Preclinical models to support therapeutic assessment for acute kidney injury and fibrosis.
Oncodesign Services provides preclinical kidney models covering acute injury and renal fibrosis. By combining renal function monitoring with histopathology and mechanism-relevant readouts, we help you detect and interpret treatment effects that may not be captured by standard kidney biomarkers in isolation.
Feasibility and study design for liver-related disease programs
Acute and chronic inflammatory diseases of the kidney can be triggered by several causes of tissue injury such as exposure to toxins, autoimmune conditions, diabetes, or infections. Rodent models of kidney inflammation and injury are helpful in understanding the triggers and mechanisms of inflammatory kidney diseases, and the therapeutic response expected in human patients.
Typical readouts for kidney inflammation models:
- Clinical scoring
- Plasma and urine biochemistry and hemogram
- Body weight
- Histopathology
- Biomarker / drug monitoring
- Gene expression in kidneys by qPCR / dPCR
- Immune profiling (IHC, flow cytometry)
Histology slide (H&P stain) of kidney with acute kidney injury (AKI) induced by Cisplatin. Here we can see tubular necrosis and tubular casts.
Established kidney inflammation models available for preclinical studies:
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Acute Kidney Injury (AKI) Model
Acute kidney injury is characterized by a rapid decline in renal function following toxic, ischaemic, or inflammatory damage. An appropriate AKI model can be used to evaluate treatments intended to protect renal tissue, limit injury, or support recovery.
Our cisplatin-induced acute kidney injury mouse model reproduces the nephrotoxicity associated with this widely used chemotherapy. It is directly relevant to candidates designed to reduce cisplatin-associated kidney damage and can also support broader investigation of therapies targeting renal cellular injury.
The cisplatin AKI model can be adapted to address acute or more sustained kidney injury. Dose and study duration are selected according to the intended severity, disease kinetics, and therapeutic question, supporting the evaluation of both protective and recovery-focused interventions.
Renal function can be monitored using blood urea nitrogen (BUN), creatinine, and urine analysis. Histopathology provides a central assessment of tissue injury and treatment response, while gene-expression analysis, inflammatory biomarkers, immunohistochemistry, and immune profiling can be incorporated according to the candidate’s mechanism of action.
- Acute kidney injury model in mice, induced by Cisplatin(1)
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Unilateral Ureteral Obstruction (UUO) Model
The unilateral ureteral obstruction, or UUO, model is an established kidney fibrosis model. It produces progressive inflammation and tissue remodeling following controlled restriction of urinary flow from one kidney, making it relevant to compounds intended to prevent or reduce renal fibrosis.
In the UUO kidney model, restricted urinary flow leads to pressure within the affected kidney and an associated inflammatory response. This progressively alters the renal cortex and medulla and promotes collagen deposition.
Although obstruction initiates the pathology, the downstream inflammatory and profibrotic pathways make the UUO model useful for studying kidney fibrosis beyond obstructive renal disease. It provides a defined system for investigating extracellular matrix deposition, inflammatory tissue remodeling, and direct antifibrotic activity.
Histology, digital image analysis, and pathological review can be used to assess changes in kidney architecture and quantify fibrosis. Gene-expression analysis, immunohistochemistry, cytokine measurements, and immune profiling can provide additional mechanistic evidence tailored to the compound and study objectives.
- UUO kidney fibrosis model
Experimental example: Acute kidney injury induced via Cisplatin
While cisplatin induces toxicity on various systems, including gastrotoxicity, myelosuppression, ototoxicity and allergic reactions, the major dose-limiting side effect is nephrotoxicity.
It is estimated that 20% of patients receiving high-dose Cisplatin develop severe renal dysfunction and approximately one third of patients experience kidney injury just days following the first treatment.
Typically, serum creatinine and urea rise within 3 days of Cisplatin treatment. Necrostatin (RIPK-1 inhibitor) alleviates kidney dysfunction induced by Cisplatin.
Histological slides (H&P stain) comparing kidney tissue in healthy controls (left) and in mice having received 20mg/kg Cisplatin 3 days prior (right).
Quantification of damage caused by Cisplatin (20mg/kg) 3 days after administration, and comparison with healthy controls and animals treated with Necrostatin (RIPK1 inhibitor) at 3 and 10mg/kg BID.
Learn more about partnering with Oncodesign Services:
Oncodesign Services combines translational inflammation experience with a flexible approach to preclinical research, supporting both standard and customized study designs. Alongside an extensive portfolio of acute and chronic inflammatory disease models, we offer bespoke model development to address specific scientific questions and emerging therapeutic approaches.
