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Abstract: FR-PO1067

The Adenine-Induced Mouse Model of CKD Shows Rapid Development of Impaired Kidney Function, Renal Fibrosis, Muscle Wasting, and Anemia

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms


  • Ougaard, Maria Katarina, Gubra, Hoersholm, Denmark
  • Sembach, Frederikke Emilie, Gubra, Hoersholm, Denmark
  • Nøhr-Meldgaard, Jacob, Gubra, Hoersholm, Denmark
  • Marstrand-Jørgensen, Adam Bøgh, Gubra, Hoersholm, Denmark
  • Hansen, Henrik H., Gubra, Hoersholm, Denmark
  • Christensen, Michael, Gubra, Hoersholm, Denmark

Translational rodent models are essential to identify more efficacious treatment options for patients with chronic kidney disease (CKD). However, most preclinical CKD models do not demonstrate impaired kidney function as determined by decreased glomerular filtration rate (GFR). Here, we characterize an adenine diet-induced (ADI) mouse model of CKD that enables clinical translational studies of CKD.


Male C57BL/6j mice (11 weeks old) were randomized into study groups (n=8-10 per group) based on body weight. ADI mice received a control diet from study day -2 and a CKD-inducing diet containing 0.2% adenine from study day 1, while control mice received a control diet from day -2 and continued with it throughout the study period. All groups received oral vehicle dosing once daily starting from day 1 until termination. Transdermal GFR (tGFR), urine creatinine-to-albumin ratio, and plasma cystatin C(pCyC) were evaluated at week 3 and 5. Blood was collected for glycated haemoglobin analysis, and gastrocnemius muscle and kidney tissue were sampled and weighed. Kidneys were collected for RNA sequencing or processed for histological evaluation of markers of macrophage infiltration (F4/80) and fibrosis (Col1a1).


Compared to controls, ADI mice showed a significant tGFR decline correlating with an increased pCyC and marked albuminuria at 3 and 5 weeks after diet-induction. At termination, ADI mice showed significantly decreased glycated haemoglobin (14.7 vs 17.6 g/dL) and gastrocnemius muscle weight compared to mice receiving the control diet (0.12 vs 0.15 g). Furthermore, Quantitative kidney histomorphometric analysis demonstrated an increase in kidney fibrosis (Col1a1) and macrophage infiltration (F4/80) in ADI mice. Consistent with tGFR decline and kidney histology, the renal transcriptome signature in ADI mice indicated upregulation of gene expression markers of fibrosis (e.g. Col1a1, Grem1), inflammation (e.g. Il6, Il1b), and angiogenesis (e.g. Ednra, Agt).


ADI mice rapidly develop functional, biochemical and histological hallmarks of CKD complicated by anaemia and muscle wasting. Consequently, ADI mice are highly relevant in preclinical target and drug discovery for CKD.


  • Commercial Support – Gubra