Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Off-pump coronary artery bypass grafting (CABG) has been advocated to cause less inflammation, morbidity, and mortality than the more traditional on-pump technique. This meta-analysis compares these two surgical techniques with respect to causing acute kidney injury (AKI). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study searched for randomized controlled trials in MEDLINE and abstracts from the proceedings of scientific meetings through February 2010. Included were trials comparing off-pump to on-pump CABG that reported the incidence of AKI, as defined by a mixture of criteria including biochemical parameter/urine output/dialysis requirement. Mortality was evaluated among the studies that reported kidney-related outcomes. For primary and subgroup analyses, fixed-effect meta-analyses of odds ratios (OR) were performed. RESULTS: In 22 identified trials (4819 patients), the weighted incidence of AKI in the on-pump CABG group was 4.0% (95% confidence interval [CI] 1.8%, 8.5%), dialysis requirement 2.4% (95% CI 1.6%, 3.7%), and mortality 2.6% (95% CI 1.6%, 4.0%). By meta-analysis, off-pump CABG was associated with a 40% lower odds of postoperative AKI (OR 0.60; 95% CI 0.43, 0.84; P = 0.003) and a nonsignificant 33% lower odds for dialysis requirement (OR 0.67; 95% CI 0.40, 1.12; P = 0.12). Within the selected trials, off-pump CABG was not associated with a significant decrease in mortality. CONCLUSIONS: Off-pump CABG may be associated with a lower incidence of postoperative AKI but may not affect dialysis requirement, a serious complication of cardiac surgery. However, the different definitions of AKI used in individual trials and methodological concerns preclude definitive conclusions.

Identification of separate structural features that affect rate and cation concentration dependence of self-cleavage by the Neurospora VS ribozyme.

The cleavage site of the Neurospora VS ribozyme is located in an internal loop in a hairpin called stem-loop I. Stem-loop I undergoes a cation-dependent structural change to adopt a conformation, termed shifted, that is required for activity. Using site-directed mutagenesis and kinetic analyses, we show here that the insertion of a single-stranded linker between stem-loop I and the rest of the ribozyme increases the observed self-cleavage rate constant by 2 orders of magnitude without affecting the Mg(2+) requirement of the reaction. A distinct set of mutations that favors the formation of the shifted conformation of stem-loop I decreases the Mg(2+) requirement by an order of magnitude with little or no effect on the observed cleavage rate under standard reaction conditions. Similar trends were seen in reactions that contained Li(+) instead of Mg(2+). Mutants with lower ionic requirements also exhibited increased thermostability, providing evidence that the shifted conformation of stem-loop I favors the formation of the active conformation of the RNA. In natural, multimeric VS RNA, where a given ribozyme core is flanked by one copy of stem-loop I immediately upstream and another copy 0.7 kb downstream, cleavage at the downstream site is strongly preferred, providing evidence that separation of stem-loop I from the ribozyme core reflects the naturally evolved organization of the RNA.