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INTRODUCTION: This study aimed to evaluate the association between the NephroCheck® test AKIRisk® score, diuretic efficiency (DE), and the odds of worsening kidney function (WKF) within the first 72 h of admission in patients hospitalized for acute heart failure (AHF). METHODS: The study prospectively enrolled 125 patients admitted with AHF. NephroCheck® test was obtained within the first 24 h of admission. DE was defined as net fluid urine output per 40 mg of furosemide equivalents. RESULTS: The median AKIRisk® score was 0.11 (IQR 0.06-0.34), and 38 (30.4%) patients had an AKIRisk® score >0.3. The median cumulative DE at 72 h was 1,963 mL (IQR 1317-3,239 mL). At 72 h, a total of 10 (8%) patients developed an absolute increase in sCr ≥0.5 mg/dL (WKF). In a multivariable setting, there was an inverse association between the AKIRisk® score and DE within the first 72 h. In fact, the highest the AKIRisk® score (centered at 0.3), the higher the likelihood of poor DE (below the median) and WKF at 72 h (odds ratio [OR] 2.04; 95%; CI: 1.02-4.07; p = 0.043, and OR 3.31, 95% CI: 1.30-8.43; p = 0.012, respectively). CONCLUSION: In patients with AHF, a higher NephroCheck® AKIRisk® score is associated with poorer DE and a higher risk of WKF at 72 h. Further research is needed to confirm the role of urinary cell cycle arrest biomarkers in the AHF scenario.

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Biomarcadores , Diuréticos , Insuficiencia Cardíaca , Humanos , Masculino , Femenino , Insuficiencia Cardíaca/orina , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Anciano , Biomarcadores/orina , Estudios Prospectivos , Diuréticos/uso terapéutico , Enfermedad Aguda , Puntos de Control del Ciclo Celular/efectos de los fármacos , Persona de Mediana Edad , Anciano de 80 o más Años , Furosemida/administración & dosificación , Furosemida/uso terapéutico , Furosemida/farmacología , Tasa de Filtración Glomerular/fisiología , Tasa de Filtración Glomerular/efectos de los fármacos

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Background: Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are G1 cell arrest biomarkers that have demonstrated accuracy and validity in predicting and diagnosing acute kidney injury (AKI). This study aimed to evaluate the validity of [TIMP-2]×[IGFBP7] in diagnosing acute allograft dysfunction and its utility in distinguishing acute rejection (AR) from nonrejection causes in kidney transplantation. Methods: This study included 48 adult living donor kidney transplant recipients (KTRs; 18 with AR, 15 with nonrejection causes of AKI, and 15 with stable grafts). Urinary TIMP-2 and IGFBP7 were measured, and [TIMP-2]×[IGFBP7] was calculated in all subjects. Results: IGFBP7, TIMP-2, and [TIMP-2]×[IGFBP7] were statistically significantly higher in KTRs with acute allograft dysfunction than in those with stable grafts. [TIMP-2]×[IGFBP7] was statistically significantly higher in KTRs with AR than in those with nonrejection AKI. [TIMP-2]×[IGFBP7] at a cutoff level of 0.278 (ng/mL)2/1,000 had an area under the curve (AUC) of 0.99 with a sensitivity of 100% and a specificity of 93.3% in diagnosing acute allograft dysfunction, while at a cutoff level of 0.803 (ng/mL)2/1,000 had an AUC of 0.939 with a sensitivity of 94.4% and a specificity of 83.3% in diagnosing AR. Conclusions: Besides its role in the early detection of acute allograft dysfunction, [TIMP-2]×[IGFBP7] may help to differentiate between AR and nonrejection causes in KTRs. However, whether and how urinary [TIMP-2]×[IGFBP7] can be used in clinical diagnosis still requires further research.

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PURPOSE: Although epidemiological studies have enhanced our understanding of acute kidney injury, defining the biologic processes corresponding to the clinical phenotype remains challenging. We have examined biomarkers associated with renal stress plus markers of glomerular function to assess whether this approach may aid prediction of AKI or other relevant endpoints. MATERIALS & METHODS: Urinary [TIMP-2]·[IGFBP7], serum creatinine, plasma cystatin C and plasma proenkephalin 119-159 2 were analyzed in patients enrolled in the prospective, international, Sapphire study. Heterogenous critically ill patients (n = 723) were examined with a primary endpoint of development of KDIGO stage 2-3 within 12 h and a secondary endpoint of major adverse kidney events at 30 days (MAKE30). RESULTS: 100 patients (14%) reached the primary endpoint. Markers of renal stress outperformed those associated with glomerular function. Combining [TIMP-2]•[IGFBP7] with serum creatinine, but not the other functional markers, significantly (p = 0.02) increased the area under the ROC curve (AUC) from 0.80 (0.76-0.84) to 0.85 (0.81-0.89). In patients who did not develop AKI, all markers of glomerular filtration, but not [TIMP-2]·[IGFBP7], were significantly elevated in patients with a history of CKD (p < 0.05). CONCLUSIONS: The combination of cell-cycle arrest biomarkers, TIMP-2 and IGFBP7, with serum creatinine but not cystatin C or PENK improved risk stratification for the development of stage 2 or 3 AKI over [TIMP-2]·[IGFBP7] alone.

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Lesión Renal Aguda , Inhibidor Tisular de Metaloproteinasa-2 , Biomarcadores , Creatinina , Humanos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Riñón/fisiología , Valor Predictivo de las Pruebas , Estudios Prospectivos

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BACKGROUND: Acute kidney injury (AKI) is routinely diagnosed by creatinine-based guidelines, which is sub-optimal marker after injury due to renal and non-renal factors. This has necessitated the need for more specific and sensitive biomarkers for early detection of AKI in at risk patients. This prospective cross-sectional study used the biomarkers of cell cycle arrest and Neutrophil Gelatinase Associated Lipocalin (NGAL) to assess AKI among hospitalized patients. METHODS: We conveniently enrolled 151 in-patients at the Trauma and Specialist Hospital, Winneba in Ghana. Socio-demographic and clinical information were collected using structured questionnaires. Blood samples were collected for the estimation of serum creatinine, and AKI diagnosed and staged using the KDIGO guideline. Fresh urine samples were collected and urinary NGAL, TIMP-2 (tissue inhibitor metalloproteinase 2) and IGFBP-7 (insulin-like growth factor binding protein 7) were estimated using ELISA kits. RESULTS: The cell cycle arrest biomarkers and NGAL were significantly (P < 0.001) higher among participants with AKI than those without AKI. [TIMP-2]∗[IGFBP-7] showed the best diagnostic performance (AUC = 0.94, CI = 0.90-0.98) followed by [IGFBP-7]∗NGAL] (AUC = 0.93, CI = 0.87-0.99), with NGAL having the least (AUC = 0.62, CI = 0.46-0.78). The cut-off for [TIMP-2]∗[IGFBP-7] showed the best predictive ability (95.8% sensitivity, 77.2% specificity, 44.2% PPV and 99% NPV). The cut-off for NGAL, on the other hand, showed the least predictive ability (62.5% sensitivity, 42.5% specificity, 17.0% PPV and 85.7% NPV). CONCLUSION: Tissue inhibitor metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) best predicts the development of AKI, and can be used in high risk patients for early diagnosis of AKI.