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RED CELL DISTRIBUTION WIDTH (RDW) is a routinely available biomarker of likely erythropoietic dysfunction, which may be associated with adverse outcomes after cardiac surgery. This systematic review and meta-analysis aimed to clarify the prognostic value of RDW in patients undergoing cardiac surgery. The authors searched MEDLINE, Embase, and the Cochrane Library from inception to May 10, 2022 for studies investigating the association between elevated RDW (as defined by the authors of included studies) and adverse outcomes after cardiac surgery. Herein, the authors extracted maximally adjusted hazard ratios (HRs) and odds ratios (ORs) with associated CIs, and pooled them using random-effects inverse- variance modeling. The authors explored interstudy heterogeneity using metaregression. The authors included 26 studies involving 48,092 patients who had undergone cardiac surgery. Elevated preoperative RDW was associated with long-term mortality (pooled HR 1.63, 95% CI 1.05-2.52), short-term mortality (pooled OR 2.16, 95% CI 1.21-3.87), acute kidney injury (AKI; pooled OR 1.30, 95% CI 1.19-1.41) and postoperative atrial fibrillation (POAF; pooled OR 1.44, 95% CI 1.05-1.96). Some studies suggested a significant association between preoperative RDW elevation and neurologic complications; however, their number was insufficient for meta-analysis. The postoperative RDW levels were less consistently reported and could not be meta-analyzed. In conclusion, the authors found that elevated preoperative RDW was associated with increased short- and long-term mortality, POAF, and AKI after cardiac surgery. Further research is needed to investigate its role in the risk stratification of patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Poor medullary oxygenation is implicated in the evolution of acute kidney injury. The authors sought to determine if increasing systemic flow and mean arterial pressure could improve urine oxygen tension (PuO 2) measured in the bladder, a surrogate of kidney medullary oxygenation, in patients undergoing on-pump cardiac surgery. Randomized crossover study. University-affiliated hospital. Twenty adult patients undergoing cardiopulmonary bypass (CPB) with expected cross-clamp time of >60 minutes and estimated glomerular filtration rate of >30 mL/min/1.73m2. Sequential 20-minute periods of 2 interventions: Intervention H ("High") or Intervention N ("Normal"). The order of interventions was determined by randomization. Intervention H: targeted CPB flow 3.0 L/min/m2 and mean arterial pressure (MAP) 80 mmHg. Intervention N: targeted CPB flow 2.4 L/min/m2 and MAP 65 mmHg. PuO 2 was measured by an oxygen sensor introduced into the bladder via a urinary catheter. Clear separation was achieved in CPB flow and MAP between intervention periods (p < 0.001 for group-time interaction). PuO 2 during Intervention H was higher than during Intervention N (p < 0.001 for group-time interaction). After 17 minutes, PuO 2 was statistically higher in Intervention H at each time point. There were no differences in markers of hemolysis between interventions. PuO 2 was higher when systemic flow and MAP were increased during CPB. These findings suggest that PuO 2 is responsive to changes in hemodynamics and that higher flow and pressure may improve medullary oxygenation. [ABSTRACT FROM AUTHOR]

Objective: To develop a simple model for the prediction of acute kidney injury (AKI) and renal replacement therapy (RRT) that could be used in clinical or research risk stratification. Design: Retrospective analysis. Setting: Multi-institutional. Participants: All cardiac surgery patients from September 2016 to December 2018. Interventions: Observational. Measurements and Main Results: The study cohort was divided into a development set (75%) and validation set (25%). The following 2 data epochs were used: preoperative data and immediate postoperative data (within 4 h of intensive care unit admission). Univariate statistics were used to identify variables associated with AKI or RRT. Stepwise logistic regression was used to develop a parsimonious model. Model discrimination and calibration were evaluated in the test set. Models were compared with previously published models and with a more comprehensive model developed using the least absolute shrinkage and selection operator. The study included 22,731 patients at 33 hospitals. The incidences of AKI (any stage) and RRT for the present analysis were 5,829 patients (25.6%) and 488 patients (2.1%), respectively. Models were developed for AKI, with an area under the receiver operating curve (AU-ROC) of 0.67 and 0.69 preoperatively and postoperatively, respectively. Models for RRT had an AU-ROC of 0.77 and 0.80 preoperatively and postoperatively, respectively. These models contained between 3 and 5 variables. Comparatively, comprehensive least absolute shrinkage and selection operator models contained between 21 and 26 variables, with an AU-ROC of 0.71 and 0.72 for AKI and 0.84 and 0.87 for RRT respectively. Conclusion: In the present study, simple, clinically applicable models for predicting AKI and RRT preoperatively and immediate postoperatively were developed. Even though AKI prediction remained poor, RRT prediction was good with a parsimonious model. [ABSTRACT FROM AUTHOR]

