Chronic kidney disease (CKD) in rats

Species

Rat

Fields of application

Chronic kidney disease (CKD) is progressive loss in kidney function over a period of months or years. CKD is a worldwide health problem that might lead to end-stage renal disease.

Adenine models of chronic kidney disease are relatively easy to perform and generate clinically relevant outcomes. Unlike surgical models they have high survival rates. One can distinguish between the adenine diet models for which an adenine diet is fed for several weeks and the adenine systemic injection model. The adenine injection model has two big advantages. (I) The experimenter has the complete control over the adenine dose administered. This makes the model highly reproducible and (II) the weight loss which is remarkable in the adenine diet model is almost absent. Thus, the adenine i.p. injection model is also the gentlest for the animals.

The adenine i.p. CKD model is associated with significant changes in the following parameters: marked structure changes of kidneys, increased plasma phosphate and creatinine, a decrease in plasma calcium, in creatinine, phosphate in urine, in creatinine clearance, and a decrease of around 6 % in body weight.

  • Pharmacodynamics and pharmacokinetics
  • (Patho)physiological processes
  • Therapeutic efficacy
  • Proof of concept

Endpoints / outcome parameter

  • Score (severity of clinical symptoms; in vivo)
  • Clinical chemistry of full blood and urine (in vivo, diverse parameters, e.g. phosphate, urea, creatinine, creatinine clearance)
  • Hemogram
  • Blood pressure (in vivo)
  • Kidney enlargement (in vivo (CT); post mortem)
  • Aorta calcification (in vivo (CT); post mortem)
  • Pathophysiological changes in kidneys (post mortem)

Readout parameter

  • Scoring
  • Clinical chemistry
  • Metabolic cages
  • Blood pressure measurements (non-invasive)
  • Computer tomography (CT)
  • Histology (various classical histological stains)
  • Immunohistochemistry

Quality management and validation

  • Controls
  • Blinded induction
  • Blinded data collection and analysis
  • Randomisation
  • Allocation concealment
  • Biometric expertise
  • Internal quality management

References

Leichsenring A, Eichentopf R, Grunwald T, Friedrich D, Leibrock C, Lange F. Refinement of the adenine model for chronic kidney disease in rats. Laboratory Animals 2019; 53(1S): 28-203

 

HE staining of the kidneys of Wistar rats
HE staining of the kidneys of Wistar rats. Representative HE stained kidney sections of adenine (Ba+b (medium dose adenine), Ca+b (high dose adenine)) and NaCl (Aa+b) treated rats. Sections of adenine treated rats (Ba–Cb) clearly showed serious pathologic alterations including inclusions (Bb + Cb: brown deposits, arrows), fibrotic alterations, and inflammation.
Von Kossa stained aortae of Wistar rats counterstained with aniline blue-orange G.
Von Kossa stained aortae of Wistar rats counterstained with aniline blue-orange G. Representative histological sections of aortae of adenine (Ba+b (medium dose adenine), Ca+b (high dose adenine)) and NaCl (Aa+b) treated rats. Sections of aortae of adenine treated rats (Ba – Cb) showed sub-endothelial and intimal mineral deposits (Ba - Cb: brown deposits, arrows).
CT imaging, 3D reconstruction of organs, and calculation of kidney volumes of Wistar rats
CT imaging, 3D reconstruction of organs, and calculation of kidney volumes of Wistar rats. CT measurements were performed with the SARRP under isoflurane/oxygen anaesthesia. Animals were examined before and after injections. A shows a 3D reconstruction of aorta abdominalis (reddish brown) of a rat injected with medium dose adenine. B depicts a raw CT scan of a healthy rat before start of adenine injections. Kidneys are marked with blue circles. C: 3D reconstruction of a right kidney (reddish brown) of a healthy rat before start of injections. D: Bar diagram of kidney volumes before and after adenine injections.