CCL14 Predicts Oliguria and Dialysis Requirement in Patients with Moderate to Severe Acute Kidney Injury.

INTRUDUCTION: AKI is a frequent complication in critical illness and portends poor outcome. CCL14 has been validated to predict persistent severe AKI in critically ill patients. We examined the association of CCL14 with urine output within 48 hours. METHODS: In pooled data from 2 studies of critically ill patients with KDIGO stage 2-3 AKI, CCL14 was measured by NEPHROCLEAR™CCL14 Test on the Astute 140® Meter, and divided to low, intermediate and high categories (1.3 and 13 ng/mL). Average hourly urine output over 48 hours, stage 3 AKI per urine output criterion on day 2, and composite of dialysis or death within 7 days were examined using multivariable mixed, and logistic regression models. RESULTS: Of the 497 subjects with median age of 65 [56-74] years, 49% (242/497) were on diuretics. CCL14 concentration was low in 219 (44%), intermediate in 217 (44%), and high in 61 (12%) patients. In mixed regression analysis, urine output trajectory over time was different within each CCL14 risk category based on diuretic use due to significant three-way interaction (p < 0.001). In logistic regression analysis CCL14 risk category was independently associated with low urine output on day 2 (KDIGO stage 3) adjusted for diuretic use and baseline clinical variables and composite of dialysis or death within 7 days (adjusted for urine output within 48 hours of CCL14 measurement). CONCLUSIONS: CCL14 measured in patients with moderate to severe AKI is associated with urine output trajectory within 48 hours, oliguria on day 2, and dialysis within 7 days.

Potential of Urine Biomarkers CHI3L1, NGAL, TIMP-2, IGFBP7, and Combinations as Complementary Diagnostic Tools for Acute Kidney Injury after Pediatric Cardiac Surgery: A Prospective Cohort Study.

Acute kidney injury (AKI) is common after pediatric cardiac surgery (CS). Several urine biomarkers have been validated to detect AKI earlier. The objective of this study was to evaluate urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® as predictors for AKI ≥ 1 in pediatric CS after 48 h and AKI ≥ 2 after 12 h. Pediatric patients (age < 18 year; body weight ≥ 2 kg) requiring CS were prospectively included. Urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® were measured during surgery and intensive care unit (ICU) stay and corrected for urine dilution. One hundred and one pediatric patients were included. AKI ≥ 1 within 48 h after ICU admission occurred in 62.4% and AKI ≥ 2 within 12 h in 30.7%. All damage biomarkers predicted AKI ≥ 1 within 48 h after ICU admission, when corrected for urine dilution: CHI3L1 (AUC-ROC: 0.642 (95% CI, 0.535-0.741)), NGAL (0.765 (0.664-0.848)), TIMP-2 (0.778 (0.662-0.868)), IGFBP7 (0.796 (0.682-0.883)), NephroCheck® (0.734 (0.614-0.832)). Similarly, AKI ≥ 2 within 12 h was predicted by all damage biomarkers when corrected for urine dilution: uCHI3L1 (AUC-ROC: 0.686 (95% CI, 0.580-0.780)), NGAL (0.714 (0.609-0.804)), TIMP-2 (0.830 (0.722-0.909)), IGFBP7 (0.834 (0.725-0.912)), NephroCheck® (0.774 (0.658-0.865)). After pediatric cardiac surgery, the damage biomarkers urine CHI3L1, NGAL, TIMP-2, IGFBP7, and NephroCheck® reliably predict AKI after correction for urine dilution.

Fluid balance and renal replacement therapy initiation strategy: a secondary analysis of the STARRT-AKI trial.

