A randomized clinical trial of high volume peritoneal dialysis versus extended daily hemodialysis for acute kidney injury patients

Background

Acute kidney injury (AKI) requiring dialysis in critically ill patients is associated with an in-hospital mortality rate of 50–80 %. Extended daily hemodialysis (EHD) and high volume peritoneal dialysis (HVPD) have emerged as alternative modalities.

Methods

A double-center, randomized, controlled trial was conducted comparing EHD versus HVPD for the treatment for AKI in the intensive care unit (ICU). Four hundred and seven patients were randomized and 143 patients were analyzed. Principal outcome measure was hospital mortality, and secondary end points were recovery of renal function and metabolic and fluid control.

Results

There was no difference between the two groups in relation to median ICU stay [11 (5.7–20) vs. 9 (5.7–19)], recovery of kidney function (26.9 vs. 29.6 %, p = 0.11), need for chronic dialysis (9.7 vs. 6.5 %, p = 0.23), and hospital mortality (63.4 vs. 63.9 %, p = 0.94). The groups were different in metabolic and fluid control. Blood urea nitrogen (BUN), creatinine, and bicarbonate levels were stabilized faster in EHD group than in HVPD group. Delivered Kt/V and ultrafiltration were higher in EHD group. Despite randomization, there were significant differences between the groups in some covariates, including age, pre-dialysis BUN, and creatinine levels, biased in favor of the EHD. Using logistic regression to adjust for the imbalances in group assignment, the odds of death associated with HVPD was 1.4 (95 % CI 0.7–2.4, p = 0.19). A detailed investigation of the randomization process failed to explain the marked differences in patient assignment.

Conclusions

Despite faster metabolic control and higher dialysis dose and ultrafiltration with EHD, this study provides no evidence of a survival benefit of EHD compared with HVPD. The limitations of this study were that the results were not presented according to the intention to treat and it did not control other supportive management strategies as nutrition support and timing of dialysis initiation that might influence outcomes in AKI.     

Platelet aggregation at discharge: A useful tool in acute coronary syndromes?

IntroductionInhibition of platelet aggregation appears two hours after the first dose of clopidogrel, becomes significant after the second dose, and progresses to a steady-state value of 55% by day seven. Low response to clopidogrel has been associated with increased risk of stent thrombosis and ischemic events, particularly in the context of stable heart disease treated by percutaneous coronary intervention.ObjectiveTo stratify medium-term prognosis of an acute coronary syndrome (ACS) population by platelet aggregation.MethodsWe performed a prospective longitudinal study of 70 patients admitted for an ACS between May and August 2009. Platelet function was assessed by ADP-induced platelet aggregation using a commercially available kit (Multiplate^® analyzer) at discharge. The primary endpoint was a combined outcome of mortality, non-fatal myocardial infarction, or unstable angina, with a median follow-up of 136.0 (79.0–188.0) days.ResultsThe median value of platelet aggregation was 16.0 U (11.0–22.5 U) with a maximum of 41.0 U and a minimum of 4.0 U (normal value according to the manufacturer: 53–122 U). After ROC curve analysis with respect to the combined endpoint (AUC 0.72), we concluded that a value of 18.5 U conferred a sensitivity of 75.0% and a specificity of 68% to that result. We therefore created two groups based on that level: group A – platelet aggregation <18.5 U, n = 44; and group B – platelet aggregation ≥18.5 U, n = 26. The groups were similar with respect to demographic data (age 60.5 [49.0–65.0] vs. 62.0 [49.0–65.0] years, p = 0.21), previous cardiovascular history, and admission diagnosis. There were no associations between left ventricular ejection fraction, GRACE risk score, or length of hospital stay and platelet aggregation. The groups were also similar with respect to antiplatelet, anticoagulant, proton pump inhibitor (63.6 vs. 46.2%, p = 0.15) and statin therapy. The variability in platelets and hemoglobin was also similar between groups. Combined event-free survival was higher in group A (96.0 vs. 76.7%, log-rank p < 0.01). Platelet aggregation higher than 18.5 U was an independent predictor of the combined event (HR 6.75, 95% CI 1.38–32.90, p = 0.02).ConclusionIn our ACS population platelet aggregation at discharge was a predictor of medium-term prognosis.     

