Zebrafish Renal Pathology: Emerging Models of Acute Kidney Injury

Abstract

The renal system is vital to maintain homeostasis in the body, where the kidneys contain nephron functional units that remove metabolic waste from the bloodstream, regulate fluids, and balance electrolytes. Severe organ damage from toxins or ischemia that occurs abruptly can cause acute kidney injury (AKI) in which there is a rapid, life-threatening loss of these activities. Humans have a limited but poorly understood ability to regenerate damaged nephrons after AKI. However, researchers studying AKI in vertebrate animal models such as mammals, and more recently the zebrafish, have documented robust regeneration within the nephron blood filter and tubule following injury. Further, zebrafish kidneys contain progenitors that create new nephrons after AKI. Here, we review investigations in zebrafish which have established a series of exciting renal pathology paradigms that complement existing AKI models and can be implemented to discover insights into kidney regeneration and the roles of stem cells.

Keywords: Acute kidney injury; Nephron; Regeneration; Renal progenitor; Renal stem cell; Zebrafish.

Fig. 1

Nephron composition is conserved across vertebrates, and renal regeneration in zebrafish involves two distinct pathological responses. Vertebrate nephron segmental anatomy comparison between a generic mammalian kidney (a), zebrafish embryo (b), and zebrafish adult (c) follows the conserved pattern of blood filter, tubule and duct, where the tubule comprised multiple segments that typically include proximal and distal regions and possibly intermediate segments. d Histology time course of kidney regeneration in the adult zebrafish using periodic acid–Schiff staining. Proximal and distal tubule segments (PT, DT) can be distinguished in healthy nephrons based on the deep magenta staining of the PT brush border. AKI was induced by gentamicin injection, and at 1-day post-injury (dpi), DT is filled with casts (*) that have been cleared by 3 dpi (**). From 5 to 14 dpi, basophilic bodies (arrowheads) correspond to new nephrons that elongate (arrows) to form new nephrons. At 21 dpi, AKI pathology is completely ameliorated, and the tissue is indistinguishable from the uninjured state. e Schematic representation of AKI and regenerative events in the zebrafish kidney. [Schematics and images adapted from the following Open Access, Creative Commons Attribution License publications: •, ••]