Assessment of fractional excretion of urea for early diagnosis of cardiac surgery associated acute kidney injury

Abstract

Background: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS). Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine, but it is not widely used in clinical practice. Fractional excretion of urea (FeU) has been referred to as a useful tool to discriminate between prerenal and established AKI. The aim of our study is to evaluate the sensitivity and specificity of FeU, in the early diagnosis of AKI in patients undergoing CS. Methods: We performed a prospective study on adults undergoing CS. AKI was defined by AKIN criteria. Individuals suffering from CKD, were excluded. Sensitivity and specificity of FeU, fractional excretion of sodium (FeNa) and urine NGAL, measured at 1, 6 and 24?h following CS, were assessed. Results: We included 66 patients (26% female) aging 68?±?11 years. AKI prevalence was 24% and mortality was 3.28%. Patients with AKI had a significantly lower FeU compared to those without AKI (23.89?±?0.67% vs. 34.22?±?0.58%; p?<?0.05) 6?h after CS, but not at the 1- and 24-h time points. NGAL was also statistically significant between both groups. FeU showed a 75% sensitivity and 79.5% specificity; the AUC was 0.786. ROC analysis of FeU and NGAL yielded similar values (p?=?NS). Conclusion: FeU is useful as an early biomarker to predict AKI after CS and it is comparable to the new biomarker NGAL.     

Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure

BACKGROUND: Fractional excretion of sodium (FENa) has been used in the diagnosis of acute renal failure (ARF) to distinguish between the two main causes of ARF, prerenal state and acute tubular necrosis (ATN). However, many patients with prerenal disorders receive diuretics, which decrease sodium reabsorption and thus increase FENa. In contrast, the fractional excretion of urea nitrogen (FEUN) is primarily dependent on passive forces and is therefore less influenced by diuretic therapy. METHODS: To test the hypothesis that FEUN might be more useful in evaluating ARF, we prospectively compared FEUN with FENa during 102 episodes of ARF due to either prerenal azotemia or ATN. RESULTS: Patients were divided into three groups: those with prerenal azotemia (N = 50), those with prerenal azotemia treated with diuretics (N = 27), and those with ATN (N = 25). FENa was low only in the patients with untreated plain prerenal azotemia while it was high in both the prerenal with diuretics and the ATN groups. FEUN was essentially identical in the two pre-renal groups (27.9 +/- 2.4% vs. 24.5 +/- 2.3%), and very different from the FEUN found in ATN (58.6 +/- 3.6%, P < 0.0001). While 92% of the patients with prerenal azotemia had a FENa <1%, only 48% of those patients with prerenal and diuretic therapy had such a low FENa. By contrast 89% of this latter group had a FEUN <35%. CONCLUSIONS: Low FEUN (相似文献   

Comparison between fractional excretions of urea and sodium in children with acute kidney injury

Fractional excretion of sodium (FENa) has been said to be the most sensitive index for differentiating prerenal failure (PRF) from intrinsic renal failure (IRF). However, there are several instances of high FENa (>2%) in cases of PRF and low FENa (<1%) in IRF patients. In contrast, the fractional excretion of urea nitrogen (FEUN) is primarily dependent on passive forces, and many confounding variables that affect FENa have little effect on FEUN, if any. To compare FEUN with FENa, pediatric patients with acute kidney injury (AKI) were prospectively evaluated by history, physical examination, and obtaining appropriate laboratory data during a 1-year interval. Diagnosis of PRF or IRF was made in each patient, and renal failure indices were compared between two groups using chi-square and t test, as appropriate. Probability value (P value) <0.05 was considered significant. Receiver operating characteristic (ROC) plots for FEUN and FENa were drawn to compare the discriminative power of each index. Forty-three patients were enrolled in the study. There were 27 patients in the PRF and 16 in the IRF group. FENa was 2 ± 0.4 in PRF and 4.5 ± 1% in IRF patients (P < 0.05), and low FENa (<1%) was only seen in 44.4% of PRF patients, which was not statistically different from those with IRF (P > 0.05). FEUN was 23.6 ± 4.9% in PRF and 41.6 ± 4.8% in IRF patients (P < 0.05), and low FEUN (<35%) was seen in 77.8% of the PRF group (P < 0.05). Cutoff values of 30% and 1.6% were reached for FEUN and FENa, respectively. In conclusion, FEUN < 35% had higher sensitivity and specificity than FENa < 1% for differentiation of PRF from IRF.     

