Hung-Bin Tsai

Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality

Existing chronic kidney disease (CKD) is among the most potent predictors of postoperative acute kidney injury (AKI). Here we quantified this risk in a multicenter, observational study of 9425 patients who survived to hospital discharge after major surgery. CKD was defined as a baseline estimated glomerular filtration rate <45 ml/min per 1.73 m(2). AKI was stratified according to the maximum simplified RIFLE classification at hospitalization and unresolved AKI defined as a persistent increase in serum creatinine of more than half above the baseline or the need for dialysis at discharge. A Cox proportional hazard model showed that patients with AKI-on-CKD during hospitalization had significantly worse long-term survival over a median follow-up of 4.8 years (hazard ratio, 1.7) [corrected] than patients with AKI but without CKD.The incidence of long-term dialysis was 22.4 and 0.17 per 100 person-years among patients with and without existing CKD, respectively. The adjusted hazard ratio for long-term dialysis in patients with AKI-on-CKD was 19.8 compared to patients who developed AKI without existing CKD. Furthermore, AKI-on-CKD but without kidney recovery at discharge had a worse outcome (hazard ratios of 4.6 and 213, respectively) for mortality and long-term dialysis as compared to patients without CKD or AKI. Thus, in a large cohort of postoperative patients who developed AKI, those with existing CKD were at higher risk for long-term mortality and dialysis after hospital discharge than those without. These outcomes were significantly worse in those with unresolved AKI at discharge.

Pegylated Interferon-α2a With or Without Low-Dose Ribavirin for Treatment-Naive Patients With Hepatitis C Virus Genotype 1 Receiving Hemodialysis: A Randomized Trial

BACKGROUND Data are limited on the efficacy and safety of pegylated interferon plus ribavirin for patients with hepatitis C virus genotype 1 (HCV-1) receiving hemodialysis. OBJECTIVE To compare the efficacy and safety of combination therapy with pegylated interferon plus low-dose ribavirin and pegylated interferon monotherapy for treatment-naive patients with HCV-1 receiving hemodialysis. DESIGN Open-label, randomized, controlled trial. (ClinicalTrials.gov: NCT00491244). SETTING 8 centers in Taiwan. PATIENTS 205 treatment-naive patients with HCV-1 receiving hemodialysis. INTERVENTION 48 weeks of pegylated interferon-α2a, 135 µg weekly, plus ribavirin, 200 mg daily (n = 103), or pegylated interferon-α2a, 135 µg weekly (n = 102). MEASUREMENTS Sustained virologic response rate and adverse event-related withdrawal rate. RESULTS Compared with monotherapy, combination therapy had a greater sustained virologic response rate (64% vs. 33%; relative risk, 1.92 [95% CI, 1.41 to 2.62]; P < 0.001). More patients receiving combination therapy had hemoglobin levels less than 8.5 g/dL than those receiving monotherapy (72% vs. 6%; risk difference, 66% [CI, 56% to 76%]; P < 0.001). Patients receiving combination therapy required a higher dosage (mean, 13 946 IU per week [SD, 6449] vs. 5833 IU per week [SD, 1169]; P = 0.006) and longer duration (mean, 29 weeks [SD, 9] vs. 18 weeks [SD, 7]; P = 0.004) of epoetin-β than patients receiving monotherapy. The adverse event-related withdrawal rates were 7% in the combination therapy group and 4% in the monotherapy group (risk difference, 3% [CI, -3% to 9%]). LIMITATION Open-label trial; results may not be generalizable to patients on peritoneal dialysis. CONCLUSION In treatment-naive patients with HCV-1 receiving hemodialysis, combination therapy with pegylated interferon plus low-dose ribavirin achieved a greater sustained virologic response rate than pegylated interferon monotherapy. PRIMARY FUNDING SOURCE National Center of Excellence for Clinical Trial and Research.

Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury

IntroductionSepsis is the leading cause of acute kidney injury (AKI) in critical patients. The optimal timing of initiating renal replacement therapy (RRT) in septic AKI patients remains controversial. The objective of this study is to determine the impact of early or late initiation of RRT, as defined using the simplified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification (sRIFLE), on hospital mortality among septic AKI patients.MethodsPatient with sepsis and AKI requiring RRT in surgical intensive care units were enrolled between January 2002 and October 2009. The patients were divided into early (sRIFLE-0 or -Risk) or late (sRIFLE-Injury or -Failure) initiation of RRT by sRIFLE criteria. Cox proportional hazard ratios for in hospital mortality were determined to assess the impact of timing of RRT.ResultsAmong the 370 patients, 192 (51.9%) underwent early RRT and 259 (70.0%) died during hospitalization. The mortality rate in early and late RRT groups were 70.8% and 69.7% respectively (P > 0.05). Early dialysis did not relate to hospital mortality by Cox proportional hazard model (P > 0.05). Patients with heart failure, male gender, higher admission creatinine, and operation were more likely to be in the late RRT group. Cox proportional hazard model, after adjustment with propensity score including all patients based on the probability of late RRT, showed early dialysis was not related to hospital mortality. Further model matched patients by 1:1 fashion according to each patients propensity to late RRT showed no differences in hospital mortality according to head-to-head comparison of demographic data (P > 0.05).ConclusionsUse of sRIFLE classification as a marker poorly predicted the benefits of early or late RRT in the context of septic AKI. In the future, more physiologically meaningful markers with which to determine the optimal timing of RRT initiation should be identified.

Transient Elastography to Assess Hepatic Fibrosis in Hemodialysis Chronic Hepatitis C Patients

BACKGROUND AND OBJECTIVES Although percutaneous liver biopsy (PLB) is the gold standard for staging hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC) before renal transplantation or antiviral therapy, concerns exist about serious postbiopsy complications. Using transient elastography (TE, Fibroscan(®)) to predict the severity of hepatic fibrosis has not been prospectively evaluated in these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 284 hemodialysis patients with CHC were enrolled. TE and aspartate aminotransferase-to-platelet ratio index (APRI) were performed before PLB. The severity of hepatic fibrosis was staged by METAVIR scores ranging from F0 to F4. Receiver operating characteristic curves were used to assess the diagnostic accuracy of TE and APRI, taking PLB as the reference standard. RESULTS The areas under curves of TE were higher than those of APRI in predicting patients with significant hepatic fibrosis (≥F2) (0.96 versus 0.84, P<0.001), those with advanced hepatic fibrosis (≥F3) (0.98 versus 0.93, P=0.04), and those with cirrhosis (F4) (0.99 versus 0.92, P=0.13). Choosing optimized liver stiffness measurements of 5.3, 8.3, and 9.2 kPa had high sensitivity (93-100%) and specificity (88-99%), and 87, 97, and 93% of the patients with a fibrosis stage of ≥F2, ≥F3, and F4 were correctly diagnosed without PLB, respectively. CONCLUSIONS TE is superior to APRI in assessing the severity of hepatic fibrosis and can substantially decrease the need of staging PLB in hemodialysis patients with CHC.

Advanced age affects the outcome-predictive power of RIFLE classification in geriatric patients with acute kidney injury.

The RIFLE (risk, injury, failure, loss, and end-stage) classification is widely used to gauge the severity of acute kidney injury, but its efficacy has not been formally tested in geriatric patients. To correct this we conducted a prospective observational study in a multicenter cohort of 3931 elderly patients (65 years of age or older) who developed acute kidney injury in accordance with the RIFLE creatinine criteria after major surgery. We studied the predictive power of the RIFLE classification for in-hospital mortality and investigated the potential interaction between age and RIFLE classification. In general, the survivors were significantly younger than the nonsurvivors and more likely to have hypertension. In patients 76 years of age and younger, RIFLE-R, -I, or -F classifications were significantly associated with increased hospital mortality in a stepwise manner. There was no significant difference, however, in hospital mortality in those over 76 years of age between patients with RIFLE-R and RIFLE-I, although RIFLE-F patients had significantly higher mortality than both groups. Thus, the less severe categorizations of acute kidney injury per RIFLE classification may not truly reflect the adverse impact on elderly patients.