Renal tissue hypoxia has been implicated as a critical mediatory factor in multiple forms of acute kidney injury (AKI), including in sepsis. In sepsis, whole-kidney measures of macrocirculatory flow and oxygen delivery appear to be poor predictors of microcirculatory abnormalities. Studies in experimental hyperdynamic septic AKI have shown that the renal medulla is particularly susceptible to hypoxia early in sepsis, even in the presence of increased global renal blood flow and oxygen delivery. It has been proposed that an early onset of progressive renal medullary hypoxia, leading to oxidative stress and inflammation, can initiate a downward spiral of cellular injury culminating in AKI. Recent experimental studies have shown that clinical therapies for septic AKI, including, fluids, vasopressors, and diuretics, have distinct effects on renal macrocirculation and microcirculation. Herein, we review the clinical and experimental evidence of alterations in global and regional kidney perfusion and oxygenation during septic AKI and associated therapies. We justify the need for investigation of the effects of therapies on renal microcirculatory perfusion and oxygenation. We propose that interventions that do not worsen the underlying renal pathophysiologic and reparative processes in sepsis will reduce the development and/or progression of AKI more effectively. [ABSTRACT FROM AUTHOR]

To determine whether a continuous intravenous infusion of standard amino acids could preserve kidney function after on-pump cardiac surgery. Adult patients scheduled to receive cardiac surgery lasting longer than 1 hour on-pump were randomized to standard care (n = 36) or an infusion of amino acids initiated immediately after induction of anesthesia (n = 33). The study's primary outcome measurements assessed renal function. These assessments included duration of renal dysfunction, duration and severity of acute kidney injury (AKI), estimated glomerular filtration rate (eGFR) over time, urine output, and use of renal-replacement therapy. Complications and other measures of morbidity were also assessed. Sixty-nine patients (mean age 71.5 [standard deviation 9.2] years; 19 of 69 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (37/69), valve surgery (24/69), coronary artery bypass graft and valve surgery (6/69), or other procedures (2/69). Mean on-pump time was 268 [standard deviation 136] minutes. Duration of renal dysfunction did not differ between the groups (relative risk, 0.86; 95% confidence interval [CI], 0.19-3.79, P =.84). However, patients who received the amino acid infusion had a reduced duration of AKI (relative risk, 0.02; 95% CI, 0.005-0.11, P <.0001) and greater eGFR (+10.8%; 95% CI, 1.0%-20.8%, P =.033). Daily mean urine output was also significantly greater in patients who received the amino acid infusion (1.4 ± 0.5 vs 1.7 ± 0.9 L/d; P =.046). Commencing an infusion of standard amino acids immediately after the induction of anesthesia did not alter duration of renal dysfunction; however, other key measures of renal function (duration of AKI, eGFR and urine output) were significantly improved. These results warrant replication in multicenter clinical trials. [ABSTRACT FROM AUTHOR]

Objectives Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker in the effort to predict acute kidney injury (AKI) after cardiac surgery. The authors aimed to identify the specific time point in the perioperative period at which measurement of either urinary or serum concentrations of NGAL would have the highest predictive power for AKI. The authors also investigated whether change in NGAL from baseline was a better predictor of AKI than absolute NGAL values. Design A prospective, investigator-blinded observational study. Setting The cardiac surgical unit of a university teaching hospital. Participants The study consisted of 50 patients undergoing cardiac surgery who were classified preoperatively as high risk for developing postoperative AKI. Interventions No changes to standard practice were required. Measurements and Main Results The authors performed serial measurements of urinary and serum NGAL concentrations at 18 time points throughout the first 48 postoperative hours and assessed the variables required to diagnose AKI with standard criteria. Statistical analysis of predictive ability was performed using the area under receiver operator curves (AUROC) calculated for each time point. It was demonstrated that urinary NGAL performed marginally better than serum NGAL in predicting AKI. Urinary sampling at 4 and 24 hours after initiation of cardiopulmonary bypass provided the greatest diagnostic ability (AUROC, 0.702 and 0.712, respectively). Absolute NGAL values performed better than changes in NGAL values in predicting AKI. Conclusions Urinary NGAL performed better than serum NGAL in predicting AKI and was most accurate when measured at 24 hours after initiation of cardiopulmonary bypass; however, NGAL appeared to be at best only a fair predictor of cardiac surgery-associated AKI. [ABSTRACT FROM AUTHOR]

