Huaizhou You

The ratio of CRP to prealbumin levels predict mortality in patients with hospital-acquired acute kidney injury

BackgroundAnimal and human studies suggest that inflammation and malnutrition are common in acute kidney injury (AKI) patients. However, only a few studies reported CRP, a marker of inflammation, albumin, prealbumin and cholesterol, markers of nutritional status were associated with the prognosis of AKI patients. No study examined whether the combination of inflammatory and nutritional markers could predict the mortality of AKI patients.Methods155 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. C-reactive protein (CRP), and the nutritional markers (albumin, prealbumin and cholesterol) measured at nephrology consultation were analyzed in relation to all cause mortality of these patients. In addition, CRP and prealbumin were also measured in healthy controls (n = 45), maintenance hemodialysis (n = 70) and peritoneal dialysis patients (n = 50) and then compared with AKI patients.ResultsCompared with healthy controls and end-stage renal disease patients on maintenance hemodialysis or peritoneal dialysis, patients with AKI had significantly higher levels of CRP/prealbumin (p < 0.001). Higher level of serum CRP and lower levels of albumin, prealbumin and cholesterol were found to be significant in the patients with AKI who died within 28 days than those who survived >28 days. Similarly, the combined factors including the ratio of CRP to albumin (CRP/albumin), CRP/prealbumin and CRP/cholesterol were also significantly higher in the former group (p < 0.001 for all). Multivariate analysis (Cox regression) revealed that CRP/prealbumin was independently associated with mortality after adjustment for age, gender, sepsis and sequential organ failure assessment (SOFA, p = 0.027) while the others (CRP, albumin, prealbumin, cholesterol, CRP/albumin and CRP/cholesterol) became non-significantly associated. The hazard ratio was 1.00 (reference), 1.85, 2.25 and 3.89 for CRP/prealbumin increasing according to quartiles (p = 0.01 for the trend).ConclusionsInflammation and malnutrition were common in patients with AKI. Higher level of the ratio of CRP to prealbumin was associated with mortality of AKI patients independent of the severity of illness and it may be a valuable addition to SOFA score to independent of the severity of illness and it may be a valuable addition to SOFA score to predict the prognosis of AKI patients.

Mannitol is an independent risk factor of acute kidney injury after cerebral trauma: a case-control study

We retrospectively studied a random cohort of patients with cerebral trauma to investigate the risk factors of acute kidney injury (AKI) following cerebral trauma. AKI was determined using the RIFLE (risk, injury, failure, loss, or end-stage kidney) staging criteria. About 171 patients were chosen in the study, with 53 patients in AKI group and 118 patients without AKI in non-AKI group. By logistic regression analysis, univariate analysis revealed that age, hypertension, emergent surgery, systemic inflammatory response syndrome (SIRS), Glasgow coma score (GCS), sequential organ failure assessment (SOFA) score, the respiration, coagulation, and cardiovascular components of the SOFA score, mechanical ventilation time, red blood cell transfusion, plasma transfusion, and the accumulative doses of furosemide, torsemide, and mannitol were significantly related to AKI after cerebral trauma. Logistic multivariate regression analysis showed that SOFA score [odds ratio (OR) = 1.516, 95% confidence interval (CI) 1.222–1.881, p < 0.001], the accumulative doses of torsemide (OR = 0.016, 95% CI 1.002–1.031, p = 0.016), and the accumulative doses of mannitol (OR = 2.687, 95% CI 1.062–6.800, p = 0.037) were independent risk factors of AKI. This model had a good discrimination for AKI with an area under the receiver operating characteristic (ROC) curve of 0.901 (p < 0.001). The accumulative doses of mannitol as a risk factor of AKI were identified by propensity score match (PSM) method. We concluded that AKI was a common complication in patients with cerebral trauma. SOFA score and the accumulative doses of torsemide and mannitol were independent risk factors of AKI following cerebral trauma.

