Comprehensive Kidney Disease Models

Kidney disease models, nephrotic syndrome, diabetic nephropathy, CKD, acute kidney injury

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.

Acute Kidney Injury

Acute Kidney Injury Models

Acute Kidney InjuryCisplatin-induced acute kidney injury model
Acute Kidney InjuryLPS-induced acute kidney injury model
Acute Kidney Injury PAN-induced renal podocyte injury model
Renal IschemiaUnilateral renal ischemia & reperfusion
Renal IschemiaBilateral renal ischemia & reperfusion
Acute Kidney InjuryIgA nephropathy-induced by anti-thy1 antibodies

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.

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

Nephrotic Syndrome


Minimal Change Disease/ Glome ModelPuromycin aminonucleoside (PA) induction
Membranous Nephritis ModelPassive Heymann nephropathy, Fx1A antibody induction

Chronic Kidney Diseases

Chronic and progressive nephropathy models

Hypertension ModelDeoxycorticosterone acetate (DOCA) salt induction
Chronic Kinney Damage Model5/6 nephrectomy
Nephropathy Model Doxorubicin (DOX) induction
Kidney FibrosisUnilateral Ureteral Obstruction (UUO)-induced renal fibrosis
Renal Anemia ModelAdenine-induced chronic and progressive nephropathy

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).

Unilateral Ureteral Obstruction (UUO) renal kidney fibrosis and tubular injury model, Sirius red staining
Figure 3a: Sirius Red staining for fibrosis (X200)
Unilateral Ureteral Obstruction (UUO) renal kidney fibrosis and tubular injury model, IHC staining
Figure 3b: IHC staining for smooth muscle actin (X200)
kidney fibrosis and tubular injury model, Sirius red quantitative morphometry
Figure 3c: Quantitative measurement of Sirius Red staining

Diabetic Nephropathy

Chronic and progressive nephropathy models

Diabetic Nephropathy Modeldb/db mouse
Diabetic Nephropathy ModelBTBR ob/ob mouse
Diabetic Nephropathy ModelKK-Ay  mouse
Diabetic Nephropathy ModelStreptozotocin (STZ) induction

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

BTBR ob/ob Diabetic Nephropathy, mesangial sclerosis
Figure 2a. Similar diffuse mesangial sclerosis and nodular mesangial sclerosis between human diabetic nephropathy and BTBR ob/ob mouse at 12 weeks after induction.
BTBR ob/ob Diabetic Nephropathy, mesangial sclerosis; interstitial inflammatory infiltration
Figure 2b. Evaluation of drug therapeutic effect in BTBR ob/ob mice.

Test Parameters

Mouse | Rat

Animal characteristics
Body weight, tissue weight, food/water intake and metabolic evaluation
Kidney function and biomarker analysis
Proteinuria: serum creatinine and BUN
Serum KIM-1 and other renal tubular biomarkers
Determination of hydrooxyproline and/or collagen content
Gene expression (qPCR, Microarray, RNA-seq, etc..)
Protein and metabolite profiling (WB, ELISA, mass spectrometry, etc.)
Pathological analysis
H&E staining/Analysis in tissues
Periodic Acid Schiff (PAS) staining
Collagen deposition evaluation in tissues by “Mason Trichrome” staining
Tissue a-SMAIHC staining and quantification
IHC stains and makers for specific targets, i.e. collagen subtypes, macrophage intersital infiltrates and other downstream signaling biomakers

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.

Efficacy measured by anti-proliferative and anti-fibrotic assays, NRK47F cells pre-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.