Peng-cheng He

Contrast medium volume to creatinine clearance ratio: a predictor of contrast-induced nephropathy in the first 72 hours following percutaneous coronary intervention.

Objectives: To investigate the predictive value of the contrast media volume to creatinine clearance (V/CrCl) ratio for the risk of contrast‐induced nephropathy (CIN) (i.e., within 48–72 hr) and to determine a relatively safe V/CrCl cut‐off value to avoid CIN in patients following percutaneous coronary intervention (PCI). Background: The V/CrCl ratio is a pharmacokinetic risk factor for an early abnormal increase in serum creatinine (i.e., within 24 hr) after PCI. Methods: V/CrCl ratios were obtained from 1,140 consecutive consenting patients after unselective PCI. Receiver‐operator characteristic (ROC) curves were used to identify the optimal sensitivity for the observed range of V/CrCl. The predictive value of V/CrCl for the risk of CIN was assessed using multivariate logistic regression. Results: Fifty‐five (4.8%) patients out of 1,140 developed CIN. There was a significant association between higher V/CrCl ratio values and risk of CIN in the overall population: 1.4%, 1.4%, 5.7%, and 10.9% for quartile 1 (Q1) of the V/CrCl value (<1.56, n = 283), Q2 (1.56–2.27, n = 289), Q3 (2.28–3.42, n = 282), and Q4 (>3.42, n = 285) of contrast, respectively (P < 0.001). ROC curve analysis indicated that a V/CrCl ratio of 2.62 was a fair discriminator for CIN (C‐statistic 0.73). After adjusting for other known predictors of CIN, V/CrCl ratios > 2.62 remained significantly associated with CIN (odds ratio: 2.20; 95% confidence interval: 1.00–4.81, P < 0.05). Conclusion: A V/CrCl ratio > 2.62 was a significant and independent predictor of CIN after PCI in unselected patients.

Statins for the Prevention of Contrast-Induced Nephropathy After Coronary Angiography/Percutaneous Interventions A Meta-analysis of Randomized Controlled Trials

Background: Statins have been demonstrated to prevent the development of contrast-induced nephropathy (CIN). Nevertheless, clinical research has indicated conflicting results. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effects of statins on CIN and the requirement of renal replacement therapy (RRT) in patients undergoing coronary angiography/percutaneous interventions. Methods: PubMed, MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central RCTs were searched for RCTs from inception to February 2014 to compare statins with placebo treatment for preventing CIN in patients undergoing coronary angiography/percutaneous interventions. Results: Nine RCTs were identified and analyzed in a total of 5143 patients involving 2560 patients with statin pretreatment and 2583 patients as control. Patients who received statin therapy had a 53% lower risk of CIN with different definitions (within 48 or 72 hours) compared to the control group based on a fixed effect model (risk ratio = 0.47, 95% confidence interval = 0.37-0.60, P < .0001) and were less likely to require RRT based on Peto fixed effect. Subgroup analysis showed that statin pretreatment could decrease the incidence of CIN in patients with preexisting renal dysfunction or diabetes mellitus. In addition, patients on rosuvastatin had a similar reduced incidence of CIN compared to patients on atorvastatin. Conclusion: This updated meta-analysis demonstrated that preprocedural statin treatment could reduce the risk of CIN and the need for RRT in patients undergoing coronary angiography/percutaneous interventions. Moreover, statin therapy would be helpful in reducing the incidence of CIN in high-risk patients with preexisting renal dysfunction or diabetes mellitus. Additionally, rosuvastatin and atorvastatin had similar efficacies in preventing CIN development.

Safe Limits of Contrast Vary With Hydration Volume for Prevention of Contrast-Induced Nephropathy After Coronary Angiography Among Patients With a Relatively Low Risk of Contrast-Induced Nephropathy