Objectives To determine the ability of urinary neutrophil gelatinase-associated lipocalin (uNGAL) to predict cardiac surgery-associated acute kidney injury (CSA-AKI), continuous renal replacement therapy (CRRT), mortality, and a composite outcome of major adverse kidney events at 365 days (MAKE 365 ), and to investigate the influence of cardiopulmonary bypass (CPB) on NGAL release. Design A prospective observational study. Setting A single-center university hospital. Participants A cohort of 288 adult cardiac surgery patients. Interventions uNGAL was measured at baseline, immediately after surgery, and on days 1 and 2 postoperatively. The authors used the recent Kidney Disease Improving Global Outcomes consensus criteria to define CSA-AKI. Measurements and Main Results CSA-AKI occurred in 36.1% of patients. uNGAL rapidly became significantly higher in patients who developed AKI, with peak value immediately after surgery (349.9 [76.6-1446.6] v 90.1 [20.8-328] ng/mg creatinine; p<0.001). No measure of uNGAL (peak, postsurgery, day 1 or 2 postsurgery) accurately predicted CSA-AKI, CRRT, mortality, or MAKE 365 . However, immediately after surgery, CPB induced greater uNGAL release compared with off-pump surgery (265.5 µmol/L [71-989.6] v 48.7 ng/mg creatinine [17-129.8]; p<0.001). Moreover, such early uNGAL release correlated with CPB duration (r = 0.505; p<0.001) but not with peak serum creatinine values on day 3 or 7 after surgery. Conclusions uNGAL had a limited predictive ability for CSA-AKI or other relevant clinical outcomes after cardiac surgery and appeared to be more closely related to the use and duration of CPB. Thus, its levels may represent the aggregate effect of an inflammatory response to CPB as well as a renal response to cardiac surgery and inflammation. [ABSTRACT FROM AUTHOR]

Objective To assess whether or not a positive fluid balance masks acute kidney injury (AKI) and is associated with adverse outcomes after cardiac surgery. Design Retrospective analysis. Setting Tertiary university-affiliated metropolitan hospital: single center. Participants Three thousand two hundred seven consecutive cardiac surgical patients admitted to the ICU from July 1, 2004 to June 30, 2012. Interventions None. Measurements and Main Results The authors used AKI Network criteria to classify AKI. They then adjusted creatinine levels for weight-corrected fluid balance and categorized patients into 3 groups: group A (No AKI); group B (AKI only after adjustment); group C (AKI before and after adjustment). No patients had “AKI” before but “No AKI” after adjustment. Among 2,171 patients with weight and baseline creatinine available, after adjusting for fluid balance, the proportion of patients classified with AKI increased from 25.3% to 37.2% (p<0.001). In patients with AKI only after adjustment (group B), ICU mortality approximated that of group C (1.9% v 3.1%, p = 0.35) but was almost 3 times greater than group A (1.9% v 0.7%, p = 0.04). For group B, use of renal replacement therapy also was greater than group A (4.3% v 1.5%, p = 0.004) but less than group C (4.3% v 14.4%, p<0.001). The same trend was found for ICU length of stay (p≤0.001) and other adverse outcomes. Conclusions Patients with AKI diagnosed after correction for the effect of a positive fluid balance on serum creatinine concentration have more adverse outcomes than patients without AKI by conventional criteria, but fewer than patients with AKI by conventional criteria. [ABSTRACT FROM AUTHOR]

