Zebrafish Acute Kidney Injury Models

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens outcomes in a large number of hospitalized patients. AKI is also considered a risk factor for chronic kidney disease (CKD), and patients with severe AKI are at increased risk of end-stage renal disease. AKI is primarily caused by multifactorial damage, including but not limited to decreased renal blood flow, urinary tract obstruction, exposure to toxic substances, and sepsis. Recent advances in clinical and basic research will help to define the syndrome more precisely and elucidate its pathogenesis. Animal models of acute kidney injury allow researchers to conduct more accurate epidemiological studies to better understand the impact of this syndrome.

For more than a decade, zebrafish researchers have been developing larval and adult models of AKI. The development and function of zebrafish kidneys are nearly identical to those of humans, and their key pronephros genes have been identified as homologous to humans. The larval pronephros begins to function as early as 48 hours after fertilization. In addition, nephrotoxic AKI and laser ablation-induced AKI were successfully developed using zebrafish larvae. The successful development of the zebrafish model will enrich the AKI research toolkit and contribute to a better understanding of the mechanisms of AKI.

Fig.1 Summary of zebrafish kidney injury models.

Our Zebrafish Acute Kidney Injury Models

Creative Biogene mainly establishes zebrafish acute kidney injury models by injecting nephrotoxin, directly inducing injury by surgical intervention, or by generating transgenic lines that express compounds in a tissue-specific manner. Specifically, we provide larval and adult models of gentamicin AKI as well as models of injury induced by laser ablation, puromycin aminonucleoside, etc., which recapitulate several key features of human AKI , including upregulation of cytokines, host transcriptional response to injury, decreased renal function, and increased expression of biomarkers of renal tubular injury. In addition, we provide an AKI-inducible transgenic line of zebrafish for understanding the function of genes involved in kidney development and regeneration.

Our zebrafish models are important complement to vertebrate models of AKI, not only because of the similar pathological features, but also because of the unique advantages of zebrafish. The larval model inherits the important advantages of zebrafish such as fecundity, rapid development, optical transparency, and the availability of multiple genetic manipulation tools. It is also less time-consuming than the classic mammalian model. Our models can also target immune effector cell-tubule cell interactions, mechanisms of host cell injury and recovery, and high-throughput drug screening.

Advantages

• Live imaging assesses renal excretory function in larvae
• Availability of multiple genetic manipulation tools
• High-throughput gene/drug screening

References

1. Wen X, et al. A zebrafish model of infection-associated acute kidney injury. Am J Physiol Renal Physiol. 2018, 315(2):F291-F299.
2. Cirio MC, de Caestecker MP, Hukriede NA. Zebrafish Models of Kidney Damage and Repair. Curr Pathobiol Rep. 2015, (2):163-170.
3. Morales Fénero C, et al. Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish. J Vis Exp. 2021, (171):10.3791/61575.

For research use only. Not intended for any clinical use.