Fluid balance as an early indicator of acute kidney injury in CV surgery.

BACKGROUND: We hypothesized that positive fluid balance (FB) is the result of intraoperative kidney injury and associated renal vasoconstriction, and therefore may be an early clinical indicator of acute kidney injury (AKI). Since rapid changes in fluid volume occur during cardiovascular (CV) surgery, we investigated the influence of immediate postoperative FB on AKI. MATERIALS AND METHODS: Data from the Nesiritide Study were retrospectively analyzed to investigate the association between FB and AKI. RESULTS: Patients were classified into a negative FB (NegFB, median -1,221 ml, IQR -1,974 to -653 ml, n = 71) and a PosFB (median 849 ml, IQR 328 - 1,552 ml, n = 19) group based on FB status in the first 24 h postoperatively. The PosFB group had a higher incidence of AKI (NegFB 25.3% vs. PosFB 47.3%, p = 0.090) compared to the NegFB group. The difference in the incidence of AKI was significantly higher (NegFB 25.3% vs. high- PosFB 80%, p = 0.001) in the subset of patients who had FB ≥ 849 ml (highPosFB, n = 10). The highPosFB group demonstrated a significantly elevated risk for AKI in both unadjusted (OR = 9.8, 95% CI 1.9 - 51.2, p = 0.007) and multivariate models (OR = 8.1, 95% CI 1.5 - 45.1, p = 0.03). CONCLUSIONS: PosFB in the immediate postoperative period may be an independent early indicator of AKI in patients undergoing CV surgery.

Perioperative fluid balance and acute kidney injury.

BACKGROUND: Positive fluid balance (FB) has been linked to adverse clinical outcomes. We performed this study to explore the relationship between perioperative fluid balance and acute kidney injury (AKI). METHODS: The relationships between FB and AKI were explored using a prospective, observational design. Patients were divided into quartiles based on FB status in the first 24 h from initiation of surgery in order to further explore this relationship. RESULTS: One hundred adult patients undergoing cardiovascular surgery were included in the analysis. The major finding of the study was that positive FB occurred early in the intraoperative period and progressed into the postoperative period and that fluid administration was not clearly associated with any identifiable volume-sensitive event. The evolution of positive FB preceded the rise in serum creatinine. Progressive severity of positive FB was associated with increased incidence of AKI. The highest quartile FB group had a five-fold increased risk for AKI (adjusted odds ratio 4.98, 95 % confidence interval 1.38-24.10, p = 0.046) compared to the lowest quartile group, higher postoperative peak serum creatinine values (p < 0.001), surgery-related complications (p < 0.001) and intensive care unit (p < 0.001) and hospital length of stay (p = 0.048). CONCLUSIONS: Positive FB was associated with increased incidence of AKI.

Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery.

PURPOSE: Serum uric acid (SUA) is a novel risk factor for acute kidney injury (AKI), which adversely affects renal blood flow autoregulation, glomerular filtration rate (GFR), and promotes inflammation and angiogenesis. This pilot study investigated the effect of lowering SUA therapy on AKI, by using traditional and non-traditional markers. MATERIALS AND METHODS: In this prospective, double-blind, placebo-controlled, randomized pilot trial, 26 hyperuricemic patients undergoing cardiac surgery were randomized to receive rasburicase or placebo in the preoperative period. RESULTS: Subjects receiving rasburicase showed no difference in serum creatinine compared with the control group receiving placebo. Despite no difference in primary endpoint, the rasburicase group had less evidence of renal structural injury as reflected by urine neutrophil-associated lipocalin (uNGAL) concentrations, especially in subjects with higher SUA levels, more severe renal dysfunction (baseline GFR ≤ 45 mL/min/1.73 m(2)) or heart failure (left ventricular ejection fraction ≤45 %). CONCLUSIONS: In this study, rasburicase showed no benefit on postoperative serum creatinine in hyperuricemic subjects undergoing cardiac surgery. However, the observation that markers of structural renal injury such as uNGAL tended to be lower in rasburicase-treated subjects suggests potential different effects of uricase treatment on hemodynamic alterations in renal function versus structural mechanisms of kidney injury.

Update on clinical trials for the prevention of acute kidney injury in patients undergoing cardiac surgery.

BACKGROUND: Effective therapeutic agents for the prevention and treatment of acute kidney injury (AKI) after cardiac surgery remain elusive despite the tremendous advances in surgical techniques, technology, and understanding of disease processes. Recent developments and their effect on the incidence of AKI after cardiac surgery are discussed. DATA SOURCES: Published clinical trials in PubMed, strength of evidence assessed by the guidelines of the American Family Physicians. CONCLUSIONS: The definition of AKI has changed, and the focus of interventions has shifted from treatment to prevention to recovery from AKI. Antioxidants and biological agents have been added to classic armaments of hydration and diuretics in addition to tighter metabolic control to prevent AKI. Although the treatment options remain unsatisfactory, a lot of progress nevertheless continues to be made in the prevention and treatment of AKI.