Summary Traditionally, renal ischemia has been regarded as central to the pathogenesis of sepsis-associated acute kidney injury (SA-AKI). Accordingly, hemodynamic management of SA-AKI has emphasized restoration of renal perfusion, whereas, experimentally, ischemia reperfusion models have been emphasized. However, in human beings, SA-AKI usually is accompanied by hyperdynamic circulation. Moreover, clinical and experimental evidence now suggests the importance of inflammatory mechanisms in the development of AKI and microcirculatory dysfunction more than systemic alteration in renal perfusion. In this review, we examine systemic, regional, and microcirculatory hemodynamics in SA-AKI, and attempt to rationalize the hemodynamic management of this condition. [ABSTRACT FROM AUTHOR]

Objective: To investigate the ability of early urinary neutrophil gelatinase-associated lipocalin to predict postoperative complications in adult patients with ventricular dysfunction undergoing cardiac surgery. Design: Prospective observational study. Setting: Single-center study, university hospital. Participants: Fifty-six adult high-risk cardiac surgical patients with preoperative cardiac failure. Interventions: None. Measurements and Main Results: Demographic and clinical characteristics were obtained, and neutrophil gelatinase-associated lipocalin was measured at baseline and at several time points after surgery. Patient characteristics and neutrophil gelatinase-associated lipocalin levels were related to renal and patient outcome. On multivariate analyses, preoperative urinary neutrophil gelatinase-associated lipocalin was an independent predictor of length of intensive care stay (p = 0.004) and in-hospital stay (p = 0.04), but not of acute kidney injury or renal replacement therapy and was not associated with baseline renal function. Conclusions: In a cohort of high-risk cardiac surgery patients, preoperative urinary neutrophil gelatinase-associated lipocalin value provided prognostic information that was independent of the onset of acute kidney injury or of preoperative renal function. [Copyright &y& Elsevier]

Purpose: To evaluate the characteristics and outcomes of critically ill patients with severe acute kidney injury (AKI) treated and not treated with renal replacement therapy (RRT). Methods: Secondary analysis of a multi-centre cohort study. Primary exposure was RRT. Primary outcome was propensity and multi-variable adjusted-hospital mortality. Results: We studied 1250 patients (71.3%) who received and 502 (28.7%) who did not receive RRT. Reasons for not starting RRT (not mutually exclusive) were limitations of support (33.6%, n=169), adequate urine output (46.2%; n=232), plan to observe (56.4%; n=283), and advanced age (12.6%; n=63). Mortality was higher in those not receiving RRT due to limitations and advanced age but lower for adequate urine output and plan to observe. Propensity and multi-variable adjusted analysis showed no statistical difference in hospital mortality (adj-OR 1.47; 95% CI, 0.93-2.24) in patients receiving RRT. Results were similar in a sensitivity analysis restricted to patients fulfilling risk, injury, failure, loss, end-stage kidney disease-FAILURE criteria (37.0%; n= 446) (adj-OR 1.36; 95% CI, 0.70-2.66). Conclusion: In this cohort, reasons for not starting RRT included limitations of support and perception of impending renal recovery. Despite similar risk of mortality after adjusting for selection bias and confounders, RRT-treated patients were fundamentally different from non-treated patients across a spectrum of variables that precludes valid comparison in observational data. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the biochemical effects of Phoxilium (containing phosphate at 1.2 mmol/L; Gambro Lundia AB, Lund, Sweden) and Hemosol-B0 (Gambro Lundia AB) as dialysate and/or replacement fluid during continuous renal replacement therapy (CRRT). Methods: We examined serum biochemistry in critically ill patients for 42 hours of Phoxilium administration for the prevention of hypophosphatemia during CRRT and compared them with corresponding results in random historical controls who received Hemosol-B0. Results: We studied 15 patients in each arm (Phoxilium vs Hemosol-B0). Respective median ages were 57 (49-68) and 64 (57-67) years. Baseline patient illness severity scores, prescribed CRRT effluent rates, and cumulative phosphate intakes were comparable. After 36 to 42 hours of Phoxilium administration, serum phosphate levels increased from 0.95 (0.81-1.13) to 1.44 (1.23-1.78) mmol/L, in contrast to the decline from 1.71 (1.09-2.00) to 0.83 (0.55-1.59) mmol/L with Hemosol-B0 (P = .0001). Serum ionized calcium levels decreased from 1.27 (1.22-1.37) to 1.12 (1.06-1.21) mmol/L with Phoxilium, compared with an increase from 1.09 (0.90-1.19) to 1.20 (1.16-1.25) mmol/L with Hemosol-B0 (P b .0001). Serum bicarbonate, base excess levels, and effective strong ion difference decreased with Phoxilium and were lower than those with Hemosol-B0 at 36 to 42 hours (P b .05). Conclusion: Phoxilium effectively prevented hypophosphatemia during CRRT but was associated with relative metabolic acidosis and hypocalcemia compared with Hemosol-B0 use. [ABSTRACT FROM AUTHOR]