Biomarkers for the diagnosis of acute kidney injury

PURPOSE OF REVIEW: The identification of acute kidney injury relies on tests like blood urea nitrogen and serum creatinine that were identified and incorporated into clinical practice several decades ago. This review summarizes clinical studies of newer biomarkers that may permit earlier and more accurate identification of acute kidney injury. RECENT FINDINGS: The urine may contain sensitive and specific markers of kidney injury that are present due to either impaired tubular reabsorption and catabolism of filtered molecules or release of tubular cell proteins in response to ischemic or nephrotoxic injury. Many potential markers have been studied. Promising injury markers in the urine include N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and interleukin-18. Serum cystatin C may be a better measure of glomerular filtration rate than serum creatinine or blood urea nitrogen. SUMMARY: New biomarkers of kidney injury and glomerular filtration rate hold the promise of substantially improving the diagnostic approach to acute kidney injury. Adequately powered clinical studies of multiple biomarkers are needed to qualify the biomarkers before they can be fully adopted in clinical practice. Once adopted, more sensitive biomarkers of acute kidney injury hold the potential to transform the care of patients with renal disease.     

Fenoldopam for acute kidney injury in children

We report two cases of children with severe cardiomyopathy requiring treatment with ventricular assist devices who developed acute kidney injury and were treated with fenoldopam. Therapy with fenoldopam appeared successful in one case in that renal replacement therapy was avoided with improvement in urine output and renal function. These are the first reported cases of fenoldopam use in children with acute kidney injury receiving mechanical circulatory support.     

Epidemiology and diagnosis of acute kidney injury

The development of recent standardized definitions of acute kidney injury (AKI) has allowed us to begin understanding pediatric AKI epidemiology and risk factors and to stratify outcome by AKI severity. AKI incidence will vary with illness severity of the population studied and definition type, ranging from less than 1% when need for dialysis is used to 82% when less conservative definitions (such as > or =1.5 times baseline serum creatinine) are used to define AKI. The most common AKI causes are secondary, such as sepsis, nephrotoxic medication, and ischemia, each leading to acute tubular necrosis (ATN). Children undergoing cardiopulmonary bypass surgery, stem cell transplantation, or with multiple organ dysfunction syndrome are at high risk for these events. A key feature in diagnosis and management includes identifying the presence of ATN versus a reversible hypovolemic state because patients with ATN may quickly develop fluid overload with overaggressive fluid therapy, requiring dialytic removal. Despite advances in acute pediatric dialysis therapy and in overall care of critically ill children, severe AKI still is associated with a high mortality rate, necessitating more research in early AKI identification and therapeutic trials.     

Incidence of acute kidney injury in hospitalized children

Objective To investigate the prevalence, missed diagnosis rate and causes of acute kidney injury (AKI) in hospitalized children, and its impact on hospitalization cost, length of stay and outcome. Methods The data of children admitted in Children's Hospital Affiliated to Capital Institute of Pediatrics from December 1st to 31st 2014 were collected, and those whose serum creatinine (Scr) were measured at least two times were selected. Patients were diagnosed as AKI according to the diagnostic criteria of 2012 Kidney Disease: Improving Global Outcomes, then divided into AKI group and non-AKI group, the former of which was further divided into AKI1 group (Scr peak value in normal range) and AKI2 group (Scr peak value above normal range). The causes and impact of AKI on hospitalization cost, length of stay and outcome in different groups were compared and analyzed. Results (1) Among 921 patients with at least two Scr results, 170 patients met with the diagnostic criteria of AKI, including 100 males and 70 females. There were 112(65.9%) in AKI stage 1, 43(25.3%) in stage 2, and 15(8.8%) in stage 3. The overall prevalence of AKI was 18.5%. With only 7 cases getting diagnosed, the diagnostic rate was 4.1%, while 95.9% of patients missed diagnosis. (2) Among AKI patients, 67 cases had pre-renal causes, 103 cases had intra-renal causes and mixed factors. 100(58.8%) cases got complete recovery, 34(20.0%) cases recovered partially and 36(21.2%) cases did not improve, including 4 cases of death. (3) The prevalence of AKI among those below 1-year old was higher than children elder than 1-year (23.0% vs 15.5%, P=0.004). The prevalence of AKI in surgical ward was higher than medical ward (30.7% vs 15.8%, P＜0.001). (4) Compared with those in non-AKI group, there was lower age [1.1(0.2, 3.5) year vs 2.0(0.3, 4.9) year] and higher hospitalization time[12.5(8.0, 20.0) d vs 8.0(6.0, 11.0) d], hospitalization costs [25 279.2(13 822.8, 48 856.7) yuan vs 12 616.9(8680.1, 19 345.1) yuan] and mortality (2.4% vs 0.3%) in AKI group (all P＜0.05). (5) There were 126 cases in AKI1 group and 44 cases in AKI2 group. The costs of hospitalization, outcome and mortality showed no difference between two groups (all P＞0.05). The hospitalization time in AKI2 group was shorter than that in AKI1 group (P=0.038). Conclusions Among hospitalized children the missed diagnosis rate of AKI is high. Pre-renal factor is the main cause of AKI. Children younger than 1-year old are more susceptible to AKI. AKI children have lower age and higher hospitalization time, hospitalization costs and mortality than non-AKI children. The effect of Scr fluctuation within normal levels needs to be further studied.     