BACKGROUND: Among critically ill patients with acute kidney injury (AKI), earlier initiation of renal replacement therapy (RRT) may mitigate fluid accumulation and confer better outcomes among individuals with greater fluid overload at randomization. METHODS: We conducted a pre-planned post hoc analysis of the STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial. We evaluated the effect of accelerated RRT initiation on cumulative fluid balance over the course of 14 days following randomization using mixed models after censoring for death and ICU discharge. We assessed the modifying effect of baseline fluid balance on the impact of RRT initiation strategy on key clinical outcomes. Patients were categorized in quartiles of baseline fluid balance, and the effect of accelerated versus standard RRT initiation on clinical outcomes was assessed in each quartile using risk ratios (95% CI) for categorical variables and mean differences (95% CI) for continuous variables. RESULTS: Among 2927 patients in the modified intention-to-treat analysis, 2738 had available data on baseline fluid balance and 2716 (92.8%) had at least one day of fluid balance data following randomization. Over the subsequent 14 days, participants allocated to the accelerated strategy had a lower cumulative fluid balance compared to those in the standard strategy (4509 (- 728 to 11,698) versus 5646 (0 to 13,151) mL, p = 0.03). Accelerated RRT initiation did not confer greater 90-day survival in any of the baseline fluid balance quartiles (quartile 1: RR 1.11 (95% CI 0.92 to 1.34), quartile 2: RR 1.03 (0.87 to 1.21); quartile 3: RR 1.08 (95% CI 0.91 to 1.27) and quartile 4: RR 0.87 (95% CI 0.73 to 1.03), p value for trend 0.08). CONCLUSIONS: Earlier RRT initiation in critically ill patients with AKI conferred a modest attenuation of cumulative fluid balance. Nonetheless, among patients with greater fluid accumulation at randomization, accelerated RRT initiation did not have an impact on all-cause mortality. TRIAL REGISTRATION: ClinicalTrials.gov number, https://clinicaltrials.gov/ct2/show/NCT02568722 , registered October 6, 2015.

Acute and chronic cardiovascular consequences of acute kidney injury: a systematic review and meta-analysis.

INTRODUCTIONː We examined whether patients with acute kidney injury (AKI) have a higher risk of developing atrial fibrillation (AF), heart failure (HF), acute coronary syndrome (ACS) and major adverse cardiac events (MACE) in the short- and long-term compared to patients without AKI, and if that risk is related to the severity of AKI. Furthermore, we investigated the influence of a cardiac event following AKI on the risk of all-cause mortality, length of stay in the intensive care unit and in the hospital. METHODS: We included English and Dutch retrospective and prospective cohort studies on adults (≥15 years) with AKI. Studies lacking epidemiological data, studies not using the consensus definitions (RIFLE, AKIN, KDIGO), animal studies and studies on children were excluded. Studies were identified using the PubMed and Embase search engines. The last search was performed on the first of August 2021. For assessment of method quality, NOS (Newcastle-Ottawa Scale) for assessing risk of bias was used for cohort studies and heterogeneity was determined by the I²-statistic. Statistical analysis was performed using the Cochrane Review Manager (RevMan 5.3). The risk ratio (RR) and 95% confidence interval (CI) were calculated using the Mantel-Haenszel test. Results were presented a summary caterpillar plot. RESULTSː We evaluated 14 studies comprising 736 210 patients. AKI was defined according to the RIFLE consensus in 1 article, to the AKIN criteria in 7 and to the KDIGO guidelines in 6. Of the 14 included studies, 4 were prospective and 10 were retrospective. In comparison to patients without AKI, we found that patients with AKI had a 94% increased risk of developing AF in the short term (RR: 1.94, 95% CI 1.35 to 2.79; P = 0.0004). In the long-term, patients with AKI stage 1 had a 59% increased risk of developing HF and a 77% risk of developing ACS. (RR: 1.59, 95% CI 1.07 to 2.34, P = 0.02 and RR: 1.77, 95% CI 1.68 to 1.88, P < 0.00001, respectively). Patients with AKI stage 2 had a 45% increased risk of ACS development (RR: 1.45, 95% CI 1.11 to 1.90, P = 0.006). AKI stage 3 was associated with a 164% increased risk of HF and a 95% increased risk of ACS development. (RR: 2.64, 95% CI 1.71 to 4.08, P < 0.00001 and RR: 1.95, 95% CI 1.35 to 2.82, P = 0.0004, respectively). Analysis of studies not subdividing AKI in groups showed a 74% increased risk of HF, a 12% increased risk of ACS and a 30% increased risk of developing MACE. (RR: 1.74, 95% CI 1.51 to 2.01, P < 0.00001, RR: 1.12, 95% CI 1.07 to 1.17, P < 0.00001 and RR: 1.30, 95% CI 1.25 to 1.35, P < 0.00001, respectively). CONCLUSIONSː Patients who developed AKI have an increased risk of developing AF at short-term follow-up and HF, ACS and MACE beyond 30 days.