Purpose: Determine whether there are unique patterns to the urine biochemistry profile in septic compared with non-septic acute kidney injury (AKI) and whether urinary biochemistry predicts worsening AKI, need for renal replacement therapy and mortality. Materials and Methods: Prospective cohort study of critically ill patients with septic and non-septic AKI, defined by the RIFLE (Risk, Injury, Failure, Loss, End-Stage) criteria. Urine biochemistry parameters were compared between septic and non-septic AKI and were correlated with neutrophil gelatinaseassociated lipocalin (NGAL), worsening AKI, renal replacement therapy (RRT), and mortality. Results: Eighty-three patients were enrolled, 43 (51.8%) with sepsis. RIFLE classwas not different between groups (P = .43). Urine sodium (UNa) b 20 mmol/L, fractional excretion of sodium (FeNa) b1%, and fractional excretion of urea (FeU) b 35% were observed in 25.3%, 57.8%, and 33.7%, respectively. Septic AKI had lower UNa compared with non-septic AKI (P = .04). There were no differences in FeNa or FeU between groups. Urine NGALwas higher for FeNa.1%compared to FeNab1%(177.4 ng/mL [31.9-956.5] vs 48.0 ng/mL [21.1-232.4], P = .04). FeNa showed low correlation with urine NGAL (P = .05) and plasma NGAL (P = .14). There was poor correlation between FeU and urine NGAL (P =.70) or plasmaNGAL (P = .41). UNa, FeNa, and FeU showed poor discrimination for worsening AKI, RRT and mortality. Conclusion: Urine biochemical profiles do not discriminate septic and non-septicAKI. UNa, FeNa, and FeU do not reliably predict biomarker release, worsening AKI, RRT ormortality. These data imply limited utility for these measures in clinical practice in critically ill patients with AKI. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate circuit lifespan (CL) and bleeding risk during continuous renal replacement therapy (CRRT), in combined liver and renal failure. Methods: Single-center retrospective analysis of adults with acute liver failure or decompensated cirrhosis who received CRRT, without anticoagulation or with heparinization in intensive care unit. Results: Seventy-one patients with 539 CRRT circuits were evaluated. Median overall CL was 9 (6-16) hours. CL was 12 (7-24) hours in 51 patients never anticoagulated for CRRT. In 20 patients who subsequently received heparinization, CL was 7 (5-11) hours without anticoagulation, which did not improve with systemic or regional heparinization (P = .231), despite higher peri-circuit activated partial thromboplastin time (APTT) and heparin dose. Using multivariate linear regression, patients with higher baseline APTT or serum bilirubin, or who were not mechanically ventilated, had longer CL (P < .05). Additionally, peri-circuit thrombocytopenia (P < .0001) or higher international normalized ratio (P < .05) predicted longer CL. Of 71 patients, 33 had significant bleeding events. Using multivariate logistic regression, patients with higher baseline APTT, vasoactive drug use >24 hours, or thrombocytopenia, had more bleeding complications (P < .05). Decreasing platelet counts (especially <50 x 109/mm³) had an incremental effect on CL (P < .0001). Conclusion: CRRT CL is short in patients with liver failure despite apparent coagulopathy. Thrombocytopenia predicts longer CL and bleeding complications. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: It is controversial whether all critically ill patients with risk, injury, failure, loss, and end-stage renal failure (RIFLE) F class acute kidney injury (AKI) should receive renal replacement therapy (RRT). We reviewed the outcome of open heart surgery patients with severe RIFLE-F AKI who did not receive RRT. Materials and Methods: We identified all patients with AKI after cardiac surgery over 4 years and obtained baseline characteristics, intraoperative details, and in-hospital outcomes. We analyzed physiologic and biochemical features at RRT initiation or at peak creatinine if no RRT was provided. Results: We reviewed 1504 patients. Of these, 137 (9.1%) developed postoperative AKI with 71 meeting RIFLE-F criteria and 23 (32.4% of RIFLE-F cases) not receiving RRT. Compared with RRT-treated RIFLE-F patients, “no-RRT” patients had lower Acute Physiology and Chronic Health Evaluation III scores, less intra-aortic balloon pump requirements, shorter intensive care stay, and a trend toward lower mortality. At peak RIFLE score, their urinary output, arterial pH, and Pao 2/fraction of inspired oxygen ratio were all significantly higher. Their serum creatinine was also higher (304 vs 262 μmol/L; P = .02). Only 3 RIFLE-F no-RRT patients died in-hospital. Detailed review of cause and mode of death was consistent with non–RRT-preventable deaths. In contrast, 27 patients with RIFLE-R or RIFLE-I class received RRT. Compared with RRT-treated RIFLE-F patients, such RIFLE-R or RIFLE-I treated patients had a more severe presentation and higher mortality (51.8% vs 29.2%; P = .02). Conclusions: After cardiac surgery, RRT was typically applied to patients with the most severe clinical presentation irrespective of creatinine levels. A RIFLE score–based trigger for RRT is unlikely to improve patient survival. [Copyright &y& Elsevier]