The fractional excretion of urea: a new diagnostic test for acute renal allograft rejection

Fractional excretion of fsodium (FE_Na) has been used in the diagnosis of acute renal allograft failure on the assumption that poor allograft perfusion should result in a low FE_Na. However, many patient receive medications which affect the active transport of Na⁺ and thus FE_Na. In contrast, the fractional excretion of urea (FE_urea) is mostly dependent on passive forces and is therefore less influenced by drug therapy. To test the hypothesis that FE_urea might be more useful than FE_Na in evaluating graft failure, we compared FE_urea with FE_Na during 79 episodes of acute renal allograft dysfunction due to acute rejection (AR), cyclosporine nephrotoxicity (CsA-Nx), viral infection, or bacterial infection in 32 children and young adults with renal transplants. There was no significant difference between groups in FE_Na. However, FE_urea was significantly lower (P<0.05) in patients with CsA-Nx (32.6±1.9%) and viral infection (32.9±3.2%) than those with AR (45.1±1.7%) or bacterial infection (38.9±2.5%). FE_urea was < 35% in 20 of 28 (71.4%) episodes of CsA-Nx and 8 of 11 (72.2%) of viral infection, but only 5 of 36 (13.9%) of AR (P<0.05). FE_urea was also measured during stable graft function, 7–14 days prior to allograft dysfunction. CsA-Nx was associated with a 30.5±8.3% decrease in FE_urea. FE_urea did not change in patients with AR. Based on these findings, we present an algorithm to aid in the differential diagnosis of acute renal allograft failure.     

Urinary biomarkers in the early diagnosis of acute kidney injury

A change in the serum creatinine is not sensitive for an early diagnosis of acute kidney injury. We evaluated urinary levels of matrix metalloproteinase-9 (MMP-9), N-acetyl-beta-D-glucosaminidase (NAG), and kidney injury molecule-1 (KIM-1) as biomarkers for the detection of acute kidney injury. Urine samples were collected from 44 patients with various acute and chronic kidney diseases, and from 30 normal subjects in a cross-sectional study. A case-control study of children undergoing cardio-pulmonary bypass surgery included urine specimens from each of 20 patients without and with acute kidney injury. Injury was defined as a greater than 50% increase in the serum creatinine within the first 48 h after surgery. The biomarkers were normalized to the urinary creatinine concentration at 12, 24, and 36 h after surgery with the areas under the receiver-operating characteristic curve compared for performance. In the cross-sectional study, the area under the curve for MMP-9 was least sensitive followed by KIM-1 and NAG. Combining all three biomarkers achieved a perfect score diagnosing acute kidney injury. In the case-control study, KIM-1 was better than NAG at all time points, but combining both was no better than KIM-1 alone. Urinary MMP-9 was not a sensitive marker in the case-control study. Our results suggest that urinary biomarkers allow diagnosis of acute kidney injury earlier than a rise in serum creatinine.     

急性肾损伤实验室诊断的研究进展

急性肾损伤(acute kidney injury,AKI)是指由外科手术、循环血量低灌注、药毒性、烧伤外伤等原因引起的肾脏功能迅速衰退,导致氨代谢产物体液堆积,电解质紊乱、酸碱平衡紊乱并引起全身各种并发症的急重临床综合征[1].AKI的发生机制涉及多个方面,其中缺血、炎症、溶血、氧化应激、胆固醇栓塞和内源性或外源性毒...     