Advanced Oxidation Protein Products Induce Vascular Calcification by Promoting Osteoblastic Trans-Differentiation of Smooth Muscle Cells via Oxidative Stress and ERK Pathway

Vascular calcification is an actively regulated process similar to bone formation. Advanced oxidation protein products (AOPPs) have been demonstrated to be novel markers of oxidant-mediated protein damage. The present study investigated the role of AOPPs in inducing osteoblastic trans-differentiation and calcification of smooth muscle cells in vitro. We found that AOPPs directly increased the calcium deposition and expression of core binding factor-α1 (CBF-α1) and osteopontin (OPN) and significantly decreased SM-α-actin expression in human aortic smooth muscle cells (HASMCs). AOPPs increased intracellular oxidative stress, which was inhibited by vitamin E. Vitamin E also inhibited AOPP-induced calcium content and osteoblast differentiation of HASMCs. Furthermore, the inhibitor of ERK significantly suppressed the effects of AOPPs on calcification and osteoblast marker expression. These findings suggest that AOPPs induce vascular calcification by promoting osteoblast differentiation of smooth muscle cells via oxidative stress and ERK pathway.

Comparing the Autoantibody Levels and Clinical Efficacy of Double Filtration Plasmapheresis, Immunoadsorption, and Intravenous Immunoglobulin for the Treatment of Late‐onset Myasthenia Gravis

The aim of this study was to investigate the effects of double‐filtration plasmapheresis (DFPP), immunoadsorption (IA) and intravenous immunoglobulin (IVIg) in the treatment of late‐onset myasthenia gravis (MG). A total of 40 late‐onset MG patients were randomly divided into three groups: 15 patients were treated with DFPP; 10 patients were treated with IA; and 15 patients received IVIg. The titers of titin antibodies (Titin‐ab), acetylcholine receptor antibodies (AChR‐ab), presynaptic membrane antibody (Prsm‐ab) were detected before and after the treatment, and the quantitative MG score (QMG score) was assessed by blinded examiners before and immediately after the entire course of treatment. The clinical efficacy, duration of respiratory support, hospital stay, and the correlation between the three antibodies and the QMG score were also analyzed. Compared to pre‐treatment, the values of Titin‐ab, AChR‐ab, and PrsmR‐ab were all dramatically decreased (P < 0.05); meanwhile the value of Titin‐ab in the DFPP and IA groups decreased much more than in the IVIg group (P < 0.01); however, no statistical difference was found between the DFPP and IA groups (P > 0.05). Although the QMG score significantly improved in all three groups, it decreased much more in both the DFPP and IA groups than that in the IVIg group (P < 0.01). Symptoms were also effectively ameliorated by all treatments, but the clinical efficacy of the DFPP and IA groups was higher than the IVIg group (P < 0.05), as was the remission time (P < 0.01), the duration of hospital stay (P < 0.05), and the number of respiratory supports required (P < 0.05). Using Pearsons correlation, the decrease of Titin‐ab showed a longitudinal correlation with the decrease of QMG score (r = 0.6107, P < 0.01). Both DFPP and IA showed better short‐term clinical effectiveness than immunoglobulin transfusion, rapidly and effectively clearing the pathogenic antibodies in late‐onset MG patients, especially for Titin‐ab.

Aqueous extract of Astragali Radix ameliorates proteinuria in adriamycin nephropathy rats through inhibition of oxidative stress and endothelial nitric oxide synthase

AIM OF THE STUDY To investigate the effects of aqueous extract of Astragali Radix (ARE) on the oxidative stress status and endothelial nitric oxide synthase level in adriamycin (ADR) nephropathy rats. MATERIALS AND METHODS ADR nephropathy rats were randomly treated with ARE (2.5 g/kg/d, n=6, ARE group), or benazepril (10mg/kg/d, n=6, angiotensin-converting enzyme inhibitor (ACEI) group) for ten weeks. Serum urea nitrogen, creatinine, albumin, total protein, cholesterol and 24-h urinary protein concentration were determined. Renal cortex catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA) activities, and 24-h urinary NO(3)(-)/NO(2)(-) excretion were determined by chromatometry. Renal cortex cyclic guanosine monophosphate (cGMP) level was measured by enzyme immunoassay and eNOS expression was determined by immunohistochemistry. RESULTS ARE and ACEI treatments could remarkably reduce more 24h urinary protein excretion than that in ADR group (88.32±9.96 mg, 81.78±16.28 mg vs. 153.91±28.63 mg, P<0.01), and there was no difference between ARE and ACEI group. Renal cortex CAT, GSH-Px activities in ARE and ACEI group were significantly higher than ADR group, and renal cortex SOD activity in ARE group was higher than ADR group. Renal cortex MDA activity, cGMP level, and glomerular and tubular eNOS expression in ARE and ACEI group were lower than that in ADR group, and 24-h urinary NO(3)(-)/NO(2)(-) excretion in ARE group was lower than ADR group. Renal cortex MDA content (r=0.895, P<0.01), cGMP content (r=0.666, P<0.01) and eNOS expression in glomerulus (r=0.910, P<0.01) were strongly positively associated with 24h urinary protein excretion. And renal cortex SOD content was negatively associated with 24h urinary protein excretion (r=-0.861, P<0.01). CONCLUSIONS ARE may ameliorate the proteinuria by suppressing the over expression of eNOS, and inhibiting the oxidative injury in ADR nephropathy rats.

