Diagnosis Of AKI Research Articles

Increased prothrombotic property as a risk factor of acute kidney injury after surgical repair of abdominal aortic aneurysm: a prospective observational study.

BackgroundAcute kidney injury (AKI) is one of the major morbidities after surgical repair of abdominal aortic aneurysm (AAA); however, precise pathogenesis of this morbidity has not been well determined. Since prothrombotic coagulation abnormality may precede organ dysfunction in systemic inflammatory state, we examined the kinetics of von Willebrand factor (VWF) and a disintegrin-like metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13), a cleaving enzyme of VWF, on the development of AKI after AAA surgery.MethodsThe kinetics of ADAMTS13 and VWF were examined in ten patients who underwent surgical repair of AAA. The changes in plasma neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker for AKI, and serum creatinine concentration were also examined at four points until seventh postoperative day (POD). Clinical diagnosis of AKI was based on the change in serum creatinine concentration and urine output according to Acute Kidney Injury Network (AKIN) criteria.ResultsADAMTS13 activity was significantly lower than normal level before the surgery and showed a trend of decrease toward 3POD. The VWF/ADAMTS13 ratio showed a significant increase on 1POD, which persisted until 7POD. None of patents was diagnosed as AKI based on AKIN criteria, although two patients received furosemide and/or carperitide therapy because of decreased urine output less than 0.5 ml/kg/h for several hours in ICU. Plasma NGAL showed a trend to increase after the surgery, which was significant on 3POD. The change in plasma NGAL was significantly correlated with VWF/ADAMTS13 ratio (P < 0.01).ConclusionsThis study has shown that patients undergoing AAA surgery were prothrombotic after the surgery because of high VWF/ADAMTS13 ratio. Correlation between VWF/ADAMTS13 ratio and NGAL might indicate contribution of thrombotic event to subclinical AKI in the patients undergoing AAA surgery.

Plasma NGAL for the Diagnosis of AKI in Patients Admitted from the Emergency Department Setting

The purpose of this study was to determine the accuracy of plasma neutrophil gelatinase-associated lipocalin as a marker of AKI in patients admitted from the emergency department. In this prospective cohort study, patients (n=616) admitted from the emergency department from March to November of 2008 were classified according to clinical criteria as AKI, transient azotemia, stable CKD, and normal function. Plasma neutrophil gelatinase-associated lipocalin was measured serially. A logistic regression model using clinical characteristics was fitted to the data, and a second model included discretized plasma neutrophil gelatinase-associated lipocalin. Performance of the models was evaluated by Hosmer-Lemeshow goodness-of-fit test, area under the receiver operating characteristic curve, net reclassification improvement, integrated discrimination improvement, and predictiveness curve. Twenty-one percent of patients were classified as AKI; the highest median levels of plasma neutrophil gelatinase-associated lipocalin were in the AKI group (146-174 ng/ml at various time points) and increased with AKI severity (207-244 ng/ml for Acute Kidney Injury Network classification stage>2). The discriminative ability of plasma neutrophil gelatinase-associated lipocalin for AKI diagnosis (area under the curve, 0.77-0.82 at various time points) improved with higher grades of severity (area under the curve, 0.85-0.89 for AKIN>2). Plasma neutrophil gelatinase-associated lipocalin discriminated AKI from normal function and transient azotemia (area under the curve, 0.85 and 0.73, respectively). Patients were classified into three grades of AKI risk according to plasma neutrophil gelatinase-associated lipocalin levels (low, moderate [i.e., the gray zone], and high). Patients with plasma neutrophil gelatinase-associated lipocalin in the high-risk category displayed a 10-fold greater risk of AKI (odds ratio, 9.8; 95% confidence interval, 5.6 to 16.9). The addition of plasma neutrophil gelatinase-associated lipocalin to the clinical model yielded a net reclassification improvement of 94.3% and an integrated discrimination improvement of 0.122. Plasma neutrophil gelatinase-associated lipocalin is an accurate biomarker for prediction of AKI in patients admitted from the emergency department. This work proposes a three-grade classification of AKI risk based on plasma neutrophil gelatinase-associated lipocalin levels.