Cardiorenal syndromes are disorders of the heart and kidneys whereby acute or long-term dysfunction in one organ may induce acute or long-term dysfunction of the other. The management of cardiovascular diseases and risk factors may influence, in a beneficial or harmful way, kidney function and progression of kidney injury. In this review, we assess therapeutic strategies and discuss treatment options for the management of patients with heart failure with decreased kidney function and highlight the need for future high-quality studies in patients with coexisting heart and kidney disease. [ABSTRACT FROM AUTHOR]

Cardiac surgery-associated acute kidney injury (AKI) is common and carries a poor prognosis. Hemodynamic and inflammatory factors and the release of labile iron, contributing to oxidation from reactive oxygen species are among the major determinants of cardiac surgery-associated AKI. The diagnosis of AKI is typically delayed because of the limitations of currently used clinical biomarkers indicating loss of renal function. However, several novel renal biomarkers, which predict AKI or protection from AKI after cardiopulmonary bypass (CPB), have been identified as early markers of kidney injury. In this state-of-the-art review, the authors analyze the pathophysiological implications of recent findings regarding novel renal biomarkers in relation to CPB-associated AKI. Neutrophil gelatinase–associated lipocalin, liver-type fatty acid-binding protein, and alpha-1 microglobulin predict the development of CPB-associated AKI, while hepcidin isoforms appear to predict protection from it, and these biomarkers are involved in iron metabolism. Neutrophil gelatinase-associated lipocalin participates in local iron transport. Liver-type fatty acid–binding protein and alpha-1 microglobulin function as high-affinity heme-binding proteins in different species, while hepcidin is central to iron sequestration and when increased in the urine appears to protect from CPB-associated AKI. Free iron-related, reactive oxygen species–mediated kidney injury appears to be the unifying pathophysiological connection for these biomarkers. Such novel findings on renal tubular biomarkers were further combined with other lines of evidence related to hemolysis during CPB, the associated excess of free heme and iron, knowledge of the effect of free iron on renal tubular cells, and recent trial evidence targeting free iron-mediated mechanisms of AKI. Novel biomarkers point toward free iron-mediated toxicity to be an important mechanism of AKI in patients receiving cardiac surgery with CPB. [Copyright &y& Elsevier]