Background—Few studies have investigated the safe limits of contrast to prevent contrast-induced nephropathy (CIN) based on hydration data. We aimed to investigate the relative safe maximum contrast volume adjusted for hydration volume in a population with a relatively low risk of CIN. Methods and Results—The ratios of contrast volume-to-creatinine clearance (V/CrCl) and hydration volume to body weight (HV/W) were determined in patients undergoing cardiac catheterization. Receiver–operator characteristic curve analysis based on the maximum Youden index was used to identify the optimal cutoff for V/CrCl in all patients and in HV/W subgroups. Eighty-six of 3273 (2.6%) patients with mean CrCl 71.89±27.02 mL/min developed CIN. Receiver–operator characteristic curve analysis indicated that a V/CrCl ratio of 2.44 was a fair discriminator for CIN in all patients (sensitivity, 73.3%; specificity, 70.4%). After adjustment for other confounders, V/CrCl >2.44 continued to be significantly associated with CIN (adjusted odds ratio, 4.12; P<0.001) and the risk of death (adjusted hazard ratio, 2.62; P<0.001). The mean HV/W was 12.18±7.40. We divided the patients into 2 groups (HV/W ⩽12 and >12 mL/kg). The best cutoff value for V/CrCl was 1.87 (sensitivity, 67.9%; specificity, 64.4%; adjusted odds ratio, 3.24; P=0.011) in the insufficient hydration subgroup (HV/W, ⩽12 mL/kg; CIN, 1.32%) and 2.93 (sensitivity, 69.0%; specificity, 65.0%; adjusted odds ratio, 3.04; P=0.004) in the sufficient hydration subgroup (HV/W, >12 mL/kg; CIN, 5.00%). Conclusions—The V/CrCl ratio adjusted for HV/W may be a more reliable predictor of CIN and even long-term outcomes after cardiac catheterization. We also found a higher best cutoff value for V/CrCl to predict CIN in patients with a relatively sufficient hydration status, which may be beneficial during decision-making about contrast dose limits in relatively low-risk patients with different hydration statuses.

Outcomes and Morphologic Changes of Immediate Type Ia Endoleak following Endovascular Repair of Acute Type B Aortic Dissection

BACKGROUND The clinical significance of immediate type Ia endoleaks after thoracic endovascular aortic repair (TEVAR) for aneurysms has been described in detail. However, this phenomenon is still controversial in TEVAR patients treated for acute type B aortic dissection. METHODS A single-institution study was conducted in 81 prospectively evaluated patients treated between January 2012 and June 2012 for acute type B aortic dissection. Preoperative and postoperative computed tomography angiography (CTA) images were analyzed using 3-dimensional reconstruction to measure the areas and indices of the true lumen, false lumen, and total aorta in the proximal, middle, and distal descending thoracic aorta. Data were analyzed and compared between the 2 groups of patients, with and without immediate type Ia endoleaks. RESULTS The average follow-up period was 12 months (range 10-13 months) after the procedure. TEVAR was successfully performed in all patients (mean age 53 years; 86% men). Thirty-six of the 81 patients were diagnosed with complicated type B dissection, including persistent pain (19/36, 52.7%), refractory hypertension (4/36, 11.1%), and end-organ ischemia (13/36, 36.1%). Of all the patients, 37 (45.7%) were diagnosed with immediate type Ia endoleaks. The differences between the 30-day and 1-year all-cause mortality rates between the 2 groups were nonsignificant (13.5% vs. 2.2%, P = 0.08; 16.2% vs. 4.5%, P = 0.13). No stroke or paraplegia occurred during the follow-up. Reintervention was performed in 2 patients for delayed type I endoleaks in the group without immediate type Ia endoleaks. Pre- and postoperative CTA images were available for analysis in 54 patients. Among them, 24 patients had type Ia endoleaks. Patients with immediate type Ia endoleaks had a significantly larger preoperative distal false lumen area (498 ± 274 vs. 284 ± 213 mm(2), P = 0.02) and a larger distal aortic area (759 ± 275 vs. 624 ± 185 mm(2), P = 0.03). The 1-year follow-up CTA demonstrated significantly smaller true lumen indices and larger false lumen areas and false lumen indices in the proximal, middle, and distal sections in patients with immediate type Ia endoleaks. Differences in the postoperative morphological changes of the whole descending thoracic aorta were significant between the 2 groups, with the maximum area and the proximal, middle, and distal regions involved. The occurrence of endoleaks and the rates of postoperative false lumen thrombosis throughout the length of stent grafts were not significant at 1-year follow-up. CONCLUSIONS The majority of immediate type Ia endoleaks following TEVAR in acute type B aortic dissections could seal spontaneously, without additional procedures needed. However, the appearance of such complications could be a risk factor of poorer aortic remodeling. Careful surveillance is recommended more frequently in patients with immediate type Ia endoleaks.

