Targeting Endogenous Repair Pathways after AKI

Abstract

AKI remains a highly prevalent disease associated with poor short- and long-term outcomes and high costs. Although significant advances in our understanding of repair after AKI have been made over the last 5 years, this knowledge has not yet been translated into new AKI therapies. A consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 and reviewed new evidence on successful kidney repair to identify the most promising pathways that could be translated into new treatments. In this paper, we provide a summary of current knowledge regarding successful kidney repair and offer a framework for conceptualizing the therapeutic targeting that may facilitate this process. We outline gaps in knowledge and suggest a research agenda to more efficiently bring new discoveries regarding repair after AKI to the clinic.

Keywords: CKD; acute renal failure; cell biology and structure; cell survival; interstitial fibrosis; stem cell.

Figure 1.

Cartoon illustrating that productive repair is restoration of both structure and recovery of function. The upper left reflects a normal, uninjured kidney, which is characterized by the absence of injury biomarkers (x axis) and unimpaired GFR (y axis). An episode of AKI moves the patient to the lower right, which characterized by elevated injury biomarkers and reduced GFR. Complete functional repair occurs along the black line, and this is the process that should be targeted therapeutically. However, after an AKI episode, some patients may experience a normalization in injury biomarkers without restoration of GFR (lower left). This would occur in cortical necrosis or end stage kidneys, where an absence of live parenchyma explains the reduction in injury biomarkers rather than an absence of injury. In other cases, after AKI, some patients may recover GFR but have residual injury, which reflected by ongoing injury biomarker levels (upper right). These patients have structural kidney damage that may manifest as hypertension, microalbuminuria, tubular dysfunction, or decreased reserve, despite the apparently normal GFR. It will be critical to target repair along the black line rather than either white line (www.adqi.net). HTN, hypertension; mAlb, microalbuminuria.