Improving outcomes from acute kidney injury: report of an initiative

Acute kidney injury (AKI) is a clinical condition characterized by acute decline in renal function, with manifestations ranging from minimal elevation of serum creatinine concentration to anuric renal failure. Keeping in view that acquisition of knowledge and research in this important area requires multi-disciplinary collaboration, a group representing members of the Acute Dialysis Quality Initiative and nephrology and critical care societies has established the Acute Kidney Injury Network (AKIN). The First Consensus Conference of this network focused on defining diagnostic and staging criteria for AKI. Changes in serum creatinine levels and urine output were used to define and stage three levels of renal dysfunction. These criteria require evaluation and validation in prospective clinical studies and, perhaps, modifications as more sensitive markers of kidney injury are identified. Other issues that need to be examined include global epidemiology and outcome of AKI and development of strategies to improve outcomes. The vital role of multi-disciplinary conferences for disseminating knowledge and clarifying issues in clinical practice was recognized.     

Improving outcomes of acute kidney injury: report of an initiative

Acute kidney injury (AKI) is a complex disorder comprising several etiological factors and occurring in multiple settings. The disorder has a variety of clinical manifestations that range from minimal elevation in serum creatinine level to anuric renal failure. We describe the formation of a multidisciplinary collaborative network focused on AKI. This Acute Kidney Injury Network has proposed uniform standards for diagnosing and classifying AKI. These proposed standards will need to be validated in future studies, a process that will be facilitated by the Acute Kidney Injury Network, which offers a forum that encourages acquisition of knowledge to improve patient outcomes.     

Attenuation of acute lung injury following lower limb ischemia/reperfusion: the pharmacological approach

AIM: The purpose of this study was to examine the effects of N-acetylcysteine (NAC), calcium dobesilate (DOBE) and aprotinin on the amelioration of lung damage following ischemia/reperfusion injury in a rat hind limb model. A well known antioxidant dimethyl-sulfoxide (DMSO) was also tested for comparison. METHODS: Ischemia was induced in the lower limb for 4 h by vascular clamping and followed by 1 h of reperfusion. Lung injury was evaluated in 5 groups as a saline (control), DMSO, NAC, DOBE and aprotinin group. Plasma creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS) as well as lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. P<0.005 was considered statistically significant. RESULTS: Plasma TBARS values were found to be significantly lower in the DMSO (P<0.005), NAC (P<0.005) and aprotinin (P<0.005) groups compared to the control group. Lung TBARS values were significantly lower in the DMSO, NAC, DOBE and aprotinin groups compared to the control group (P<0.001, P<0.001, P<0.001). Also in the aprotinin group lung TBARS values were found to be significantly lower compared to DMSO (P<0.001), NAC (P<0.001) and DOBE (P<0.001) groups. Histological examination showed less prominent peribronchial leukostasis (P<0.005) and interstitial leukostasis (P<0.005) in all drug groups compared to the control group. CONCLUSION: These observations indicate that DOBE and NAC, which are known to have antioxidant properties and aprotinin, a serine proteinase inhibitor, acted effectively on the prevention of lung injury in a rat hind limb ischemia/reperfusion model. The reason why aprotinin exerts a more protective effect than the other drugs is not clear, however, its clinical use may have the dual advantage of hemostasis and lung protection in surgical practice.     

急性肾损伤的一体化管理

急性肾损伤是影响患者临床预后、住院时间和医疗费用的临床综合征,是全球广泛流行且威胁人类健康的世界性公共卫生问题。近年来随着对疾病的重视,关于急性肾损伤的研究大幅增加,并在早期诊断、发病机制、预防治疗等方面取得显著进展,为改善急性肾损伤的综合管理提供了新的方向。本文将重点从急性肾损伤的定义、流行病学、发病机制、预防和治疗以及目前的现状等方面阐述急性肾损伤的一体化管理。     

严重的下肢损伤

目的探讨严重下肢损伤的保肢与截肢问题。方法对70例72肢下肢严重开放性骨折患者的病史、年龄、体检、治疗时间及方法进行综合性研究。患者入院后急诊行全面体检以及X线片检查。根据Gustilo和Andserson分类,ⅢB型和ⅢC型分别为48肢和24肢。16肢患肢除严重的下肢损伤外,还伴有其它严重的复合伤,其中伴头颅外伤包括脊柱外伤患肢7肢(占9.7%),伴腹部外伤患肢5肢(占6.9%),伴胸部外伤患肢4肢(占5.6%)。结果72肢患肢,截肢16肢,其中ⅢB型7肢,ⅢC型9肢。患者年龄在50岁以上者的患肢8肢,截肢4肢,截肢率为50.0%;年龄在50岁以下者的患肢64肢,截肢12肢,截肢率为18.8%,两者比较差异有显著性意义(χ2=4.018,P<0.05)。单纯下肢损伤和复合伤的患者相比,骨科急诊手术时间分别为(8.50±6.54)h和(16.72±8.45)h,两者比较差异有非常显著性意义(t=4.146,P<0.01);软组织重建手术时间分别为(9.45±7.43)d和(23.89±12.24)d,两者比较差异有显著性意义(t=5.098,P<0.01);其相应的截肢率分别为16.1%和43.8%,两者比较差异有显著性意义(χ2=5.516,P<0.05)。动脉断裂患肢14肢,热缺血时间>6h的患肢4肢,全部截肢;热缺血时间<6h的患肢10肢,仅1肢截肢,两者比较差异有显著性意义(χ2=10.08,P<0.05)。有3肢患肢为小腿下1/3的损伤,热缺血时间分     

