Sunday, December 2, 2012

eJournal Club - Albuminuria and AKI

This month’s eJournal club concerns biomarkers of AKI. There has been considerable interest in developing novel biomarkers of AKI and CKD and a lot of effort has been focused on novel biomarkers such as NGAL, KIM-1 and IL-18. The TRIBE-AKI consortium has published a number of well-designed studies investigating novel and traditional biomarkers. The reason that these biomarkers are desired is because creatinine elevations tend to occur relatively late in the course of AKI and therefore, the sense is that this is too late to initiate therapies which may prevent progression of AKI. However, the results of these biomarker studies have been relatively disappointing and they have not yet entered regular clinical practice.

This month in CJASN, a study was published looking at the performance of post-operative albuminuria as a biomarker of AKI in patients following cardiac surgery. The highest quintile of albuminuria was associated with a RR of 2.97 for AKI relative to the lowest quintile. While this appears good and the AUC for a model including albuminuria to predict AKI was 0.81, the majority of patients with albuminuria did not develop AKI and the model missed a significant number of patients with AKI. Still, when you combine this with other studies showing that the urinalysis is an excellent predictor of outcome in patients with AKI, older biomarkers are not looking so bad after all. Perhaps we will be able to come up with a combination of biomarkers which will allow us to better predict those patients at greater risk of AKI. To me, it seems that the bigger issue is low sensitivity rather than low specificity. I would rather have a model which will allow me to rapidly rule out those who will not develop AKI than one that will misclassify patients into a low risk group.

It was interesting in this study that ACR was not a good predictor of AKI – the absolute level of albumin performed better. This is at odds with the majority of studies which suggest that albumin should be corrected for creatinine level. This is possibly due to the large variation in creatinine generation in patients in the ICU – although relatively constant under normal circumstances, the amount of creatinine produced daily changes rapidly in sick patients – as was evidenced by a recent study of creatinine excretion in patients on CRRT.

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