RESUMO
Biomarkers for acute kidney injury (AKI) have been used to predict the progression of AKI, but a systematic comparison of the prognostic ability of each biomarker alone or in combination has not been performed. In order to assess this, we measured the concentration of 32 candidate biomarkers in the urine of 95 patients with AKIN stage 1 after cardiac surgery. Urine markers were divided into eight groups based on the putative pathophysiological mechanism they reflect. We then compared the ability of the markers alone or in combination to predict the primary outcome of worsening AKI or death (23 patients) and the secondary outcome of AKIN stage 3 or death (13 patients). IL-18 was the best predictor of both outcomes (AUC of 0.74 and 0.89). L-FABP (AUC of 0.67 and 0.85), NGAL (AUC of 0.72 and 0.83), and KIM-1 (AUC of 0.73 and 0.81) were also good predictors. Correlation between most of the markers was generally related to their predictive ability, but KIM-1 had a relatively weak correlation with other markers. The combination of IL-18 and KIM-1 had a very good predictive value with an AUC of 0.93 to predict AKIN 3 or death. Thus, a combination of IL-18 and KIM-1 would result in improved identification of high-risk patients for enrollment in clinical trials.
Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Interleucina-18/urina , Glicoproteínas de Membrana/urina , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/urina , Procedimentos Cirúrgicos Cardíacos/mortalidade , Progressão da Doença , Feminino , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Receptores Virais , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Estados Unidos , UrináliseRESUMO
Using multiplex bead assays to measure urine proteins has a great potential for biomarker discovery, but substances in urine (the matrix) can interfere with assay measurements. By comparing the recovery of urine spiked with known quantities of several common analytes, this study demonstrated that the urine matrix variably interfered with the accurate measurement of low abundance proteins. Dilution of the urine permitted a more accurate measure of these proteins, equivalent to the standard dilution technique when the diluted analytes were above the limits of detection of the assay. Therefore, dilution can be used as an effective technique for over-coming urine matrix effects in urine immunoassays. These results may be applicable to other biological fluids in which matrix components interfere with assay performance.