Biomarkers of acute kidney injury in pediatric cardiac surgery

ObjectivesAcute kidney injury (AKI) is a significant problem in children undergoing cardiopulmonary bypass (CPB). The aims of this study were to assess the diagnostic validity of serum CysC (sCysC), serum neutrophil gelatinase lipocalin (sNGAL), urine neutrophil gelatinase lipocalin (uNGAL), urine kidney injury molecule (uKIM)-1, and urine liver fatty acid-binding protein (uL-FABP) to predict AKI presence and severity in children undergoing CPB. Design and methodsWe performed a prospective single-center evaluation of sCysC, sNGAL, uNGAL, uKIM-1 and uL-FABP at 0, 2, 6, 24 and 48h postoperatively in children undergoing CPB during cardiac surgery. AKI was defined as ≥25% decrease in the estimated creatinine clearance (eCCl) from pre-operative baseline at 48h after surgery. ResultsOf the 112 patients, 18 patients (16.1%) developed AKI; four of them needed acute dialysis treatment and three AKI patients died. In the AKI compared to the non-AKI group, sCysC at 2h, and uNGAL and uL-FABP at 2–48h were significantly increased, as well as CPB, aortic cross clamp time and length of hospital stay. Biomarkers increased with worsening AKI severity. At 2h after CPB the best accuracy for diagnosis of AKI had uL-FABP and sCysC with area under the receiver operator curve (AUC) of 0.89 and 0.73, respectively. At 6 and 24h after CPB the best AUC was found for uL-FABP (0.75 and 0.87 respectively) and for uNGAL (0.70 and 0.93, respectively). ConclusionssCysC, uNGAL and uL-FABP are reliable early predictors for AKI after CPB. By allowing earlier timing of injury and earlier intervention, they could improve AKI outcome.

Performance of Kidney Injury Molecule-1 and Liver Fatty Acid-Binding Protein and Combined Biomarkers of AKI after Cardiac Surgery

AKI is common and novel biomarkers may help provide earlier diagnosis and prognosis of AKI in the postoperative period. This was a prospective, multicenter cohort study involving 1219 adults and 311 children consecutively enrolled at eight academic medical centers. Performance of two urine biomarkers, kidney injury molecule-1 (KIM-1) and liver fatty acid-binding protein (L-FABP), alone or in combination with other injury biomarkers during the perioperative period was evaluated. AKI was defined as doubling of serum creatinine or need for acute dialysis. KIM-1 peaked 2 days after surgery in adults and 1 day after surgery in children, whereas L-FABP peaked within 6 hours after surgery in both age groups. In multivariable analyses, the highest quintile of the first postoperative KIM-1 level was associated with AKI compared with the lowest quintile in adults, whereas the first postoperative L-FABP was not associated with AKI. Both KIM-1 and L-FABP were not significantly associated with AKI in adults or children after adjusting for other kidney injury biomarkers (neutrophil gelatinase-associated lipocalin and IL-18). The highest area under the curves achievable for discrimination for AKI were 0.78 in adults using urine KIM-1 from 6 to 12 hours, urine IL-18 from day 2, and plasma neutrophil gelatinase-associated lipocalin from day 2 and 0.78 in children using urine IL-18 from 0 to 6 hours and urine L-FABP from day 2. Postoperative elevations of KIM-1 associate with AKI and adverse outcmes in adults but were not independent of other AKI biomarkers. A panel of multiple biomarkers provided moderate discrimination for AKI.

Clinical Utility of Biomarkers of AKI in Cardiac Surgery and Critical Illness

AKI is a common and serious complication that is associated with several adverse outcomes in hospitalized patients. The past several years have seen a large number of multicenter investigations of biomarkers of AKI in the setting of cardiac surgery and critical illness. This review summarizes these biomarker results to identify applications for clinical use. The Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) study showed that blood and urine biomarkers measured preoperatively, immediately postoperatively, and at the time of the clinical increase in serum creatinine in the setting of cardiac surgery all had the ability to improve patient risk stratification for a variety of important clinical end points. Analyses of biomarkers concentrations from the Acute Respiratory Distress Syndrome Network, EARLY ARF, and other studies of critically ill subjects have similarly shown that biomarkers measured early in the clinical course can forecast the development of AKI and need for renal replacement therapy as well as inpatient mortality. Although biomarkers have informed the diagnosis, prognosis, and treatment of AKI and are inching closer to clinical application, large multicenter interventional clinical trials to prevent AKI using biomarkers should continue to be an active area of clinical investigation.

Biomarkers of acute kidney injury

Creatinine remains the standard for laboratory diagnosis of AKI. Efforts to prevent nephrotoxicity have been harmed by the delay in the diagnosis of AKI criteria by using only the creatinine as a marker, therefore there is great interest in identifying early reliable biomarkers. Moreover, early treatment of ARF can be correlated with a better prognosis and identification of biomarkers for early diagnosis would improve the efficacy of a therapeutic strategy. Thus, it becomes imperative to find biomarkers that can stratify correctly the extent of renal damage that each patient has suffered and the risk of developing chronic kidney disease (CKD). Here, we review the main features of emerging biomarkers in nephrology.

