Clearance and beyond: the complementary roles of GFR measurement and injury biomarkers in acute kidney injury (AKI)

2011 ◽  
Vol 301 (4) ◽  
pp. F697-F707 ◽  
Author(s):  
Zoltán H. Endre ◽  
John W. Pickering ◽  
Robert J. Walker

Acute kidney injury (AKI) is a common and frequently fatal illness in critically ill patients. The reliance on daily measurements of serum creatinine as a surrogate of glomerular filtration rate (GFR) not only delays diagnosis and development of successful therapies but also hinders insight into the pathophysiology of human AKI. Measurement of GFR under non-steady-state conditions remains an elusive gold standard against which biomarkers of renal injury need to be judged. Approaches to the rapid (near real-time) measurement of GFR are explored. Even if real-time GFR was available, absent baseline information will always limit diagnosis of AKI based on GFR or serum creatinine to a detection of change. Biomarkers of renal cellular injury have provided new strategies to facilitate detection and early intervention in AKI. However, the diagnostic and predictive performance of urinary biomarkers of injury vary, depending on both the time after renal injury and on the preinjury GFR. Progress in understanding the role of each novel biomarker in the causal pathways of AKI promises to enhance their diagnostic potential. We predict that combining rapid measures of GFR with biomarkers of renal injury will yield substantive progress in the treatment of AKI.

2017 ◽  
Vol 20 (5) ◽  
pp. 214 ◽  
Author(s):  
Miha Antonic

Background: Even minor postoperative reductions in renal function influence the outcome of cardiac surgery. The mechanisms of postoperative renal injury in cardiac surgery are multifactorial and include ischemia-reperfusion injury. The study investigates the effect of the antioxidant ascorbic acid on the postoperative acute kidney injury after elective CABG surgery.Methods: A prospective randomized single-center trial was conducted in on-pump coronary artery bypass patients. The patients in the ascorbic acid group received 2 grams of ascorbic acid 24 hours and 2 hours preoperatively and 1 gram twice daily five days after the surgery.  Postoperatively, the subjects were monitored for renal dysfunction and other complications.Results: 100 patients were included, with 50 patients in each study group. The groups were well matched for baseline demographics, preoperative medications, comorbidities, and had similar intraoperative characteristics. The incidence of postoperative acute kidney injury in the ascorbic acid group was 16% and 14% in the control group (P = .779). The groups also did not differ in peak postoperative serum creatinine (83 [33] µmol/L versus 83 [39] µmol/L; P = .434), the lowest postoperative creatinine clearance (96.40 ± 35.78 mL/min versus 90.89 ± 36.18 mL/min; P = .766), and time from surgery to the onset of peak postoperative serum creatinine (1.64 ± 1.34 days versus 1.92 ± 1.54 days; P = .393). There was no dialysis required in any patient. Conclusion: The results of this study did not demonstrate a significant protective effect of ascorbic acid on the incidence of postoperative acute renal injury in elective on-pump CABG patients.


2008 ◽  
Vol 294 (4) ◽  
pp. F731-F738 ◽  
Author(s):  
W. Brian Reeves ◽  
Osun Kwon ◽  
Ganesan Ramesh

Acute kidney injury is an important complication in hospitalized patients often diagnosed late and associated with high mortality and morbidity. Although biomarkers for nephrotoxicity are available, they often lack sensitivity and specificity for detecting tubular injury. Netrin-1 is a laminin-like molecule highly expressed in many organs including kidney. To determine the value of netrin-1 as a biomarker of renal injury, we analyzed its urinary excretion following ischemia-reperfusion-, cisplatin-, folic acid-, and endotoxin-induced renal injury in mice. Urinary netrin-1 levels increased markedly within 3 h of ischemia-reperfusion (40 ± 14-fold, P < 0.01 vs. baseline), reached a peak level at 6 h, and decreased thereafter, returning to near baseline by 72 h. Serum creatinine significantly increased only after 24 h of reperfusion. Similarly, in cisplatin-, folic acid-, and lipopolysaccharide-treated mice, urine netrin-1 excretion increased as early as 1 h and reached a peak level at 6 h after injection. However, serum creatinine was raised significantly after 6, 24, and 72 h after folic acid, lipopolysaccharide, and cisplatin administration, respectively. NGAL excretion in folic acid- and lipopolysaccharide-treated mice urine samples could only be detected by 24 h after drug administration. Furthermore, urinary netrin-1 excretion increased dramatically in 13 acute renal failure patients, whereas none was detected in 6 healthy volunteer urine samples. Immunohistochemical localization showed that netrin-1 is highly expressed in tubular epithelial cells in transplanted human kidney. We conclude that urinary netrin-1 is a promising early biomarker of renal injury.