Predictive value of the renal resistive index in the immediate postoperative period after kidney transplantation on short- and long-term graft and patient outcomes.

INTRODUCTION: During the postoperative stay in the intensive care unit after kidney transplantation, the renal resistive index (RI) is routinely measured. An increased RI, measured months posttransplant, is associated with a higher mortality. We wanted to investigate the value of the RI immediately posttransplant in predicting both short- and long-term outcome. METHODS: We performed a retrospective single-center study. The RI was collected <48 h posttransplant in patients undergoing kidney transplantations between 2005 and 2014. Short-term outcome was evaluated by delayed graft function (DGF). The long-term endpoints were kidney function and mortality at 30 days, 1 year and 5 years. RESULTS: We included 478 recipients, 91.4% of whom reached the end of the 5-year follow-up. A higher RI < 48 h posttransplant was significantly associated with DGF. This association was particularly strong in patients receiving grafts from donors after brain death and expanded criteria donors. A higher RI also correlated with mortality and death with functioning graft but not with graft failure. After adjustment for confounders, we found an association between increased RI and DGF, but not with long-term kidney function or mortality. CONCLUSION: The RI routinely measured <48 h posttransplant is an independent predictor of short-term kidney function.

Impact of mean perfusion pressure and vasoactive drugs on occurrence and reversal of cardiac surgery-associate acute kidney injury: A cohort study.

PURPOSE: Low cardiac output and kidney congestion are associated with acute kidney injury after cardiac surgery (CSA-AKI). This study investigates hemodynamics on CSA-AKI development and reversal. MATERIALS AND METHODS: Adult patients undergoing cardiac surgery were retrospectively included. Hemodynamic support was quantified using a new time-weighted vaso-inotropic score (VISAUC), and hemodynamic variables expressed by mean perfusion pressure and its components. The primary outcome was AKI stage ≥2 (CSA-AKI ≥2) and secondary outcome full AKI reversal before ICU discharge. RESULTS: 3415 patients were included. CSA-AKI ≥2 occurred in 37.4%. Mean perfusion pressure (MPP) (OR 0.95,95%CI 0.94-0.96, p < 0.001); and central venous pressure (CVP) (OR 1.17, 95%CI 1.13-1.22, p < 0.001) are associated with CSA-AKI ≥2 development, while VISAUC/h was not (p = 0.104). Out of 1085 CSA-AKI ≥2 patients not requiring kidney replacement therapy, 76.3% fully recovered of AKI. Full CSA-AKI reversal was associated with MPP (OR 1.02 per mmHg (95%CI 1.01-1.03, p = 0.003), and MAP (OR = 1.01 per mmHg (95%CI 1.00-1.02), p = 0.047), but not with VISAUC/h (p = 0.461). CONCLUSION: Development and full recovery of CSA-AKI ≥2 are affected by mean perfusion pressure, independent of vaso-inotropic use. CVP had a significant effect on AKI development, while MAP on full AKI reversal.

Patients with Severe Lactic Acidosis in the Intensive Care Unit: A Retrospective Study of Contributing Factors and Impact of Renal Replacement Therapy.