Efficient generation of extended plasma waveguides with the axicon ignitor-heater scheme

By using an axicon lens in conjunction with the ignitor-heater scheme, a 1.2-cm-long high-quality plasma waveguide is generated efficiently, which can extend the range of laser-plasma interaction much beyond the limit of Rayleigh range

Pegylated Interferon Alfa-2a Monotherapy for Hemodialysis Patients with Acute Hepatitis C

BACKGROUND Hemodialysis patients are at risk of hepatitis C virus (HCV) infection. However, little is known about the efficacy and safety of pegylated interferon (IFN) therapy for hemodialysis patients with acute hepatitis C. METHODS From 2005 through 2008, 35 hemodialysis patients with acute hepatitis C who did not have spontaneous clearance of HCV by 16 weeks were treated with pegylated IFN alfa-2a at a dosage of 135 microg weekly for 24 weeks. In contrast, 7 patients with clearance of HCV by 16 weeks were under observation only. Thirty-six hemodialysis patients from 2002-2005 who had acute hepatitis C but did not receive treatment served as historical controls. The primary efficacy and safety end points were sustained virologic response (undetectable HCV RNA levels at 24 weeks after therapy) by intention-to-treat analysis and treatment-related withdrawal. RESULTS The rate of sustained virologic response in the treatment group was significantly higher than the rate of spontaneous HCV clearance in the control group (88.6% vs 16.7%; P < .001). Two patients (5.7%) prematurely terminated treatment at 8 and 10 weeks because of constitutional symptoms, and both did not have sustained virologic response. All but one patient had rapid virologic response (undetectable HCV RNA levels at 4 weeks of therapy), and all patients who received >12 weeks of therapy had early and end-of-treatment virologic responses. All patients who had clearance of HCV by 16 weeks had undetectable HCV RNA levels until the end of follow-up. CONCLUSIONS Pegylated IFN alfa-2a monotherapy is safe and efficacious for hemodialysis patients with acute hepatitis C. It is suggested that patients without spontaneous clearance of HCV by week 16 should receive therapy.

Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised trial

Objective Data comparing the efficacy and safety of combination therapy with peginterferon plus low-dose ribavirin and peginterferon monotherapy in treatment-naive haemodialysis patients with hepatitis C virus genotype 2 (HCV-2) infection are limited. Design In this randomised trial, 172 patients received 24 weeks of peginterferon alfa-2a 135 μg/week plus ribavirin 200 mg/day (n=86) or peginterferon alfa-2a 135 μg/week (n=86). The efficacy and safety endpoints were sustained virological response (SVR) rate and adverse event (AE)-related withdrawal rate. Results Compared with monotherapy, combination therapy had a greater SVR rate (74% vs 44%, relative risk (RR): 1.68 [95% CI 1.29 to 2.20]; p<0.001). The beneficial effect of combination therapy was more pronounced in patients with baseline viral load ≥800 000 IU/mL than those with baseline viral load <800 000 IU/mL (RR: 3.08 [95% CI 1.80 to 5.29] vs RR: 1.11 [95% CI 0.83 to 1.45]; interaction p=0.001). Patients receiving combination therapy were more likely to have a haemoglobin level of <8.5 g/dL (70% vs 8%, risk difference (RD): 62% [95% CI 50% to 73%]; p<0.001) and required a higher dosage [mean: 13 417vs 6667 IU/week, p=0.027] of epoetin β to manage anaemia than those receiving monotherapy. The AE-related withdrawal rates were 6% and 3% in combination therapy and monotherapy groups, respectively (RD: 2% [95% CI −4% to 9%]). Conclusions In treatment-naive haemodialysis patients with HCV-2 infection, combination therapy with peginterferon plus low-dose ribavirin achieved a greater SVR rate than peginterferon monotherapy. Most haemodialysis patients can tolerate combination therapy. Trial registration number ClinicalTrial.gov number, NCT00491244.