Our scientific team is available to provide guidance from study planning through data interpretation, with comprehensive readouts including histology, clinical scoring, biomarkers, and functional endpoints. Histology samples are also available to support feasibility assessments and model selection before study initiation.
Contact our team to discuss your research objectives, explore the most appropriate models and endpoints, or request a quotation.
Oncodesign Services (ODS) has been a trusted preclinical partner for several years. The team consistently demonstrates scientific excellence and reliability, tailoring preclinical protocols to our exact needs.
Their ability to rapidly action and deliver projects has made collaboration in oncology research efficient and straightforward. Clear, responsive communication is crucial to us, and the strong working relationship with our client manager makes coordination very easy.
We appreciate the professionalism, confidence, and flexibility ODS brings to every project.
Oncology Biopharma Organization (Europe)
Can kidney disease studies be customized to our research needs?
Yes. Every program can be tailored to your scientific objectives, including animal strain, dosing regimen, treatment timing, disease severity, endpoint selection, and sample collection.
Do you help with study design?
Absolutely. Our scientific team collaborates with clients to optimize study design, including model selection, group size, treatment schedule, statistical considerations, and endpoint strategy.
Do you perform histopathology and fibrosis analysis for kidney disease studies?
Yes. We are able to offer access to a dedicated veterinary pathologist, and our pathology services include:
- H&E staining
- PAS staining
- Masson’s Trichrome
- Sirius Red staining
- Semi-quantitative pathology scoring
- Digital image analysis
- Immunohistochemistry and immunofluorescence
Do you provide PK/PD or biomarker support?
Yes. We can integrate pharmacokinetic, pharmacodynamic, biomarker, and target engagement assessments into efficacy studies.
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References
(1) Acute kidney injury model in mice, induced by Cisplatin
Luan Z, Wei Y, Huo X, Sun X, Zhang C, Ming W, Luo Z, Du C, Li Y, Xu H, Lu H, Zheng F, Guan Y, Zhang X. Pregnane X receptor (PXR) protects against cisplatin-induced acute kidney injury in mice. Biochim Biophys Acta Mol Basis Dis. 2021 Mar 1;1867(3):165996. doi: 10.1016/j.bbadis.2020.165996. Epub 2020 Oct 27. Erratum in: Biochim Biophys Acta Mol Basis Dis. 2022 Feb 1;1868(2):166305. PMID: 33127475. https://www.sciencedirect.com/science/article/pii/S0925443920303446?via%3Dihub
Chen X, Wei W, Li Y, Huang J, Ci X. Hesperetin relieves cisplatin-induced acute kidney injury by mitigating oxidative stress, inflammation and apoptosis. Chem Biol Interact. 2019 Aug 1;308:269-278. doi: 10.1016/j.cbi.2019.05.040. Epub 2019 May 31. PMID: 31153982. https://www.sciencedirect.com/science/article/abs/pii/S0009279719302819?via%3Dihub
Zhu L, Yuan Y, Yuan L, Li L, Liu F, Liu J, Chen Y, Lu Y, Cheng J. Activation of TFEB-mediated autophagy by trehalose attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury. Theranostics. 2020 Apr 27;10(13):5829-5844. doi: 10.7150/thno.44051. PMID: 32483422; PMCID: PMC7255003. https://pubmed.ncbi.nlm.nih.gov/32483422/
Lu Q, Wang M, Gui Y, Hou Q, Gu M, Liang Y, Xiao B, Zhao AZ, Dai C. Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis. Cell Death Dis. 2020 May 13;11(5):364. doi: 10.1038/s41419-020-2539-4. PMID: 32404875; PMCID: PMC7221100. https://www.nature.com/articles/s41419-020-2539-4