INTRODUCTION: Hyperlactatemia is a regular condition in the intensive care unit, which is often associated with adverse outcomes. Control of the triggering condition is the most effective treatment of hyperlactatemia, but since this is mostly not readily possible, extracorporeal renal replacement therapy (RRT) is often tried as a last resort. The present study aims to evaluate the factors that may contribute to the decision whether to start RRT or not and the potential impact of the start of RRT on the outcome in patients with severe lactic acidosis (SLA) (lactate ≥5 mmol/L). MATERIALS AND METHODS: We conducted a retrospective single-center cohort analysis over a 3-year period including all patients with a lactate level ≥5 mmol/L. Patients were considered as treated with RRT because of SLA if RRT was started within 24 h after reaching a lactate level ≥5 mmol/L. RESULTS: Overall, 90-day mortality in patients with SLA was 34.5%. Of the 1,203 patients who matched inclusion/exclusion criteria, 11% (n = 133) were dialyzed within 24 h. The propensity to receive RRT was related to the lactate level and to the SOFA renal and cardio score. The most frequently used modality was continuous RRT. Patients who were started on RRT versus those who did not have 2.3 higher odds of mortality, even after adjustment for the propensity to start RRT. CONCLUSIONS: Our analysis confirms the high mortality rate of patients with SLA. It adds that odds for mortality is even higher in patients who were started on RRT versus not. We suggest keeping an open mind to the factors that may influence the decision to start dialysis and bear in mind that without being a bridge to correction of the underlying condition, dialysis is unlikely to affect the outcome.

Prediction of cardiac surgery associated - acute kidney injury (CSA-AKI) by healthcare professionals and urine cell cycle arrest AKI biomarkers [TIMP-2]*[IGFBP7]: A single center prospective study (the PREDICTAKI trial).

PURPOSE: Cardiac surgery associated acute kidney injury (CSA-AKI) is a contributor to adverse outcomes. Preventive measures reduce AKI incidence in high risk patients, identified by biomarkers [TIMP-2]*[IGFBP7] (Nephrocheck®). This study investigate clinical AKI risk assessment by healthcare professionals and the added value of the biomarker result. MATERIALS AND METHODS: Adult patients were prospectively included. Healthcare professionals predicted CSA-AKI, with and without biomarker result knowledge. Predicted outcomes were AKI based on creatinine, AKI stage 3 on urine output, anuria and use of kidney replacement therapy (KRT). RESULTS: One-hundred patients were included. Consultant and ICU residents were best in AKI prediction, respectively AUROC 0.769 (95% CI, 0.672-0.850) and 0.702 (95% CI, 0.599-0.791). AUROC of NephroCheck® was 0.541 (95% CI, 0.438-0.642). AKI 3 occurred in only 4 patients; there was no anuria or use of KRT. ICU nurses and ICU residents had an AUROC for prediction of AKI 3 of respectively 0.867 (95% CI, 0.780-0.929) and 0.809 (95% CI, 0.716-0.883); for NephroCheck® this was 0.838 (95% CI, 0.750-0.904). CONCLUSIONS: Healthcare professionals performed poor or fair in predicting CSA-AKI and knowledge of Nephrocheck® result did not improved prediction. No conclusions could be made for prediction of severe AKI, due to limited number of events.

Impact of AKI care bundles on kidney and patient outcomes in hospitalized patients: a systematic review and meta-analysis.

BACKGROUND: A bundle of preventive measures can be taken to avoid acute kidney injury (AKI) or progression of AKI. We performed a systematic review and meta-analysis to evaluate the compliance to AKI care bundles in hospitalized patients and its impact on kidney and patient outcomes. METHODS: Randomized controlled trials, observational and interventional studies were included. Studied outcomes were care bundle compliance, occurrence of AKI and moderate-severe AKI, use of kidney replacement therapy (KRT), kidney recovery, mortality (ICU, in-hospital and 30-day) and length-of-stay (ICU, hospital). The search engines PubMed, Embase and Google Scholar were used (January 1, 2012 - June 30, 2021). Meta-analysis was performed with the Mantel Haenszel test (risk ratio) and inverse variance (mean difference). Bias was assessed by the Cochrane risk of bias tool (RCT) and the NIH study quality tool (non-RCT). RESULTS: We included 23 papers of which 13 were used for quantitative analysis (4 RCT and 9 non-randomized studies with 25,776 patients and 30,276 AKI episodes). Six were performed in ICU setting. The number of trials pooled per outcome was low. There was a high variability in care bundle compliance (8 to 100%). Moderate-severe AKI was less frequent after bundle implementation [RR 0.78, 95%CI 0.62-0.97]. AKI occurrence and KRT use did not differ between the groups [resp RR 0.90, 95%CI 0.76-1.05; RR 0.67, 95%CI 0.38-1.19]. In-hospital and 30-day mortality was lower in AKI patients exposed to a care bundle [resp RR 0.81, 95%CI 0.73-0.90, RR 0.95 95%CI 0.90-0.99]; this could not be confirmed by randomized trials. Hospital length-of-stay was similar in both groups [MD -0.65, 95%CI -1.40,0.09]. CONCLUSION: This systematic review and meta-analysis shows that implementation of AKI care bundles in hospitalized patients reduces moderate-severe AKI. This result is mainly driven by studies performed in ICU setting. Lack of data and heterogeneity in study design impede drawing firm conclusions about patient outcomes. Moreover, compliance to AKI care bundles in hospitalized patients is highly variable. Additional research in targeted patient groups at risk for moderate-severe AKI with correct and complete implementation of a feasible, well-tailored AKI care bundle is warranted. (CRD42020207523).

