Biomarkers for prediction of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis

Klein, Sebastian; Brandtner, Anna; Lehner, Georg; Ulmer, Hanno; Bagshaw, Sean M.; Wiedermann, Christian J.; Joannidis, Michael

doi:10.1007/s00134-018-5126-8

Cited by 142 publications

(117 citation statements)

References 103 publications

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“…The safety concern involves the risk of exposing critically ill patients to AKI-related complications (severe fluid overload, uremia, hyperkalemia, and metabolic acidosis). Furthermore, recent advancements in novel biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], cystatin, calprotectin, and [insulin-like growth factor-binding protein 7] × [tissue inhibitor of metalloproteinase 2]) may provide insights into AKI patient triage, accelerating AKI or acute tubular necrosis (ATN) diagnosis and improving AKI prognosis and RRT prediction [16][17][18][19][20][21][22]. Moreover, biomarker-guided AKI intervention may lead to improved outcomes [23].…”

Section: Introductionmentioning

confidence: 99%

Comparison between watchful waiting strategy and early initiation of renal replacement therapy in the critically ill acute kidney injury population: an updated systematic review and meta-analysis

Chen

Lee

Kuo

et al. 2020

Ann. Intensive Care

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Background: The optimal timing of renal replacement therapy (RRT) initiation is debatable. Many articles in this field enrolled trials not based on acute kidney injury. The safety of the watchful waiting strategy has not been fully discussed, and late RRT initiation criteria vary across studies. The effect of early RRT initiation in the AKI population with high plasma neutrophil gelatinase-associated lipocalin (NGAL) has not been examined yet. Methods:In accordance with PRISMA guidelines, the PubMed, Embase, and Cochrane databases were systemically searched for randomized controlled trials (RCTs). Trials not conducted in the AKI population were excluded. Data of study characteristics, primary outcome (all-cause mortality), and related secondary outcomes [mechanical ventilation (MV) days, length of hospital stay, RRT days, and length of ICU stay] were extracted. The outcomes were compared between early and late RRT groups by estimating the pooled odds ratio (OR) for binary outcomes and the weighted mean difference for continuous outcomes. Prospective trials were also examined and analyzed using the same method.Results: Nine RCTs with 1938 patients were included. Early RRT did not provide a survival benefit (pooled OR, 0.88; 95% confidence interval [CI] 0.62-1.27). However, the early RRT group had significantly fewer MV days (pooled mean difference, − 3.98 days; 95% CI − 7.81 to − 0.15 days). Subgroup analysis showed that RCTs enrolling the surgical population (P = .001) and the AKI population with high plasma NGAL (P = .031) had favorable outcomes regarding RRT days in the early initiation group. Moreover, 6 of 9 RCTs were selected for examining the safety of the watchful waiting strategy, and no significant differences were found in primary and secondary outcomes between the early and late RRT groups. Conclusions:Overall, early RRT initiation did not provide a survival benefit, but a possible benefit of fewer MV days was detected. Early RRT might also provide the benefit of shorter MV or RRT support in the surgical population and in AKI patients with high plasma NGAL. Depending on the conventional indication for RRT initiation, the watchful waiting strategy is safe on the basis of all primary and secondary outcomes.

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Section: Introductionmentioning

confidence: 99%

Comparison between watchful waiting strategy and early initiation of renal replacement therapy in the critically ill acute kidney injury population: an updated systematic review and meta-analysis

Chen

Lee

Kuo

et al. 2020

Ann. Intensive Care

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“…In spite of these limitations, most AKI biomarker studies report discriminant statistics. Consequently, Klein et al had to rely on AUCs as the common denominator to compare the performance of biomarkers for prediction of the need for RRT [4]. This has some validity, as the future need for RRT is contingent on renal failure that may already be present at the time of biomarker sampling.…”

Section: Discrimination Vs Risk Stratificationmentioning

confidence: 99%

“…Biomarkers of kidney damage have been extensively studied for their accuracy in early diagnosis of AKI. Their role in distinguishing patients with high versus low likelihood of renal recovery is less clear.In a recent article in this journal, Klein et al report the results of a systematic review which meta-analyzed the ability of biomarkers to identify patients with and without subsequent need for RRT [4]. The largest body of evidence exists for NGAL that showed only fair discrimination.…”

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AKI biomarkers are poor discriminants for subsequent need for renal replacement therapy, but do not disqualify them yet

