Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes

In established acute kidney injury (AKI), serum creatinine poorly differentiates prerenal from intrinsic AKI. In this study, we tested whether urinary neutrophil gelatinase-associated lipocalin (NGAL) distinguishes between intrinsic and prerenal AKI, and tested its performance in predicting a composite outcome that included progression to a higher RIFLE (Risk, Injury, Failure, Loss of function, End stage renal disease) class, dialysis, or death. Urinary NGAL was measured using a standardized clinical platform in 161 hospitalized patients with established AKI. Sixteen patients were excluded because of postrenal obstruction or insufficient clinical information. Of the remaining 145 patients, 75 had intrinsic AKI, 32 had prerenal AKI, and 38 patients could not be classified. Urinary NGAL levels effectively discriminated between intrinsic and prerenal AKI (area under the receiver-operating characteristic curve 0.87). An NGAL level over 104?μg/l indicated intrinsic AKI (likelihood ratio 5.97), whereas an NGAL level <47?μg/l made intrinsic AKI unlikely (likelihood ratio 0.2). Patients experiencing the composite outcome had significantly higher median urinary NGAL levels on inclusion. In logistic regression analysis, NGAL independently predicted the composite outcome when corrected for demographics, comorbidities, creatinine, and RIFLE class. Hence, urinary NGAL is useful in classifying and stratifying patients with established AKI.     

Etiology,clinical profile and short-term outcome of acute kidney injury in children at a tertiary care pediatric nephrology center in Pakistan

Background: The reported prevalence rates and etiologies of acute kidney injury (AKI) are quite variable in different regions of the world. The current study was planned to determine the etiology, clinical profile, and short-term outcome of pediatric AKI at our hospital.

Methods: A prospective, observational study was carried out from April 2014 to March 2015. All pediatric patients (1 month to?≤15 years) diagnosed as AKI using modified pRIFLE criteria were studied and followed for 3 months to document short-term outcome.

Results: AKI was diagnosed in 116 children. The mean age was 7.5?±?4.4 years and males were predominant (60.3%). At presentation, 83.6% had oliguria/anuria, 37.1% hypertension and 17.2% severe anemia. Etiology included primary renal (74/116; 63.8%), postrenal (28/116; 24.1%) and prerenal (11/116; 9.5%) causes. Postinfectious glomerulonephritis (PIGN) and crescentic glomerulonephritis in primary renal, obstructive urolithiasis in postrenal and sepsis in prerenal, were the most common etiologies. At presentation, 89/116 (76.7%) patients were in pRIFLE Failure category. Regarding outcome, 68 (58.6%) patients recovered, six (5.2%) died, 18 (15.5%) developed chronic kidney disease (CKD) and 22 (19%) end-stage renal disease (ESRD). Comparison of recovered and unrecovered AKI showed that characteristics such as hypertension, severe anemia, edema, volume overload, requirement of mechanical ventilation, initiation of dialysis and need of >5 sessions of dialysis had statistically significant (p?<0.05) association with nonrecovery.

Conclusion: Glomerulonephritides (PIGN and crescentic) and obstructive urolithiasis are major causes of pediatric AKI at our center. A fairly high percentage of cases recovered and these mainly comprised of PIGN and obstructive urolithiasis.     

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ICU中急性肾损伤(AKI)病人营养支持的主要目的在于确保适当的热量,预防组织蛋白和瘦肉组织不必要的浪费,改善组织修复,支持免疫系统,降低病死率。应首选肠内途径,但即便如此,仍然经常需要辅以肠外营养,以满足目标营养的需求。需要特别关注肾脏替代治疗(RRT)对三大营养素和微量营养素的影响以及可能导致并发症的防范。事实上,由于肾脏体液平衡功能的急性丢失,常需要RRT治疗,AKI病人尤其易出现血糖异常、高甘油三酯血症以及体液、酸碱、电解质的失衡。     

Perioperative renal protection

AKI is the term to describe an abrupt reduction in kidney function and it replaces all previous terms such as ARF. The new definition for AKI needs to be validated by future research. Further development of biomarkers of AKI may aid in the early diagnosis and treatment of the syndrome. Mortality due to perioperative AKI often exceeds 50% and small changes in SCr correlate to significant increases in mortality. Preoperative risk factors for the development of AKI include a past history of renal dysfunction, elevated SCr, decreased cardiac performance, and cardiac and vascular surgery. Perioperative renal protection should focus on maintenance of euvolemia, preservation of adequate renal perfusion, and avoidance of any nephrotoxins. Intraoperative fluid management should be titrated to hemodynamic parameters and UO while avoiding excess fluid administration. The ideal fluid to administer is unknown as crystalloids and colloids each have their own advantages and disadvantages. Renal perfusion should be maintained by keeping MAP >65 mmHg and research may identify new techniques to monitor and individualize therapy to maintain renal perfusion. Recent data suggest that fenoldopam may alter outcome in patients with AKI.     

