Urinary biomarkers predict progression and adverse outcomes of acute kidney injury in critical illness

Duff, Stephen; Irwin, Ruairí; Côté, Jean-Maxime; Redahan, Lynn; McMahon, Blaithin A.; Marsh, Brian; Nichol, Alistair; Holden, Sinéad; Doran, Peter; Murray, Patrick

doi:10.1093/ndt/gfab263

Cited by 11 publications

(8 citation statements)

References 23 publications

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“…On the other hand, elevations of IL-1β serum concentrations in human sepsis can be mild [ 174 ] or irregular [ 175 ], are dependent on the phase of septic state [ 176 ], and, in addition, the kidney has a role in IL-1β removal in sepsis as long as diuresis is preserved [ 177 ]. Recently, a study reported the association of urinary IL-18 protein concentrations with AKI progression in critically ill patients at the intensive care unit [ 178 ] and a meta-analysis of biomarkers in S-AKI reported a correlation of urinary IL-18 and the diagnosis of S-AKI [ 179 ].…”

Section: Inflammasome Components In Akimentioning

confidence: 99%

Involvement of Inflammasome Components in Kidney Disease

et al. 2022

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Inflammasomes are multiprotein complexes with an important role in the innate immune response. Canonical activation of inflammasomes results in caspase-1 activation and maturation of cytokines interleukin-1β and -18. These cytokines can elicit their effects through receptor activation, both locally within a certain tissue and systemically. Animal models of kidney diseases have shown inflammasome involvement in inflammation, pyroptosis and fibrosis. In particular, the inflammasome component nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) and related canonical mechanisms have been investigated. However, it has become increasingly clear that other inflammasome components are also of importance in kidney disease. Moreover, it is becoming obvious that the range of molecular interaction partners of inflammasome components in kidney diseases is wide. This review provides insights into these current areas of research, with special emphasis on the interaction of inflammasome components and redox signalling, endoplasmic reticulum stress, and mitochondrial function. We present our findings separately for acute kidney injury and chronic kidney disease. As we strictly divided the results into preclinical and clinical data, this review enables comparison of results from those complementary research specialities. However, it also reveals that knowledge gaps exist, especially in clinical acute kidney injury inflammasome research. Furthermore, patient comorbidities and treatments seem important drivers of inflammasome component alterations in human kidney disease.

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Section: Inflammasome Components In Akimentioning

confidence: 99%

Involvement of Inflammasome Components in Kidney Disease

et al. 2022

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“…Interestingly, that association was maintained in the adjusted model, similar to previously published data. 19 This study was not designed to confirm the clinical benefit of NGAL testing in optimizing management and outcomes following an AKI episode. However, as shown by the post-NGAL questionnaire, the use of that novel biomarker in clinics was globally appreciated by consultant nephrologists.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, that association was maintained in the adjusted model, similar to previously published data. 19 …”

Section: Discussionmentioning

confidence: 99%

Clinical Implementation of NGAL Testing to Improve Diagnostic Assessment of AKI Episodes in a Canadian Center

Côté

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Éthier

et al. 2022

Can J Kidney Health Dis

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Background: The differential diagnosis of acute kidney injury (AKI) episodes is often challenging. Novel AKI biomarkers have shown their utility to improve prognostic prediction and diagnostic assessment in various research populations but their implementation in standard clinical practice is still rarely reported. Objective: To report the differential diagnostic ability and associated clinical utility of the neutrophil gelatinase-associated lipocalin (NGAL) testing in a real-life setting of a heterogeneous AKI population. Design: This is a retrospective cohort study combined with a clinical audit using questionnaires distributed to consultant nephrologists following NGAL results. Setting: The first 250 consecutive patients with a confirmed AKI where an NGAL test (plasma NGAL [pNGAL] or urine NGAL [uNGAL]) was ordered from a large academic center in Montreal, Canada from January 2021 to August 2021. Patients: Patients were classified into 3 groups based on the final AKI etiology category (functional, intrarenal, and postrenal) following definitive adjudication by 2 independent nephrologists. Methods: The ability of plasma NGAL (pNGAL), urine NGAL (uNGAL), and uNGAL-to-creatinine ratio (uNGAL/Cr) to discriminate intrarenal from functional AKI etiologies was compared to standard urine chemistry (FENa) and proteinuria. A logistic regression was used to evaluate the association between intrarenal AKI and increased biomarker levels. The overall clinical utility and appreciation of the NGAL test was evaluated using a questionnaire completed prospectively by the consultant nephrologist at the time of receiving the NGAL result. The NGAL results were prospectively available to clinicians with a median time of 2.9 (1.3-7.4) hours from the initial order. Results: A total of 214 uNGAL and 44 pNGAL were ordered from 100 functional, 139 intrarenal and 11 postrenal AKI episodes after final adjudication. The discriminative ability of FENa (AUC 0.68 [95% CI: 0.61-0.75]) was lower than uNGAL (AUC 0.80 [95% CI: 0.73-0.86]) and uNGAL/Cr (AUC 0.83 [95% CI: 0.77-0.88]) but better than pNGAL (AUC 0.66 [95% CI: 0.48-0.85]). According to consultant nephrologists, the NGAL testing has led to a change in clinical management in 42% of cases. Limitations: Data reported came from a single center and NGAL was reserved for more complex cases, which limits generalizability. No biopsy has been performed for most AKI cases as the final adjudication was based on a retrospective review of the hospitalization episode. Conclusions: Neutrophil gelatinase-associated lipocalin testing can be successfully integrated as part of the diagnostic workup for AKI in clinical practice. The integration of tubular damage biomarkers to functional biomarkers can further improve the differential diagnostic assessment. However, the impact of such biomarkers on AKI management and associated outcomes still needs further validation.

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“…The urinary panel consisted of NGAL, albumin, KIM-1, L-FABP, and cystatin C. Thirty-eight percent of the patients developed AKI, 215 (84%) during the first 48 h and 42 (16%) after 48 h but before seven days [ 117 ]. A secondary analysis of the DAMAGE study assessed 14 urinary biomarkers [ 118 ]. In the group of patients that presented AKI stage 1 or 2 within 48 h after ICU admission, eight biomarkers were associated with progression to worse AKI stages, KRT, or death in 7 days.…”

Section: Biomarker Panelmentioning

confidence: 99%