Author(s):  
John R. Prowle

Acute kidney injury (AKI) is a common complication of critical illness and its occurrence has been independently associated with both short- and longer-term morbidity and mortality. However, conventional diagnosis of AKI, based on rises in serum creatinine, can be delayed and inaccurate, particularly in the context of critical illness. These diagnostic limitations potentially prevent timely intervention and appropriate follow-up of patients experiencing AKI. Recently, a number of novel urinary and serum biomarkers of AKI have been described that may provide earlier and more precise diagnosis. Importantly, a number of these substances are biologically-linked to the pathophysiology of acute tubular injury. However, true validation and widespread clinical uptake of these biomarkers is likely to require demonstration of improved patients’ outcomes as a consequence of biomarker-driven clinical interventions.


2019 ◽  
Vol 71 (2) ◽  
pp. 426-432 ◽  
Author(s):  
Sean N Avedissian ◽  
Gwendolyn M Pais ◽  
Jiajun Liu ◽  
Nathaniel J Rhodes ◽  
Marc H Scheetz

Abstract Vancomycin and piperacillin-tazobactam are 2 of the most commonly prescribed antibiotics in hospitals. Recent data from multiple meta-analyses suggest that the combination increases the risk for vancomycin-induced kidney injury when compared to alternative viable options. However, these studies are unable to prove biologic plausibility and causality as randomized controlled trials have not been performed. Furthermore, these studies define acute kidney injury according to thresholds of serum creatinine rise. Serum creatinine is not a direct indicator of renal injury, rather a surrogate of glomerular function. More reliable, specific, and sensitive biomarkers are needed to truly define if there is a causal relationship with increased toxicity when piperacillin-tazobactam is added to vancomycin. This viewpoint will explore the available evidence for and against increased acute kidney injury in the setting of vancomycin and piperacillin-tazobactam coadministration.


2018 ◽  
Vol 32 (2-3) ◽  
pp. 50-59
Author(s):  
Preeti Malhotra ◽  
Simran Kaur Syal ◽  
Ankush Singh ◽  
Karuna Thapar

Objective: To investigate asphyxiated neonates for acute kidney injury, compare the occurrence between preterms and terms and to correlate the severity and type of renal injury with the degree of asphyxia and hypoxic ischemic encephalopathy (HIE) grading. Materials and Methods: Renal functions were assessed using urine output and biochemical parameters such as blood urea, serum creatinine, serum sodium, potassium, and calcium. These were evaluated on alternate days till day 7 or recovery or death. Results: Total 108 asphyxiated neonates were enrolled: 63 term and 45 preterm. A total of 28 (25.9%) developed acute kidney injury: 9 (32.1%) had oliguric acute renal injury and the rest 19 (67.8%) had nonoliguric acute renal injury. A total of 77.7% neonates had a prerenal cause and the other 22.2% had an intrinsic cause for the kidney injury. Levels of blood urea and serum creatinine were maximally elevated on day 5 of life. Biochemical derangements correlated well with the Apgar score at birth and severity of HIE. No statistically significant difference was observed in the incidence of renal injury between preterm and term asphyxiated neonates. Conclusion: Perinatal asphyxia is an important cause of renal injury in neonates. A majority of neonates had nonoliguric and pre renal type of acute kidney injury. The more severe the degree of asphyxia, the more prone they were to develop renal complications.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Nina Rank ◽  
Boris Pfahringer ◽  
Jörg Kempfert ◽  
Christof Stamm ◽  
Titus Kühne ◽  
...  