The ratio of aminotransferase to platelets is a useful index for predicting hepatic fibrosis in hemodialysis patients with chronic hepatitis C

Percutaneous liver biopsy is the gold standard for staging hepatic fibrosis of hemodialysis patients with chronic hepatitis C before renal transplantation or antiviral therapy. Concerns exist, however, about serious post-biopsy complications. To evaluate a more simple approach using standard laboratory tests to predict hepatic fibrosis and its evolution, we studied 279 consecutive hemodialysis patients with chronic hepatitis C and a baseline biopsy. Among them, 175 receiving antiviral therapy underwent follow-up biopsy to evaluate the histological evolution of fibrosis. Multivariate analysis of routine laboratory tests at baseline showed the aspartate aminotransferase-to-platelet ratio index was an independent predictor of significant hepatic fibrosis. The areas under curves of this ratio to predict fibrosis stages F2-4 were 0.83 and 0.71 in the baseline and follow-up sets; and 0.75 and 0.80 respectively, for patients with sustained or non-sustained virological response groups in the follow-up sets. By a judicious setting of cut-off levels for the baseline and non-sustained groups, and the sustained virological response group, almost half and 60 percent of the baseline and follow-up sets could be correctly diagnosed without biopsy. Our study found the aminotransferase-to-platelet ratio index is accurate and reproducible for assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C. Applying this simple index could decrease the need of percutaneous liver biopsy in this clinical setting.

U-curve association between timing of renal replacement therapy initiation and in-hospital mortality in postoperative acute kidney injury.

Background Postoperative acute kidney injury (AKI) is associated with poor outcomes in surgical patients. This study aims to evaluate whether the timing of renal replacement therapy (RRT) initiation affects the in-hospital mortality of patients with postoperative AKI. Methodology This multicenter retrospective observational study, which was conducted in the intensive care units (ICUs) in a tertiary hospital (National Taiwan University Hospital) and its branch hospitals in Taiwan between January, 2002, and April, 2009, included adult patients with postoperative AKI who underwent RRT for predefined indications. The demographic data, comorbid diseases, types of surgery and RRT, and the indications for RRT were documented. Patients were categorized according to the period of time between the ICU admission and RRT initiation as the early (EG, ≦1 day), intermediate (IG, 2–3 days), and late (LG, ≧4 days) groups. The in-hospital mortality rate censored at 180 day was defined as the endpoint. Results Six hundred forty-eight patients (418 men, mean age 63.0±15.9 years) were enrolled, and 379 patients (58.5%) died during the hospitalization. Both the estimated probability of death and the in-hospital mortality rates of the three groups represented U-curves. According to the Cox proportional hazard method, LG (hazard ratio, 1.527; 95% confidence interval, 1.152–2.024; P = 0.003, compared with IG group), age (1.014; 1.006–1.021), diabetes (1.279; 1.022–1.601; P = 0.031), cirrhosis (2.147; 1.421–3.242), extracorporeal membrane oxygenation support (1.811; 1.391–2.359), initial neurological dysfunction (1.448; 1.107–1.894; P = 0.007), pre-RRT mean arterial pressure (0.988; 0.981–0.995), inotropic equivalent (1.006; 1.001–1.012; P = 0.013), APACHE II scores (1.055; 1.037–1.073), and sepsis (1.939; 1.536–2.449) were independent predictors of the in-hospital mortality (All P<0.001 except otherwise stated). Conclusions The current study found a U-curve association between the timing of the RRT initiation after the ICU admission and patients’ in-hospital mortalities, and alerts physicians of certain factors affecting the outcome after the RRT initiation.