Preoperative prediction of acute kidney injury—from clinical scores to biomarkers

Early acute kidney injury (AKI) diagnosis in critically ill children has been an important recent research focus because of the known association of AKI with poor outcomes and the requirement of early intervention to mitigate negative effects of AKI. In children having surgery, the preoperative period offers a unique opportunity to predict postoperative acute kidney injury (AKI), well before AKI occurs. Pediatric AKI epidemiologic studies have begun to identify which preoperative factors may predict development of postoperative cardiac surgery. Using these clinical risk factors, it may be possible to derive preoperative clinical risk scores and improve upon our ability to risk-stratify children into AKI treatment trials, pre-emptively provide conservative renal injury prevention strategies, and ultimately improve patient outcomes. Developing risk scores requires rigorous methodology and validation before widespread use. There is little information currently on the use of preoperative biological or physiological biomarkers to predict postoperative AKI, representing an important area of future research. This review will provide an overview of methodology of preoperative risk score development, discuss pediatric-specific issues around deriving such risk scores, including the combination of preoperative clinical and biologic biomarkers for AKI prediction, and suggest future research avenues.     

Acute kidney injury: an intensivist’s perspective

The changing epidemiology of acute kidney injury (AKI) in adults and children has resulted in more patients being treated for kidney injury occurring in the context of multi-organ failure requiring treatment in the intensive care unit (ICU). AKI complicating critical illness has complex, multi-factorial etiology, and supportive care, including organ support, remains the mainstay of therapy. In the day-to-day management of AKI in the ICU two of the major challenges are the inadequacy of current diagnostics for the early identification of AKI and the relationship between hemodynamic resuscitation strategies and the development of AKI. This review focuses on these areas from the intensivist’s perspective. Given that the diagnosis of AKI is often delayed, the prevention of complications and limitation of secondary renal injury are of particular importance. Fluid overload is increasingly being associated with adverse patient outcomes in critical illness and may contribute to persistent renal dysfunction. Thus, hemodynamic management strategies in AKI should be tailored to limit fluid overload as much as possible.     

老年急性肾损伤的特点与诊治

急性肾损伤(AKI)是老年人常见的危急重症,发病率逐年增加。随着年龄的增长,肾脏出现增龄性改变,同时由于机体功能衰退及常常合并多种器官病变等,使得老年人更容易发生肾脏损伤。感染、血容量不足、肾毒性药物、心血管事件、外科手术等是老年医院获得性AKI的常见病因。AKI不仅增加患者病死率,也是发展至慢性肾脏病的独立危险因素。改善AKI预后的关键是早期诊断和早期干预。目前仍采用血清肌酐(Scr)和尿量作为AKI诊断和分期标准,但老年人尿量常常受利尿剂、尿路梗阻等因素影响;而血清肌酐也并非是反映肾功能变化的敏感指标,因此可能会导致延迟诊断。除了支持治疗外,老年AKI尚没有足够证据证实存在行之有效的治疗方法。本文就以上具体内容进行综述。     

Neutrophil gelatinase-associated lipocalin curve and neutrophil gelatinase-associated lipocalin extended-range assay: a new biomarker approach in the early diagnosis of acute kidney injury and cardio-renal syndrome

