Rodent Models of Renal Disease

Optimised preclinical renal disease models

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"CrownBio brings clarity to drug discovery around the world by helping biopharmaceutical companies solve some of today's most pressing problems in oncology, cardiovascular, and metabolic disease.

Leveraging our industry expertise, CrownBio's global resources help customers answer the most challenging questions about human biology. We begin with the end insight to help you achieve your goals"

Dr Jean-Pierre Wery
CEO, Crown Bioscience Inc.

A Range of Solutions for Your Renal Disease Research

Polycystic Kidney Disease Models

Polycystic kidney disease (PKD) is a genetic disorder in which abnormal cysts develop and grow in the kidneys. The cysts are fluid filled, and if they become too numerous or large, kidney damage occurs. PKD is one of the leading causes of kidney failure and has, at present, no available cure.

CrownBio provides genetically relevant rodent PKD models with a close correlation to human disease for use in novel agent efficacy evaluation:

  • pcy and jck mice
  • PCK rat

The models develop PKD associated with the genes that cause human disease, providing translatable rodent models, which closely mirror human PKD development. They have been thoroughly characterized at CrownBio for their disease progression and response to treatment. All models respond positively to reference compounds, providing a high level of confidence in your drug discovery studies.

Model

jck Mouse

pcy Mouse

PCK rat (maintained at CRL)

Rodent Strain

C57Bl/6J-nek8jck

CD-1-pcyIusm

PCK/Crl-Pkhd1pck/Crl

Gene Affected

Associated with the same gene that causes human nephronophthisis type 9

Associated with the same gene that causes human nephronophthisis type 3

Mutated in the same gene that causes human autosomal recessive PKD (ARPKD; PKHD1)

Disease Symptoms and Progression

Slowly progressing renal cystic disease. Cysts develop in multiple regions of the nephron and are more severe in male mice

Slowly progressive renal cystic disease. Cysts develop in the collecting tubules, other segments of the nephron become cystic as disease progresses. Male and female mice are similarly affected by the disease

Slowly progressing form of ARPKD. Displays significant kidney and liver cyst development similar to most humans with PKD

Our optimized study designs include different administration routes, dosing schedules, and endpoints to meet your needs.

Model

jck Mouse

pcy Mouse

PCK rat (maintained at CRL)

Rodent Age

5 weeks

5 weeks

4 weeks

Test Substance Administration Route

Oral gavage or admixed in diet

Admixed in diet

Oral gavage or admixed in diet

Typical Dosing Length

5 weeks

15 weeks

12 weeks

Endpoints

Cyst volume and fibrosis in kidney, including histological verification

Kidney weight/%body weight

Serum BUN

Concentration of test article in the blood

Other analyses relevant to cellular mechanisms may be included

Body weight and food intake recorded weekly

Cyst volume and fibrosis in kidney, including histological verification

Kidney weight

Serum BUN

Concentration of test article in the blood

Other analyses relevant to the target may be included

Body weight and food intake recorded weekly

Cyst volume and fibrosis in kidney and liver, including histological verification

Kidney and liver weight

Serum BUN, ALT, AST, and bilirubin

Concentration of test article in the blood

Other analyses relevant to cellular mechanisms may be included

Body weight and food intake recorded weekly

Positive Control

CDK inhibitor roscovitine

Vasopressin receptor-2 (V2) antagonist tolvaptan

PPARγ agonist pioglitazone

Uni-Nephrectomy, Aldosterone-Induced Renal Disease Model

Renal disease can be induced in Sprague-Dawley (SD) rats by uni-nephrectomy followed by aldosterone treatment and increasing salt intake, and the resulting model is used as an industry standard for evaluating mineralocorticoid receptor antagonists.

At CrownBio we have established this model and validated its response to the administration of clinically approved, mineralocorticoid receptor antagonists. Endpoints include collection of 24 hour urine samples, as well as histological study of the kidney and heart, which shows that eplerenone treatment prevents a rise in urinary albumin, as well as inhibiting kidney weight increases and changes in renal and cardiac pathology.

Type 2 Diabetic Nephropathy Model

In patients with diabetes, damage to small blood vessels in the kidneys leads to nephropathy. This can cause kidney failure, and eventually death. Diabetic nephropathy is the leading cause of dialysis and kidney transplant in developed countries, and preclinical models are required to further nephropathy research.

CrownBio’s ZDSD rat is an inbred polygenic model for metabolic syndrome, obesity, diabetes, and diabetic complications. Unlike other rodent models of metabolic disease, the ZDSD rat does not rely on monogenetic leptin or leptin receptor mutations for development of obesity and Type 2 diabetes (T2D), which more closely mimics human disease development. This results in a more translatable choice for evaluating your therapeutic agents.

The ZDSD rat displays diabetes progression similar to the human disease, with diabetic complications including nephropathy occurring around 24 weeks of age.

Diabetic nephropathy is evaluated by assessing the presence of typical biomarkers for renal dysfunction (i.e. IL6, TNF-α, NGAL, KIM-1, VEGF, etc.) as well as assessing albuminuria, free fatty acid levels, and via histological analysis. ACE inhibitor treatment reduces urinary albumin in the ZDSD rat, validating the use of this model in nephropathy research.

Contact us today to discuss your renal disease project needs and to experience the value of our expert service.

PRECLINOMICS