Original Title: Avis - Détection de l’insuffisance rénale aigüe par dosage de la NGAL

Authors' objectives: A request for including a new test in the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the Répertoire) was submitted by the Centre hospitalier de l'Université de Montréal and forwarded to the Institut national d'excellence en santé et en services sociaux (INESSS) via the mechanism for evaluating new medical biology assays. The context of this mandate is the possible addition of the assay of NGAL (neutrophil gelatinase-associated lipocalin), as a biomarker of renal tubular damage, to the standard tests currently used for the early diagnosis of acute kidney injury (AKI). The Ministère de la Santé et des Services sociaux (MSSS) therefore deems it necessary that the relevance of using the NGAL assay to detect AKI be assessed. The request submitted to INESSS is that NGAL be measured as a biomarker of renal tubular damage in patients at risk for AKI for the early prediction of its occurrence or worsening, to determine its etiology once already diagnosed, and to guide patient management. During AKI, damaged tubular cells release neutrophil gelatinase-associated lipocalin (NGAL). NGAL production is therefore significantly increased in the urine and blood within the first few hours after renal insult. The main advantage of this biomarker is that it can be measured well before creatinine and is indicative of renal tubular damage. Furthermore, NGAL measurements are not affected by factors such as diuretic use, blood volume, metabolic alkalosis, etc. On the other hand, NGAL is also released during a systemic or urinary tract infection, even if there is no renal damage, which can lead to false-positive results. The proposed technique consists in quantitatively measuring urine and plasma NGAL levels using an immunoturbidimetric assay.

Authors' results and conclusions: RESULTS: The overall scientific data show that the performance of the NGAL assay is acceptable only in certain patient subpopulations. Indeed, the test appears to have predictive value for AKI in patients who have undergone a coronary intervention during which a contrast agent was injected, in patients with hepatorenal syndrome or sepsis, and in pediatrics. However, the level of scientific evidence is moderate or even insufficient for diagnosing hepatorenal syndrome. The NGAL assay also appears to have diagnostic value for distinguishing prerenal from intrarenal AKI in hospitalized patients and those with hepatorenal syndrome. However, the small amount of data for these indications calls for caution regarding their clinical validity. Thus, the identified studies that have evaluated the efficacy of the NGAL detection test for the prediction and differential diagnosis of AKI are insufficient to rule on its costeffectiveness in the Québec context. Moreover, since no data that could be used to assess its clinical utility were found, INESSS cannot evaluate the cost-effectiveness of this detection test in the identified populations. Since the NGAL detection test would be added to the current tests, additional costs of approximately $167,100 are anticipated for the 3 years following its possible inclusion in the Repertoire. In short, the scientific evidence is insufficient to recommend routine use of this test to assess the risk of AKI in hospitalized patients. In addition, further studies are needed to demonstrate how this test can provide added value (incremental benefit) to the existing standard care. ISSUE, FINDINGS, AND UNCERTAINTIES: The experts pointed out that there are relatively few tools available for the early detection of AKI or for identifying patients who will progress from prerenal AKI to intrarenal AKI, and those that are available do not provide the expected clinical performance or do not perform as well as they should. Furthermore, they do not expect any single marker to influence health outcomes. They believe that no single marker can perfectly predict AKI or guide its management. In specific clinical situations where the renal insult is known and isolated, a normal NGAL test result could alter management and potentially improve the patient’s clinical outcomes. On the other hand, there remains the risk that an equivocal result on this test could prolong the hospital stay and lead to further tests. However, these parameters are difficult to assess and quantify. Since hospitalized patients who might benefit from the NGAL assay are referred to nephrology for a consultation, access to the test should be limited to nephrologists and intensivist internists, at least in the large urban centres. However, the experts are concerned about access to these specialists in the regions. To address this, access to the test could be expanded to include critical care physicians.

Authors' recommendations: RESULTS: The overall scientific data show that the performance of the NGAL assay is acceptable only in certain patient subpopulations. Indeed, the test appears to have predictive value for AKI in patients who have undergone a coronary intervention during which a contrast agent was injected, in patients with hepatorenal syndrome or sepsis, and in pediatrics. However, the level of scientific evidence is moderate or even insufficient for diagnosing hepatorenal syndrome. The NGAL assay also appears to have diagnostic value for distinguishing prerenal from intrarenal AKI in hospitalized patients and those with hepatorenal syndrome. However, the small amount of data for these indications calls for caution regarding their clinical validity. Thus, the identified studies that have evaluated the efficacy of the NGAL detection test for the prediction and differential diagnosis of AKI are insufficient to rule on its costeffectiveness in the Québec context. Moreover, since no data that could be used to assess its clinical utility were found, INESSS cannot evaluate the cost-effectiveness of this detection test in the identified populations. Since the NGAL detection test would be added to the current tests, additional costs of approximately $167,100 are anticipated for the 3 years following its possible inclusion in the Repertoire. In short, the scientific evidence is insufficient to recommend routine use of this test to assess the risk of AKI in hospitalized patients. In addition, further studies are needed to demonstrate how this test can provide added value (incremental benefit) to the existing standard care. ISSUE, FINDINGS, AND UNCERTAINTIES: The experts pointed out that there are relatively few tools available for the early detection of AKI or for identifying patients who will progress from prerenal AKI to intrarenal AKI, and those that are available do not provide the expected clinical performance or do not perform as well as they should. Furthermore, they do not expect any single marker to influence health outcomes. They believe that no single marker can perfectly predict AKI or guide its management. In specific clinical situations where the renal insult is known and isolated, a normal NGAL test result could alter management and potentially improve the patient’s clinical outcomes. On the other hand, there remains the risk that an equivocal result on this test could prolong the hospital stay and lead to further tests. However, these parameters are difficult to assess and quantify. Since hospitalized patients who might benefit from the NGAL assay are referred to nephrology for a consultation, access to the test should be limited to nephrologists and intensivist internists, at least in the large urban centres. However, the experts are concerned about access to these specialists in the regions. To address this, access to the test could be expanded to include critical care physicians.

Authors' methods: The evaluation approach included a review of the scientific literature, a search of the grey literature, and consultations with experts and other stakeholders. The methodology was deployed around five evaluation questions concerning the ability to predict the occurrence of AKI, the impact of the NGAL test on management and quality of life, and the cost-effectiveness of measuring this protein as an early diagnostic marker for AKI. Subsequently, a budget impact analysis considering the costs related to including the assay in the Répertoire was performed. The costs were projected over a three-year time horizon from a healthcare system perspective. All scientific, contextual, and experiential data were interpreted and assessed using a synthesis grid to guide the deliberative process of the Comité scientifique permanent (CDP) – Approches Diagnostiques et dépistage for the development of recommendations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/detection-de-linsuffisance-renale-aiguee-par-dosage-de-la-ngal.html

Year Published: 2023

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/detection-de-linsuffisance-renale-aiguee-par-dosage-de-la-ngal.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)