Cardio-Renal syndrome (CRS) is a common and complex clinical condition in which multiple causative factors are involved. The time window between renal insult and development of acute kidney injury (AKI) in acute heart failure (AHF) can be varied in different patients and AKI often is diagnosed too late, only when the effects of the insult become evident with a loss or decline of renal function. For this reason, pharmaceutical interventions for AKI that have been shown to be renoprotective or beneficial when tested in experimental conditions do not display similar results in the clinical setting. In most cases patients with AHF are admitted with clinical signs and symptoms of congestion and fluid overload. Loop diuretics, typically used to induce an enhanced diuresis in these congested patients, often are associated with a subsequent significant decrease in glomerular filtration rate and cause a creatinine increase that is apparent within 72 hours. Early detection of AKI is not possible with the use of serum creatinine and there is a need for a timely diagnostic tool able to address renal damage while it is happening. We need to define the diagnosis of both AHF and AKI in the early phases of CRS type 1 by coupling a kidney damage marker such as neutrophil gelatinase-associated lipocalin (NGAL) with B-type natriuretic peptide (BNP). Indeed, it would be ideal to make available a panel including whole blood or plasma cardiac and renal biomarkers building specific, pathophysiologically based, molecular profiles. Based on current knowledge and consensus, we can use kidney damage biomarkers such as plasma NGAL for an early diagnosis of AKI. However, differences in individual patient values and uncertainties about the ideal cut-off values may currently limit the application of these biomarkers. We propose that NGAL may increase its usefulness in the diagnosis and prevention of CRS if a curve of plasma values rather than a single plasma measurement is determined. To apply the concept of measuring an NGAL curve in AHF patients, however, assay performance in the lower-range values becomes a critical factor. For this reason, we propose the use of the new extended-range plasma NGAL assay that may contribute to remarkably improve the sensitivity of AKI diagnosis in AHF and lead to more effective intervention strategies.     

Klotho in acute kidney injury: biomarker, therapy, or a bit of both?

Acute kidney injury (AKI) diagnosis is based on an increase in serum creatinine or a decrease in urine output. To be effective, treatment of AKI should be started very early after the insult and well before the rise of serum creatinine. Thus, sensitive biologic markers of renal tubular injury in AKI are strongly needed. Hu et al. suggest that Klotho could be a novel biomarker and therapeutic target of ischemia-induced AKI.     

Neutrophil gelatinase-associated lipocalin: a novel biomarker in acute kidney injury

Acute kidney injury (AKI) is a frequent complication in critically ill patients and is associated with high morbidity and mortality; therefore, its prophylaxis, diagnosis and intervention positively impact patient evolution. Neutrophil gelatinase-associated lipocalin (NGAL) or lipocalin, a protein synthesized by renal tubular cells, has the property to transport lipophilic molecules such as vitamins, hormones and antigenic agents. It is a novel biomarker of AKI of several etiologies and is increased in both serum and urine 48 h before the increase of creatinine. It has a strong correlation with early diagnosis of AKI. NGAL is of the most investigated and promising biomarkers for early diagnosis of AKI in different clinical scenarios, most notably in sepsis, cardiorenal syndrome, cardiac surgery, kidney transplant, contrast nephropathy and hemolytic uremic syndrome. Lipocalin guides the early institution of therapeutic interventions to improve prognosis in AKI of several etiologies.     

Impact of the etiology of acute kidney injury on outcomes following liver transplantation: acute tubular necrosis versus hepatorenal syndrome

Acute kidney injury (AKI) at the time of liver transplantation (LT) has been associated with increased morbidity and mortality. In patients with potentially reversible renal dysfunction, predicting whether there will be sufficient return of native kidney function is sometimes difficult. Previous studies have focused mainly on the effect of the severity of renal dysfunction or the duration of pretransplant dialysis on posttransplant outcomes. We performed a retrospective analysis of patients who underwent LT at our center after Model for End-Stage Liver Disease-based allocation so that we could determine the impact of the etiology of AKI [acute tubular necrosis (ATN) versus hepatorenal syndrome (HRS)] on post-LT outcomes. The patients were stratified according to the severity of AKI at the time of LT as described by the Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (RIFLE) classification: risk, injury, or failure. The RIFLE failure group was further subdivided according to the etiology of AKI: HRS or ATN. The patient survival and renal outcomes 1 and 5 years after LT were significantly worse for those with ATN. At 5 years, the incidence of chronic kidney disease (stage 4 or 5) was statistically higher in the ATN group versus the HRS group (56% versus 16%, P < 0.001). A multivariate analysis revealed that the presence of ATN at the time of LT was the only variable associated with higher mortality 1 year after LT (P < 0.001). Our study is the first to demonstrate that the etiology of AKI has the greatest impact on patient and renal outcomes after LT.     