3. Laboratory Examination for the Diagnosis of CKD or AKI

3. Laboratory Examination for the Diagnosis of CKD or AKI

AKI Associated with Synthetic Cannabinoids

SPICE, or K2, encompasses preparations of synthetic cannabinoids marketed as incense products, bath additives, and air fresheners and used for recreational purposes. These preparations are usually smoked for their cannabis-like effects and do not appear on routine urine toxicology screens. We report four cases of oliguric AKI associated with SPICE use in previously healthy men. All showed improvement in renal function without need for renal replacement therapy. Renal biopsy, performed in three of the patients, revealed acute tubular necrosis. The close temporal and geographic associations between the clinical presentation and the development of AKI strongly suggest an association between these SPICE preparations and AKI. Further investigations are required to identify the potential nephrotoxic agent(s). Nephrotoxicity from designer drugs should be included in the differential diagnosis of AKI, especially in young adults with negative urine drug screens.

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Introduction: Estimation of renal function is essential in antimicrobial dosing. The Cockcroft-Gault (CG) equation is used as a gold standard, but it is not validated in AKI and changing renal function. Estimation methods by Jelliffe, Chiou, and Brater have been proposed in AKI, but not studied for drug dosing. Hypothesis: The objective of this study is to compare creatinine clearance (CrCl) estimates using the CG equation with estimates using the Jelliffe, Chiou, and Brater equations in patients with AKI. We hypothesize that these estimates will result in differences in antimicrobial dosing. Methods: In this retrospective study, discharge records were screened to identify patients with a diagnosis of AKI. A sample size of 300 patients provided 80% power to detect a 10ml/min difference in CrCl. Data points collected were age, height, weight, gender, race, and serum creatinine measures. Peak serum creatinine and two values pre/post peak measures were collected. CrCl estimates for the Jelliffe, Chiou, and Brater equations with worsening and improving renal function were compared to CG estimates using the Wilcoxon matched-pairs signed-ranks test. Dosing recommendations for piperacillin/tazobactam were calculated with each estimate. Results: 314 patients were included; average age was 61.4 years and 162 subjects were male. For improving renal function, the average difference between the CG and each equation was: Jelliffe 18ml/min (p<0.0001); Chiou 18ml/min (p<0.0001); and Brater 17ml/min (p=0.0614). For worsening renal function, average difference between CG and each equation was: Jelliffe 14ml/min (p=0.003); Chiou 13ml/min; and Brater 15ml/min (p=0.318). Variations in estimates resulted in different dosing recommendations for piperacillin/tazobactam in 55% of patients with the Jelliffe equation and 43% with the Chiou equation. Conclusions: Significant differences in renal function estimates exist between the CG equation (current standard) and the Jelliffe and Chiou equations for estimation in AKI. These may impact dosing for piperacillin/tazobactam, a commonly used antimicrobial. Further studies with laboratory measurements to determine CrCl are needed to optimize antimicrobial dosing regimens.

The early diagnosis of acute kidney injury after liver transplantation by urine lactate dehydrogenase, cystatin C and neutrophil gelatinase-associated lipocalin

Objective To investigate the value of urinary lactate dehydrogenase(LDH),Cystatin C (Cys-C) and neutrophil gelatinase-associated lipocalin (NGAL) in early diagnosis of acute kidney injury after liver transplantation. Methods From January 2011 to October 2011,45 patients were recruited.Blood and urinary samples were collected before operation and the end of the operation,and used to determine serum creatinine (SCr),Cys-C,LDH,and total bilirubin,as well as urinary LDH,Cys-C and NGAL.All the patients were divided into AKI and non-AKI groups,according to the Acute Kidney Injury Network (AKIN) criteria of AKI.The statistics were used along ROC analysis to evaluate the diagnose value of selected biomarkers. Results There were no significant differences in clinical parameters between AKI and non-AKI groups while 20 of the 45 patients suffered AKI [ ( 140±54)vs (81±20),P＜0.05].Urine LDH,Cys-C and NGAL raised in all the samples,and the level of the 3 enzymes in AKI group increased significantly [ (6.50±2.86)vs (3.21±1.63),P＜0.05 ],[ ( 1.55±0.54)vs (0.86±0.31),P＜0.05 ],[ ( 107±59)vs (43±11 ),P＜0.05 ].ROC analysis revealed that (AUC 0.853,0.833,0.880) the 3 enzymes are capable of early diagnosis of AKI. Conclusions Urinary LDH,Cys-C and NGAL appear to be sensitive and specific biomarkers of AKI in liver transplant recipients,but further research are needed in the future for the clinical diagnosis. Key words: Liver transplantation; Acute kidney injury ; Lactate dehydrogenase ; Cystatin C; Neutrophil gelatinaseassociated lipocalin