Biomarker-guided implementation of the KDIGO guidelines to reduce the occurrence of acute kidney injury in patients after cardiac surgery (PrevAKI-multicentre): protocol for a multicentre, observational study followed by randomised controlled feasibility trial.

INTRODUCTION: Acute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial. METHODS AND ANALYSIS: We plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes. ETHICS AND DISSEMINATION: The PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial. TRIAL REGISTRATION NUMBER: NCT03244514.

Effect of Human Recombinant Alkaline Phosphatase on 7-Day Creatinine Clearance in Patients With Sepsis-Associated Acute Kidney Injury: A Randomized Clinical Trial.

Importance: Sepsis-associated acute kidney injury (AKI) adversely affects long-term kidney outcomes and survival. Administration of the detoxifying enzyme alkaline phosphatase may improve kidney function and survival. Objective: To determine the optimal therapeutic dose, effect on kidney function, and adverse effects of a human recombinant alkaline phosphatase in patients who are critically ill with sepsis-associated AKI. Design, Setting, and Participants: The STOP-AKI trial was an international (53 recruiting sites), randomized, double-blind, placebo-controlled, dose-finding, adaptive phase 2a/2b study in 301 adult patients admitted to the intensive care unit with a diagnosis of sepsis and AKI. Patients were enrolled between December 2014 and May 2017, and follow-up was conducted for 90 days. The final date of follow-up was August 14, 2017. Interventions: In the intention-to-treat analysis, in part 1 of the trial, patients were randomized to receive recombinant alkaline phosphatase in a dosage of 0.4 mg/kg (n = 31), 0.8 mg/kg (n = 32), or 1.6 mg/kg (n = 29) or placebo (n = 30), once daily for 3 days, to establish the optimal dose. The optimal dose was identified as 1.6 mg/kg based on modeling approaches and adverse events. In part 2, 1.6 mg/kg (n = 82) was compared with placebo (n = 86). Main Outcomes and Measures: The primary end point was the time-corrected area under the curve of the endogenous creatinine clearance for days 1 through 7, divided by 7 to provide a mean daily creatinine clearance (AUC1-7 ECC). Incidence of fatal and nonfatal (serious) adverse events ([S]AEs) was also determined. Results: Overall, 301 patients were enrolled (men, 70.7%; median age, 67 years [interquartile range {IQR}, 59-73]). From day 1 to day 7, median ECC increased from 26.0 mL/min (IQR, 8.8 to 59.5) to 65.4 mL/min (IQR, 26.7 to 115.4) in the recombinant alkaline phosphatase 1.6-mg/kg group vs from 35.9 mL/min (IQR, 12.2 to 82.9) to 61.9 mL/min (IQR, 22.7 to 115.2) in the placebo group (absolute difference, 9.5 mL/min [95% CI, -23.9 to 25.5]; P = .47). Fatal adverse events occurred in 26.3% of patients in the 0.4-mg/kg recombinant alkaline phosphatase group; 17.1% in the 0.8-mg/kg group, 17.4% in the 1.6-mg/kg group, and 29.5% in the placebo group. Rates of nonfatal SAEs were 21.0% for the 0.4-mg/kg recombinant alkaline phosphatase group, 14.3% for the 0.8-mg/kg group, 25.7% for the 1.6-mg/kg group, and 20.5% for the placebo group. Conclusions and Relevance: Among patients who were critically ill with sepsis-associated acute kidney injury, human recombinant alkaline phosphatase compared with placebo did not significantly improve short-term kidney function. Further research is necessary to assess other clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02182440.