Cellular changes in acute renal failure: functional and therapeutic consequences.

Prerenal, renal and postrenal forms of acute renal failure (ARF) are distinguishable. Prerenal forms are reversible by effective treatment of the underlying extrarenal disorder(s). Damage of the endothelium and the tubular epithelium indicates progress of prerenal to renal ARF or induction of primary renal ARF. A continuous survey of renal function based on the cellular and functional pathophysiologic pathways of ARF allows adequate and specific therapy. As both extra- and intrarenal causes of ARF may occur simultaneously under clinical conditions, a broad therapeutic approach should be used: treatment of the extrarenal disorder augmented by measures to reduce the cellular workload, cell-protective therapy, support of microcirculation rheology, and inhibition of prerenal vasoconstriction.     

Frequency and outcome of patients with acute renal failure have more causes than one in etiology

In literature, there was little data about frequency and outcome of ARF with two or more causes in etiology. Therefore, the aim of this study was to search this issue. This series included 339 patients with ARF from Jan 1,1987 to Jan 1,1999. Fourty-six (30 males) of all patients (13.5%) had two or more causes in etiology of ARF. Of these patients, causes were prerenal and renal in 26 (56%), prerenal, renal and postrenal in 12 (26%), renal and postrenal in 4 (9%), and prerenal and postrenal in 4 (9%). The most frequent cause is diarrhea and vomiting in prerenal, gentamycin usage in renal and prostate hypertrophy in postrenal. Of these patients, there was oliguria in 32 (70%), anuria in 8 (17%) and non-oliguria in 6 (13%). Treatment modalities of patients was only medical in 19 (41%), dialysis in addition to medical therapy in 27 (59%). In spite of treatment, 5 (10.8) of patients with two or more causes in etiology died. Causes of death were uremic coma in 2, cardiac disorders in 2 and septic shock in 1. Three (11.2%) of other patients with one cause died. Mortality rates were not different (chi2: 0.0298, p > 0.5). Cortical necrosis was diagnosed in one patient with multiple etiology and 2 of other patients. Finally, frequency of ARF with two or more etiologic causes was 13.5%, and most frequent causes were hypovolemia and nephrotoxic drugs. Outcome of these patients was similar to other patients with one cause.     

How to optimize drug delivery in renal replacement therapy

Drug dosing in the setting of acute kidney injury (AKI) is complicated by several factors such as pharmacokinetic changes in renal failure, inaccuracy of renal estimating equations in this setting, lack of therapeutic drug monitoring capability for most drugs, and use of extracorporeal renal replacement. Pharmacokinetic changes include decreases in protein binding and drug metabolism. Renal estimating equations most often overestimate renal clearance in AKI. Additionally, it is well recognized that some drugs are significantly cleared by extracorporeal therapy. Patients with AKI are therefore at risk for adverse outcomes of drug therapy. It has been reported that approximately half of patients with reduced renal clearance receive drug doses that are 2.5 times higher than the recommended maximum dose. To ensure efficacy and prevent toxicity, therapeutic drug monitoring is highly recommended. However, in the absence of drug monitoring, adequate concentrations can only be inferred from clinical response. A clinician must weigh the risks and benefits of possible over-dosing or under-dosing based on the therapeutic index of the drug and the clinical situation. This article will review the important factors to consider for drug dosing in patients with AKI receiving continuous renal replacement therapy and sustained low-efficiency dialysis.     

