Publications by authors named "Hilde R H de Geus"

22 Publications

  • Page 1 of 1

The Seraph®-100 Microbind Affinity Blood Filter Does Not Affect Vancomycin, Tacrolimus, and Mycophenolic Acid Plasma Concentrations.

Blood Purif 2021 Mar 29:1-5. Epub 2021 Mar 29.

Department of Intensive Care, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.

Extracorporeal blood purification is considered an adjunct therapy in critically ill patients with life-threatening conditions such as sepsis and septic shock. It consists of cytokine removal, removal of endotoxins, a combination of both, or the removal of pathogens themselves. The latter technique was introduced for clinical application very recently. This case study describes a case of a 69-year-old female lung transplant recipient patient with a persistent VV-ECMO-related septic deep vein thrombosis with continuous renal replacement therapy-dependent acute kidney injury initiated on the Seraph®-100 Microbind Affinity Filter in order to control the persistent bacteraemia with coagulase-negative staphylococci. Drug plasma concentrations (vancomycin, tacrolimus, and mycophenolic acid) were measured before and after the device to calculate absorber-related drug clearance.
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http://dx.doi.org/10.1159/000514523DOI Listing
March 2021

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

Am J Kidney Dis 2020 12 15;76(6):826-841.e1. Epub 2020 Jul 15.

Columbia University Vagelos College of Physicians and Surgeons, New York, NY.

Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

Setting & Study Populations: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.

Selection Criteria For Studies: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.

Data Extraction: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.

Analytical Approach: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.

Results: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively.

Limitations: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies.

Conclusions: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.
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http://dx.doi.org/10.1053/j.ajkd.2020.05.015DOI Listing
December 2020

Successful Reduction of Creatine Kinase and Myoglobin Levels in Severe Rhabdomyolysis Using Extracorporeal Blood Purification (CytoSorb®).

Blood Purif 2020 28;49(6):743-747. Epub 2020 Feb 28.

Department of Intensive Care, Erasmus Medical Centre, University Medical Center, Rotterdam, The Netherlands.

Rhabdomyolysis, if severe, can lead to acute kidney injury (AKI). Myoglobin is an iron and oxygen-binding protein that is freely filtered by the glomerulus. Precipitation of myoglobin in the nephrons' distal parts is responsible for tubular damage with AKI as a consequence. Extracorporeal clearance of myoglobin is conventionally attempted by the use of continuous renal replacement therapy (CRRT) with high cut-off dialysis membranes to limit the extent of the damage. We describe a case of a 56-year-old man with traumatic crush injury and a persistent source of muscle ischaemia unresponsive to high dose CRRT with EMiC-2 filter. Due to therapy failure, he was subsequently treated with the addition of a haemoadsorber (CytoSorb®) to the circuit. This reduced myoglobin and creatine kinase levels successfully despite ongoing tissue ischaemia. However, CytoSorb® was not enough to maintain microcirculatory perfusion, resulting in the eventual demise of the patient due to severity of the injury. Our report indicates that myoglobin was efficiently removed with CytoSorb® following exchange with the conventional high cut-off filter in continuous venovenous haemodialysis in severe traumatic rhabdomyolysis.
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http://dx.doi.org/10.1159/000505899DOI Listing
June 2021

Successful Treatment of Severe Hyperammonaemia with Ultra-High Dose Continuous Veno-Venous Haemodiafiltration.

Blood Purif 2019 3;48(3):283-285. Epub 2019 May 3.

Department of Intensive Care, Erasmus Medical Centre, Rotterdam, The Netherlands.

Hyperammonaemia is a severe condition and often requires a multimodal treatment regimen. Dialysis has been described as a potential treatment option, but currently it is not the standard of care. In this report, we describe a case of a 40-year-old postpartum woman who developed severe hyperammonaemia due to liver failure and acute kidney injury (AKI) combined with a large intra-abdominal haematoma producing nitrogen waste products. She was treated successfully with continuous veno-venous haemodiafiltration using an ultra-high effluent rate (100 mL/kg/h) and was discharged alive 32 days after the initial admission. Our report indicates that successful ammonia clearance in the setting of AKI can be obtained only by using this high effluent rate. This treatment modality should be considered in all patients with AKI and severe hyperammonaemia when other treatment modalities fail to lower ammonia levels within hours to prevent irreversible but preventable neurological damage.
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http://dx.doi.org/10.1159/000499829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114906PMC
February 2020

The aftermath of acute kidney injury: a narrative review of long-term mortality and renal function.