Association of N-terminal Pro-b-type Natriuretic Peptide With Contrast-induced Nephropathy and Long-term Outcomes in Patients With Chronic Kidney Disease and Relative Preserved Left Ventricular Function

AbstractThe aim of the present article was to evaluate the association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with contrast-induced nephropathy (CIN) and long-term outcomes in patients with chronic kidney disease (CKD) and relative preserved left ventricular function (LVF) undergoing percutaneous coronary intervention (PCI).We prospectively enrolled 1203 consecutive patients with CKD and preserved LVF undergoing elective PCI. The primary end point was the development of CIN, defined as an absolute increase in serum creatinine (SCr) ≥0.5 mg/dL, from baseline within 48 to 72 hours after contrast medium exposure.CIN incidence varied from 2.2% to 5.2%. Univariate logistic analysis showed that lg-NT-pro-BNP was significantly associated with CIN (odds ratio [OR] = 3.93, 95% confidence interval [CI], 2.22–6.97, P < 0.001). Furthermore, lg-NT-pro-BNP remained a significant predictor of CIN (OR = 3.30, 95% CI, 1.57–6.93, P = 0.002), even after adjusting for potential confounding risk factors. These results were confirmed by using other CIN criteria, which were defined as elevations of the SCr by 25% or 0.5 and 0.3 mg/dL from the baseline. The best cutoff value of lg-NT-pro-BNP for detecting CIN was 2.73 pg/mL (537 pg/mL) with 73.1% sensitivity and 70.0% specificity according to the receiver operating characteristic (ROC) analysis (C statistic = 0.754, 95% CI, 0.67–0.84, P < 0.001). In addition, NT-pro-BNP ≥537 pg/mL (2.73 pg/mL, lg-NT-pro-BNP) was associated with an increased risk of all-cause mortality and composite end points during 2.5 years of follow-up.NT-pro-BNP ≥537 pg/mL is independently associated with an increased risk of CIN with different definitions and poor clinical outcomes in patients with CKD and relative preserved LVF undergoing PCI.

Prognostic value of hypoalbuminemia for adverse outcomes in patients with rheumatic heart disease undergoing valve replacement surgery

High-risk patients with rheumatic heart disease (RHD) who were undergoing valve replacement surgery (VRS) were not identified entirely. This study included 1782 consecutive patients with RHD who were undergoing VRS to explore the relationship between hypoalbuminemia and adverse outcomes and to confirm whether hypoalbuminemia plays a role in risk evaluation. A total of 27.3% of the RHD patients had hypoalbuminemia. In-hospital deaths were significantly higher in the hypoalbuminemic group than in the non-hypoalbuminemic group (6.6% vs 3.1%, P = 0.001). Hypoalbuminemia was an independent predictor of in-hospital death (OR = 1.89, P = 0.014), even after adjusting for the Euro score. The addition of hypoalbuminemia to Euro score enhanced net reclassification improvement (0.346 for in-hospital death, P = 0.004; 0.306 for 1-year death, p = 0.005). A Kaplan-Meier curve analysis revealed that the cumulative rate of 1-year mortality after the operation was higher in patients with a new Euro score ≥6. These findings indicated that hypoalbuminemia was an independent risk factor for in-hospital and 1-year mortality after VRS in patients with RHD, which might have additive prognostic value to Euro score.

Canada Acute Coronary Syndrome Score: A Preprocedural Risk Score for Contrast-Induced Nephropathy After Primary Percutaneous Coronary Intervention:

In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention, contrast-induced nephropathy (CIN) is a serious complication associated with poor outcomes. We assessed the predictive value of the Canada Acute Coronary Syndrome (C-ACS) score for CIN in these patients. A total of 394 consecutive patients with STEMI were enrolled and divided into 3 groups according to their C-ACS scores—group 1, score 0; group 2, score 1; and group 3, score ≥2. The clinical outcomes were CIN and major adverse clinical events (MACEs) during hospital and follow-up; 8.4% of patients developed CIN. Patients with high C-ACS scores were more likely to develop CIN, in-hospital death, and MACEs (P < .001). The C-ACS score was an independent predictor of CIN (odds ratio = 2.87; 95% confidence interval = 1.78-4.63; P < .001) and risk factor for long-term MACEs. The C-ACS score had good predictive values for CIN, in-hospital morality, MACEs, and long-term mortality. Patients with high C-ACS risk scores exhibited a worse survival rate than those with low scores (death, P = .02; MACEs, P = .006). In conclusion, in patients with STEMI, the C-ACS could predict CIN and clinical outcomes.