Grooth

Parienti²,

Schetz

2018

Intensive Care Med

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An important controversy and uncertainty still exists around the optimal timing to start renal replacement therapy (RRT) in ICU patients with acute kidney injury (AKI) that do not present with absolute indications for RRT. Recent RCT's comparing "early" and "late" initiation of RRT provided contradictory messages, potentially related to the difference in study population, design (single-versus multicenter), illness severity, modality of RRT and definitions of early and late [1][2][3]. Reliable quantitative tools that predict whether AKI patients will recover would allow avoiding unnecessary RRT. Moreover, by identifying a more severe subset of patients with AKI, an evaluation of the advantages and disadvantages of early starting of RRT could be performed in an enriched population that would probably need RRT sooner or later during their ICU stay. Biomarkers of kidney damage have been extensively studied for their accuracy in early diagnosis of AKI. Their role in distinguishing patients with high versus low likelihood of renal recovery is less clear.In a recent article in this journal, Klein et al. report the results of a systematic review which meta-analyzed the ability of biomarkers to identify patients with and without subsequent need for RRT [4]. The largest body of evidence exists for NGAL that showed only fair discrimination. The markers of cell cycle arrest, the product of [TIMP-2]* , showed the best discrimination with a pooled area under the ROC curve (AUROC) of 0.857 (0.789-0.925). This result (based on four studies with 280 patients and 50 RRT received) was rather homogeneous (I 2 = 24.9%), increasing the confidence of this estimate.On the other hand, the homogeneity of this result probably relates to the more homogeneous patient populations with clearly defined insult (mainly surgery) in the included studies whereas studies on NGAL included more heterogeneous populations where the timing of the renal insult is less clear. A summary of the most important findings can be found in the Supplementary Table (Table S). This enormous amount of work, for which the authors are to be congratulated, cannot overcome the limitations of the included original studies. The most important limitation is the absence of a gold standard for the endpoint (RRT): substantial practice variation exists in the initiation of RRT and many of the included studies did not use predefined indications. In 85% of the studies, the prediction of RRT was not the main purpose. The study populations are heterogeneous and not all patients had AKI at the time of biomarker sampling, which could explain the large variability of RRT need (Table S). The delay between sampling of the biomarker and the start of RRT, when reported, was variable, increasing the observed betweenstudy heterogeneity and biomarker performance (Fig. 1). Biomarkers were not compared with readily available clinical parameters nor was their additive value assessed, for example with the net reclassification index.Finally, we share the authors' interpretation that the use of bi...

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“…6 Although several biomarkers have been used for detecting and treating AKI recently, these indicators are not widely accepted because the results are often contradictory. 7 It has been widely accepted that both diffusion-weighted (DW) 8,9 and blood oxygenation level-dependent (BOLD) 10,11 magnetic resonance imaging (MRI) can serve as reliable indicators for focal severe regional ischemia before renal damage occurs. BOLD can be used to evaluate the condition of renal oxygen metabolism, while DWI can be used to reflect the diffusion level of water molecules in tissues.…”

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confidence: 99%

Comparison of blood oxygen level‐dependent imaging and diffusion‐weighted imaging in early diagnosis of acute kidney injury in animal models

Zhang

Wang

et al. 2019

Magnetic Resonance Imaging

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Background Early diagnosis of acute kidney injury (AKI) has clinical importance. Current methods are neither adequately sensitive nor specific. Blood oxygen level‐dependent (BOLD) imaging and diffusion‐weighted imaging (DWI) may help to assess AKI in the early phase. Purpose To investigate the feasibility of BOLD imaging and DWI in the assessment of AKI and compare the sensitivities of both techniques in early detection of renal damage. Study Type Prospective animal study. Animal Model Thirty New Zealand white rabbits. Field Strength/Sequence 3 T clinical MRI/BOLD and DWI. Assessment Thirty rabbits were divided into three groups (severe AKI group, mild AKI group, and control group). Transarterial renal embolization with different doses of microspheres was performed to create severe and mild AKI disease models. All the MRI scans of kidneys were conducted within 2 hours after the embolization procedure. Histological examinations with hematoxylin and eosin staining were performed to validate renal damage. Statistical Tests Analysis of variance (ANOVA) for comparisons between groups, and paired t‐test for tests within the same group. P < 0.05 was considered statistically significant. Results Both R2* and apparent diffusion coefficient (ADC) showed significant differences between the severe AKI group (56.34 ± 3.45 s‐1 for R2*, 1.14 ± 0.23 mm2/s for ADC) and the control group (28.24 ± 2.26 s‐1 for R2*, 1.94 ± 0.33 mm2/s for ADC, both P < 0.01). However, the ADC values did not show significant differences (P = 0.41) between mild AKI group (1.88 ± 0.31 mm2/s for ADC) and the control group (1.94 ± 0.33 mm2/s for ADC), while R2* was still useful in differentiating the two groups (52.32 ± 4.1 s‐1 vs. 28.24 ± 2.26 s‐1 for R2*, P < 0.01). The histopathologic results were found to be correlated with MRI findings. Data Conclusion BOLD contrast and DW images are both effective in detecting AKI noninvasively, but BOLD imaging is more sensitive in early detection of mild ischemia than DWI. Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:719–724.

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Biomarkers for prediction of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis

Cited by 142 publications

References 103 publications

Comparison between watchful waiting strategy and early initiation of renal replacement therapy in the critically ill acute kidney injury population: an updated systematic review and meta-analysis

Comparison between watchful waiting strategy and early initiation of renal replacement therapy in the critically ill acute kidney injury population: an updated systematic review and meta-analysis

AKI biomarkers are poor discriminants for subsequent need for renal replacement therapy, but do not disqualify them yet

Comparison of blood oxygen level‐dependent imaging and diffusion‐weighted imaging in early diagnosis of acute kidney injury in animal models

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