Apoptosis of the thick ascending limb results in acute kidney injury

Ischemia- or toxin-induced acute kidney injury is generally thought to affect the cells of the proximal tubule, but it has been difficult to define the involvement of other tubular segments because of the widespread damage caused by ischemia/reperfusion or toxin-induced injury in experimental models. For evaluation of whether thick ascending limb (TAL)-specific epithelial injury results in acute kidney injury, a novel transgenic mouse model that expresses the herpes simplex virus 1 thymidine kinase gene under the direction of the TAL-specific Tamm-Horsfall protein promoter was generated. After administration of gancyclovir, these mice demonstrated apoptosis only in TAL cells, with little evidence of neutrophil infiltration. Compared with control mice, blood urea nitrogen and creatinine levels were at least five-fold higher in the transgenic mice, which also developed oliguria and impaired urinary concentrating ability. These findings suggest that acute injury targeted only to the TAL is sufficient to cause severe acute kidney injury in mice with features similar to those observed in humans.     

Ischemic preconditioning before lower limb ischemia--reperfusion protects against acute lung injury

OBJECTIVE: Prolonged limb ischemia followed by reperfusion (I/R) is associated with a systemic inflammatory response syndrome and remote acute lung injury. Ischemic preconditioning (IPC), achieved with repeated brief periods of I/R before the prolonged ischemic period, has been shown to protect skeletal muscle against ischemic injury. The aim of this study was to ascertain whether IPC of the limb before I/R injury also attenuates systemic inflammation and acute lung injury in a fully resuscitated porcine model of hind limb I/R. METHODS: This prospective, randomized, controlled, experimental animal study was performed in a university-based animal research facility with 18 male Landrace pigs that weighed from 30 to 35 kg. Anesthetized ventilated swine were randomized (n = 6 per group) to three groups: sham-operated control group, I/R group (2 hours of bilateral hind limb ischemia and 2.5 hours of reperfusion), and IPC group (three cycles of 5 minutes of ischemia/5 minutes of reperfusion immediately preceding I/R). Plasma was separated and stored at -70 degrees C for later determination of plasma tumor necrosis factor-alpha and interleukin-6 with bioassay as markers of systemic inflammation. Circulating phagocytic cell priming was assessed with a whole blood chemiluminescence assay. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were markers of edema and neutrophil sequestration, respectively. The alveolar-arterial oxygen gradient and pulmonary artery pressure were indices of lung function. RESULTS: In a porcine model, bilateral hind limb (I/R) injury significantly increased plasma interleukin-6 concentrations, circulating phagocytic cell priming, and pulmonary leukosequestration, edema, and impaired gas exchange. Conversely, pigs treated with IPC before the onset of the ischemic period had significantly reduced interleukin-6 levels, circulating phagocytic cell priming, and experienced significantly less pulmonary edema, leukosequestration, and respiratory failure. CONCLUSION: Lower limb IPC protects against systemic inflammation and acute lung injury in lower limb I/R injury.     

Treatment of acute kidney injury: an update on the management of renal replacement therapy

PURPOSE OF REVIEW: Renal replacement therapy remains the cornerstone of management for the patient with severe acute kidney injury. Although the technology for providing renal replacement therapy has markedly advanced over the past few decades, fundamental issues regarding its management, including timing of initiation, selection of modality and dosing of therapy, remain unresolved. RECENT FINDINGS: Although several retrospective and observational studies of the timing of initiation of renal replacement therapy have suggested improved survival with early initiation of treatment, the design of these studies does not allow definitive conclusions. Recent randomized trials have not demonstrated any benefit with regard to survival or recovery of renal function with continuous renal replacement therapy compared with intermittent hemodialysis. Increased intensity of renal support appears to be associated with improved survival; however more definitive studies are ongoing. SUMMARY: The optimal management of renal replacement therapy in patients with acute kidney injury remains uncertain. Appropriately designed studies evaluating timing of initiation of therapy need to be undertaken. Current data suggest that modality of therapy does not impact outcome. More intensive renal support may be associated with improved outcomes; however several large randomized controlled trials assessing this question are ongoing.     

