Hsp72 is an early and sensitive biomarker to detect acute kidney injury: Hsp72 as a novel biomarker to detect AKI

Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
EMBO Molecular Medicine (Impact Factor: 8.67). 01/2011; 3(1):5-20. DOI: 10.1002/emmm.201000105
Source: PubMed


This study was designed to assess whether heat shock protein Hsp72 is an early and sensitive biomarker of acute kidney injury (AKI) as well as to monitor a renoprotective strategy. Seventy-two Wistar rats were divided into six groups: sham-operated and rats subjected to 10, 20, 30, 45 and 60 min of bilateral ischemia (I) and 24 h of reperfusion (R). Different times of reperfusion (3, 6, 9, 12, 18, 24, 48, 72, 96 and 120 h) were also evaluated in 30 other rats subjected to 30 min of ischemia. Hsp72 messenger RNA (mRNA) and protein levels were determined in both kidney and urine. Hsp72-specificity as a biomarker to assess the success of a renoprotective intervention was evaluated in rats treated with different doses of spironolactone before I/R. Renal Hsp72 mRNA and protein, as well as urinary Hsp72 levels, gradually increased relative to the extent of renal injury induced by different periods of ischemia quantified by histomorphometry as a benchmark of kidney damage. Urinary Hsp72 increased significantly after 3 h and continued rising until 18 h, followed by restoration after 120 h of reperfusion in accord with histopathological findings. Spironolactone renoprotection was associated with normalization of urinary Hsp72 levels. Accordingly, urinary Hsp72 was significantly increased in patients with clinical AKI before serum creatinine elevation. Our results show that urinary Hsp72 is a useful biomarker for early detection and stratification of AKI. In addition, urinary Hsp72 levels are sensitive enough to monitor therapeutic interventions and the degree of tubular recovery following an I/R insult.

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    • "Supporting this finding, we previously found in critically ill patients with two or more organ failure that urinary Hsp72 level only increased in the patients diagnosed with AKI (Barrera-Chimal et al., 2011). Moreover, we recently showed that Hsp72 was enough sensitive and specific to predict AKI in critically ill patients up to 3 d before the diagnosis. "
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    ABSTRACT: We demonstrated that urinary heat shock protein of 72 KDa (Hsp72) is a sensitive biomarker for the early detection of acute kidney injury (AKI). However, whether Hsp72 induction during an AKI episode is kidney-specific is unknown, as well as, the degree of Hsp72 stability in urine samples. In rats that underwent bilateral renal ischemia and reperfusion (I/R), Hsp72 levels were evaluated in several tissues and in collected urines under different storage and temperature conditions, as well as in variable numbers of freeze-thaw cycles. The effect of room temperature and five freeze-thaw cycles on urinary Hsp72 levels was also evaluated in urine samples from AKI patients. We found that Hsp72 increased exclusively in the renal cortex of I/R group, emphasizing its performance as an AKI biomarker. Urinary-Hsp72 remained constant at room temperature (48 h), during 9 months of storage and was not affected by five freeze/thaw cycles.
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    • "GG genotype has been linked to elevated Hsp70 circulating levels or gene expression in chronic heart failure (Gombos et al. 2008) and in diabetes-atherosclerotic patients (Giacconi et al. 2005), suggesting an increased vascular damage in GG carriers (Ogawa et al. 2008). Hsp70 is also considered a sensitive biomarker of renal injury and it is overexpressed in diabetic nephropathy (Barrera-Chimal et al. 2011; Calabrese et al. 2007). Some evidence shows an association of GG genotype with an increased risk to develop renal complications in diabetes with a faster progression to the end-stage of renal failure (Buraczynska et al. 2009). "
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