Routinely, kidney dysfunction and decreased glomerular filtration rate (GFR) are diagnosed by the evaluation of changes in the serum creatinine (SCr) and blood urea nitrogen (BUN) concentrations. However, neither of these tests is sensitive or specific enough for the early diagnosis of impaired kidney function because they are both affected by other renal and nonrenal factors. Furthermore, kidney injury can be present in the absence of kidney dysfunction. Renal reserve enables normal GFR even when nephrons are damaged. Renal biomarkers, especially those present in urine, may be useful for the study of both acute and chronic nephropathies. The aim of this review is to describe the current status of urinary biomarkers as diagnostic tools for kidney injury in dogs with particular focus on acute kidney injury (AKI). The International Renal Interest Society (IRIS) canine AKI grading system and the implementation of urinary biomarkers in this system also are discussed. The discovery of novel urinary biomarkers has emerged from hypotheses about the pathophysiology of kidney injury, but few proteomic urine screening approaches have been described in dogs. Lack of standardization of biomarker assays further complicates the comparison of novel canine urinary biomarker validation results among studies. Future research should focus on novel biomarkers of renal origin and evaluate promising biomarkers in different clinical conditions. Validation of selected urinary biomarkers in the diagnosis of canine kidney diseases must include dogs with both renal and nonrenal diseases to evaluate their sensitivity, specificity as well as their negative and positive predictive values.

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BackgroundAcute kidney injury (AKI) occurs frequently and adversely affects patient and kidney outcomes, especially when its severity increases from stage 1 to stages 2 or 3. Early interventions may counteract such deterioration, but this requires early detection. Our aim was to evaluate whether the novel renal damage biomarker urinary chitinase 3-like protein 1 (UCHI3L1) can detect AKI stage ≥2 more early than serum creatinine and urine output, using the respective Kidney Disease | Improving Global Outcomes (KDIGO) criteria for definition and classification of AKI, and compare this to urinary neutrophil gelatinase-associated lipocalin (UNGAL).MethodsThis was a translational single-center, prospective cohort study at the 22-bed surgical and 14-bed medical intensive care units (ICU) of Ghent University Hospital. We enrolled 181 severely ill adult patients who did not yet have AKI stage ≥2 based on the KDIGO criteria at time of enrollment. The concentration of creatinine (serum, urine) and CHI3L1 (serum, urine) was measured at least daily, and urine output hourly, in the period from enrollment till ICU discharge with a maximum of 7 ICU-days. The concentration of UNGAL was measured at enrollment. The primary endpoint was the development of AKI stage ≥2 within 12 h after enrollment.ResultsAfter enrollment, 21 (12 %) patients developed AKI stage ≥2 within the next 7 days, with 6 (3 %) of them reaching this condition within the first 12 h. The enrollment concentration of UCHI3L1 predicted the occurrence of AKI stage ≥2 within the next 12 h with a good AUC-ROC of 0.792 (95 % CI: 0.726–0.849). This performance was similar to that of UNGAL (AUC-ROC of 0.748 (95 % CI: 0.678–0.810)). Also, the samples collected in the 24-h time frame preceding diagnosis of the 1st episode of AKI stage ≥2 had a 2.0 times higher (95 % CI: 1.3–3.1) estimated marginal mean of UCHI3L1 than controls. We further found that increasing UCHI3L1 concentrations were associated with increasing AKI severity.ConclusionsIn this pilot study we found that UCHI3L1 was a good biomarker for prediction of AKI stage ≥2 in adult ICU patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1192-x) contains supplementary material, which is available to authorized users.

BackgroundA common and serious complication of cardiac surgery prompting early detection and intervention is cardiac surgery-associated acute kidney injury (CSA-AKI). Urinary chitinase 3-like protein 1 (UCHI3L1) was found to predict AKI associated with critical illness in adults. Our aims were therefore to evaluate whether UCHI3L1 can also be used to predict AKI associated with elective cardiac surgery in adults, and to compare this predictive ability with that of urinary neutrophil gelatinase-associated lipocalin (UNGAL), more frequently assessed early serum creatinine (SCr) measurements, and various two-biomarker panels.MethodsThis was a single-centre prospective cohort study at the eight-bed cardiac surgery ICU of Ghent University Hospital. AKI was diagnosed and classified according to the Kidney Disease|Improving Global Outcomes definitions for the diagnosis and staging of AKI, which are based on SCr and urine output (UO). Of the 211 enrolled elective cardiac surgery patients, we included 203 patients who had no AKI pre-operatively and at time of post-operative ICU admission (t1) in the primary endpoint analysis (i.e. AKI stage ≥1 within 48 h after t1), while 210 patients without AKI stage ≥2 pre-operatively and at t1 were included in the secondary endpoint analysis (i.e. AKI stage ≥2 within 12 h after t1). Systemic and/or urine concentrations of Cr, CHI3L1 and NGAL were measured more frequently than SCr in routine early post-operative ICU practice. UO was monitored hourly in the ICU.ResultsWithin 48 h after t1, 46.8% of the patients had developed AKI (70.5% stage 1, 20.0% stage 2 and 9.5% stage 3). In the early post-operative period, only SCr was a good predictor of AKI within 48 h after t1 (primary endpoint). SCHI3L1 combined with either UCHI3L1 or UNGAL was a good predictor of AKI stage ≥2 within 12 h after t1 (secondary endpoint). However, SCr and its absolute difference from pre-operative to early measures after surgery outperformed these combinations.ConclusionsWe found that more frequent assessment of the functional biomarker SCr in the early post-operative ICU period (first 4 h) after elective cardiac surgery in adult patients had good to excellent predictive value for CSA-AKI, indicating that routine SCr assessment must become more frequent in order to detect AKI more early. This performance was in contrast with the inadequate predictive value of the urinary renal stress or damage biomarkers UCHI3L1 and UNGAL.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0251-z) contains supplementary material, which is available to authorized users.

NGAL and urinary [TIMP-2] [IGFBP7], in combination with pretest assessment, are promising tools for early detection and treatment in CSA-AKI.

Background: Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)•insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk®. Methods: Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers. Results: Of 660 included patients, 49 (7.4%) had AKI stages 2-3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs < 0.700. The combination uCHI3L1•TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk® cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk® cutoff of 0.3.

In the past decade, analysis of the urinary proteome (urinary proteomics) has intensified in response to the need for novel biomarkers that support early diagnosis of kidney diseases. In particular, this also applies to acute kidney injury, which is a heterogeneous complex syndrome with a still-increasing incidence at the intensive care unit. Unfortunately, this major need remains largely unmet to date. The current report aims to explain why attempts to implement urinary proteomic-discovered acute kidney injury diagnostic candidates in the intensive care unit setting have not yet led to success. Subsequently, some key notes are provided that should enhance the chance of translating selected urinary proteomic candidates to valuable tools for the nephrologist and intensivist in the near future.

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