Akutes Nierenversagen nach kardiochirurgischen Eingriffen

Acute kidney injury (AKI) occurs, according to current definitions, in up to 30% of all patients undergoing cardiac surgery. AKI that requires renal replacement therapy has an incidence of approximately 1%. The development of AKI increases mortality to 15?C30%, independently of other comorbidities. Full recovery of renal function is only observed in 50% of surviving patients. Thus, due to its significance, the term cardiac surgery-associated acute kidney injury (CSA AKI) was coined. The underlying mechanisms leading to CSA AKI are not limited to the use of cardiopulmonary bypass. In fact, predominant causes include endogenous and exogenous nephrotoxins, inflammation, hypoperfusion, and metabolic and neurohormonal disturbances. Since no causal therapy is available for CSA AKI, primary and secondary prevention is critical to correct all avoidable and modifiable risk factors of AKI. Renal replacement therapy is only supportive to bridge the gap until the kidneys recover.     

Acute Kidney Injury Associated with Metamizole Sodium Ingestion

Abstract

Metamizole sodium, a nonsteroidal anti-inflammatory drug, has been widely used in the last 100 years. Its efficacy as an analgesic and antipyretic is unquestionable. Only few cases of acute kidney injury (AKI) induced by metamizole sodium were reported in the medical literature. We report 11 adult patients with AKI that resulted from metamizole sodium ingestion. The data suggest a good prognosis in these cases of AKI. Renal biopsies, corticosteroids treatment, or renal replacement therapy seem to be not necessary. Hydration was sufficient to ensure spontaneous recovery.     

Discrepancy between cystatin C and creatinine points leading to a diagnosis of postrenal acute kidney injury and its reversibility: three case reports

We report on three patients with postrenal acute kidney injury (AKI) showing a remarkably low level of cystatin C (CysC) compared with that of creatinine (Cr). The levels of Cr and CysC (Cr/CysC) were respectively as follows: 12.16 mg/dl/1.26 mg/l, 17.92 mg/dl/0.95 mg/l and 18.94 mg/dl/0.55 mg/l. The causes of urinary tract obstruction were benign prostatic hypertrophy, urinary bladder carcinoma and urethral stenosis due to radiation therapy for bladder carcinoma. Renal function was promptly recovered after relief of the obstruction. It is considered that the discrepancy strongly indicated AKI because of urinary tract obstruction and encouraged relief of the obstruction in order to recover renal function. Although the precise mechanism for the discrepancy was not determined, the maintenance of glomerular filtration and proximal tubular reabsorption of CysC long after the cessation of Cr excretion because of urinary tract obstruction seemed to be involved. This finding may be beneficial for the diagnosis and reversal of postrenal AKI and provides new insight into the process of postrenal AKI.     

Acute kidney injury associated with metamizole sodium ingestion

Metamizole sodium, a nonsteroidal anti-inflammatory drug, has been widely used in the last 100 years. Its efficacy as an analgesic and antipyretic is unquestionable. Only few cases of acute kidney injury (AKI) induced by metamizole sodium were reported in the medical literature. We report 11 adult patients with AKI that resulted from metamizole sodium ingestion. The data suggest a good prognosis in these cases of AKI. Renal biopsies, corticosteroids treatment, or renal replacement therapy seem to be not necessary. Hydration was sufficient to ensure spontaneous recovery.     

Survival akin to injury, hospitalized patients with acute kidney injury based on the AKIN classification

Introduction: Acute kidney injury (AKI) is often associated with severe consequences. The aim of the study was to determine whether the acute kidney injury network classification predicts hospital stay, renal recovery and mortality. Methods: Hospitalized patients who were referred to the nephrology service over 6 months were studied retrospective with further 12 months prospective follow up. Statistical analysis was performed on their demography and outcome. Results: Among the 238 patients who were referred, 166 had AKI, median age 74 years and 32% were diabetics. 10% (n = 17) required acute renal replacement therapy. The overall all-cause mortality of AKI group (n = 166) compared to non-AKI group (n = 72) at 1 year was 55% as opposed to 27.8% (p < 0.001). There was a significant statistical difference in the composite outcome and survival between the AKI stages in terms of renal recovery (p = 0.018). The AKI group had a median 8 day increase in length of stay compared to the non-AKI group (20 vs. 12 days; p = 0.0175). However, there was no significant statistical difference between pre and post admission AKI (p value = 0.191). Conclusion: The AKIN staging of AKI predicts both early and late mortality. AKI has a major impact on inpatient and 1-year-survival, renal recovery and length of stay. AKI and renal recovery following the insult were independent prognosticators. Early identification and management of AKI cases can help to prevent progression of the severity of AKI and therefore, mandates timely referral to nephrology team to prevent progression of AKIN class and its consequences.     