Elevated uric acid increases the risk for acute kidney injury.

BACKGROUND: Uric acid has been proposed to play a role in acute kidney injury. We therefore investigated the potential influence of preoperative serum uric acid (SUA) on acute kidney injury in patients undergoing cardiovascular (CV) surgery. The primary aims were to investigate the incidence of acute kidney injury, peak serum creatinine (SCr) concentrations, hospital length of stay, and days on mechanical ventilation. METHODS: Retrospective study included patients who underwent CV surgery and had preoperative SUA available. Acute kidney injury was defined as an absolute increase in SCr ≥0.3 mg/dL from baseline within 48 hours after surgery. Univariate and multivariate logistic regression analysis was performed to determine the odds ratio for acute kidney injury. RESULTS: There were 190 patients included for analysis. SUA were divided into deciles. The incidences of acute kidney injury were higher with higher deciles of SUA. When the incidences of acute kidney injury were plotted against all available values of SUA at increments of 0.5 mg/dL, a J-shaped curve emerged demonstrating higher incidences of acute kidney injury associated with both hypo- and hyperuricemia. In the univariate analysis, SUA ≥5.5 mg/dL was associated with a 4-fold (odds ratio [OR] 4.4; 95% confidence interval [CI], 2.4-8.2), SUA ≥6 mg/dL with a 6-fold (OR 5.9; 95% CI, 3.2-11.3), SUA ≥6.5 mg/dL with an 8-fold (OR 7.9; 95% CI, 3.9-15.8), and SUA ≥7 mg/dL with a 40-fold (OR 39.1; 95% CI, 11.6-131.8) increased risk for acute kidney injury. In the multivariate analysis, SUA ≥7 mg/dL also was associated with a 35-fold (OR 35.4; 95% CI, 9.7-128.7) increased risk for acute kidney injury. The 48-hour postoperative and hospital-stay mean peak SCr levels also were higher in the SUA ≥5.5 mg/dL group compared with the SUA <5 mg/dL group. SUA ≥7 mg/dL was associated with increased length of hospital stay (SUA <7 mg/dL, 18.5 ± 1.8 days vs SUA ≥7 mg/dL, 32.0 ± 6.8 days, P = 0.058) and a longer duration of mechanical ventilation support (SUA <7 mg/dL, 2.4 ± 0.4 days vs SUA ≥7 mg/dL, 20.4 ± 4.5 days, P = 0.001). CONCLUSION: Preoperative SUA was associated with increased incidence and risk for acute kidney injury, higher postoperative SCr values, and longer hospital length of stay and duration of mechanical ventilation support in patients undergoing cardiac surgery. A J-shaped relationship appears to exist between SUA and acute kidney injury.

Post-operative serum uric acid and acute kidney injury.

BACKGROUND: We hypothesized that post-operative serum uric acid (SUA) may be associated with acute kidney injury (AKI). METHODS: In this prospective, observational study, the relationships between SUA, urine neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin-18 (uIL-18), serum monocyte chemoattractant protein-1 (sMCP-1) and tumor necrosis factor-alpha (sTNF-alpha), and incidence of AKI were determined. SUA were divided into tertiles and their association with AKI investigated. RESULTS: A total of 100 cardiac surgery patients were included for analyses. The 1st, 2nd, and 3rd SUA tertiles were associated with 15.1%, 11.7%, and 54.5% incidence of AKI, respectively. The 3rd SUA tertile, compared to the referent 1st tertile, was associated with an eightfold (OR 8.38, CI95% 2.13-33.05, p=0.002) increased risk for AKI. Patients with AKI on post-operative day 1 (n=11) were then excluded for the purpose of determining the predictive value of SUA to diagnose AKI on postoperative day 2 and during hospital stay. In comparison to the referent 1st tertile, the 3rd tertile SUA was associated with an eightfold increased risk for AKI on post-operative day 2 (adjusted OR 7.94, CI95% 1.50-42.08, P=.015) and a five-fold increased risk for AKI during hospital stay (OR 4.83, CI95% 1.21-19.20, P=.025), respectively. SUA (Area Under Curve, AUC 0.77 (CI95% 0.66-0.88, P<.001), serum creatinine (0.73, CI95% 0.62-0.84, P<.001) and sTNF-alpha (0.76, CI95% 0.65-0.87, P<.001) had the best diagnostic performance measured by the Receiver Operating Characteristics curves. CONCLUSIONS: We conclude that post-operative SUA is associated with an increased risk for AKI and compares well to conventional markers of AKI.

Lowering serum uric acid to prevent acute kidney injury.

Epidemiological, experimental and clinical studies support a role for uric acid in acute kidney injury (AKI). We discuss how the conventional role of uric acid in AKI has now evolved from intratubular crystal deposition to pro-inflammatory, anti-angiogenic and immunological function. Data from recent studies are presented to support the hypothesis that uric acid may have a role in AKI via a crystal-independent process in addition to its traditionally accepted role to induce injury via crystal-dependent pathways.