Crit Care 2019 Jan 24;23(1):24. Epub 2019 Jan 24.

Department of Internal Medicine, Division of Nephrology, and Transplantation, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.

Acute kidney injury (AKI) is a frequent complication of hospitalization and is associated with an increased risk of chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality. While AKI is a known risk factor for short-term adverse outcomes, more recent data suggest that the risk of mortality and renal dysfunction extends far beyond hospital discharge. However, determining whether this risk applies to all patients who experience an episode of AKI is difficult. The magnitude of this risk seems highly dependent on the presence of comorbid conditions, including cardiovascular disease, hypertension, diabetes mellitus, preexisting CKD, and renal recovery. Furthermore, these comorbidities themselves lead to structural renal damage due to multiple pathophysiological changes, including glomeruloscleroses and tubulointerstitial fibrosis, which can lead to the loss of residual capacity, glomerular hyperfiltration, and continued deterioration of renal function. AKI seems to accelerate this deterioration and increase the risk of death, CDK, and ESRD in most vulnerable patients. Therefore, we strongly advocate adequate hemodynamic monitoring and follow-up in patients susceptible to renal dysfunction. Additionally, other potential renal stressors, including nephrotoxic medications and iodine-containing contrast fluids, should be avoided. Unfortunately, therapeutic interventions are not yet available. Additional research is warranted and should focus on the prevention of AKI, identification of therapeutic targets, and provision of adequate follow-up to those who survive an episode of AKI.
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http://dx.doi.org/10.1186/s13054-019-2314-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346585PMC
January 2019

Discussion on "Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial".

Intensive Care Med 2018 02 9;44(2):273-274. Epub 2018 Jan 9.

Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1 Geb. A1, 48149, Münster, Germany.

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http://dx.doi.org/10.1007/s00134-017-5014-7DOI Listing
February 2018

Acute kidney injury after liver transplantation: Recent insights and future perspectives.

Best Pract Res Clin Gastroenterol 2017 Apr 12;31(2):161-169. Epub 2017 Apr 12.

Department of Adult Intensive Care, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.

Acute kidney injury (AKI) is a common postoperative complication after liver transplantation (LT). The occurrence of postoperative AKI after LT (Post-LT AKI) is associated with inferior patient and graft outcomes. Post-LT AKI is multifactorial in origin and has been related to the severity of liver disease, pre-LT renal dysfunction, graft quality, perioperative events and toxicity of immunosuppressive therapy. Furthermore it is thought that hepatic ischaemia reperfusion injury might be a driving force in the aetiology of post-LT AKI. Novel biomarkers for AKI are emerging and can be useful for early identification and characterization of AKI. There is a clear need for strategies aimed at preventing or treating post-LT AKI. Several pharmacological and non-pharmacological interventions have been studied, but so far failed to show any benefit in the prevention of post-LT AKI. Further studies are needed to develop and evaluate new interventions aimed at preventing post-LT AKI and improve patient outcomes.
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http://dx.doi.org/10.1016/j.bpg.2017.03.004DOI Listing
April 2017

Neutrophil Gelatinase-Associated Lipocalin as a Diagnostic Marker for Acute Kidney Injury in Oliguric Critically Ill Patients: A Post-Hoc Analysis.

Nephron 2016 10;134(2):81-88. Epub 2016 Aug 10.

Department of Intensive Care, Erasmus MC - University Medical Center, Rotterdam, The Netherlands.

Background: Oliguria occurs frequently in critically ill patients, challenging clinicians to distinguish functional adaptation from serum-creatinine-defined acute kidney injury (AKIsCr). We investigated neutrophil gelatinase-associated lipocalin (NGAL)'s ability to differentiate between these 2 conditions.

Methods: This is a post-hoc analysis of a prospective cohort of adult critically ill patients. Patients without oliguria within the first 6 h of admission were excluded. Plasma and urinary NGAL were measured at 4 h after admission. AKIsCr was defined using the AKI network criteria with pre-admission serum creatinine or lowest serum creatinine value during the admission as the baseline value. Hazard ratios for AKIsCr occurrence within 72 h were calculated using Cox regression and adjusted for risk factors such as sepsis, pre-admission serum creatinine, and urinary output. Positive predictive values (PPV) and negative predictive values (NPV) were calculated for the optimal cutoffs for NGAL.