Predictors of acute kidney injury post-cardiopulmonary bypass in children

Objective  

To investigate the incidence, implicating factors and outcome of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) in patients admitted to a pediatric cardiothoracic intensive care unit (ICU).     

Etiology and outcome of acute kidney injury in children

The aim of this prospective, multicenter study was to define the etiology and clinical features of acute kidney injury (AKI) in a pediatric patient cohort and to determine prognostic factors. Pediatric-modified RIFLE (pRIFLE) criteria were used to classify AKI. The patient cohort comprised 472 pediatric patients (264 males, 208 females), of whom 32.6% were newborns (median age 3 days, range 1–24 days), and 67.4% were children aged?>1 month (median 2.99 years, range 1 month–18 years). The most common medical conditions were prematurity (42.2%) and congenital heart disease (CHD, 11.7%) in newborns, and malignancy (12.9%) and CHD (12.3%) in children aged?>1 month. Hypoxic/ischemic injury and sepsis were the leading causes of AKI in both age groups. Dialysis was performed in 30.3% of newborns and 33.6% of children aged?>1 month. Mortality was higher in the newborns (42.6 vs. 27.9%; p?<?0.005). Stepwise multiple regression analysis revealed the major independent risk factors to be mechanical ventilation [relative risk (RR) 17.31, 95% confidence interval (95% CI) 4.88–61.42], hypervolemia (RR 12.90, 95% CI 1.97–84.37), CHD (RR 9.85, 95% CI 2.08–46.60), and metabolic acidosis (RR 7.64, 95% CI 2.90–20.15) in newborns and mechanical ventilation (RR 8.73, 95% CI 3.95–19.29), hypoxia (RR 5.35, 95% CI 2.26–12.67), and intrinsic AKI (RR 4.91, 95% CI 2.04–11.78) in children? aged >1 month.     

尿肾损伤分子-1对肺移植术后早期并发急性肾损伤患者的早期诊断

目的 探讨尿肾损伤分子-1(KIM-1)在肺移植术后急性肾损伤(AKI)中的早期诊断价值.方法 前瞻性收集本院52例肺移植手术患者在手术前后不同时相的血、尿标本,分别测定血肌酐(Scr)和尿KIM-1.根据AKI的诊断标准,将患者分为AKI组和非AKI组,观察两组Scr和尿KIM-1的动态变化.用受试者工作特征曲线(ROC)评价尿KIM-1对AKI的诊断作用.结果 52例患者中,术后发生AKI的有19例,发生率为36.5％.AKI组Scr在术后的第24h上升至基础值的1.80倍,达到AKI的诊断标准.AKI组术后4h尿KIM-1较基线值明显上升[(1.7±0.6) ng/mL比(0.5±0.3)ng/mL,P＜0.05].术后4h,尿KIM-1的ROC曲线下面积为0.837,95％的可信区间为0.729～0.946,以1.6ng/mL作为AKI的诊断界限时,敏感性和特异性分别为73.7％和75.8％.结论 尿KIM-1可较Scr更早诊断肺移植术后AKI的发生.尿KIM-1可能为肺移植术后并发AKI患者的早期诊断的标记物.     

Value of kidney injury molecule -1 in the diagnosis of acute kidney injury: a Meta analysis

Objective To access the early diagnosis value of kidney injury molecule-1 (KIM-1) in patients with acute kidney injury (AKI) by Meta-analysis. Methods Databases MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and WanFang Data were retrieved to collect the diagnostic tests on KIM-1 for AKI published before July 2013. The literatures were screened independently by two reviewers according to the inclusion and exclusion criteria, the data were extracted, and the methodological quality was assessed. Statistic software Meta-Disc 1.4 and STATA 12.0 were used to conduct analyses. Results Eighteen articles were included in this study with a total of 3 427 patients. The summary for urinary KIM-1 in the diagnosis of AKI were sensitivity 0.67(95%CI: 0.63, 0.70), specificity 0.80 (95%CI: 0.78, 0.81), positive likelihood ratio 3.53(95%CI：2.73, 4.56), negative likelihood ratio 0.30 (95%CI: 0.21, 0.42), diagnostic odds ratio 15.13(95%CI: 8.40, 27.25), and the area under the curve (AUC) of summary receiver operating characteristic curves (SROC) was 0.865 2. Subgroup analysis revealed the sensitivity, specificity and diagnostic odds ratio of urinary KIM-1 measured after 2 to12 h post operation in diagnosis of AKI after cardiac surgery were 0.88(95%CI: 0.81, 0.93), 0.75(95%CI: 0.71, 0.79) and 30.22 (95%CI: 16.19, 56.42), respectively. The AUC of SROC was 0.923 7. Conclusions KIM-1 as a single indicator has moderate accuracy for early diagnosing AKI, especially with a high diagnostic accuracy in AKI after cardiac surgery.     