Hamano H, Ikeda Y, Goda M, Fukushima K, Kishi S, Chuma M, Yamashita M, Niimura T, Takechi K, Imanishi M, Zamami Y, Horinouchi Y, Izawa-Ishizawa Y, Miyamoto L, Ishizawa K, Fujino H, Tamaki T, Aihara KI, Tsuchiya K. Diphenhydramine may be a preventive medicine against cisplatin-induced kidney toxicity. Kidney Int. 2021 Apr;99(4):885-899. doi: 10.1016/j.kint.2020.10.041. Epub 2020 Dec 9. PMID: 33307103. : https://www.kidney-international.org/article/S0085-2538(20)31411-3/fulltext
(2) Diabetic nephropathy model in BTBRob/ob mice
- Review:
Alpers CE, Hudkins KL. Mouse models of diabetic nephropathy. Curr Opin Nephrol Hypertens. 2011 May;20(3):278-84. doi: 10.1097/MNH.0b013e3283451901. PMID: 21422926; PMCID: PMC3658822. https://journals.lww.com/co-nephrolhypertens/Abstract/2011/05000/Mouse_models_of_diabetic_nephropathy.12.aspx
- Model characteristics:
Hudkins KL, Pichaiwong W, Wietecha T, Kowalewska J, Banas MC, Spencer MW, Mühlfeld A, Koelling M, Pippin JW, Shankland SJ, Askari B, Rabaglia ME, Keller MP, Attie AD, Alpers CE. BTBR Ob/Ob mutant mice model progressive diabetic nephropathy. J Am Soc Nephrol. 2010 Sep;21(9):1533-42. doi: 10.1681/ASN.2009121290. Epub 2010 Jul 15. PMID: 20634301; PMCID: PMC3013527. https://journals.lww.com/jasn/Abstract/2010/09000/BTBR_Ob_Ob_Mutant_Mice_Model_Progressive_Diabetic.20.aspx
Opazo-Ríos L, Tejera-Muñoz A, Soto Catalan M, Marchant V, Lavoz C, Mas Fontao S, Moreno JA, Fierro Fernandez M, Ramos R, Suarez-Alvarez B, López-Larrea C, Ruiz-Ortega M, Egido J, Rodrigues-Díez RR. Kidney microRNA Expression Pattern in Type 2 Diabetic Nephropathy in BTBR Ob/Ob Mice. Front Pharmacol. 2022 Mar 16;13:778776. doi: 10.3389/fphar.2022.778776. PMID: 35370692; PMCID: PMC8966705. https://www.frontiersin.org/articles/10.3389/fphar.2022.778776/full
Li Y, Hu Q, Li C, Liang K, Xiang Y, Hsiao H, Nguyen TK, Park PK, Egranov SD, Ambati CR, Putluri N, Hawke DH, Han L, Hung MC, Danesh FR, Yang L, Lin C. PTEN-induced partial epithelial-mesenchymal transition drives diabetic kidney disease. J Clin Invest. 2019 Mar 1;129(3):1129-1151. doi: 10.1172/JCI121987. Epub 2019 Feb 11. PMID: 30741721; PMCID: PMC6391108. https://www.jci.org/articles/view/121987
- Testing of compounds:
Sugahara M, Tanaka S, Tanaka T, Saito H, Ishimoto Y, Wakashima T, Ueda M, Fukui K, Shimizu A, Inagi R, Yamauchi T, Kadowaki T, Nangaku M. Prolyl Hydroxylase Domain Inhibitor Protects against Metabolic Disorders and Associated Kidney Disease in Obese Type 2 Diabetic Mice. J Am Soc Nephrol. 2020 Mar;31(3):560-577. doi: 10.1681/ASN.2019060582. Epub 2020 Jan 29. PMID: 31996409; PMCID: PMC7062217. https://journals.lww.com/jasn/Abstract/2020/03000/Prolyl_Hydroxylase_Domain_Inhibitor_Protects.12.aspx
Locatelli M, Zoja C, Conti S, Cerullo D, Corna D, Rottoli D, Zanchi C, Tomasoni S, Remuzzi G, Benigni A. Empagliflozin protects glomerular endothelial cell architecture in experimental diabetes through the VEGF-A/caveolin-1/PV-1 signaling pathway. J Pathol. 2022 Apr;256(4):468-479. doi: 10.1002/path.5862. Epub 2022 Feb 23. PMID: 35000230. https://onlinelibrary.wiley.com/doi/10.1002/path.5862
(3) Kidney fibrosis model in rats, induced by unilateral ureteral obstruction
- Compound efficacy:
Tingskov SJ, Jensen MS, Pedersen CT, de Araujo IBBA, Mutsaers HAM, Nørregaard R. Tamoxifen attenuates renal fibrosis in human kidney slices and rats subjected to unilateral ureteral obstruction. Biomed Pharmacother. 2021 Jan;133:111003. doi: 10.1016/j.biopha.2020.111003. Epub 2020 Nov 20. PMID: 33227702. https://www.sciencedirect.com/science/article/pii/S0753332220311951?via%3Dihub
Mizutani A, Endo A, Saito M, Hara T, Nakagawa M, Sakuraya K, Murano Y, Nishizaki N, Hirano D, Fujinaga S, Ohtomo Y, Shimizu T. Hydrogen-rich water reduced oxidative stress and renal fibrosis in rats with unilateral ureteral obstruction. Pediatr Res. 2022 Jun;91(7):1695-1702. doi: 10.1038/s41390-021-01648-7. Epub 2021 Aug 7. PMID: 34365467 https://www.nature.com/articles/s41390-021-01648-7
Case study:
Cisplatin-induced acute kidney injury: Same references as above.