Nitrotyrosine Level Was Associated with Mortality in Patients with Acute Kidney Injury

Background To examine the characteristics of oxidative stress in patients with acute kidney injury (AKI) and investigate the association between plasma nitrotyrosine levels and 90-day mortality in patients with AKI. Methodology/Principal Findings 158 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. Twelve critically ill patients without AKI and 15 age and gender-matched healthy subjects served as control. Plasma 3-nitrotyrosine was analyzed in relation to 90-day all cause mortality of patients with AKI. The patients with AKI were followed up for 90 days and grouped according to median plasma 3-nitrotyrosine concentrations. Highest 3-NT/Tyr was detected in patients with AKI compared with healthy subjects, and critically ill patients without AKI (ANOVA p<0.001). The 90-day survival curves of patients with high 3-NT/Tyr showed significant differences compared with the curves of individuals with low 3-NT/Tyr (p = 0.001 by log rank test). Multivariate analysis (Cox regression) revealed that 3-NT/Tyr (p = 0.025) was independently associated with mortality after adjustment for age, gender, sepsis and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Conclusions/Significance There is excess plasma protein oxidation in patients with AKI, as evidenced by increased nitrotyrosine content. 3-NT/Tyr level was associated with mortality of AKI patients independent of the severity of illness.

Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury.

Introduction Regional citrate anticoagulation (RCA) is gaining popularity in continous renal replacement therapy (CRRT) for critically ill patients. The risk of citrate toxicity is a primary concern during the prolonged process. The aim of this study was to assess the pharmacokinetics of citrate in critically ill patients with AKI, and used the kinetic parameters to predict the risk of citrate accumulation in this population group undergoing continuous veno-venous hemofiltration (CVVH) with RCA. Methods Critically ill patients with AKI (n = 12) and healthy volunteers (n = 12) were investigated during infusing comparative dosage of citrate. Serial blood samples were taken before, during 120 min and up to 120 min after infusion. Citrate pharmacokinetics were calculated and compared between groups. Then the estimated kinetic parameters were applied to the citrate kinetic equation for validation in other ten patients’ CVVH sessions with citrate anticoagulation. Results Total body clearance of citrate was similar in critically ill patients with AKI and healthy volunteers (648.04±347.00 L/min versus 686.64±353.60 L/min; P = 0.624). Basal and peak citrate concentrations were similar in both groups (p = 0.423 and 0.247, respectively). The predicted citrate curve showed excellent fit to the measurements. Conclusions Citrate clearance is not impaired in critically ill patients with AKI in the absence of severe liver dysfunction. Citrate pharmacokinetic data can provide a basis for the clinical use of predicting the risk of citrate accumulation. Trial Registration ClinicalTrials.gov Identifier NCT00948558

Is the Serum Vitamin D Level at the Time of Hospital-Acquired Acute Kidney Injury Diagnosis Associated with Prognosis?

Background Low circulating vitamin D levels have been suggested to potentially contribute to acute complications in critically ill patients. However, in patients with acute kidney injury (AKI), whether vitamin D deficiency occurs and is a potential contributor to worse early outcomes at the time of AKI diagnosis remains unclear. Methodology/Principal Findings Two hundred patients with AKI were enrolled in our study. Healthy subjects and critically ill patients without AKI served as controls. Serum vitamin D concentrations were measured in the three groups. The patients with AKI were followed up for 90 days and grouped according to median serum vitamin D concentrations. In addition, vitamin D receptor polymorphisms (BsmI and FokI) were measured in these patients; they were also followed up for 90 days and grouped according to vitamin D receptor gene mutations. Low serum 1,25-dihydroxyvitamin D levels (59.56±53.00 pmol/L) were detected in patients with AKI and decreased with increasing severity of AKI. There were no significant findings with respect to 25-hydroxyvitamin D. The 90-day survival curves of individuals with high vitamin D concentrations showed no significant differences compared with the curves of individuals with low concentrations. The survival curves of patients with BB/Bb or FF/Ff genotypes also showed no significant differences compared with patients with bb or ff genotypes. In Cox regression analysis, the vitamin D status in patients with AKI was not an independent prognostic factor as adjusted by age, sex, Sequential Organ Failure Assessment score, or vitamin D receptor polymorphisms. Conclusions/Significance Patients with AKI manifested a marked decrease in the 1,25-dihydroxyvitamin D level at the time of AKI diagnosis, and the degree of 1,25-dihydroxyvitamin D deficiency increased with the severity of AKI. No association between the serum vitamin D level at the time of AKI diagnosis and 90-day all-cause mortality was found in patients with AKI.

