Cardiorenal syndrome defines a synergistic pathology of the heart and kidneys where failure of one organ causes failure in the other. The incidence of cardiovascular mortality caused by this syndrome, is 20 fold higher in the
end stage renal disease (
ESRD) population compared to the population as a whole thus necessitating the need for improved therapeutic strategies to combat reno-cardiac pathologies. Murine in vivo models play a major role in such research permitting precise genetic modification thus reducing miscellany, however presently there is no steadfast model of
reno-cardiac syndrome in the most common genetically modified mouse strain, the C57BL/6 mouse. In this study we have modified an established model of
chronic renal disease using
adenine diet and extended the associated pathology achieving
chronic renal failure and consequent
reno-cardiac syndrome in the C57BL/6 mouse. Eight week-old male C57BL/6 mice were acclimatized for 7 days before administration of a 0.15%
adenine diet or control diet for 20 weeks after which the experiment was terminated and blood, urine and organs were collected and analyzed biochemically and by immunohistochemistry. Administration of 0.15%
adenine diet caused progressive
renal failure resulting in a
reno-cardiac syndrome confirmed by a significantly increased heart to
body weight ratio (P < 0.0001). Blood biochemistry showed that
adenine fed mice had significantly increased serum
creatinine,
urea (P < 0.0001), and a significantly reduced glomerular filtration rate (P < 0.05), while immunohistochemistry of the kidneys for α-SMA,
collagen 1 and
collagen 3 showed severe
fibrosis. We present a novel regimen of
adenine diet which induces both
chronic kidney disease and
reno-cardiac syndrome in the C57BL/6 mouse strain. The non-surgical nature of this model makes it highly reproducible compared to other models currently available.