AKI in the ICU: definition, epidemiology, risk stratification, and outcomes

Acute kidney injury (AKI) has emerged as a major public health problem that affects millions of patients worldwide and leads to decreased survival and increased progression of underlying chronic kidney disease (CKD). Recent consensus criteria for definition and classification of AKI have provided more consistent estimates of AKI epidemiology. Patients, in particular those in the ICU, are dying of AKI and not just simply with AKI. Even small changes in serum creatinine concentrations are associated with a substantial increase in the risk of death. AKI is not a single disease but rather a syndrome comprising multiple clinical conditions. Outcomes from AKI depend on the underlying disease, the severity and duration of renal impairment, and the patient's renal baseline condition. The development of AKI is the consequence of complex interactions between the actual insult and subsequent activation of inflammation and coagulation. Contrary to the conventional view, recent experimental and clinical data argue against renal ischemia-reperfusion as a sine qua non condition for the development of AKI. Loss of renal function can occur without histological signs of tubular damage or even necrosis. The detrimental effects of AKI are not limited to classical well-known symptoms such as fluid overload and electrolyte abnormalities. AKI can also lead to problems that are not readily appreciated at the bedside and can extend well beyond the ICU stay, including progression of CKD and impaired innate immunity. Experimental and small observational studies provide evidence that AKI impairs (innate) immunity and is associated with higher infection rates.     

急性肾损伤的诊断和早期预警

急性肾损伤(AKI)是临床常见的急危重症，涉及多学科，预后较差。但该病在临床工作中，仍存在较高的漏诊率和治疗不足。改善AKI预后的关键是疾病的早期诊断。实现AKI的早期诊断首先需要识别高危人群和纠正可逆的危险因素。其次，随着实验技术的发展，一些生物学标志物如肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关性脂质运载蛋白(NGAL)及N-乙酰-β-D-氨基葡萄糖苷酶(NAG)等均能在早期反映肾功能变化，已越来越多的应用于临床中。尿沉渣镜检、多普勒超声阻力指数及近年来报告的便携式荧光分析仪快速测量肾小球滤过率等在AKI的早期诊断中也发挥着重要作用。另外，结合电子健康记录或临床信息系统的AKI电子预警系统，在医疗工作中也越来越受到了临床医生的重视。本文将就辅助AKI早期诊断的上述问题做一讨论。     

Late initiation of continuous veno-venous hemofiltration therapy is associated with a lower survival rate in surgical critically ill patients with postoperative acute kidney injury

There is controversy about the appropriate timing for renal replacement therapy in patients with acute kidney injury (AKI). We are interested in the appropriate timing for initiation of continuous renal replacement therapy in critically ill surgical patients with postoperative acute kidney injury. Seventy-three critically ill surgical patients with postoperative AKI who received continuous renal replacement therapy (CRRT) were enrolled. Indications for CRRT were: 1) AKI with hyperkalemia, 2) metabolic acidosis, 3) pulmonary edema refractory to diuretics, and 4) oliguria with progressive azotemia, especially in unstable hemodynamics. Using RIFLE (Risk, Injury, Failure, Loss, End stage) classification, patients who received CRRT in the "Risk" stage were defined as early group, whereas those in the "Injury/ Failure" stage were labeled as late group. We used continuous veno-venous hemofiltration as CRRT in this series. There were 20 patients in the early group and 53 patients in the late group. The mean ages were 61.5 ± 21.8 years versus 60.8 ± 17.5 years. The mortality rate was 50 per cent versus 84.9 per cent. There were no significant differences in demographic characteristics or type of surgery or physiological scores. Our data show that late initiation of CRRT is associated with a lower survival rate in critically ill surgical patients with postoperative AKI; however, further studies are required.     

