Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions

Vascular progenitor recruitment in critically ill patients with acute kidney injury

PURPOSE: Endothelial-like vascular progenitor cells (VPCs) are blood-derived angiogenic precursors that can facilitate vascular repair. The mobilization of peripheral blood VPCs and their role in recovery were investigated in patients with acute kidney injury (AKI) in the intensive care unit (ICU) setting. <p/>METHODS: Blood samples were drawn on days 0, 3, 7 and 14 in 38 patients admitted to ICU: 30 with AKI and in eight controls with normal renal function. Circulating VPC levels were quantified by the early outgrowth cell cluster-forming assay and/or by flow cytometry. <p/>RESULTS: AKI patients (16 males, mean age 62.4) were classified as Risk (R, n=5), Injury (I, n=11) and Failure (F, n=14) according to the RIFLE criteria. VPC clusters increased over time following the diagnosis of AKI (p < 0.01 for day 0 vs. day 14) while VPC clusters were higher at enrollment in control patients and decreased over time (p=0.02). Greater mobilization of VPCs occurred in patients with more severe AKI at enrollment (I and F categories compared with R, p=0.05). A trend towards greater mobilization of VPC clusters was observed in patients with improved renal function (p=0.07). <p/>CONCLUSION: Time-dependent increases in circulating VPCs occur in critically ill patients with established AKI. Greater mobilization of VPCs may be associated with recovery of renal function, suggesting a potential role for VPCs in repair after kidney injury

Co-enrollment of critically ill patients into multiple studies: Patterns, predictors and consequences

Introduction: Research on co-enrollment practices and their impact are limited in the ICU setting. The objectives of this study were: 1) to describe patterns and predictors of co-enrollment of patients in a thromboprophylaxis trial, and 2) to examine the consequences of co-enrollment on clinical and trial outcomes.Methods: In an observational analysis of an international thromboprophylaxis trial in 67 ICUs, we examined the co-enrollment of critically ill medical-surgical patients into more than one study, and examined the clinical and trial outcomes among co-enrolled and non-co-enrolled patients.Results: Among 3,746 patients enrolled in PROTECT (Prophylaxis for ThromboEmbolism in Critical Care Trial), 713 (19.0%) were co-enrolled in at least one other study (53.6% in a randomized trial, 37.0% in an observational study and 9.4% in both). Six factors independently associated with co-enrollment (all P 10 years' experience compared to persons with none), center size (all ORs > 10 for ICUs with > 15 beds), affiliation with trials groups (OR 5.59, 3.49 to 8.95), and main trial rather than pilot phase (all ORs > 8 for recruitment year beyond the pilot). Co-enrollment did not influence clinical or trial outcomes or risk of adverse events.Conclusions: Co-enrollment was strongly associated with features of the patients, research personnel, setting and study. Co-enrollment had no impact on trial results, and appeared safe, acceptable and feasible. Transparent reporting, scholarly discourse, ethical analysis and further research are needed on the complex topic of co-enrollment during critical illness. © 2013 Cook et al.; licensee BioMed Central Ltd