Abstract: Purpose: The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. Methods: This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients. Results: Timing of RRT was stratified into “early” and “late” by median urea and creatinine at the time RRT was started. Timing was also categorized temporally from ICU admission into early (<2 days), delayed (2-5 days), and late (>5 days). Renal replacement therapy timing by serum urea showed no significant difference in crude (63.4% for urea ≤24.2 mmol/L vs 61.4% for urea >24.2 mmol/L; odds ratio [OR], 0.92; 95% confidence interval [CI], 0.73-1.15; P = .48) or covariate-adjusted mortality (OR, 1.25; 95% CI, 0.91-1.70; P = .16). When stratified by creatinine, late RRT was associated with lower crude (53.4% for creatinine >309 μmol/L vs 71.4% for creatinine ≤309 μmol/L; OR, 0.46; 95% CI, 0.36-0.58; P < .0001) and covariate-adjusted mortality (OR, 0.51; 95% CI, 0.37-0.69; P < .001). However, for timing relative to ICU admission, late RRT was associated with greater crude (72.8% vs 62.3% vs 59%, P < .001) and covariate-adjusted mortality (OR, 1.95; 95% CI, 1.30-2.92; P = .001). Overall, late RRT was associated with a longer duration of RRT and stay in hospital and greater dialysis dependence. Conclusion: Timing of RRT, a potentially modifiable factor, might exert an important influence on patient survival. However, this largely depended on its definition. Late RRT (days from admission) was associated with a longer duration of RRT, longer hospital stay, and higher dialysis dependence. [Copyright &y& Elsevier]

Perioperative hypotension is common and associated with poor outcomes, including acute kidney injury (AKI). The mechanistic link between perioperative hypotension and AKI is at least partly a consequence of the susceptibility of the kidney, and particularly the renal medulla, to ischaemia and hypoxia. Several critical gaps in our knowledge lead to uncertainty about when and how to intervene to prevent AKI attributable to perioperative hypotension. First, although we know that the risk of AKI varies with both the severity and duration of hypotensive episodes, 'safe' levels of arterial pressure have not been identified. Second, there have been few adequately powered clinical trials of interventions to avoid perioperative hypotension. Thus, most evidence surrounding perioperative hypotension is observational rather than based on randomised clinical trials. This means that the link between perioperative hypotension and AKI may represent association (where both phenomena reflect illness severity) rather than causation. Third, there is little information regarding the relative risks and benefits of various clinically available therapies (e.g. vasoconstrictors, i.v. fluids, or both) to treat and prevent perioperative hypotension, particularly with regard to renal medullary perfusion and oxygenation. Fourth, there are currently no validated, clinically feasible methods for real-time clinical monitoring of renal perfusion or oxygenation. Thus, future developments in perioperative kidney-protective strategies must rely on the development of methods to better monitor renal perfusion and oxygenation in the perioperative period, and thereby guide timing, intensity, type, and duration of interventions. [ABSTRACT FROM AUTHOR]

Objective This study aimed to determine the biomarker-specific outcome patterns and short-and long-term prognosis of cardiac surgery–asoociated acute kidney injury (AKI) identified by standard criteria and/or urinary kidney biomarkers. Methods Patients enrolled (N = 200), originated a German multicenter study ( NCT00672334 ). Standard risk injury, failure, loss, and end-stage renal disease classification (RIFLE) criteria (including serum creatinine and urine output) and urinary kidney biomarker test result (neutrophil gelatinase-associated lipocalin, midkine, interleukin 6, and proteinuria) were used for diagnosis of postoperative AKI. Primary end point was acute renal replacement therapy or in-hospital mortality. Long-term end points among others included 5-year mortality. Patients with single-biomarker-positive subclinical AKI (RIFLE negative) were identified. We controlled for systemic inflammation using C-reactive protein test. Results Urinary biomarkers (neutrophil gelatinase-associated lipocalin, midkine, and interleukin 6) were identified as independent predictors of the primary end point. Neutrophil gelatinase-associated lipocalin, midkine, or interleukin 6 positivity or de novo/worsening proteinuria identified 21.1%, 16.9%, 30.5%, and 48.0% more cases, respectively, with likely subclinical AKI (biomarker positive/RIFLE negative) additionally to cases with RIFLE positivity alone. Patients with likely subclinical AKI (neutrophil gelatinase-associated lipocalin or interleukin 6 positive) had increased risk of primary end point (adjusted hazard ratio, 7.18; 95% confidence interval, 1.52-33.93 [ P = .013] and hazard ratio, 6.27; 95% confidence interval, 1.12-35.21 [ P = .037]), respectively. Compared with biomarker-negative/RIFLE-positive patients, neutrophil gelatinase-associated lipocalin positive/RIFLE-positive or midkine-positive/RIFLE-positive patients had increased risk of primary end point (odds ratio, 9.6; 95% confidence interval, 1.4-67.3 [ P = .033] and odds ratio, 14.7; 95% confidence interval, 2.0-109.2 [ P = .011], respectively). Three percent to 11% of patients appear to be influenced by single-biomarker-positive subclinical AKI. During follow-up, kidney biomarker-defined short-term outcomes appeared to translate into long-term outcomes. Conclusions Urinary kidney biomarkers identified RIFLE-negative patients with high-risk subclinical AKI as well as a higher risk subgroup of patients among RIFLE-AKI-positive patients. These findings support the concept that urinary biomarkers define subclinical AKI and higher risk subpopulations with worse long-term prognosis among standard patients with AKI. [ABSTRACT FROM AUTHOR]