Acute kidney injury in the elderly population

The elderly population is more prone to acute kidney injury (AKI) than younger populations. Older patients have less renal reserve because of reduced glomerular filtration rates due to anatomic/functional changes, and concomitant diseases such as hypertension, diabetes, atherosclerosis, heart failure, ischemic renal disease, and obstructive uropathy. The risk of AKI may also increase as a result of aggressive diagnostic and therapeutic procedures, which include medical agents, radiology, and surgical intervention. AKI in the elderly has a multifactorial physiopathology due to different etiologies. Studies that have specifically compared prognosis of AKI in elderly versus young over the recent years suggest that age is a predictor of long-term outcome. In most cases, the treatment of AKI is similar for all age groups. The majority of critically ill patients with AKI will eventually need renal replacement therapy (RRT). The influence of RRT on renal outcome remains a subject of intense investigation and debate. Avoiding situations that could damage the kidney is an important strategy to prevent AKI development in the elderly, besides medical and interventional therapeutics.     

Biomarkers of acute kidney injury

The diagnosis of acute kidney injury (AKI) is usually based on measurements of blood urea nitrogen (BUN) and serum creatinine. BUN and serum creatinine are not very sensitive or specific for the diagnosis of AKI because they are affected by many renal and nonrenal factors that are independent of kidney injury or kidney function. Biomarkers of AKI that are made predominantly by the injured kidney have been discovered in preclinical studies. In clinical studies of patients with AKI, some of these biomarkers (eg, interleukin-18, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1) have been shown to increase in the urine before the increase in serum creatinine. These early biomarkers of AKI are being tested in different types of AKI and in larger clinical studies. Biomarkers of AKI may also predict long-term kidney outcomes and mortality.     

Portulaca Oleracea-associated oxalate nephropathy complicated with an ANCA-positive acute renal injury: A case report

Oxalate nephropathy is a rare disease that can lead to acute kidney injury (AKI). In clinical practice, as renal biopsy is required for diagnosis, physicians often do not have sufficient understanding of this disease. When AKI is associated with positive blood anti-neutrophil cytoplasmic antibodies (ANCA), a diagnosis of renal injury due to ANCA-associated vasculitis is likely to be made, leading to treatment with immunosuppressive therapy. A case of AKI after eating a large quantity of Portulaca oleracea is reported. While blood P-ANCA was positive, both urine proteinuria and urine occult blood were negative. Renal biopsy was performed and identified an acute tubulointerstitial injury: disc-shaped crystals were seen in the lumen of renal tubules that demonstrated birefringence under polarized light, and an oxalate nephropathy was therefore diagnosed. Typical histological changes of an ANCA-associated vasculitis with renal injury such as cellulose-like necrosis and crescent formation were not present. After the patient stopped eating P. oleracea, and following rehydration and hemodialysis, renal function returned to normal. In patients with AKI, the secondary causes of hyperoxalemia should be sought and attention paid to excluding an oxalate nephropathy. In patients with AKI who are ANCA-positive, it is prudent to complete the renal pathological diagnostic process before assuming that the renal injury is caused by an ANCA-associated vasculitis, and before starting hormone and immunosuppressive therapy.     

A retrospective study of short- and long-term effects on renal function after acute renal infarction

Purpose: Acute renal infarction is often missed or diagnosed late due to its rarity and non-specific clinical manifestations. This study analyzed the clinical and laboratory findings of patients diagnosed with renal infarction to determine whether it affects short- or long-term renal prognosis. Methods: We retrospectively reviewed the medical records of 100 patients diagnosed as acute renal infarction from January 1995 to September 2012 at Gyeongsang National University Hospital, Jinju, South Korea. Results: Acute kidney injury (AKI) occurred in 30 patients. Infarct size was positively correlated with the occurrence of AKI (p?=?0.004). Compared with non-AKI patients, AKI occurrence was significantly correlated with degree of proteinuria (p?p?=?0.035). AKI patients had higher levels of aspartate transaminase (p?p?p?=?0.027). AKI after acute renal infarction was more common in patients with chronic renal failure (CRF) (eGFR?60?mL/min (p?=?0.003). Most patients recovered from AKI, except for seven patients (7%) who developed persistent renal impairment (chronic kidney disease progression) closely correlated with magnitude of infarct size (p?=?0.015). Six AKI patients died due to combined comorbidity. Conclusions: AKI is often associated with acute renal infarction. Although most AKI recovers spontaneously, renal impairment following acute renal infarction can persist. Thus, early diagnosis and intervention are needed to preserve renal function.     

