Progression after AKI

Abstract

Recent clinical studies indicate a strong link between AKI and progression of CKD. The increasing prevalence of AKI must compel the nephrology community to consider the long-term ramifications of this syndrome. Considerable gaps in knowledge exist regarding the connection between AKI and CKD. The 13th Acute Dialysis Quality Initiative meeting entitled "Therapeutic Targets of Human Acute Kidney Injury: Harmonizing Human and Experimental Animal Acute Kidney Injury" convened in April of 2014 and assigned a working group to focus on issues related to progression after AKI. This article provides a summary of the key conclusions and recommendations of the group, including an emphasis on terminology related to injury and repair processes for both clinical and preclinical studies, elucidation of pathophysiologic alterations of AKI, identification of potential treatment strategies, identification of patients predisposed to progression, and potential management strategies.

Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

“…Only when active injury outpaces repair or compensatory adaptation will the progression become evident. 4 Equally important, many animals with recognized CKD maintain relatively "static" or non-progressive kidney function over extended periods of time. 40,41 These patients may justify different diagnostic, monitoring, and therapeutic attention.…”

“…4,[11][12][13][14][15][16][17][18]20 Following an acute insult, injured tubular epithelial cells may become fatally injured and undergo necrosis or apoptosis, proliferate and regenerate the damaged epithelium, or undergo failed regeneration but survive cell death in a state of cell cycle G2/M arrest. 4,13,14,15,16,17,27 Arrested cells reprieved from apoptosis, however, fail to participate in regenerative repair and upregulate maladaptive signaling pathways for myofibroblast proliferation and fibrosis in the interstitium predisposing to progression of CKD.…”

“…However, when the stress or injury is sustained or insurmountable, these same cellular responses may become maladaptive or the cell is programmed to die. 4,15 These latter responses are expressed clinically as acute kidney injury with variable recovery, kidney death, or more subtly as progressive chronic kidney disease. If the kidney recovers, many of these adaptive cellular responses become pathways for the transition of overt acute kidney injury to progressive chronic kidney disease.…”

“…Unfortunately, static kidney function tests only detect the impact of these active processes after substantial functional or structural damage has occurred. 4,24 A sensitive and specific predictor that discriminates whether a patient is likely to progress or remain stable with CKD would provide tremendous diagnostic and therapeutic advantage. 4,17,23 For patients with identified progressive CKD, this could provide earlier opportunity to seek subclinical conditions which might be injuring the kidneys and institute more timely monitoring of the disease.…”

“…4,24 A sensitive and specific predictor that discriminates whether a patient is likely to progress or remain stable with CKD would provide tremendous diagnostic and therapeutic advantage. 4,17,23 For patients with identified progressive CKD, this could provide earlier opportunity to seek subclinical conditions which might be injuring the kidneys and institute more timely monitoring of the disease. It also would provide an opportunity to initiate therapies that might ameliorate progression or development of clinical signs as well as indicate the effectiveness of therapeutic interventions.…”