Results: Oliguria occurred in 176 patients, and 61 (35%) patients developed AKIsCr. NGAL was a predictor for AKIsCr in univariate and multivariate analysis. When NGAL was added to a multivariate model including sepsis, pre-admission serum creatinine and lowest hourly urine output, it outperformed the latter model (plasma p = 0.001; urinary p = 0.048). Cutoff values for AKIsCr were 280 ng/ml for plasma (PPV 80%; NPV 79%), and 250 ng/ml for urinary NGAL (PPV 58%; NPV 78%).

Conclusions: NGAL can be used to distinguish oliguria due to the functional adaptation from AKIsCr, directing resources to patients more likely to develop AKIsCr.
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http://dx.doi.org/10.1159/000447602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296920PMC
July 2017

The cardiac surgery-associated neutrophil gelatinase-associated lipocalin (CSA-NGAL) score: A potential tool to monitor acute tubular damage.

J Thorac Cardiovasc Surg 2016 Jun 12;151(6):1476-81. Epub 2016 Feb 12.

Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Acute kidney injury (AKI), defined as a rise in serum creatinine (functional AKI), is a frequent complication after cardiac surgery. The expression pattern of acute tubular damage biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) has been shown to precede functional AKI and, therefore, may be useful to identify very early tubular damage. The term subclinical AKI represents acute tubular damage in the absence of functional AKI (biomarker positivity without a rise in serum creatinine) and affects hard outcome measures. This potentiates an tubular-damage-based identification of renal injury, which may guide clinical management, allowing for very early preventive-protective strategies. The aim of this paper was to review the current available evidence on NGAL applicability in adult cardiac surgery patients and combine this knowledge with the expert consensus of the authors to generate an NGAL based tubular damage score: The cardiac surgery-associated NGAL Score (CSA-NGAL score). The CSA-NGAL score might be the tool needed to improve awareness and enable interventions to possibly modify these detrimental outcomes. In boldly doing so, it is intended to introduce a different approach in study designs, which will undoubtedly expand our knowledge and will hopefully move the AKI biomarker field forward.
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http://dx.doi.org/10.1016/j.jtcvs.2016.01.037DOI Listing
June 2016

Targeting oliguria reversal in perioperative restrictive fluid management does not influence the occurrence of renal dysfunction: A systematic review and meta-analysis.

Eur J Anaesthesiol 2016 Jun;33(6):425-35

From the Department of Intensive Care, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Background: Interest in perioperative fluid restriction has increased, but it could lead to hypovolaemia. Urine output is viewed as a surrogate for renal perfusion and is frequently used to guide perioperative fluid therapy. However, the rationale behind targeting oliguria reversal - achieving and maintaining urine output above a previously defined threshold by additional fluid boluses - is often questioned.

Objective: We assessed whether restrictive fluid management had an effect on oliguria, acute renal failure (ARF) and fluid intake. We also investigated whether targeting oliguria reversal affected these parameters.

Design: Systematic review of randomised controlled trials with meta-analyses. We used the definitions of restrictive and conventional fluid management as provided by the individual studies.

Data Sources: We searched MEDLINE (1966 to present), EMBASE (1980 to present), and relevant reviews and articles.

Eligibility Criteria: We included randomised controlled trials with adult patients undergoing surgery comparing restrictive fluid management with a conventional fluid management protocol and also reporting the occurrence of postoperative ARF.

Results: We included 15 studies with a total of 1594 patients. There was insufficient evidence to associate restrictive fluid management with an increase in oliguria [restrictive 83/186 vs. conventional 68/230; odds ratio (OR) 2.07; 95% confidence interval (CI), 0.97 to 4.44; P = 0.06; I = 23.7%; Nstudies = 5]. The frequency of ARF in restrictive and conventional fluid management was 20/795 and 20/799, respectively (OR 1.07; 95% CI, 0.60 to 1.92; P = 0.8; I = 17.5%; Nstudies = 15). There was no statistically significant difference in ARF occurrence between studies targeting oliguria reversal and not targeting oliguria reversal (OR 0.31; 95% CI, 0.08 to 1.22; P = 0.088). Intraoperative fluid intake was 1.89 l lower in restrictive than in conventional fluid management when not targeting oliguria reversal (95% CI, -2.59 to -1.20 l; P < 0.001; I = 96.6%; Nstudies = 7), and 1.63 l lower when targeting oliguria reversal (95% CI, -2.52 to -0.74 l; P < 0.001; I = 96.6%; Nstudies = 6).

