Rodent models of AKI-CKD transition

Abstract

Acute kidney injury (AKI) is a contributing factor in the development and progression of chronic kidney disease (CKD). Despite rapid progresses, the mechanism underlying AKI-CKD transition remains largely unclear. Animal models recapitulating this process are crucial to the research of the pathophysiology of AKI-CKD transition and the development of effective therapeutics. In this review, we present the commonly used rodent models of AKI-CKD transition, including bilateral ischemia-reperfusion injury (IRI), unilateral IRI, unilateral IRI with contralateral nephrectomy, multiple episodes of IRI, and repeated treatment of low-dose cisplatin, diphtheria toxin, aristolochic acid, or folic acid. The main merits and pitfalls of these models are also discussed. This review provides helpful information for establishing reliable and clinically relevant models for studying post-AKI development of chronic renal pathologies and the progression to CKD.

New mouse model of chronic kidney disease transitioned from ischemic acute kidney injury

“…In renal IRI models, ischemic duration and kidney temperature are two key determinants for the severity of AKI. The time length of renal pedicle clamping in mice varied from 14 to 90 min, with plasma creatinine values from 1.4 to 2.8 mg/dl, in different laboratories (13,22,28,39,53). We think that the huge variation in ischemic time and renal injury is mainly because of the kidney temperature during ischemia.…”

“…Several experimental animal models for AKI to CKD transition have been generated, which are widely used and have advanced our understanding of the pathophysiological mechanisms for the transition from AKI to CKD. However, none of them exhibit the typical changes in GFR and PCr, the hallmarks of AKI to CKD transition (3,13,56).…”

Peer Review #2 of "Metabolomic and biochemical characterization of a new model of the transition of acute kidney injury to chronic kidney disease induced by folic acid (v0.2)"

“…In addition, it has been shown that FA has nephrotoxic activity at various levels of the nephron because it induces a pro-oxidant state by increasing lipid binding and reducing protective anti-oxidant enzymes (Gupta et al 2012). It has been suggested recently that the residual structural damage that is produced by FA could lead to CKD pathology (Fu et al 2018). Creatinine and BUN levels have been used traditionally in clinical practice as markers of renal function.…”

“…This has been suggested to lead to an alteration in cellular architecture and generate oxidative stress and fibrosis that could progress to CKD (Stallons et al 2014). Fu et al hypothesized that the repeated injury by multiple administrations of FA could be sufficient to cause the transition from AKI to CKD (Fu et al 2018). To establish whether the pharmacological AKI induced by repetitive FA dosing progresses to CKD, the effect of FA on distinctive parameters of renal function must be explored.…”

DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice

“…For ischemic acute kidney injury, it was induced by the duration of bilateral clamping for 28 min and followed by reperfusion 43 . For cisplatin injury, mice were intraperitoneally injected with 10 mg/kg cisplatin at weeks 0, 1, and 3 44 . For aristolochic acid injury, mice were intraperitoneally injected with 250 mg/kg aristolochic acid 45 .…”