Cheng-Chieh Hung

Prognosis of Patients on Extracorporeal Membrane Oxygenation: The Impact of Acute Kidney Injury on Mortality

BACKGROUNDnExtracorporeal membrane oxygenation (ECMO) has been utilized for patients in critical condition, such as those with life-threatening respiratory failure or postcardiotomy cardiogenic shock. This study analyzed the outcomes of patients treated with ECMO and identified the relationship between prognosis and the Acute Kidney Injury Network (AKIN) scores obtained at pre-ECMO support (AKIN0-hour); and at post-ECMO support 24 hours (AKIN24-hour) and 48 hours (AKIN48-hour).nnnMETHODSnThis study reviewed the medical records of 102 critically ill patients on ECMO support at a specialized intensive care unit at a tertiary care university hospital between March 2002 and January 2008. Demographic, clinical, and laboratory variables were retrospectively collected as survival predicators.nnnRESULTSnThe overall mortality rate was 57.8%. The most common condition requiring ECMO support was cardiogenic shock. Goodness-of-fit was good for AKIN0-hour, AKIN24-hour, and AKIN48-hour criteria. The AKIN0-hour, AKIN24-hour, and AKIN48-hour scoring systems also had excellent areas under the receiver operating characteristic curve (0.804±0.046, 0.811±0.045, and 0.858±0.040, respectively). Furthermore, multiple logistic regression analysis indicated that AKIN48-hour, age, and Glasgow Coma Scale score on the first day of intensive care unit admission were independent risk factors for hospital mortality. Finally, cumulative survival rates at 6-month follow-up after hospital discharge differed significantly (p<0.05) for AKIN48-hour stage 0 versus AKIN48-hour stages 1, 2, and 3; and AKIN48-hour stage 1 and 2 versus AKIN48-hour stage 3.nnnCONCLUSIONSnDuring ECMO support, the AKIN48-hour scoring system proved to be a reproducible evaluation tool with excellent prognostic abilities for these patients.

Resveratrol ameliorates early diabetic nephropathy associated with suppression of augmented TGF-β/smad and ERK1/2 signaling in streptozotocin-induced diabetic rats.

Diabetic nephropathy (DN) is the major cause of end-stage renal disease. The early changes in DN are characterized by an increased in kidney size, glomerular volume, and kidney function, followed by the accumulation of glomerular extracellular matrix, increased urinary albumin excretion (UAE), glomerular sclerosis, and tubular fibrosis. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. In the present study, we examined the beneficial effects of RSV on DN and explored the possible mechanism of RSV action. Male Sprague-Dawley rats were injected with streptozotocin at 65mg/kg body weight. The induction of diabetes mellitus (DM) was confirmed by a fasting plasma glucose level ≥300mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75mg/kg body weight 3 times a day for 8 weeks. Animals were sacrificed and kidney histology was examined by microscopy. Urinary albumin excretion, glomerular hypertrophy and expressions of fibronectin, collagen IV, and TGF-β in the glomeruli were alleviated in RSV-treated DM rats, but not in untreated DM rats. In addition, RSV treatment reduced the thickness of the glomerular basement membrane (GBM) to the original thickness and increased nephrin expressions to normal levels in DM rats. Moreover, RSV inhibited phosphorylation of smad2, smad3 and ERK1/2 in diabetic rat kidneys. This is the first report showing that RSV alleviates early glomerulosclerosis in DN through TGF-β/smad and ERK1/2 inhibition. In addition, podocyte injuries of diabetic kidneys are lessened by RSV.

Predictors of Mortality in Patients Successfully Weaned from Extracorporeal Membrane Oxygenation

Purpose Extracorporeal membrane oxygenation (ECMO) has been utilized for critically ill patients, such as those with life-threatening respiratory failure or post-cardiotomy cardiogenic shock. This study compares the predictive value of Acute Physiology, Age, and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Organ System Failure (OSF) obtained on the first day of ECMO removal, and the Acute Kidney Injury Network (AKIN) stages obtained at 48 hours post-ECMO removal (AKIN48-hour) in terms of hospital mortality for critically ill patients. Methods This study reviewed the medical records of 119 critically ill patients successfully weaned from ECMO at the specialized intensive care unit of a tertiary-care university hospital between July 2006 and October 2010. Demographic, clinical, and laboratory data were collected retrospectively as survival predictors. Results Overall mortality rate was 26%. The most common condition requiring ECMO support was cardiogenic shock. By using the areas under the receiver operating characteristic (AUROC) curve, the Sequential Organ Failure Assessment (SOFA) score displayed good discriminative power (AUROC 0.805±0.055, p<0.001). Furthermore, multiple logistic regression analysis indicated that daily urine output on the second day of ECMO removal (UO24–48 hour), mean arterial pressure (MAP), and SOFA score on the day of ECMO removal were independent predictors of hospital mortality. Finally, cumulative survival rates at 6-month follow-up differed significantly (p<0.001) for a SOFA score≤13 relative to those for a SOFA score>13. Conclusions Following successful ECMO weaning, the SOFA score proved a reproducible evaluation tool with good prognostic abilities.

