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Comprehensive Kidney Disease Models |
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Recent years, acute kidney injury (AKI) and chronic kidney disease (CKD) continue to cause the prolonged treatment time, patient suffering and mortality with increasing prevalence in population. Due to the limited understanding of the disease pathogenies and the lack of suitable disease models, the discovery and development of therapeutic products |
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With over 15 years of experience, HDB has successfully developed and validated a comprehensive collection of the clinical-relevant rodent models representing AKI, CDK and Kidney fibrosis(KF). In additional to drug efficacy evaluations, the valuable MOA and biomarker information at protein and gene levels can also be provided by multiple endpoints by qPCR, ELISA, WB, FACS, LC-MS, etc. The summary can be found in Table 1 |
followed by the case studies. |
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Table 1: List of HDB’s kidney disease models and relevant test parameters |
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Selected Cases |
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Cisplatin-induced Acute Kidney Injury Model |
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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 as happening in patients. The increased creatinine and KIM-1 level induced by Cisplatin are reversed by TGF-β1 |
inhibitors. |
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Figure 1. In the mouse Cisplatin-induced AKI model, plasma creatinine and KIM-1 levels were monitored for disease status and drug efficacy. |
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BTBR ob/ob Diabetic Nephropathy |
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The mouse strain BTBR with the ob/ob leptin-deficiency mutation develops severe type 2 diabetes and morphologic renal lesion characteristics of both early and advanced |
diabetic nephropathy (DN) in human as shown in Figure 2a. |
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Figure 2a. Similar diffuse mesangial sclerosis and nodular mesangial sclerosis between human diabetic nephropathy and BTBR ob/ob mouse at 12 weeks after induction. |
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In Figure 2b, Compound X significantly suppressed the inflammation (left) and the |
Glomerular Matrix Expansion Index (right) in the BTBR ob/ob model. |
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Figure 2b. Evaluation of drug therapeutic effect in BTBR ob/ob mice. |
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UUO-induced Kidney Fibrosis Model |
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Unilateral Ureteral Obstruction (UUO) causes renal fibrosis and tubular injury as a result of the obstructed urine flow. The UUO-induced renal fibrosis model in rat and mouse have been widely used for studying kidney fibrosis due to their clinical relevance and utilities 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). |
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Figure 3a. |
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Figure 3b. |
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Figure 3c. |
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Figure 3. A TGFβ1 inhibitor reverses the fibrosis induced by UUO, sham control (left), vehicle treatment (middle), TGFβ1 inhibitor treatment (right). 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 |
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In Vitro Kidney Disease Models |
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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 HDB’s integrated in-vitro assay platform, the feasible, cost |
efficient and high throughput options are offered for compound screen and MOA study. |
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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. |
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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. |
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Combining our comprehensive in-vitro screening platforms and in-vivo kidney disease models, HDB is proud to provide an end-to-end solution from lead identification, optimization and further preclinical efficacy and biomarker evaluation. For more |
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References |
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1.Siew E.D., Davenport A. The growth of acute kidney injury: a rising tide or just closer a |
ttention to detail? Kidney International. 2015;87(1):46–61. doi: 10.1038/ki.2014.293. |
2.Kalantar-Zadeh, K., Li, P.KT. Strategies to prevent kidney disease and its progression. Nat |
Rev Nephrol 16, 129–130 (2020). https://doi.org/10.1038/s41581-020-0253-1 |
3.Yin-Wu Bao.Kidney disease models: tools to identify mechanisms and potential |
therapeutic targets. Zool Res. 2018 Mar 18; 39(2): 72–86. |
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The Latest Generation of Auto Patch Clamp Platform Launched at HDB  |
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WuXi Biology/HD Biosciences Presented at Webinar of "New Technologies for Target Discovery and Validation" |
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HD Biosciences Merges with WuXi AppTec |
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