Global epidemiology and outcomes of acute kidney injury.

Acute kidney injury (AKI) is a commonly encountered syndrome associated with various aetiologies and pathophysiological processes leading to decreased kidney function. In addition to retention of waste products, impaired electrolyte homeostasis and altered drug concentrations, AKI induces a generalized inflammatory response that affects distant organs. Full recovery of kidney function is uncommon, which leaves these patients at risk of long-term morbidity and death. Estimates of AKI prevalence range from <1% to 66%. These variations can be explained by not only population differences but also inconsistent use of standardized AKI classification criteria. The aetiology and incidence of AKI also differ between high-income and low-to-middle-income countries. High-income countries show a lower incidence of AKI than do low-to-middle-income countries, where contaminated water and endemic diseases such as malaria contribute to a high burden of AKI. Outcomes of AKI are similar to or more severe than those of patients in high-income countries. In all resource settings, suboptimal early recognition and care of patients with AKI impede their recovery and lead to high mortality, which highlights unmet needs for improved detection and diagnosis of AKI and for efforts to improve care for these patients.

Update on Perioperative Acute Kidney Injury.

Acute kidney injury (AKI) in the perioperative period is a common complication and is associated with increased morbidity and mortality. A standard definition and staging system for AKI has been developed, incorporating a reduction of the urine output and/or an increase of serum creatinine. Novel biomarkers may detect kidney damage in the absence of a change in function and can also predict the development of AKI. Several specific considerations for AKI risk are important in surgical patients. The surgery, especially major and emergency procedures in critically ill patients, may cause AKI. In addition, certain comorbidities, such as chronic kidney disease and chronic heart failure, are important risk factors for AKI. Diuretics, contrast agents, and nephrotoxic drugs are commonly used in the perioperative period and may result in a significant amount of in-hospital AKI. Before and during surgery, anesthetists are supposed to optimize the patient, including preventing and treating a hypovolemia and correcting an anemia. Intraoperative episodes of hypotension have to be avoided because even short periods of hypotension are associated with an increased risk of AKI. During the intraoperative period, urine output might be reduced in the absence of kidney injury or the presence of kidney injury with or without fluid responsiveness. Therefore, fluids should be used carefully to avoid hypovolemia and hypervolemia. The Kidney Disease: Improving Global Outcomes guidelines suggest implementing preventive strategies in high-risk patients, which include optimization of hemodynamics, restoration of the circulating volume, institution of functional hemodynamic monitoring, and avoidance of nephrotoxic agents and hyperglycemia. Two recently published studies found that implementing this bundle in high-risk patients reduced the occurrence of AKI in the perioperative period. In addition, the application of remote ischemic preconditioning has been studied to potentially reduce the incidence of perioperative AKI. This review discusses the epidemiology and pathophysiology of surgery-associated AKI, highlights the importance of intraoperative oliguria, and emphasizes potential preventive strategies.

Epidemiology of cardiac surgery-associated acute kidney injury.

Acute kidney injury (AKI) is defined by the KDIGO definition into 3 stages on basis of an increase in serum creatinine or a period of oliguria. AKI is defined as rapid reversal when the episode is 48 h or less. When AKI persists for 7 days or longer, the term acute kidney disease is used. Subclinical AKI is defined by increased concentration of an AKI biomarker, without meeting the KDIGO definition for AKI. In contrast to this, functional AKI is defined by the KDIGO definition, wherein the AKI biomarker concentration is not increased. AKI is multifactorial and heterogeneous and occurs in half of ICU patients as defined by the current KDIGO definition for AKI. In this review, we specifically describe the epidemiology of cardiac surgery-associated AKI and describe the role of scoring systems and specific AKI biomarkers.