Geraniin ameliorates cisplatin-induced nephrotoxicity in mice

Abstract Geraniin, an active compound isolated from Geranium sibiricum, has been reported to have antioxidant and anti-inflammatory activities. The aim of this study was to investigate the protective effects of geraniin against cisplatin (CP)-induced kidney injury in mice. Geraniin was administrated for three consecutive days following CP (20 mg/kg) injection. The results showed that geraniin inhibited CP-induced kidney histopathologic changes, MDA, inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production in kidney tissues. Geraniin also inhibited CP-induced blood urea nitrogen (BUN) and creatinine production. Meanwhile, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) decreased by CP were reversed by the treatment of geraniin. In addition, geraniin significantly inhibited CP-induced NF-κB activation in kidney tissues. Treatment of geraniin dosedependently upregulated the expression of Nrf2 and HO-1. The anticancer effects of CP were not affected by the treatment of geraniin. In conclusion, these results indicated that geraniin protected against CP-induced nephrotoxicity by inhibiting oxidative stress and inflammatory response.

The cardiothoracic ratio: a neglected preoperative risk-stratified method for patients with rheumatic heart disease undergoing valve replacement surgery

OBJECTIVES It is common for patients with rheumatic heart disease to have an enlarged heart. We investigated the prognostic value of cardiothoracic ratio (CTR) in patients with rheumatic heart disease undergoing valve replacement surgery. METHODS A total of 1772 patients were divided into 4 groups based on the quartiles of preoperative CTR: <0.56 (n = 349), 0.56-0.61 (n = 488), 0.61-0.66 (n = 449) and ≥0.66 (n = 486). The CTR was measured from postero-anterior chest radiographs. We then investigated the association between the CTR and adverse outcomes. RESULTS In-hospital mortality was 4.0% (71/1772). Analyses of receiver operating characteristic curves showed that, at a cut-off of 0.6, the CTR exhibited 66.2% sensitivity and 64.0% specificity for detecting in-hospital death (area under curve 0.671, P < 0.001). The prevalence of in-hospital death was 7.1% in males with a CTR >0.6, which was significantly higher in males without a CTR. A similar result was observed in females (1.9 vs 5.1%, P = 0.004). Multivariable regression showed that a CTR >0.6 was an independent predictor of in-hospital (odds ratio 2.36, P = 0.005) and 1-year mortality (hazard ratio 2.06, P = 0.006). Kaplan-Meier curves, for the cumulative rate of 1-year mortality among groups, indicated that the risk of death was increased if the CTR >0.6 (log-rank 16.36, P < 0.001). CONCLUSIONS CTR, as a simple and reproducible indicator, was identified as a prognostic factor for predicting poor outcomes in patients with rheumatic heart disease undergoing valve replacement surgery.

MicroRNA-93 Regulates Hypoxia-Induced Autophagy by Targeting ULK1

The expression of the core autophagy kinase, Unc51-like kinase 1 (ULK1), is regulated transcriptionally and translationally by starvation-induced autophagy. However, how ULK1 is regulated during hypoxia is not well understood. Previously, we showed that ULK1 expression is induced by hypoxia stress. Here, we report a new ULK1-modulating microRNA, miR-93; its transcription is negatively correlated with the translation of ULK1 under hypoxic condition. miR-93 targets ULK1 and reduces its protein levels under hypoxia condition. miR-93 also inhibits hypoxia-induced autophagy by preventing LC3-I to LC3-II transition and P62 degradation; these processes are reversed by the overexpression of an endogenous miR-93 inhibitor. Re-expression of ULK1 without miR-93 response elements restores the hypoxia-induced autophagy which is inhibited by miR-93. Finally, we detected the effects of miR-93 on cell viability and apoptosis in noncancer cell lines and cancer cells. We found that miR-93 sustains the viability of MEFs (mouse embryonic fibroblasts) and inhibits its apoptosis under hypoxia. Thus, we conclude that miR-93 is involved in hypoxia-induced autophagy by regulating ULK1. Our results provide a new angle to understand the complicated regulation of the key autophagy kinase ULK1 during different stress conditions.