Abstract Acute kidney injury (AKI) is a major complication after cardiothoracic surgery. Early prediction of AKI could prompt preventive measures, but is challenging in the clinical routine. One important reason is that the amount of postoperative data is too massive and too high-dimensional to be effectively processed by the human operator. We therefore sought to develop a deep-learning-based algorithm that is able to predict postoperative AKI prior to the onset of symptoms and complications. Based on 96 routinely collected parameters we built a recurrent neural network (RNN) for real-time prediction of AKI after cardiothoracic surgery. From the data of 15,564 admissions we constructed a balanced training set (2224 admissions) for the development of the RNN. The model was then evaluated on an independent test set (350 admissions) and yielded an area under curve (AUC) (95% confidence interval) of 0.893 (0.862–0.924). We compared the performance of our model against that of experienced clinicians. The RNN significantly outperformed clinicians (AUC = 0.901 vs. 0.745, p < 0.001) and was overall well calibrated. This was not the case for the physicians, who systematically underestimated the risk (p < 0.001). In conclusion, the RNN was superior to physicians in the prediction of AKI after cardiothoracic surgery. It could potentially be integrated into hospitals’ electronic health records for real-time patient monitoring and may help to detect early AKI and hence modify the treatment in perioperative care.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Gianluca Villa ◽  
Silvia De Rosa ◽  
Caterina Scirè Calabrisotto ◽  
Alessandro Nerini ◽  
Thomas Saitta ◽  
...  

Abstract Background Postoperative acute kidney injury (PO-AKI) is a leading cause of short- and long-term morbidity and mortality, as well as progression to chronic kidney disease (CKD). The aim of this study was to explore the physicians’ attitude toward the use of perioperative serum creatinine (sCr) for the identification of patients at risk for PO-AKI and long-term CKD. We also evaluated the incidence and risk factors associated with PO-AKI and renal function deterioration in patients undergoing major surgery for malignant disease. Methods Adult oncological patients who underwent major abdominal surgery from November 2016 to February 2017 were considered for this single-centre, observational retrospective study. Routinely available sCr values were used to define AKI in the first three postoperative days. Long-term kidney dysfunction (LT-KDys) was defined as a reduction in the estimated glomerular filtration rate by more than 10 ml/min/m2 at 12 months postoperatively. A questionnaire was administered to 125 physicians caring for the enrolled patients to collect information on local attitudes regarding the use of sCr perioperatively and its relationship with PO-AKI. Results A total of 423 patients were observed. sCr was not available in 59 patients (13.9%); the remaining 364 (86.1%) had at least one sCr value measured to allow for detection of postoperative kidney impairment. Among these, PO-AKI was diagnosed in 8.2% of cases. Of the 334 patients who had a sCr result available at 12-month follow-up, 56 (16.8%) developed LT-KDys. Data on long-term kidney function were not available for 21% of patients. Interestingly, 33 of 423 patients (7.8%) did not have a sCr result available in the immediate postoperative period or long term. All the physicians who participated in the survey (83 out of 125) recognised that postoperative assessment of sCr is required after major oncological abdominal surgery, particularly in those patients at high risk for PO-AKI and LT-KDys. Conclusion PO-AKI after major surgery for malignant disease is common, but clinical practice of measuring sCr is variable. As a result, the exact incidence of PO-AKI and long-term renal prognosis are unclear, including in high-risk patients. Trial registration ClinicalTrials.gov, NCT04341974.


Author(s):  
Ahmad El Samra ◽  
Ayesa Mian ◽  
Marc Lande ◽  
Hongyue Wang ◽  
Ronnie Guillet

Objective The aim of this study was to determine the effects of a 2-day prenatal course of indomethacin on the premature kidney as reflected by serum creatinine and urinary biomarkers. Study Design Urine of infants ≤ 32 weeks was collected for the first 14 days and analyzed for cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, β2 microglobulin, epidermal growth factor, uromodulin, and microalbumin. Bivariate analysis compared serum creatinine and biomarkers of exposed (INDO) and unexposed (CONT) subjects. Results Fifty-seven infants (35 CONT and 22 INDO) were studied. The cohorts were similar in gestational age, birthweight, race, gender, nephrotoxic medication exposure, and Apgar scores. CONT had more dopamine exposure and included more pre-eclamptic mothers (p = 0.005). No difference in creatinine-based acute kidney injury or the log transformed mean, maximum, and minimum values of urinary biomarkers was detected. Conclusion Our findings suggest that a short course of tocolytic indomethacin does not result in neonatal acute kidney injury. Key Points


Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 572
Author(s):  
Jung-Yeon Kim ◽  
Jungmin Jo ◽  
Jaechan Leem ◽  
Kwan-Kyu Park

Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.


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