Acute kidney injury in the ICU: from injury to recovery: reports from the 5th Paris International Conference.

The French Intensive Care Society organized its yearly Paris International Conference in intensive care on June 18-19, 2015. The main purpose of this meeting is to gather the best experts in the field in order to provide the highest quality update on a chosen topic. In 2015, the selected theme was: "Acute Renal Failure in the ICU: from injury to recovery." The conference program covered multiple aspects of renal failure, including epidemiology, diagnosis, treatment and kidney support system, prognosis and recovery together with acute renal failure in specific settings. The present report provides a summary of every presentation including the key message and references and is structured in eight sections: (a) diagnosis and evaluation, (b) old and new diagnosis tools,

Diagnosis of cardiac surgery-associated acute kidney injury: differential roles of creatinine, chitinase 3-like protein 1 and neutrophil gelatinase-associated lipocalin: a prospective cohort study.

BACKGROUND: A common and serious complication of cardiac surgery prompting early detection and intervention is cardiac surgery-associated acute kidney injury (CSA-AKI). Urinary chitinase 3-like protein 1 (UCHI3L1) was found to predict AKI associated with critical illness in adults. Our aims were therefore to evaluate whether UCHI3L1 can also be used to predict AKI associated with elective cardiac surgery in adults, and to compare this predictive ability with that of urinary neutrophil gelatinase-associated lipocalin (UNGAL), more frequently assessed early serum creatinine (SCr) measurements, and various two-biomarker panels. METHODS: This was a single-centre prospective cohort study at the eight-bed cardiac surgery ICU of Ghent University Hospital. AKI was diagnosed and classified according to the Kidney Disease|Improving Global Outcomes definitions for the diagnosis and staging of AKI, which are based on SCr and urine output (UO). Of the 211 enrolled elective cardiac surgery patients, we included 203 patients who had no AKI pre-operatively and at time of post-operative ICU admission (t1) in the primary endpoint analysis (i.e. AKI stage ≥1 within 48 h after t1), while 210 patients without AKI stage ≥2 pre-operatively and at t1 were included in the secondary endpoint analysis (i.e. AKI stage ≥2 within 12 h after t1). Systemic and/or urine concentrations of Cr, CHI3L1 and NGAL were measured more frequently than SCr in routine early post-operative ICU practice. UO was monitored hourly in the ICU. RESULTS: Within 48 h after t1, 46.8% of the patients had developed AKI (70.5% stage 1, 20.0% stage 2 and 9.5% stage 3). In the early post-operative period, only SCr was a good predictor of AKI within 48 h after t1 (primary endpoint). SCHI3L1 combined with either UCHI3L1 or UNGAL was a good predictor of AKI stage ≥2 within 12 h after t1 (secondary endpoint). However, SCr and its absolute difference from pre-operative to early measures after surgery outperformed these combinations. CONCLUSIONS: We found that more frequent assessment of the functional biomarker SCr in the early post-operative ICU period (first 4 h) after elective cardiac surgery in adult patients had good to excellent predictive value for CSA-AKI, indicating that routine SCr assessment must become more frequent in order to detect AKI more early. This performance was in contrast with the inadequate predictive value of the urinary renal stress or damage biomarkers UCHI3L1 and UNGAL.

Recovery after Acute Kidney Injury.

RATIONALE: Little is known about how acute kidney injury (AKI) resolves, and whether patterns of reversal of renal dysfunction differ among patients with respect to ultimate recovery. OBJECTIVES: We sought to examine different patterns for AKI reversal that are found in patients and assess how they relate to postdischarge outcomes. METHODS: We studied 16,968 critically ill patients with Kidney Disease Improving Global Outcomes stage 2 or 3 AKI, using an electronic database. Reversal of AKI was defined as alive and no longer meeting criteria for even stage 1. Recovery was defined as reversal at hospital discharge. MEASUREMENTS AND MAIN RESULTS: We observed five patterns. The most common (4,508; 26.6%) was early reversal that was sustained through discharge, but almost as many patients (4,496; 26.5%) had no reversal at all. The remaining patients had late reversal after Day 7 (9.7%); early reversal with one or more relapses, but with ultimate recovery (22.5%); and relapsing without recovery (14.7%). Outcomes for patients with these phenotypes were quite different, with age-adjusted 1-year survival varying from more than 90% for early reversal to less than 40% for patients never reversing. Relapses are common (37.3%), especially in the first 72 hours after reversal, and are associated with a fivefold increased risk for death by 1 year compared with early sustained reversal. CONCLUSIONS: We have identified five distinct recovery phenotypes on the basis of the clinical course over the first week after AKI manifestation. These phenotypes may identify patients amenable to therapeutic intervention. Long-term outcomes are associated with recovery status at hospital discharge.