Pathophysiology and management of septic acute kidney injury

Acute kidney injury (AKI) is a commonly encountered complication in critically ill children and portends a worse prognosis. Sepsis-induced AKI (SAKI) is a leading contributor to AKI in children and significantly modifies the risk for less favorable outcome. It has increasingly become clear that SAKI represents a unique and distinct cause of AKI. Studies focused on renal hemodynamics, bioenergetics, and immune-mediated injury have provided further insights into the pathobiology of SAKI; however, many of the nuanced mechanisms remain incompletely understood. Although there have been numerous strategies evaluated for the prevention and management of SAKI, no specific intervention has proven unequivocally efficacious. Currently, the mainstays for managing SAKI focus on alleviating ongoing kidney damage by optimizing systemic and kidney hemodynamic support, avoiding nephrotoxins, and mitigating the anticipated complications of kidney failure. The timely referral for renal support to manage azotemia, metabolic derangements, and fluid accumulation remains critical for this population. The extracorporeal removal of inflammatory mediators has shown some potential benefit in limiting systemic and kidney immune-mediated injury; however, the precise role of these technologies in the management of SAKI has yet to be defined.     

Predicting postoperative urinary retention after lower limb arthroplasty

A simple scoring system that enables surgeons to make an estimation of the likelihood of postoperative urinary retention (POUR) in patients undergoing lower limb total joint replacement would be a useful one. This would enable selection of high risk patients who merit pre-operative catheterisation in a clean theatre environment rather than risking urinary retention and its associated complications late at night on the ward by junior, inexperienced staff. The International Prostate Symptom Score (IPSS) is such a scoring system and we assessed its reliability in predicting those male patients likely to go into POUR. We selected all male patients undergoing lower limb total joint arthroplasty under spinal anaesthesia and calculated their IPSS. We found a statistically significant increase in the likelihood of POUR as IPSS rises (p = 0.0002). We concluded that the IPSS is a quick and easy method of predicting those at risk of POUR, allowing them to be catheterised prophylactically, preventing possible complications.     

Challenges in severe lower limb injury rehabilitation

Restoration of lower limb function following severe injury is a challenge. Rehabilitation must take into account psychosocial factors and patient self-efficacy as well as functional goals. The Return to Run clinical pathway, an integrated orthotic and rehabilitation initiative, is an example of goal-oriented rehabilitation with periodic assessment aimed at restoring wounded warriors to high-level performance following severe lower extremity trauma. Objective assessment measures of surgical and rehabilitation interventions are lacking for persons with high-level performance demands, such as those required by service members. Thus, the Military Performance Laboratory at the Center for the Intrepid has established normative data for several physical performance measures, some of which are now routinely used to assess service members with severe lower extremity trauma. Patient expectations of treatment and rehabilitation are high and must be met to avoid poor outcomes attributed to nonanatomic factors.     

Role of total hip replacement arthroplasty between transplantation and acute kidney injury

Osteonecrosis of the femoral head is a severely disabling complication of steroid immunosuppression in renal transplant patients. The increased number of patients undergoing transplantation has increased the number of transplant recipients undergoing total hip replacement arthroplasty (THRA). In this study, we retrospectively assessed patients who underwent THRA from May 2004 to February 2014, and evaluated their demographic and clinical characteristics, the results of peri-operative laboratory tests, the amounts of fluids transfused during surgery, and anesthesia time. Our results found that post-operative acute kidney injury (AKI) was significantly associated with transplantation, and transplantation was an independent factor predictive of post-operative AKI, so transplant recipients are at risk for AKI following THRA. Total hip replacement is a safe and effective treatment for transplant recipients and, in view of their limited life expectancy, should be considered at an early stage in their treatment.     

Acute lower limb ischemia: Pathogenesis and management

Acute lower limb ischemia continues to be a problem both in diagnosis and management. The high mortality rate appears to be related to the metabolic consequences of ischemia, a function not only of time, but also of severity. The etiology of acute ischemia is reviewed along with the pathophysiological response. The management of the patient centers on diagnosis of cause and estimation of the severity of ischemia. Correction of metabolic disturbances and early restoration of flow is the preferred treatment, although there remains a place for late operative intervention in patients with less severe symptoms. Despite improved diagnostic and operative techniques, the thrombotic and metabolic changes that occur in the small vessels and muscular tissues appear to limit the success rate, with mortality rates remaining around 25%.     

Preoperative lower limb venography in patients undergoing total hip arthroplasty

Using bilateral ascending venography, the authors examined 93 consecutive patients undergoing total hip arthroplasty for the presence of asymptomatic preoperative leg vein thrombosis. Radiologic abnormalities were seen in only four patients, and this was not statistically significant (P greater than .1). There were no complications from the procedure. It is suggested that routine preoperative screening for deep vein thrombosis prior to hip arthroplasty is unnecessary but may be appropriate in patients at particularly high risk for thromboembolic complications.     

Spontaneous arteriorrhexis in affected lower limb following total knee arthroplasty

Total knee arthroplasty （TKA） is now a standard treatment for serious osteoarthritis all over the world. Although it is a standard treatment, it has many complications, among which deep vein thrombosis （DVT） is the exclusive blood vessel complication that has been reported. However, we found a new blood vessel complication of TKA in this study, which is spontaneous arteriorrhexis in the affected lower limb.