Background: The association between intraoperative oliguria during major abdominal surgery and the subsequent development of postoperative acute kidney injury (AKI) remains poorly defined. We hypothesised that, in such patients, intraoperative oliguria would be an independent predictor of subsequent AKI.Methods: We performed a post hoc analysis of data from the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial of conservative vs liberal fluid therapy during and after major abdominal surgery. We used χ2, logistic regression, and fractional polynomials to study the association between intraoperative oliguria defined as a urinary output <0.5 ml kg-1 h-1 and the development of postoperative AKI defined by the Kidney Disease Improving Global Outcomes consensus criteria.Results: We included 2444 of 2983 patients from the RELIEF trial in this study. A total of 889 patients (36%) met oliguric criteria intraoperatively. Oliguria occurred in 35% of those without AKI, and 44%, 48%, and 45% of those who developed postoperative AKI Stages 1-3, respectively (P<0.001 for trend). Intraoperative oliguria was associated with an increased risk of AKI, risk ratio: 1.38 (95% confidence interval: 1.14-1.44; P<0.001), but greater intensity of oliguria (urine output <0.3 ml kg-1 h-1) did not increase this risk further. Most patients with oliguria did not develop AKI; the positive predictive value of oliguria was 25.5%, and the negative predictive value was 81.6%.Conclusions: Intraoperative oliguria, defined as urine output <0.5 ml kg-1 h-1, was relatively common and was associated with postoperative AKI. However, the predictive utility of oliguria for AKI was low, whilst its absence had a good predictive value for an AKI-free postoperative course.Clinical Trial Registration: NCT01424150. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Cardiac arrest (CA) in humans causes warm renal ischemia-reperfusion injury, similar to animal models of ischemic acute kidney injury (AKI). We aimed to investigate the incidence and risk associations of AKI after CA, with or without post-resuscitation cardiogenic shock (PRCS). Methods: We examined the renal outcomes of adult patients admitted to the intensive care unit (ICU), who survived for more than 48h following successful resuscitation after CA. Results: Of 105 patients (median age 65 years; 69% male), 58 (55.2%) had PRCS and were on vasoactive drugs beyond 24h; and 9 (8.6%) (all of whom had PRCS) received renal replacement therapy. Only 3 (6.4%) of 47 patients without PRCS had RIFLE-‘I’/‘F’ AKI, compared to 30 (51.7%) of 58 patients with PRCS (p <0.001). Median peak serum creatinine in the non-PRCS group was 102μmol/L (interquartile range 85–115), compared to 155μmol/L (interquartile range 112–267) (p <0.001) in the PRCS group. On multivariate analysis, cumulative noradrenaline dose during the first 24h in ICU, PRCS, and pre-CA renin–angiotensin–aldosterone-system blockade were independently associated with RIFLE-‘I’/‘F’ AKI; while higher serum lactate 12h after CA, baseline creatinine, and PRCS were independently associated with greater rise in creatinine from pre-CA levels. Estimated time without spontaneous circulation, total adrenaline dose and initial cardiac rhythm during CA, had no independent associations with renal outcomes. Conclusions: In the absence of PRCS, CA in isolation is uncommonly associated with significant AKI. The human kidney may be more resistant to warm ischemia-reperfusion injury than previously thought. [Copyright &y& Elsevier]