Onco-Nephrology

AKI is common in patients with cancer, and it causes interruptions in therapy and increased hospital length of stay, cost, and mortality. Although cancer patients are susceptible to all of the usual causes of AKI in patients without cancer, there are a number of AKI syndromes that occur more frequently or are unique to this patient population. AKI also confers substantially increased risk of short-term death, and the ability to reverse AKI portends a better outcome in some cancers, such as multiple myeloma. Several trends in oncology, including increased survival, better supportive care, older patients who have received multiple chemotherapy regimens, and new therapeutic options, are driving an increase in the numbers of cancer patients who develop AKI. As a result, nephrologists should be increasingly familiar with the diagnosis, management, and treatment of AKI in this setting. Here, we summarize recent data on epidemiology of AKI in cancer patients, describe the most common AKI syndromes in this population, and highlight emerging areas in the growing field of onconephrology.

Biomarkers Predict Progression of Acute Kidney Injury after Cardiac Surgery

Being able to predict whether AKI will progress could improve monitoring and care, guide patient counseling, and assist with enrollment into trials of AKI treatment. Using samples from the Translational Research Investigating Biomarker Endpoints in AKI study (TRIBE-AKI), we evaluated whether kidney injury biomarkers measured at the time of first clinical diagnosis of early AKI after cardiac surgery can forecast AKI severity. Biomarkers included urinary IL-18, urinary albumin to creatinine ratio (ACR), and urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL); each measurement was on the day of AKI diagnosis in 380 patients who developed at least AKI Network (AKIN) stage 1 AKI. The primary end point (progression of AKI defined by worsening AKIN stage) occurred in 45 (11.8%) patients. Using multivariable logistic regression, we determined the risk of AKI progression. After adjustment for clinical predictors, compared with biomarker values in the lowest two quintiles, the highest quintiles of three biomarkers remained associated with AKI progression: IL-18 (odds ratio=3.0, 95% confidence interval=1.3-7.3), ACR (odds ratio=3.4, 95% confidence interval=1.3-9.1), and plasma NGAL (odds ratio=7.7, 95% confidence interval=2.6-22.5). Each biomarker improved risk classification compared with the clinical model alone, with plasma NGAL performing the best (category-free net reclassification improvement of 0.69, P<0.0001). In conclusion, biomarkers measured on the day of AKI diagnosis improve risk stratification and identify patients at higher risk for progression of AKI and worse patient outcomes.

Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: a review of the laboratory characteristics and clinical evidences

Acute kidney injury (AKI) is a common and serious condition, currently diagnosed by functional biomarkers, such as serum creatinine measurements. Unfortunately, creatinine increase is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury has hampered our ability to translate promising experimental therapies to human AKI. The recent discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed here. NGAL may be measured by several methods both in plasma and urine for the early diagnosis of AKI and for the prediction of clinical outcomes, such as dialysis requirement and mortality, in several common clinical scenarios, including in the intensive care unit, cardiac surgery and renal damage due the exposition to toxic agent and drugs, and renal transplantation. Furthermore, the predictive properties of NGAL, may play a critical role in expediting the drug development process. A systematic review of literature data indicates that further studies are necessary to establish accurate reference population values according to age, gender and ethnicity, as well as reliable and specific decisional values concerning the more common clinical settings related to AKI. Furthermore, proper randomized clinical trials on renal and systemic outcomes comparing the use of NGAL vs. standard clinical practice are still lacking and accurate cost-benefit and/or cost-utility analyses for NGAL as biomarker of AKI are also needed. However, it is important to note that NGAL, in the absence of diagnostic increases in serum creatinine, is able to detect some patients affected by subclinical AKI who have an increased risk of adverse outcomes. These results also suggest that the concept and definition of AKI might need to be reassessed.

