile, modified by volume status.

<p>All-cause mortality in relation to plasma aldosterone levels at baseline modified by the ratio of extracellular water to total body water (ECW/TBW) >48% (A) and ≤48% (B) among hemodialysis patients.</p

Hazard ratios for mortality and first cardiovascular event by categorical or continuous measure of plasma aldosterone modified by ECW/TBW.

<p>Abbreviations: CI denotes confidence interval; CV, cardiovascular; CVD, cardiovascular disease; ECW/TBW, ratio of extracellular water to total body water; HR, hazard ratio; IL-6, inerleukin-6.</p>a<p>The interaction P values assessed the modifying effect of volume overload (ECW/TBW >48%) on the risk relationship between plasma aldosterone and overall mortality and CV events.</p

Progression of Kidney Disease in Non-Diabetic Patients with Coronary Artery Disease: Predictive Role of Circulating Matrix Metalloproteinase-2, -3, and -9

<div><p>Background</p><p>Circulating matrix metalloproteinase (MMP)-2, -3 and -9 are well recognized in predicting cardiovascular outcome in coronary artery disease (CAD), but their risks for chronic kidney disease (CKD) are lacking. Therefore, the present study aimed to investigate whether circulating MMP levels could independently predict future kidney disease progression in non-diabetic CAD patients.</p><p>Methods</p><p>The prospective study enrolled 251 non-diabetic subjects referred for coronary angiography, containing normal coronary artery (n = 30) and CAD with insignificant (n = 95) and significant (n = 126) stenosis. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. eGFR decline rate was calculated and the primary endpoint was a decline in eGFR over 25% from baseline.</p><p>Results</p><p>The eGFR decline rate (ml/min/1.73 m² per year) in patients with CAD (1.22 [−1.27, 1.05]) was greater than that in those with normal coronary artery (0.21 [−2.63, 0.47], <i>P</i><0.01). The circulating MMP-2, -3 and -9 were independently associated with faster eGFR decline among CAD patients. The mean follow-up period was 8.5±2.4 years, and 39 patients reached the primary endpoint. In multivariate Cox regression model, the adjusted hazard ratios of MMP-2 ≥861 ng/mL, MMP-3 ≥227 ng/mL and MMP-9 ≥49 ng/mL for predicting CKD progression were 2.47 (95% CI, 1.21 to 5.07), 2.15 (1.12 to 4.18), and 4.71 (2.14 to 10.4), respectively. While added to a model of conventional risk factors and baseline eGFR, MMP-2, -3 and -9 further significantly improved the model predictability for CKD progression (c statistic, 0.817). In the sensitivity analyses, the results were similar no matter if we changed the endpoints of a decline of >20% in eGFR from baseline or final eGFR < 60 mL/min/1.73 m².</p><p>Conclusion</p><p>Circulating MMP-2, -3 and -9 are independently associated with kidney disease progression in non-diabetic CAD patients and add incremental predictive power to conventional risk factors.</p></div