Biomarkers of acute kidney injury in different clinical settings: a time to change the paradigm?

Acute kidney injury (AKI) is diagnosed in 5% of all hospitalized patients and in up to 50% of all ICU patients. In the last years a dramatic rise in the prevalence of AKI has been observed with virtually no change in mortality, reaching up to 50-80% in all dialyzed ICU patients. AKI may progress to end-stage renal disease, and even subclinical episodes of AKI, which are common, may also progress to end-stage renal disease. The early detection of AKI may enable timely intervention and prevention of progression; however, in animal models and in human studies the 'window of therapeutic intervention' is narrow. Different urinary and serum proteins have been intensively investigated as possible biomarkers for the early diagnosis of AKI. There are promising candidate biomarkers with the ability to detect an early and graded increase in tubular epithelial cell injury and distinguish pre-renal disease from acute tubular necrosis. In this review, new emerging biomarkers of AKI are presented and described in some clinical settings, such as cardiac surgery, contrast-induced nephropathy, delayed graft function and ICU/emergency departments, where biomarkers are urgently needed to diagnose, make prognoses and differentiate.     

Biomarkers of acute kidney injury in children: discovery, evaluation, and clinical application

Acute kidney injury (AKI) in children is associated with increased mortality and prolonged length of hospital stay and may also be associated with long-term chronic kidney disease development. Despite encouraging results on AKI treatment in animal studies, no specific treatment has yet been successful in humans. One of the important factors contributing to this problem is the lack of an early AKI diagnostic test. Serum creatinine, the current main diagnostic test for AKI, rises late in AKI pathophysiology and is an inaccurate marker of acute changes in glomerular filtration rate. Therefore, new biomarkers of AKI are needed. With great advancements in genomics, proteomics, and metabolomics, new AKI biomarkers, mainly consisting of urinary proteins that appear in response to renal tubular cell injury, have been, and continue to be, discovered. These new biomarkers offer promise for early AKI diagnosis and for the depiction of severity of renal injury occurring with AKI. This review provides a summary of what a biomarker is, why we need new biomarkers of AKI, and how biomarkers are discovered and should be evaluated. The review also provides a summary of selected AKI biomarkers that have been studied in children.     

Incidence and outcomes in acute kidney injury: a comprehensive population-based study

Epidemiological studies of acute kidney injury (AKI) and acute-on-chronic renal failure (ACRF) are surprisingly sparse and confounded by differences in definition. Reported incidences vary, with few studies being population-based. Given this and our aging population, the incidence of AKI may be much higher than currently thought. We tested the hypothesis that the incidence is higher by including all patients with AKI (in a geographical population base of 523,390) regardless of whether they required renal replacement therapy irrespective of the hospital setting in which they were treated. We also tested the hypothesis that the Risk, Injury, Failure, Loss, and End-Stage Kidney (RIFLE) classification predicts outcomes. We identified all patients with serum creatinine concentrations > or =150 micromol/L (male) or > or =130 micromol/L (female) over a 6-mo period in 2003. Clinical outcomes were obtained from each patient's case records. The incidences of AKI and ACRF were 1811 and 336 per million population, respectively. Median age was 76 yr for AKI and 80.5 yr for ACRF. Sepsis was a precipitating factor in 47% of patients. The RIFLE classification was useful for predicting full recovery of renal function (P < 0.001), renal replacement therapy requirement (P < 0.001), length of hospital stay [excluding those who died during admission (P < 0.001)], and in-hospital mortality (P = 0.035). RIFLE did not predict mortality at 90 d or 6 mo. Thus the incidence of AKI is much higher than previously thought, with implications for service planning and providing information to colleagues about methods to prevent deterioration of renal function. The RIFLE classification is useful for identifying patients at greatest risk of adverse short-term outcomes.     

