FP271
A NEW ANIMAL MODEL TO STUDY ACUTE KIDNEY INJURY-TO-CHRONIC KIDNEY DISEASE TRANSITION Free

INTRODUCTION: Acute kidney injury (AKI) represents a clinical problem due to its increasing prevalence and associations with further morbidities. Patients who suffer from AKI have a higher risk of developing chronic renal damage (CKD) in relation to the severity and frequency of their episodes. After AKI, incomplete or maladaptive repair can result in the development and progression into CKD. Although the complete process of AKI to CKD transition remains unclear, one mechanism promoting this transition is fibrosis, where functional tissue is replaced by connective tissue. Advanced fibrosis will result in the loss of both organ architecture and functionality. Hypothesising that three AKI-inducing renal insults, at discrete time intervals, would be able to promote CKD transition, we designed and characterized a new animal model. Over the course of the study, we examined the presence of histological damage (interstitial fibrosis) and monitored renal function.

METHODS: Male Wistar rats were subjected to three AKI inducing-renal interventions. Animals were treated intraperitoneally with 5 mg/kg of cisplatin (CDDP5), while control groups received saline solution. When renal function had recovered (D8), a 60-minute unilateral ischemia-reperfusion (I/R60) was performed on the left kidney. Sham rats were subjected to a simulated surgery. Two weeks later, rats were administered with 3 mg/kg of cisplatin (CDDP3) intraperitoneally, while controls received saline. Blood and urine were collected at: D0 (basal); D4 (AKI development); D8 (normalized renal function after AKI); D9 (1 day after ischemia); D15 and every week thereafter. Renal function was analysed by plasma creatinine, glomerular filtration rate, blood urea and proteinuria using colorimetric methods. At D56 all animals were sacrificed, and kidney samples were stained with Masson´s trichrome (MT) and Sirius Red (SR) to analyse the degree of fibrosis.

RESULTS: Our data show that after three renal insults, MT and SR staining revealed a progressive fibrosis increase in both kidneys in the triple injury group (CDDP5 - I/R60 - CDDP3), but not in the double or single injury groups. There are no differences in renal function after the last AKI in the triple injury group (CDDP5 - I/R60 - CDDP3) with respect to controls or the double or single injury groups.

CONCLUSIONS: The presence of fibrosis in both kidneys in our triple injury experimental group demonstrates that a maladaptive and incomplete repair mechanism occurred following AKI, although renal function seems to remain normal. Our results show the potential of this in vivo experimental model to reproduce AKI-to-CKD transition.