Conclusion: Our data suggest that, even though event numbers are small, perioperative restrictive fluid management does not increase oliguria or postoperative ARF while decreasing intraoperative fluid intake, irrespective of targeting reversal of oliguria or not.
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http://dx.doi.org/10.1097/EJA.0000000000000416DOI Listing
June 2016

Targeting Oliguria Reversal in Goal-Directed Hemodynamic Management Does Not Reduce Renal Dysfunction in Perioperative and Critically Ill Patients: A Systematic Review and Meta-Analysis.

Anesth Analg 2016 Jan;122(1):173-85

From the Departments of *Intensive Care, †Biostatistics, and ‡Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: We investigated whether resuscitation protocols to achieve and maintain urine output above a predefined threshold-including oliguria reversal as a target--prevent acute renal failure (ARF).

Methods: We performed a systematic review and meta-analysis using studies found by searching MEDLINE, EMBASE, and references in relevant reviews and articles. We included all studies that compared "conventional fluid management" (CFM) with "goal-directed therapy" (GDT) using cardiac output, urine output, or oxygen delivery parameters and reported the occurrence of ARF in critically ill or surgical patients. We divided studies into groups with and without oliguria reversal as a target for hemodynamic optimization. We calculated the combined odds ratio (OR) and 95% confidence intervals (CIs) using random-effects meta-analysis.

Results: We based our analyses on 28 studies. In the overall analysis, GDT resulted in less ARF than CFM (OR, 0.58; 95% CI, 0.44-0.76; P < 0.001; I = 34.3%; n = 28). GDT without oliguria reversal as a target resulted in less ARF (OR, 0.45; 95% CI, 0.34-0.61; P < 0.001; I = 7.1%; n = 7) when compared with CFM with oliguria reversal as a target. The studies comparing GDT with CFM in which the reversal of oliguria was targeted in both or in neither group did not provide enough evidence to conclude a superiority of GDT (targeting oliguria reversal in both protocols: OR, 0.63; 95% CI, 0.36-1.10; P = 0.09; I = 48.6%; n = 9, and in neither protocol: OR, 0.66; 95% CI, 0.37-1.16; P = 0.14; I = 20.2%; n = 12).

Conclusions: Current literature favors targeting circulatory optimization by GDT without targeting oliguria reversal to prevent ARF. Future studies are needed to investigate the hypothesis that targeting oliguria reversal does not prevent ARF in critically ill and surgical patients.
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http://dx.doi.org/10.1213/ANE.0000000000001027DOI Listing
January 2016

Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: systematic review and meta-analysis.

Crit Care 2014 Dec 5;18(6):660. Epub 2014 Dec 5.

Department of Intensive Care, Erasmus Medical Centre, Mailbox 2040, H603a, 3000CA, Rotterdam, The Netherlands.

Introduction: In Europe, vitamin D deficiency is highly prevalent varying between 40% and 60% in the healthy general adult population. The consequences of vitamin D deficiency for sepsis and outcome in critically ill patients remain controversial. We therefore systematically reviewed observational cohort studies on vitamin D deficiency in the intensive care unit.

Methods: Fourteen observational reports published from January 2000 to March 2014, retrieved from Pubmed and Embase, involving 9,715 critically ill patients and serum 25-hydroxyvitamin D3 (25 (OH)-D) concentrations, were meta-analysed.

Results: Levels of 25 (OH)-D less than 50 nmol/L were associated with increased rates of infection (risk ratio (RR) 1.49, 95% (confidence interval (CI) 1.12 to 1.99), P = 0.007), sepsis (RR 1.46, 95% (CI 1.27 to 1.68), P <0.001), 30-day mortality (RR 1.42, 95% (CI 1.00 to 2.02), P = 0.05), and in-hospital mortality (RR 1.79, 95% (CI 1.49 to 2.16), P <0.001). In a subgroup analysis of adjusted data including vitamin D deficiency as a risk factor for 30-day mortality the pooled RR was 1.76 (95% CI 1.37 to 2.26, P <0.001).

