Comprehensive Kidney Disease Models

In recent years, acute kidney injury (AKI) and chronic kidney disease (CKD) are becoming more prevalent. They cause patient suffering, result in mortality, and require prolonged treatment times. Due to the limited understanding of the disease pathogenies and the lack of suitable disease models, the discovery and development of therapeutic products in this area encounter many challenges.

With over 15 years of experience, WuXi Biology has successfully developed and validated a comprehensive collection of clinically relevant rodent models representing AKI, CDK and Kidney fibrosis (KF). In addition to drug efficacy evaluations, the valuable MOA and biomarker information at protein and gene levels can also be provided by multiple endpoints including qPCR, ELISA, WB, FACS, LC-MS, and more.

List of kidney disease models and relevant test parameters

Case Studies

  • Cisplatin-induced Acute Kidney Injury Model

It is well studied that many patients develop severe renal complications after prolonged treatment with Cisplatin. In the Cisplatin-induced AKI model, plasma creatinine and KIM-1 significantly increased in mice treated with Cisplatin. Similar results were seen in patients. The increased creatinine and KIM-1 levels induced by Cisplatin are reversed by TGF-β1 inhibitors.

Figure 1. In the mouse Cisplatin-induced AKI model, plasma creatinine and KIM-1 levels were monitored for disease status and drug efficacy.

  • BTBR ob/ob Diabetic Nephropathy

The mouse strain BTBR with the ob/ob leptin-deficiency mutation develops severe type 2 diabetes and morphologic renal lesions which are characteristics of early and advanced diabetic nephropathy (DN) in humans as shown in Figure 2a.

Figure 2a. Similar diffuse mesangial sclerosis and nodular mesangial sclerosis between human diabetic nephropathy and BTBR ob/ob mouse at 12 weeks after induction.

In Figure 2b, Compound X significantly suppressed the inflammation (left) and the Glomerular Matrix Expansion Index (right) in the BTBR ob/ob model.

Figure 2b. Evaluation of drug therapeutic effect in BTBR ob/ob mice.

  • UUO-induced Kidney Fibrosis Model

Unilateral Ureteral Obstruction (UUO) causes renal fibrosis and tubular injury as a result of obstructed urine flow. The UUO-induced renal fibrosis model in rats and mice have been widely used for studying kidney fibrosis due to their clinical relevance and utility in testing drug efficacy. As shown in Figure 3, a TGF-β1 inhibitor is shown to reverse the UUO-induced fibrosis, measured by Sirius Red staining (Fig. 3a), smooth muscle actin staining (Fig. 3b) and quantitative measurement of Sirius Red staining (Fig. 3c).

Figure 3a: Sirius Red staining for fibrosis (X200)
Figure 3b: IHC staining for smooth muscle actin (X200)
Figure 3c: Quantitative measurement of Sirius Red staining

In Vitro Kidney Disease Models

In addition to in vivo animal models, the in-vitro cell models of kidney disease and fibrosis, including primary cells or cell lines, also play important roles in efficacy evaluation. Combined with our integrated in-vitro assay platform, the feasible, cost efficient and high throughput options are offered for compound screen and MOA study.

Figure 4 has demonstrated the anti-proliferative (left) and anti-fibrotic (right) effects of Compound X in vitro when the cells were stimulated by TGF-β1.

Figure 4. In-vitro testing of drug efficacy measured by anti-proliferative (left) and anti-fibrotic (right) assays, NRK47F cells were pre-stimulated by TGF-β1.