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Review
. 2016 Nov;7(1):1-10.
doi: 10.1159/000447542. Epub 2016 Jul 21.

Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

Jun Zhang  1 , Mohammad Kazem Fallahzadeh  2 , Peter A McCullough  3
Affiliations
Review

Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

Jun Zhang et al. Cardiorenal Med. 2016 Nov.

Abstract

Background: Although there are some animal models for biomarkers of contrast-induced acute kidney injury (CI-AKI), for cardiorenal syndrome (CRS) and for acute renal failure, the interplay between CI-AKI and CRS has yet to be evaluated. Insight into the pathogenesis of CRS is urgently needed from animal models in order to foster the discovery and implementation of novel biomarkers for this disease. Specially designed animal models for type 1 and 3 CRS, particularly CI-AKI, have not yet emerged.

Summary: We hypothesize that the aging male spontaneously hypertensive rat (SHR) is likely to be a suitable model. The SHR model is able to mimic risk factors for preclinical CRS that appears in the clinical setting, specifically hypertension, age, preexisting damage and dysfunction of the heart and kidney, endothelial dysfunction, increased level of reactive oxygen species, decreased level and bioavailability of nitric oxide (NO), impairment of the L-arginine-NO pathway, and insulin resistance. In the SHR, CI-AKI results in a different profile of AKI biomarkers than is seen with preexisting chronic kidney injury.

Key messages: The SHR model can be used to evaluate the interaction between CI-AKI and CRS type 1 and 3 and to verify neutrophil gelatinase-associated lipocalin (NGAL) as a reliable CI-AKI biomarker for clinical application. Further research is warranted with a large number of aging male SHRs to prove NGAL as a sensitive, specific, highly predictive, early biomarker for CI-AKI.

Keywords: Acute kidney injury; Cardiorenal syndrome; Hypertension; Iodinated contrast media; Neutrophil gelatinase-associated lipocalin; Spontaneously hypertensive rat.

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Figures

Fig. 1
Fig. 1
Comparison of risk factors and predisposing conditions for worsening acute cardiac and renal injury and CI-AKI in SHRs and humans with preclinical CRS.
Fig. 2
Fig. 2
Renal functional reserve and clinical relevance: insights from an aging male SHR model.
See this image and copyright information in PMC

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