MCP-1 gene activation marks acute kidney injury

Monocyte chemoattractant protein 1 (MCP-1) mediates acute ischemic and toxic kidney injury, but whether this can be used as a biomarker of acute kidney injury (AKI) is unknown. We obtained kidney and urine samples from mice with intrarenal (maleate), prerenal (endotoxemia), or postrenal (ureteral obstruction) injury. We also studied the independent effects of uremia without concomitant kidney injury by performing bilateral ureteral transection in mice. Additionally, we obtained urine samples from APACHE II-matched critically ill patients with or without advancing azotemia (n = 10 in each group). We assayed selected samples for MCP-1, MCP-1 mRNA, and for an activating histone mark (H3K4m3) at urinary fragments of the MCP-1 gene and contrasted the results with those obtained for neutrophil gelatinase-associated lipocalin (NGAL), a comparator "AKI biomarker" gene. Maleate increased urinary MCP-1 protein and mRNA more than the corresponding increases in NGAL. Endotoxemia and ureteral obstruction also increased NGAL and MCP-1 gene expression. Uremia, in the absence of renal injury, induced the NGAL gene, but not MCP-1, suggesting the possibility of better specificity of MCP-1 for AKI. Clinical assessments supported the utility of MCP-1 as a biomarker (e.g., nonoverlapping concentrations of urinary MCP-1 in patients with and without AKI). Elevated levels of urinary MCP-1 mRNA and levels of H3K4m3 at the MCP-1 gene supported MCP-1 gene activation in patients with renal injury. In conclusion, these data suggest that MCP-1 has potential as a biomarker of AKI and provide "proof of concept" that urinary histone assessments provide mechanistic insight among patients with kidney disease.     

The dark side of high-intensity renal replacement therapy of acute kidney injury in critically ill patients

The impact of intensity or dose of renal replacement therapy (RRT) on outcome of critically ill patients has been a matter of controversy. Most definitions of an adequate dose of acute RRT are based on urea removal, while ignoring other crucial aspects of RRT adequacy in acute kidney injury (AKI). Although some clinical trials have found an improvement in survival with higher doses of intermittent hemodialysis or continuous RRT, results have not been consistent across all studies. The largest trials suggest that there is no additional survival benefit with doses of 35–45 ml/kg/h (CRRT) or daily intermittent hemodialysis. On the other hand, high-intensity treatment may cause life-threatening complications and thereby counteract the benefits of higher small-solute clearance. One important area for future investigations is the need to characterize the potential harm of high-dose RRT for AKI in critically ill patients.     

Renal failure and its treatment

Acute kidney injury (AKI) is a common complication of acute illness. It is associated with significant morbidity and mortality as well as a high cost to healthcare systems. There are a broad range of causes of AKI which should be considered in a systematic fashion to avoid missing multiple potential causative factors. These include pre-renal causes from hypovolaemia, intrinsic renal causes such as glomerular diseases and post-renal obstructive causes. In the intensive care unit, two-thirds of AKI cases result from renal hypoperfusion, sepsis, contrast and nephrotoxic agents; up to 5% will require renal replacement therapy. Modalities of renal replacement therapy include intermittent haemodialysis, peritoneal dialysis and continuous haemofiltration. Continuous haemofiltration is usually favoured in the intensive care setting as it has greater haemodynamic stability and greater capacity to extract fluid from patients with fluid overload. Anticoagulation is recommended with haemodialysis and haemofiltration and systemic heparin, regional citrate or zero anticoagulation are the usual options.     

Renal failure and its treatment

Acute kidney injury (AKI) is a common complication of acute illness. It is associated with signicant morbidity and mortality as well as a high cost to healthcare systems. There are a broad range of causes of AKI which should be considered in a systematic fashion to avoid missing multiple potential causative factors. These include pre-renal causes from hypovolaemia, intrinsic renal causes such as glomerular diseases and post-renal obstructive causes. In the intensive care unit, two-thirds of AKI cases result from renal hypoperfusion, sepsis, contrast and nephrotoxic agents; up to 5% will require renal replacement therapy. Modalities of renal replacement therapy include intermittent haemodialysis, peritoneal dialysis and continuous haemoltration. Continuous haemoltration is usually favoured in the intensive care setting as it has greater haemodynamic stability and greater capacity to extract uid from patients with fluid overload. Anticoagulation options can be achieved with systemic anticoagulation such as heparin or regional anticoagulation with citrate.     