Acute kidney injury biomarkers for patients in a coronary care unit: a prospective cohort study.

Background Renal dysfunction is an established predictor of all-cause mortality in intensive care units. This study analyzed the outcomes of coronary care unit (CCU) patients and evaluated several biomarkers of acute kidney injury (AKI), including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18) and cystatin C (CysC) on the first day of CCU admission. Methodology/Principal Findings Serum and urinary samples collected from 150 patients in the coronary care unit of a tertiary care university hospital between September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective demographic, clinical and laboratory data were evaluated as predictors of survival in this patient group. The most common cause of CCU admission was acute myocardial infarction (80%). According to Acute Kidney Injury Network criteria, 28.7% (43/150) of CCU patients had AKI of varying severity. Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.05) between patients with AKI versus those without AKI. For predicting AKI, serum CysC displayed an excellent areas under the receiver operating characteristic curve (AUROC) (0.895±0.031, p<0.001). The overall 180-day survival rate was 88.7% (133/150). Multiple Cox logistic regression hazard analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) and sodium on CCU admission day one were independent risk factors for 6-month mortality. In terms of 6-month mortality, urinary NGAL had the best discriminatory power, the best Youden index, and the highest overall correctness of prediction. Conclusions Our data showed that serum CysC has the best discriminative power for predicting AKI in CCU patients. However, urinary NGAL and serum IL-18 are associated with short-term mortality in these critically ill patients.

Scoring systems for 6-month mortality in critically ill cirrhotic patients: a prospective analysis of chronic liver failure - sequential organ failure assessment score (CLIF-SOFA).

Cirrhotic patients admitted to intensive care units (ICUs) have high mortality rates. The Chronic Liver Failure–Sequential Organ Failure Assessment (CLIF‐SOFA) score, a modified Sequential Organ Failure Assessment (SOFA) score, is a newly developed scoring system exclusively for patients with end‐stage liver disease.

Residual Renal Function – One of the Factors Associated with Arterial Stiffness in Peritoneal Dialysis Patients

Background: Arterial stiffness as determined by brachial-ankle pulse wave velocity (baPWV) has been demonstrated to predict cardiovascular events or mortality in patients with end-stage renal disease. Peritoneal function and residual renal function (RRF) both are important for patients undergoing peritoneal dialysis (PD). No association has yet been established between arterial stiffness, and RRF and peritoneal function in patients undergoing PD. Methods: 146 PD patients received PD lasting over 4 months. baPWV was determined using an automated, non-invasive, waveform analysis device. Results: This retrospective study revealed independent correlations between baPWV and mean arterial pressure, age, status of diabetes mellitus and RRF as well as an inverse correlation with body mass index. Conclusion: This retrospective study showed that arterial stiffness is independently correlated with RRF. Interestingly, peritoneal function test is not associated with baPWV value.

Risk Models and Scoring Systems for Predicting the Prognosis in Critically Ill Cirrhotic Patients with Acute Kidney Injury: A Prospective Validation Study

Background Cirrhotic patients with acute kidney injury (AKI) admitted to intensive care units (ICUs) show extremely high mortality rates. We have proposed the MBRS scoring system, which can be used for assessing patients on the day of admission to the ICU; this new system involves determination of mean arterial pressure (MAP) and bilirubin level and assessment of respiratory failure and sepsis. We had used this scoring system to analyze the prognosis of ICU cirrhotic patients with AKI in 2008, and the current study was an external validation of this scoring system. Methods A total of 190 cirrhotic patients with AKI were admitted to the ICU between March 2008 and February 2011. We prospectively analyzed and recorded the data for 31 demographic parameters and some clinical characteristic variables on day 1 of admission to the ICU; these variables were considered as predictors of mortality. Results The overall in-hospital mortality rate was 73.2% (139/190), and the 6-month mortality rate was 83.2% (158/190). Hepatitis B viral infection (43%) was observed to be the cause of liver disease in most of the patients. Multiple logistic regression analysis indicated that the MBRS and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of admission to the ICU were independent predictors of in-hospital mortality in patients. In the analysis of the area under the receiver operating characteristic (AUROC) curves, the MBRS scores showed good discrimination (AUROC: 0.863±0.032, p<0.001) in predicting in-hospital mortality. Conclusion On the basis of the results of this external validation, we conclude that the MBRS scoring system is a reproducible, simple, easy-to-apply evaluation tool that can increase the prediction accuracy of short-term prognosis in critically ill cirrhotic patients with AKI.

Cardiothoracic ratio association with mortality in patients on maintenance peritoneal dialysis.