肝移植术后急性肾损伤的早期诊断

背景 急性肾损伤(acute kidney injury,AKI)为肝移植术后常见严重并发症,其发生威胁患者生存.文献报道AKI发生率差异较大,原因可能与不同研究中AKI的诊断标准不一致有关. 目的 探讨肝移植术后AKI早期诊断的最新进展,以便积极预防、尽早治疗. 内容 综述肝移植术后AKI的常用诊断标准及其发生的相关危险因素,并讨论可能的诊断新指标. 趋向 血肌酐(serum creatinine,Scr)是目前诊断AKI最常用的生物标志物,但近年来研究指出,中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、肾损伤分子-1(kidney injury molecule-1,KIM-1)、胱抑素C(Cystatin C,Cys-C)等新型生物学标志物或许可替代Scr,成为早期诊断AKI的理想指标.     

Earlier diagnosis of acute kidney injury awaits effective therapy

Novel urinary biomarkers for the early, sensitive, and specific diagnosis of acute kidney injury (AKI) show promise for the improved management of patients with this treatment-resistant complication. Several biomarkers (Kim-1, lipocalin-2, osteopontin, gluthathione S-transferases) that were tested by Rouse et al. during gentamicin-induced AKI and its recovery possess renoprotective activities, capabilities that may guide the development of novel interventions. However, despite the increased commercial availability of biomarkers, effective therapies for clinical AKI await discovery.     

Clinical and pathological features of acute kidney injury in children

Objective: Based on the diagnostic and staging criteria of acute kidney injury (AKI), we analyze the clinical and pathological characteristics of children at different stages of AKI and explored their clinical significances. Methods: 165 children with AKI were divided into stage 1, stage 2, and stage 3 groups. Clinical and pathologic characteristics of AKI children were analyzed. Results: The three groups of patients showed significant differences in age, etiology, pathological damage, and the median recovery time of serum creatinine. Of the 165 patients, the incidence and duration of hematuria showed significant differences among the three groups, and the stage 1 group showed longer duration of proteinuria. Conclusion: The patients were largely in stage 1 and 3. The children with AKI in stage 1 were largely school-age children and acute glomerulonephritis (AGN) was the main etiology. The AKI children in stage 3 were mainly infants, of which the etiology was mainly drugs and septicemia. The pathological type was mainly acute tubulointerstitial nephritis, and the renal function recovery was slow.     

Metabonomics of acute kidney injury in children after cardiac surgery

Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48–72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (t_R) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO₄), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/μl for HVA-SO₄ at 12 h after surgery. We concluded that urinary HVA-SO₄ represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery.     

Nephrotoxicity as a cause of acute kidney injury in children

Many different drugs and agents may cause nephrotoxic acute kidney injury (AKI) in children. Predisposing factors such as age, pharmacogenetics, underlying disease, the dosage of the toxin, and concomitant medication determine and influence the severity of nephrotoxic insult. In childhood AKI, incidence, prevalence, and etiology are not well defined. Pediatric retrospective studies have reported incidences of AKI in pediatric intensive care units (PICU) of between 8% and 30%. It is widely recognized that neonates have higher rates of AKI, especially following cardiac surgery, severe asphyxia, or premature birth. The only two prospective studies in children found incidence rates of 4.5% and 2.5% of AKI in children admitted to PICU, respectively. Nephrotoxic drugs account for about 16% of all AKIs most commonly associated with AKI in older children and adolescents. Nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, amphotericin B, antiviral agents, angiotensin-converting enzyme (ACE) inhibitors, calcineurin inhibitors, radiocontrast media, and cytostatics are the most important drugs to indicate AKI as significant risk factor in children. Direct pathophysiological mechanisms of nephrotoxicity include constriction of intrarenal vessels, acute tubular necrosis, acute interstitial nephritis, and-more infrequently-tubular obstruction. Furthermore, AKI may also be caused indirectly by rhabdomyolysis. Frequent therapeutic measures consist of avoiding dehydration and concomitant nephrotoxic medication, especially in children with preexisting impaired renal function.