Conclusions: This meta-analysis suggests that vitamin D deficiency increases susceptibility for severe infections and mortality of the critically ill.
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http://dx.doi.org/10.1186/s13054-014-0660-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277653PMC
December 2014

Time of injury affects urinary biomarker predictive values for acute kidney injury in critically ill, non-septic patients.

BMC Nephrol 2013 Dec 9;14:273. Epub 2013 Dec 9.

Department of Intensive Care, Erasmus University Medical Center, Rotterdam, the Netherlands.

Background: The predictive value of acute kidney injury (AKI) urinary biomarkers may depend on the time interval following tubular injury, thereby explaining in part the heterogeneous performance of these markers that has been reported in the literature. We studied the influence of timing on the predictive values of tubular proteins, measured before the rise of serum creatinine (SCr) in critically ill, non-septic patients.

Methods: Seven hundred adult critically ill patients were prospectively included for urine measurements at four time-points prior to the rise in serum creatinine (T = 0, -16, -20 and -24 h). Patients with sepsis and or AKI at ICU entry were excluded. The urinary excretion of the proteins, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), which are up-regulated in the distal and proximal tubules, respectively, were measured as well as the constitutive cytoplasmatic enzymes, π- and α-glutathione-S-transferase (GST), which are released by the distal and proximal tubules, respectively.

Results: Five hundred and forty-three subjects were eligible for further analyses; however, 49 developed AKI in the first 48 h. Both NGAL (P = 0.001 at T = -24 vs. non-AKI patients) and KIM-1 (P < 0.0001 at T = 0 vs. non-AKI patients) concentrations gradually increased until AKI diagnosis, whereas π- and α-GST peaked at T = -24 before AKI (P = 0.006 and P = 0.002, respectively vs. non-AKI patients) and showed a rapid decline afterwards. The predictive values at T = -24 prior to AKI were modest for π- and α-GST, whereas NGAL sufficiently predicted AKI at T = -24 and its predictive power improved as the time interval to AKI presentation decreased (area under the receiver operating characteristic curve; AUC = 0.79, P < 0.0001). KIM-1 was a good discriminator at T = 0 only (AUC = 0.73, P < 0.0001).

Conclusions: NGAL, KIM-1, pi- and alpha-GST displayed unique and mutually incomparable time dependent characteristics during the development of non-sepsis related AKI. Therefore, the time-relationship between the biomarker measurements and the injurious event influences the individual test results.
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http://dx.doi.org/10.1186/1471-2369-14-273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878913PMC
December 2013

Novel biomarkers for the prediction of acute kidney injury in patients undergoing liver transplantation.

Biomark Med 2013 Dec;7(6):947-57

Department of Nephrology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Aim: Because of the delayed rise of serum creatinine concentrations, novel biomarkers such as NGAL, GST and KIM-1 are proposed to detect acute kidney injury (AKI). In this study we evaluated these biomarkers.

Materials & Methods: Twenty-six consecutive adult liver transplantations were evaluated. Markers were measured at four different time points during an intensive care unit admission.

Results: Plasma NGAL detected AKI with an optimal area under the curve at 8 h after admission (0.86; p = 0.004) and at 4 h after admission for urinary NGAL (0.80; p = 0.012). The other markers failed to detect AKI.

Conclusion: NGAL is a promising biomarker for detecting AKI in patients after liver transplantation.
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http://dx.doi.org/10.2217/bmm.13.91DOI Listing
December 2013

Acute normovolemic hemodilution in the pig is associated with renal tissue edema, impaired renal microvascular oxygenation, and functional loss.

Anesthesiology 2013 Aug;119(2):256-69

Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen.

Background: The authors investigated the impact of acute normovolemic hemodilution (ANH) on intrarenal oxygenation and its functional short-term consequences in pigs.

Methods: Renal microvascular oxygenation (µPO2) was measured in cortex, outer and inner medulla via three implanted optical fibers by oxygen-dependent quenching of phosphorescence. Besides systemic hemodynamics, renal function, histopathology, and hypoxia-inducible factor-1α expression were determined. ANH was performed in n = 18 pigs with either colloids (hydroxyethyl starch 6% 130/0.4) or crystalloids (full electrolyte solution), in three steps from a hematocrit of 30% at baseline to a hematocrit of 15% (H3).