Twelve weeks of pioglitazone therapy significantly attenuates dysmetabolism and reduces inflammation in continuous ambulatory peritoneal dialysis patients--a randomized crossover trial.

♦ Background: The aim of the present study was to investigate the effect of oral pioglitazone (PIO) on lipid metabolism, insulin resistance, inflammation, and adipokine metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients. ♦ Methods: In this randomized crossover trial, 36 CAPD patients with serum triglyceride levels above 1.8 mmol/L were randomly assigned to receive either oral PIO 15 mg once daily or no PIO for 12 weeks. Then, after a 4-week washout, the patients were switched to the alternative regimen. The primary endpoint was change in serum triglycerides during the PIO regimen compared with no PIO. Secondary endpoints included changes in other lipid levels, homeostatic model assessment of insulin resistance (HOMA-IR), adipocytokines, and C-reactive protein (CRP). ♦ Results: All 36 CAPD patients (age: 64 ± 11 years; 33% men; 27.8% with diabetes mellitus) completed the study. Comparing patients after PIO and no PIO therapy, we found no significant differences in mean serum triglycerides (3.83 ± 1.49 mmol/L vs 3.51 ± 1.98 mmol/L, p = 0.2). However, mean high-density lipoprotein (0.94 ± 0.22 mmol/L vs 1.00 ± 0.21 mmol/L, p = 0.004) and median total adiponectin [10.34 μg/mL (range: 2.59 - 34.48 μg/mL) vs 30.44 μg/mL (3.47 - 93.41 μg/mL), p < 0.001] increased significantly. Median HOMA-IR [7.51 (1.39 - 45.23) vs 5.38 (0.97 - 14.95), p = 0.006], mean fasting blood glucose (7.31 ± 2.57 mmol/L vs 6.60 ± 2.45 mmol/L, p = 0.01), median CRP [8.78 mg/L (0.18 - 53 mg/L) vs 3.50 mg/L (0.17 - 26.30 mg/L), p = 0.005], and mean resistin (32.70 ± 17.17 ng/mL vs 28.79 ± 11.83 ng/mL, p = 0.02) all declined. The PIO was well tolerated, with only one adverse event: lower-extremity edema in a patient with low residual renal function. ♦ Conclusions: Blood triglycerides were not altered after 12 weeks of PIO 15 mg once daily in CAPD patients, but parameters of dysmetabolism were markedly improved, including insulin resistance, inflammation, and adipokine balance, suggesting that PIO could be of value for this high-risk patient group. Larger, more definitive studies are needed to confirm these findings.

Intima-Media Thickness of the Carotid Artery and Its Correlation Factors in Maintenance Hemodialysis Patients: A Cross-Sectional Study

Background: To investigate the relationship between the intima-media thickness of the carotid artery (CA-IMT) and its major risk factors in maintenance hemodialysis (MHD) patients. Methods: Seventy-five MHD patients and 30 healthy volunteers were enrolled. The MHD patients were divided into 3 subgroups according to their CA-IMT value. Results: CA-IMT values in the MHD group were significantly higher than those in the control group. The differences in age, systolic blood pressure (SBP), and levels of serum albumin, prealbumin, cholesterol and serum phosphate between the increased IMT group and the normal IMT group were significant. SBP and serum phosphate levels were also greater in the abnormal IMT group than those in the normal IMT group. Significant relationships were found between CA-IMT and age, SBP, and serum levels of phosphate, albumin and prealbumin. In multiple regression analysis, a high serum phosphate level, low serum prealbumin level and high SBP were significant independent risk factors of increased CA-IMT. Conclusions: CA-IMT was increased dramatically in MHD patients. A high serum phosphate level, low serum prealbumin level and high SBP may be associated with advanced arteriosclerosis.