The cardiothoracic ratio (CTR) indicates the left ventricular size; however, the significance of the CTR in patients on maintenance peritoneal dialysis (PD) remains unclear. In this study, 335 PD patients were enrolled and demographic, biochemical, co‐morbidity, and dialysis‐related data were obtained. The factors determining CTR were further analyzed. All patients were followed up for two years to investigate the mortality risks. We defined a normal CTR as less than the mean CTR value, mild cardiomegaly as a CTR between the mean and meanu2003+u20031u2003SD, and moderate‐to‐severe cardiomegaly as more than the mean CTRu2003+u20031u2003SD. Among the 335 patients, 163 patients were classified as having a normal CTR (<49.2%), 112 patients as having mild cardiomegaly (CTR 49.2–55.7%), and 60 patients as having moderate‐to‐severe cardiomegaly (CTRu2003>u200355.7%). χ2‐analysis showed that the incidences of malnutrition and anemia were significantly higher in patients with severe cardiomegaly than in patients of the other groups. The CTR was positively correlated with age, but negatively correlated with albumin and hemoglobin levels. Twenty‐six patients (7.7%) had died by the end of the study. Cox multivariate analysis revealed that the CTR significantly predicts all‐cause two‐year mortality in PD patients on maintenance PD; therefore, the CTR correlates with the nutritional and anemic status of PD patients and is a reliable predictor for all‐cause two‐year mortality. The analytical results of this study support continued efforts to reduce the CTR and treat underlying causes in patients with cardiomegaly.

High correlation between clearance of renal protein-bound uremic toxins (indoxyl sulfate and p-cresyl sulfate) and renal water-soluble toxins in peritoneal dialysis patients.

Peritoneal dialysis (PD) is characterized by a slow continuous removal of solutes. Traditionally, dialysis adequacy is quantified by referring to the kinetics of urea nitrogen (UN) and creatinine (Cr) clearance. The efficacy of middle molecular substances and protein‐bound solutes as markers for peritoneal dialysis adequacy is not clear. The aim of this cross‐sectional study was to investigate correlations between the clearance of indoxyl sulfate (IS), p‐cresyl sulfate (PCS), UN, and Cr in the peritoneum and kidneys and to compare the overall clearances of IS and PCS between non‐anuric and anuric groups in PD patients. We recruited a total of 175 patients who had been undergoing continuous ambulatory PD (CAPD) or automated PD (APD) for at least 4u2003months. We measured total IS and PCS concentrations in serum, dialysate, and urine samples. Free IS and PCS concentrations were measured in all serum samples. IS and PCS clearances via both kidney and peritoneum were measured. The mean concentration of IS in the urine samples was 9.2‐fold higher than that in the dialysate samples, and concentration of PCS in the urine samples was 8.5‐fold higher than that in the dialysate samples. Peritoneal UN and Cr clearances were not correlated with peritoneal PCS clearance (Pu2003>u20030.05) but were mildly correlated with peritoneal IS clearance. The peritoneal IS and PCS clearances in the different peritoneal equilibration test groups were similar. The renal UN and Cr clearances were strongly correlated with renal PCS and IS clearances (Pu2003>u20030.89, Pu2003<u20030.001). In addition, non‐anuric patients showed better elimination of total PCS (10.3u2003mg/day [range, 1.6–19.8] vs. 5.2u2003mg/day [range, 0–14]; Pu2003<u20030.001] and IS (37.9u2003mg/day [range, 25.6–56.7] vs. 24.8u2003mg/day [range, 17.1–41.6]; Pu2003<u20030.001) than anuric patients. This cross‐sectional study showed that peritoneal clearance of water‐soluble solutes is not correlated with that of PCS but is mildly correlated with that of IS. However, the renal clearances of IS and PCS show strong positive correlation with the renal clearances of UN and Cr. This study confirms the important role of residual renal function in the removal of protein‐bound uremic toxins.

Prognostic predictors of technique and patient survival in elderly Southeast Asian patients undergoing continuous ambulatory peritoneal dialysis.

The population of elderly patients entering chronic dialysis programmes is increasing. Elderly patients are susceptible to malnutrition and have multiple complicating disorders in addition to uraemia. Selecting appropriate dialysis modality is particularly critical in elderly patients. Continuous ambulatory peritoneal dialysis (CAPD) has many advantages to elderly patients; however, the clinical outcome varies for elderly CAPD patients. In comparison with Westerners, Southeast Asians have a small body mass index and may be more suited to CAPD therapy. To identify the prognostic predictors in elderly Southeast Asian patients, this historical cohort study analysed 144 patients aged ≥u200365u2003years at initiation of CAPD. A group of haemodialysis (HD) patients aged ≥u200365u2003years was utilised as the control group. Survival curves for patient and technique were derived from Kaplan–Meier analysis and were further analysed by Cox–Mantel log‐rank test. To elucidate the impact of individual factors on patient survival, various significant univariables were further subjected to multivariate analysis. No significant increase existed for relative risk of technique failure in elderly patients compared with younger patients. This analytical data indicates that CAPD was as good as HD for elderly uraemic patients regarding to the patient survival. Diabetes, dependent patients, low albumin levels and previous HD history were significant poor prognostic factors for survival of elderly CAPD patients. In conclusion, CAPD is an effective modality of renal replacement therapy for Southeast Asian elderly patients. The technique survival was not affected by patient age.