Results: ANH with crystalloids decreased µPO2 in cortex and outer medulla approximately by 65% (P < 0.05) and in inner medulla by 30% (P < 0.05) from baseline to H3. In contrast, µPO2 remained unaltered during ANH with colloids. Furthermore, renal function decreased by approximately 45% from baseline to H3 (P < 0.05) only in the crystalloid group. Three times more volume of crystalloids was administered compared with the colloid group. Alterations in systemic and renal regional hemodynamics, oxygen delivery and oxygen consumption during ANH, gave no obvious explanation for the deterioration of µPO2 in the crystalloid group. However, ANH with crystalloids was associated with the highest formation of renal tissue edema and the highest expression of hypoxia-inducible factor-1α, which was mainly localized in distal convoluted tubules.

Conclusions: ANH to a hematocrit of 15% statistically significantly impaired µPO2 and renal function in the crystalloid group. Less tissue edema formation and an unimpaired renal µPO2 in the colloid group might account for a preserved renal function.
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http://dx.doi.org/10.1097/ALN.0b013e31829bd9bcDOI Listing
August 2013

Plasma NGAL similarly predicts acute kidney injury in sepsis and nonsepsis.

Biomark Med 2013 Jun;7(3):415-21

Department of Intensive Care, Erasmus University Medical Center, H619, PO Box 2040, 3000 CA Rotterdam, The Netherlands.

Aim: Plasma NGAL is released in sepsis irrespective of acute kidney injury (AKI). The current study investigated the effect of sepsis on the diagnostic value of NGAL for AKI.

Materials & Methods: In 700 intensive care unit admissions, NGAL was measured at four time points (<24 h) following admission.

Results: In total, 663 admissions were included in the final analysis, of which 80 patients had sepsis (12%). AKI occurred in 22% of the patients without and 66% with sepsis. NGAL levels were higher in non-AKI patients with sepsis compared with non-AKI patients without sepsis at all time points (p = 0.03 or lower). In patients with AKI a similar difference was observed (p < 0.001). The area under the curve for AKI was unaffected by the presence of sepsis (0.76 in sepsis vs 0.78 in nonsepsis; p = 0.72); however, the optimal test cutoff values were higher in the former.

Conclusion: Sepsis enhances the production of plasma NGAL in critically ill adult patients irrespective of the presence of AKI. However, the diagnostic test accuracy for AKI is unaffected by sepsis, although optimal cutoff values are elevated.
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http://dx.doi.org/10.2217/bmm.13.5DOI Listing
June 2013

Determinants of renal function at hospital discharge of patients treated with renal replacement therapy in the intensive care unit.

J Crit Care 2013 Apr 21;28(2):126-32. Epub 2012 Dec 21.

Department of Nephrology, Erasmus Medical Center, Rotterdam, The Netherlands.

Purpose: Identification of risk factors for impaired renal function at hospital discharge in critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT).

Methods: A single-center retrospective cohort study was performed evaluating demographic and clinical parameters as potential risk factors for a modest to severely impaired renal function at hospital discharge in patients with AKI requiring RRT in the intensive care unit.

Results: Of the 353 patients in our cohort, 90 (25.5%) patients had pre-existing chronic kidney disease (CKD). An estimated glomerular filtration rate (eGFR) ≤60 mL min(-1) 1.73 m(-2) at hospital discharge occurred in 64.0% of which 63.7% without known renal impairment before hospital admission and 8.2% of all cases left the hospital dialysis-dependent. Multivariable logistic regression showed that age (OR = 1.051, P < .001), serum creatinine concentration at start of RRT (OR = 1.004, P < .001) and administration of iodine-containing contrast fluid (OR = 0.830, P = .045) were associated with an eGFR ≤60 mL min(-1) 1.73 m(-2). Furthermore, a medical history of CKD (OR = 5.865, P < .001) was associated with dialysis dependence.

Conclusions: Elderly and patients with pre-existing CKD are at a high risk for modest to severely impaired renal function at hospital discharge after AKI requiring RRT.
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http://dx.doi.org/10.1016/j.jcrc.2012.10.013DOI Listing
April 2013

Biomarkers for the prediction of acute kidney injury: a narrative review on current status and future challenges.

Clin Kidney J 2012 Apr;5(2):102-108

Department of Intensive Care, Erasmus University Medical Center, Rotterdam, The Netherlands.