Diagnosis of cardiac surgery-associated acute kidney injury from functional to damage biomarkers.

PURPOSE OF REVIEW: Acute kidney injury (AKI) occurs in up to 30% after cardiac surgery and is associated with adverse outcome. Currently, cardiac surgery-associated acute kidney injury (CSA-AKI) is diagnosed by Kidney Disease: Improving Global Outcomes criteria based on creatinine and urine output. To detect and treat AKI earlier, various biomarkers have been evaluated. This review addresses the current position of the two damage biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and [TIMP-2] [IGFBP7] in clinical practice. RECENT FINDINGS: We present an updated review on the use of blood and urinary NGAL in CSA-AKI. NGAL is a good predictor, and performs better in children than adults. There is a large variation in predictive ability, possibly caused by diversity of AKI definitions used, different time of measurement of NGAL, and lack of specificity of NGAL assays.Similarly, there are conflicting data on the predictive ability of urinary [TIMP-2] [IGFBP7] for CSA-AKI.Recently, both for NGAL and for urinary [TIMP-2] [IGFBP7], a set of actions, based on pretest assessment of risk for CSA-AKI and biomarker test results, was developed. These scores should be evaluated in prospective trials. SUMMARY: NGAL and urinary [TIMP-2] [IGFBP7], in combination with pretest assessment, are promising tools for early detection and treatment in CSA-AKI.

Long-term outcome in ICU patients with acute kidney injury treated with renal replacement therapy: a prospective cohort study.

BACKGROUND: In intensive care unit (ICU) patients, acute kidney injury treated with renal replacement therapy (AKI-RRT) is associated with adverse outcomes. The aim of this study was to evaluate variables associated with long-term survival and kidney outcome and to assess the composite endpoint major adverse kidney events (MAKE; defined as death, incomplete kidney recovery, or development of end-stage renal disease treated with RRT) in a cohort of ICU patients with AKI-RRT. METHODS: We conducted a single-center, prospective observational study in a 50-bed ICU tertiary care hospital. During the study period from August 2004 through December 2012, all consecutive adult patients with AKI-RRT were included. Data were prospectively recorded during the patients' hospital stay and were retrieved from the hospital databases. Data on long-term follow-up were gathered during follow-up consultation or, in the absence of this, by consulting the general physician. RESULTS: AKI-RRT was reported in 1292 of 23,665 first ICU admissions (5.5 %). Mortality increased from 59.7 % at hospital discharge to 72.1 % at 3 years. A Cox proportional hazards model demonstrated an association of increasing age, severity of illness, and continuous RRT with long-term mortality. Among hospital survivors with reference creatinine measurements, 1-year renal recovery was complete in 48.4 % and incomplete in 32.6 %. Dialysis dependence was reported in 19.0 % and was associated with age, diabetes, chronic kidney disease (CKD), and oliguria at the time of initiation of RRT. MAKE increased from 83.1 % at hospital discharge to 93.7 % at 3 years. Multivariate regression analysis showed no association of classical determinants of outcome (preexisting CKD, timing of initiation of RRT, and RRT modality) with MAKE at 1 year. CONCLUSIONS: Our study demonstrates poor long-term survival after AKI-RRT that was determined mainly by severity of illness and RRT modality at initiation of RRT. Renal recovery is limited, especially in patients with acute-on-chronic kidney disease, making nephrological follow-up imperative. MAKE is associated mainly with variables determining mortality.