Traditional Urinary Biomarkers in the Assessment of Hospital-Acquired AKI

Traditional biomarkers, such as urine chemistries and urine microscopic elements, are used in the diagnosis and care of patients with AKI. Urine chemistries, such as fractional excretion of sodium and fractional excretion of urea, are useful for differentiating prerenal AKI from acute tubular necrosis only in select patients. Urine microscopy using a quantitative evaluation of the urine sediment for renal tubular epithelial cells, renal tubular epithelial cell casts, and granular casts has recently been shown to differentiate prerenal AKI from acute tubular necrosis and also provide prognostic information. Urine microscopy has also been noted to compare favorably with new urine biomarkers for diagnosis and prognosis of AKI. Thus, current information on urine diagnostics suggests that urine chemistries have a limited role in differential diagnosis of AKI, whereas urine microscopy and new urine biomarkers may be used together to differentiate prerenal AKI from acute tubular necrosis and predict such outcomes as worsened AKI, acute dialysis, and death.

Reply to Letter Regarding Article, “Cystatin C and Contrast-Induced Acute Kidney Injury”

We thank Drs Ribichini et al for their interest in our study on cystatin C and contrast-induced acute kidney injury (CI-AKI).1 At present, 2 consensus definitions/classification systems have been proposed for the diagnosis of AKI: the Acute Dialysis Quality Initiative's RIFLE criteria (Risk, Injury, Failure, Loss, and End Stage) and the Acute Kidney Injury Network criteria. Two aspects should be emphasized: (1) All of the proposed cutoffs predict unfavorable clinical outcome, and (2) the level of baseline kidney function influences the kinetics of serum creatine after …

Acute Kidney Injury: Controversies Revisited

This paper addresses the epidemiology of AKI specifically in relation to recent changes in AKI classification and revisits the controversies regarding the timing of initiation of dialysis and the use of peritoneal dialysis as a renal replacement therapy for AKI. In summary, the new RIFLE/AKIN classifications of AKI have facilitated more uniform diagnosis of AKI and clinically significant risk stratification. Regardless, the issue of timing of dialysis initiation still remains unanswered and warrants further examination. Furthermore, peritoneal dialysis as a treatment modality for AKI remains underutilised in spite of potential beneficial effects. Future research should be directed at identifying early reliable biomarkers of AKI, which in conjunction with RIFLE/AKIN classifications of AKI could facilitate well-designed large randomised controlled trials of early versus late initiation of dialysis in AKI. In addition, further studies of peritoneal dialysis in AKI addressing dialysis dose and associated complications are required for this therapy to be accepted more widely by clinicians.

Diagnosis and classification of AKI: AKIN or RIFLE?

Acute kidney injury is a common syndrome associated with increased morbidity and mortality, but academic advances in this field are hindered by the lack of a universally accepted definition. Two classification schemes—the AKIN and the RIFLE criteria—have been proposed, but uncertainty remains as to whether their performance is comparable.

Survey of acute kidney injury in hospitalized patients

Objective To investigate the incidence of AKI and its relationship to mortality of inpatients by analyzing the changes of serum creatinine(SCr). Methods We collected the data of SCr in Peking Union Medical College Hospital through Jun 2006 to May 2007 and then selected the patients who were subjected to SCr determination more than one time. The relationship between the frequency of SCr determination and gender, age was analyzed. The relationship of increased SCr to gender, age, frequency of determination was also analyzed. The risk stratification based on SCr was investigated. In our study, we investigated the incidence of AKI in different diagnostic groups. The relationship between AKI and mortality in ICU and MICU unit was analyzed. Results There were 36 855 patients in one year, 16 934 patients were subjected to SCr determination only one time, 15 233 patients were subjected to SCr determination at least two times. Elder men were subjected to SCr determination more frequently (P<0.01). Along with the increase of SCr concentration, the frequency of SCr determination were increased significantly (P<0.01). Using the increasing of SCr exceeding 50% as the criteria for diagnosis of AKI, the incidence of hospital-acquired AKI was 8.46%, and it was higher in patients with injury and poisoning (16.7%), infection (16.0%), hematological system diseases (16.1%), neoplasms (12.7%). The incidence of AKI was 27.7% and 55.2% in ICU and MICU, respectively. Mortality of patients in MICU was increased along with the increasing of SCr level Mortality of patients with AKI in ICU was 23.3%, that was significant higher than patients without AKI, the adjust OR was 2.7 (P<0.01). Conclusions The incidence of AKI evaluated by analyzing SCr changing is significantly higher than that using experienced clinical diagnosis. This method is convenient in clinic for early diagnosis of AKI. Key words: Kidney failure, acute; Creatinine; Mortality; Hospitalized patient