Acute kidney injury (AKI) is strongly associated with increased morbidity and mortality in critically ill patients. Efforts to change its clinical course have failed because clinically available therapeutic measures are currently lacking, and early detection is impossible with serum creatinine (SCr). The demand for earlier markers has prompted the discovery of several candidates to serve this purpose. In this paper, we review available biomarker studies on the early predictive performance in developing AKI in adult critically ill patients. We make an effort to present the results from the perspective of possible clinical utility.
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http://dx.doi.org/10.1093/ckj/sfs008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341843PMC
April 2012

Urinary Neutrophil Gelatinase-Associated Lipocalin Measured on Admission to the Intensive Care Unit Accurately Discriminates between Sustained and Transient Acute Kidney Injury in Adult Critically Ill Patients.

Nephron Extra 2011 Jan 4;1(1):9-23. Epub 2011 Aug 4.

Departments of Intensive Care, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: First we aimed to evaluate the ability of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin-C (CyC) in plasma and urine to discriminate between sustained, transient and absent acute kidney injury (AKI), and second to evaluate their predictive performance for sustained AKI in adult intensive care unit (ICU) patients.

Methods: A prospective cohort study of 700 patients was studied. Sample collection was performed over 8 time points starting on admission.

Results: After exclusion 510 patients remained for the analysis. All biomarkers showed significant differentiation between sustained and no AKI at all time points (p ≤ 0.0002) except for urine CyC (uCyC) on admission (p = 0.06). Urine NGAL (uNGAL) was the only biomarker significantly differentiating sustained from transient AKI on ICU admission (p = 0.02). Individually, uNGAL performed better than the other biomarkers (area under the curves, AUC = 0.80, 95% confidence interval, CI = 0.72-0.88) for the prediction of sustained AKI. The combination with plasma NGAL (pNGAL) showed a nonsignificant improvement (AUC = 0.83, 95% CI = 0.75-0.91). The combination of individual markers with a model of clinical characteristics (MDRD eGFR, HCO(3) (-) and sepsis) did not improve its performance significantly. However, the integrated discrimination improvement showed significant improvement when uNGAL was added (p = 0.04).

Conclusions: uNGAL measured on ICU admission differentiates patients with sustained AKI from transient or no-AKI patients. Combining biomarkers such as pNGAL, uNGAL and plasma CyC with clinical characteristics adds some value to the predictive model.
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http://dx.doi.org/10.1159/000330428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290847PMC
January 2011

Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients.

Am J Respir Crit Care Med 2011 Apr 8;183(7):907-14. Epub 2010 Oct 8.

Department of Intensive Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

Rationale: Measured at intensive care unit admission (ICU), the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) for severe acute kidney injury (AKI) is unclear.

Objectives: To assess the ability of plasma and urine NGAL to predict severe AKI in adult critically ill patients.

Methods: Prospective-cohort study consisting of 632 consecutive patients.

Measurements And Main Results: Samples were analyzed by Triage immunoassay for NGAL expression. The primary outcome measure was occurrence of AKI based on Risk-Injury-Failure (RIFLE) classification during the first week of ICU stay. A total of 171 (27%) patients developed AKI. Of these 67, 48, and 56 were classified as RIFLE R, I, and F, respectively. Plasma and urine NGAL values at ICU admission were significantly related to AKI severity. The areas under the receiver operating characteristic curves for plasma and urine NGAL were for RIFLE R (0.77 ± 0.05 and 0.80 ± 0.04, respectively), RIFLE I (0.80 ± 0.06 and 0.85 ± 0.04, respectively), and RIFLE F (0.86 ± 0.06 and 0.88 ± 0.04, respectively) and comparable with those of admission estimated glomerular filtration rate (eGFR) (0.84 ± 0.04, 0.87 ± 0.04, and 0.92 ± 0.04, respectively). Plasma and urine NGAL significantly contributed to the accuracy of the "most efficient clinical model" with the best four variables including eGFR, improving the area under the curve for RIFLE F prediction to 0.96 ± 0.02 and 0.95 ± 0.01. Serial NGAL measurements did not provide additional information for the prediction of RIFLE F.

Conclusions: NGAL measured at ICU admission predicts the development of severe AKI similarly to serum creatinine-derived eGFR. However, NGAL adds significant accuracy to this prediction in combination with eGFR alone or with other clinical parameters and has an interesting predictive value in patients with normal serum creatinine.
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http://dx.doi.org/10.1164/rccm.200908-1214OCDOI Listing
April 2011