445例急性肾损伤病因与预后分析

目的探讨急性肾损伤的病因以及影响预后的危险因素。方法回顾性分析本院2013年9月至2018年9月收治的445例急性肾损伤(AKI)患者的病因、临床特征、治疗方案等,分析其与预后的关系。结果445例患者中,男性261例,女性184例,年龄(54.66±18.21)岁;肾性因素为主,共有253例(56.85%),肾毒性药物导致的急性肾损伤有119例(26.74%);肾前性因素共有123例(27.64%),感染尤其是急性胃肠炎占比比较大;肾后性44例(9.89%),病因多为泌尿系结石及肿瘤晚期压迫,另有产源性16例(3.60%),不明原因9例(2.02%)。病因在各年龄组间差异有统计学意义(P<0.05)。有序logistic回归分析,年龄、衰竭器官个数、休克、机械通气是影响预后的独立危险因素。结论药源性及肾前性急性肾损伤需要引起更多的关注;年龄、衰竭器官个数、休克、机械通气是急性肾损伤预后的危险因素。对于此类患者,早期诊断,早期干预,有助于改善预后。     

Acute kidney injury in an infant after cardiopulmonary bypass

The infant who develops acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery presents unique challenges and opportunities to the clinician and to the investigator interested in the study of AKI pathophysiology. Infants do not have many of the comorbid conditions that confound CPB outcome studies of adults. Because the timing of the AKI event is known in this clinical setting, collaboration between cardiology intensivists, nephrologists, and perfusion technologists is essential to minimize the impact of CPB on the kidney. Early institution of ultrafiltration in the operating room and renal replacement therapy in the postoperative period may decrease the proinflammatory milieu and its resultant systemic effects. In addition, early initiation of renal replacement therapy to prevent fluid overload may result in improved infant outcomes.     

Le dosage plasmatique de Neutrophil Gelatinase-Associated Lipocalin (NGAL) prédit la défaillance rénale au cours du choc septique dès l’admission en réanimation

Purpose

To validate plasma Neutrophil Gelatinase-Associated Lipocalin (pNGAL) as an early biomarker in intensive care unit (ICU) for acute kidney injury (AKI) in critically ill adult with septic shock.

Patients and method

Fifty consecutive patients with septic shock were included in this observational cohort study. AKI was defined if patients met any RIFLE or AKIN criteria. The main objective was to evaluate diagnosis value of pNGAL measured with a point-of-care device at admission (D0), at 24 hours (D1) and at 48 hours (D2).

Results

Among the 50 patients enrolled, 86% had AKI, 48% had persistent renal AKI and 30% required renal replacement therapy (RRT) during their ICU stay. At D0, pNGAL concentration was significantly higher in patients with AKI compared to patients without AKI (471 ng/mL versus 134 ng/mL, P < 0.001). This level remained significantly higher in the AKI population at D1 and D2 and pNGAL concentration at D0 among AKI patients increased with kidney failure level. At D1, pNGAL was significantly higher for persistent renal AKI rather than transient prerenal (570 ng/mL versus 337 ng/mL, P = 0.027). pNGAL concentration below 348 ng/mL at D1 was never seen in patients with RRT.

Conclusion

Plasma NGAL is a useful, sensitive and early biomarker to predict persistent AKI in septic shock at ICU admission and help to discuss RRT.     

RIFLE标准在心脏术后急性肾损伤病人中的评价

目的 探讨RIFLE标准在心脏术后急性肾损伤(AKI)病人肾替代治疗时机选择中的作用及与预后的关系.方法 回顾分析145例心脏术后AKI病例,分为连续性静脉一静脉血液滤过(CVVH)组(98例)和非CVVH组(47例).应用RIFLE标准对AKI进行分期,对比分析各组病人的临床资料、疗效和预后.结果 AKI Ⅰ期和Ⅲ期中CVVH组与非CVVH组的医院病死率差异无统计学意义;Ⅱ期中非CVVH组的医院病死率高于CVVH组(58.8%对26.1%,P<0.0).CVVH组生存者中,CVVH治疗、尿量恢复、机械通气、ICU滞留和术后医院滞留时间随AKI分期的加重而延长.结论 RIFLE标准对心脏术后AKI早期诊断和判断预后有指导意义.必须强调肾脏替代时机的选择,在AKI Ⅱ期即行肾替代治疗可以明显改善预后,而CVVH比间断血液透析和腹膜透析更有优势.