Chronic Kidney Disease: An Inherent Risk Factor for Acute Kidney Injury?

Epidemiologic evidence suggests that chronic kidney disease (CKD) is a risk factor for acute kidney injury (AKI) due to the prevalence of CKD in patients who have episodes of AKI. However, the high burden of comorbidities such as age, diabetes, peripheral vascular, cardiovascular, and liver disease accompanying CKD, and the difficulties of defining AKI in the setting of CKD make these observations difficult to interpret. These comorbidities not only could alter the course of AKI but also may be the driving force behind the epidemiologic association between CKD and AKI because of systemic changes and/or increased exposure to potential nephrotoxic risks. Here, we contend that studies suggesting that CKD is a risk factor for AKI may suffer from residual confounding and reflect an overall susceptibility to illness rather than biologic susceptibility of the kidney parenchyma to injury. In support of our argument, we discuss the clinical evidence from epidemiologic studies, and the knowledge obtained from animal models on the pathophysiology of AKI and CKD, demonstrating a preconditioning influence of the previously impaired kidneys against subsequent injury. We conclude that, under careful analysis, factors apart from the inherent pathophysiology of the diseased kidney may be responsible for the increased frequency of AKI in CKD patients, and the impact of CKD on the risk and severity of AKI needs further investigation. Moreover, certain elements in the pathophysiology of a previously injured kidney may, surprisingly, bear out to be protective against AKI.