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A novel model of adenine-induced tubulointerstitial nephropathy in mice

Ting Jia12, Hannes Olauson1, Karolina Lindberg1, Risul Amin1, Karin Edvardsson1, Bengt Lindholm2, Göran Andersson3, Annika Wernerson1, Yves Sabbagh4, Susan Schiavi4 and Tobias E Larsson15*

Author Affiliations

1 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

2 Renal Medicine and Baxter Novum, Karolinska Institutet, Stockholm, Sweden

3 Department of Pathology, Karolinska Institutet, Stockholm, Sweden

4 Sanofi-Genzyme R&D Center, Genzyme, A Sanofi Company, Framingham, USA

5 Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden

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BMC Nephrology 2013, 14:116  doi:10.1186/1471-2369-14-116

Published: 30 May 2013



In vivo models of uremia are important tools to study numerous aspects of acute and chronic kidney disease. Mouse models are pivotal because most genetically engineered animal models are mice, which allow dissecting the impact of selected target genes in renal failure. Adenine-based protocols to induce renal failure are available in rats, but have not been adapted in mice due to their reluctance to consume adenine. In the current paper we developed a novel method for induction of renal failure through dietary delivery of adenine mixed in a casein-based diet.


After an induction phase, a stable model of renal impairment was obtained (target urea range 80–100 mg/dL), mimicking several aspects of chronic kidney disease - mineral and bone disorder including secondary hyperparathyroidism, bone abnormalities and pathological elevation of FGF23. No deaths occurred and the level of uremia was adaptable through adjustments of the adenine content, providing significant advantages compared to existing models. In an 8-week proof-of-concept study, renal histology showed mainly a tubulointerstitial damage with infiltrating leukocytes, interstitial edema and widening of the Bownman's space. Fibrosis was present in most animals as defined by histology and gene expression changes of fibrosis markers. Parathyroid cell proliferation was markedly increased but without signs of glandular hypertrophy. Skeletal histology showed increased trabecular bone and bone marrow adiposity whereas bone biomarkers (CTX and PINP) suggested higher bone formation, but surprisingly, lower bone resorption and perturbations in mineral metabolism.


We present a novel, non-surgical method for induction of renal failure in mice. This is an important complement to existing uremic models for pathophysiological studies in acute and chronic kidney disease, especially in terms of tubulointerstitial lesions.

CKD; Chronic kidney disease; CKD-MBD; FGF-23; FGF23; Mineral metabolism; Experimental renal failure