Article

Does AKI truly lead to CKD?

Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, C1-Annex, Torrance, CA 90509-2910, USA.
Journal of the American Society of Nephrology (Impact Factor: 9.34). 03/2012; 23(6):979-84. DOI: 10.1681/ASN.2011121185
Source: PubMed

ABSTRACT

Acute kidney injury (AKI) has been implicated as an independent risk factor for the development of CKD in recent observational studies. The presumption in the nephrology community is that this association represents a causal relationship. However, because of potential problems related to residual confounding (shared risk factors), ascertainment bias (sicker patients have more follow-up assessments), misclassification of exposure (problems with defining baseline kidney function and AKI representing a discrete event versus progression of renal disease), and misclassification of outcome (de novo CKD versus CKD progression), it is difficult to conclude with certainty that AKI is truly causal for CKD. In this review we highlight several of the Hill causality criteria to examine the existing evidence and point out the missing elements that preclude defining AKI as a cause of CKD in the general population. Only well-designed studies with rigorous assessment of kidney function in all participants (AKI and non-AKI) before and after the episode or hospitalization or randomized, controlled trials demonstrating that prevention or treatment of AKI reduces the incidence of subsequent CKD can clarify the causal nature of the AKI-CKD relationship.

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    • "The mortality due to AKI remains elevated, in part due to the lack of early and sensitive biomarkers and the absence of an effective therapy (Go et al., 2010; Liano & Pascual, 1996; Okusa et al., 2009; Waikar et al., 2006). More worrying is the evidence that show that AKI is associated with the development of chronic kidney disease (Barrera-Chimal et al., 2013; Block & Schoolwerth, 2007; Ishani et al., 2009; Kronenberg, 2009; Lafrance et al., 2010; Mosier et al., 2010; Murugan & Kellum, 2011; Rifkin et al., 2012; Venkatachalam et al., 2010). For years, AKI has been diagnosed by an increase in serum creatinine (SCr) and/or a reduction in urine output according to the AKIN and RIFLE classification (Joannidis et al., 2009; Mehta & Chertow, 2003; Nakamura et al., 2012). "
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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.
    Full-text · Article · Oct 2015 · Biomarkers
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    • "The incidence of AKI is on the rise in both high-income and low-income countries . Nearly 600,000 cases of AKI are reported each year in the United States (Rifkin et al., 2012). However, the numbers are more severe in China with AKI affecting approximately one in a thousand individuals per year. "

    Full-text · Dataset · Jul 2015
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    • "The incidence of AKI is on the rise in both high-income and low-income countries . Nearly 600,000 cases of AKI are reported each year in the United States (Rifkin et al., 2012). However, the numbers are more severe in China with AKI affecting approximately one in a thousand individuals per year. "
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    ABSTRACT: Acute kidney injury (AKI), associated with significant morbidity and mortality, is widely known to involve epithelial apoptosis, excessive inflammation, and fibrosis in response to ischemia or reperfusion injury, which results in either chronic pathological changes or death. Therefore, it is imperative that investigations are conducted in order to find effective, early diagnoses, and therapeutic targets needed to help prevent and treat AKI. However, the mechanisms modulating the pathogenesis of AKI still remain largely undetermined. MicroRNAs (miRNAs), small non-coding RNA molecules, play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene expression. MicroRNA-21 (miR-21) is a recently identified, typical miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fibrotic signaling pathways in AKI. As a result, miR-21 is now considered a novel biomarker when diagnosing and treating AKI. This article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI.
    Full-text · Article · Nov 2013 · Protein & Cell
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