重视急性肾损伤的临床研究

急性肾损伤(AKI)发病率和死亡率在世界范围内逐年增加。2012年改善全球肾脏病预后组织(KDIGO)指南明确了新的AKI定义与分期。AKI的新定义给基础研究和常规临床实践带来了巨大的变化,提高了AKI诊断的灵敏度,降低了漏诊率,提高了预测危重患者死亡的能力,临床实用性更强。在此基础上,中国开展了几个大型的、多中心AKI流行病学调查,初步阐明了中国AKI流行病学现状和危险因素。在急性肾损伤的治疗方面,更加强调肾脏的保护与支持,越来越认识到早期干预、液体管理、营养支持以及肾脏替代治疗(RRT)时机的综合管理对AKI预后影响的重要性。     

Predictors of Perioperative Acute Kidney Injury in Obese Patients Undergoing Laparoscopic Bariatric Surgery: a Single-Centre Retrospective Cohort Study

Background

Obesity has been associated with increased risk of perioperative acute kidney injury (AKI). We aim to establish the incidence of AKI among patients undergoing laparoscopic bariatric surgery and identify potential risk factors.

Methods

Records of 1230 patients who underwent laparoscopic bariatric surgery in a tertiary centre from 1 December 2009 to 31 January 2014 were retrospectively studied. AKI diagnosis was made by comparing the baseline and post-operative serum creatinine to determine the presence of predefined significant change based on the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Univariate analyses were performed to determine significant clinical factors, and multiple logistic regression analysis was subsequently done to determine independent predictors of AKI.

Results

Thirty-five (2.9 %) patients developed AKI during the first 72 h post-surgery. Multivariate logistic regression analysis revealed impaired renal function (OR 10.429, 95 % CI 3.560 to 30.552), use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (OR 3.038, 95 % CI 1.352 to 6.824), and body mass index (OR 1.048, 95 % CI 1.005 to 1.093) as independent predictors of perioperative acute kidney injury in the obese patients who underwent laparoscopic bariatric surgery.

Conclusions

We found that the incidence of perioperative AKI among patients who underwent laparoscopic bariatric surgery is at 2.9 %. Impaired renal function, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers and raised body mass index were found to be independent predictors of AKI. Patients with these risk factors could be considered at risk for developing perioperative AKI, and extra perioperative vigilance should be undertaken.

     

Factors associated with acute kidney injury or failure in children undergoing cardiopulmonary bypass: a case-controlled study

Acute kidney injury (AKI) is a serious complication that occurs commonly following cardiopulmonary bypass (CPB) in infants and children. Underlying risk factors for AKI remain unclear, given changes in CPB practices during recent years. This retrospective, case–control study examined the relationships between patient, perioperative factors, AKI, and kidney failure in children who underwent CPB. Methods: Cohorts of children with and without AKI were identified from the cardiac perfusion and nephrology consult databases. Demographic, perioperative, and postoperative outcome data were extracted from the databases and from medical records. Children were stratified into groups based on the Acute Dialysis Quality Initiative’s RIFLE definitions for acute kidney risk or injury (AKI‐RI) and kidney failure. Results: The study groups included 308 controls (no AKI‐RI or failure), 161 with AKI‐RI, and 89 with failure. Young age, preoperative need for mechanical ventilation, milrinone, or gentamicin; intraoperative use of milrinone and furosemide; durations of CPB and anesthesia; multiple cross‐clamp and transfusion of blood products were significantly associated with AKI or failure. Young age, perioperative use of milrinone, multiple cross‐clamps, extracorporeal membrane oxygenation, cardiac failure, neurological complications, sepsis, and failure significantly increased the odds of mortality. Conclusion: This study identified multiple perioperative risk factors for AKI‐RI, failure, and mortality in children undergoing CPB. In addition to commonly known risk factors, perioperative use of milrinone, particularly in young infants, and furosemide were independently predictive of poor renal outcomes in this sample. Findings suggest a need for the development of protocols aimed at renal protection in specific at risk patients.