Implementation of a pre-hospital network favoring primary angioplasty in STEMI to reduce mortality: the Algarve Project

ObjectiveTo analyze the impact of reperfusion by either primary percutaneous coronary intervention (PPCI) or fibrinolysis, and mortality rates of a pre-hospital fast-track network for treating patients with ST-elevation myocardial infarction (STEMI).Methods and ResultsA pre-hospital network for STEMI patients, designated the Green Lane for Acute Myocardial Infarction (GL-AMI), has been implemented in the southern region of Portugal – the Algarve Project. We performed an observational study based on a prospective registry of 1338 patients admitted to Faro Hospital between 2004 and 2009, classified in two groups according to the method of admission: emergency department group (EDG) and GL-AMI group (GLG). More patients from GLG were reperfused (p < 0.0001). PPCI was the preferred method of reperfusion, 73.1% in GLG and 45.3% in EDG. Time delays were significantly shorter in GLG, except for pre-hospital delay: pre-hospital delay (p = 0.11); door-to-needle (p < 0.0001); door-to-balloon (p < 0.0001); and delay between symptoms and reperfusion (p < 0.0001). In-hospital mortality (4.3% vs 9.2%, p = 0.0007) and 6-month mortality (6.3% vs 13.8%, p < 0.0001) were significantly lower in GLG.ConclusionsThe Algarve Project significantly reduced the time delay between onset of symptoms and reperfusion, significantly increased the rate of reperfusion, and significantly reduced in-hospital and six-month mortality.     

The effects of low-dose fluvastatin and valsartan combination on arterial function: a randomized clinical trial

BackgroundAgeing progressively diminishes arterial functions, even in the absence of traditional risk factors. Our aim was to explore whether age-related arterial changes in middle-aged males could be reversed using short-term, low-dose fluvastatin/valsartan combination intervention.MethodsForty apparently healthy, middle-aged males (43.3 ± 5.8 years) were recruited in a double-blind, randomised intervention. Individuals received either 10 mg fluvastatin/20 mg valsartan daily or placebo over 30 days. The brachial artery flow mediated dilation (FMD), pulse wave velocity (PWV) and common carotid artery β-stiffness were assessed at baseline and after 30 days, and again 5–10 months after therapy discontinuation.ResultsArterial function variables significantly improved after 30 days of intervention; FMD improved by 167.7% (P < 0.001), PWV by 10.9% (P < 0.05) and β-stiffness by 18.8% (P < 0.01), whereas no changes were obtained in the placebo group. The favourable outcomes in the intervention group were accompanied by a significant decrease of high sensitivity-C reactive protein levels (1.8-fold; P < 0.05). In contrast, lipids and blood pressure remained unchanged. Surprisingly, the beneficial arterial effects were still present to a substantial degree 7 months after completing intervention (remaining % of initial improvement: FMD 82.1%, PWV 69.5% and β-stiffness 68.5%), but declined substantially after 10 months.ConclusionOur results indicate that age-related arterial changes, at least in middle-aged males, can be reversed. Short-term treatment with a low-dose fluvastatin/valsartan combination resulted in a large and long lasting improvement of arterial function.     

Primary biliary cirrhosis in a rheumatoid arthritis patient treated with rituximab, a case-based review

Primary biliary cirrhosis (PBC) is an autoimmune disease in which intrahepatic bile ducts are targeted by an immune-mediated injury. This disease tends to progress to fibrosis and cirrhosis with hepatic failure. The authors report a case of a 50-year-old rheumatoid arthritis (RA) patient, with erosions and seropositive for rheumatoid factor and anti-citrullinated peptide antibodies, with 18 years disease duration refractory to prednisolone and several disease-modifying antirheumatic drugs, either conventional or biological (adalimumab and etanercept). In April 2007, she started therapy with rituximab (RTX) with good European League Against Rheumatism response achieved 9 months later. In June 2008, she was admitted with intrahepatic cholestasis, steatorrhea, and spontaneous fractures of various ribs. After excluding cholelitiasis, as well as infectious and neoplastic diseases a liver biopsy was performed that was compatible with the diagnosis of PBC. The antinuclear antibodies (1/160) were positive as well as the antimitochondrial antibodies (1/640). Other antibodies were negative such as anti-SSA and anti-SSB. Afterwards, the patient started ursodesoxycholic acid 15 mg kg^-1 day^-1 with progressive improvement of cholestatic markers. A labial salivary gland biopsy was performed and showed findings compatible with the concomitant diagnosis of Sjögren’s syndrome. Based on this clinical report, a detailed review of the clinical aspects of PBC is presented as well as its association with other immune-mediated inflammatory diseases, particularly, with RA.