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Renal cell models across human and preclinical species

Our renal models use freshly isolated, never-passaged proximal tubule cells from human donors, rats, mice and dogs, alongside a human thick ascending limb model. All cells are cultured under advanced conditions developed to preserve key features of their differentiated phenotype.

Nephrotoxicity screening

Why model biology matters

Proximal tubule cell phenotype influences the transporters, receptors, enzymes and injury-associated markers used to assess compound effects. Changes caused by passaging or immortalisation can diminish these features and affect how a compound’s effects are observed in vitro.

From donor kidney to nephrotoxicity data

Model preparation

  1. Four species

    • Human donor
    • Mouse
    • Rat
    • Dog

    One platform: human donor, mouse, rat and dog kidneys. Choose your species combination.

  2. Fresh isolation

    Isolated directly from fresh tissue and never passaged.

  3. Cell culture inserts

    Advanced culture and media conditions maintain the cells’ differentiated phenotype.

Testing and readout

  1. Compound exposure

    Test compounds assessed across a concentration range.

  2. Assessment of cell health and function

    • Barrier integrity
    • Morphological imaging
    • LDH
    • ATP
    • ROS
    • Injury biomarkers
    • Gene and protein analysis

    The same kinetic and endpoint readouts applied to every species.

  3. Data reporting

    • Human
    • Preclinical species

    Study-specific data packages and reporting.

Case study

Species-specific responses in human and rat proximal tubule cells

To help interpret preclinical renal findings in the context of human biology, this study compared responses in human and rat proximal tubule cells exposed to a test compound, two approved compounds and cisplatin as a positive nephrotoxicity control.

What the data showed

  • Intracellular ATP: Cisplatin caused a concentration-dependent decrease, while the test compound and approved compounds produced only minor changes.
  • Kidney injury biomarker release: Increased following cisplatin exposure, but not with the test compound or approved compounds. The decrease at the highest cisplatin concentration is consistent with cell death.
  • Pathological finding: The test compound increased the readout in rat proximal tubule cells only, consistent with in vivo findings. No increase was observed in human proximal tubule cells or with either approved compound.

Why it matters

The rat-specific response, consistent with in vivo findings, was not observed in human proximal tubule cells. Comparing responses across species can help drug-development teams assess the relevance of preclinical renal signals to human biology and inform decisions about further safety testing and compound progression.

Swipe sideways to see the full charts.

Six bar charts of results in human (left) and rat (right) proximal tubule cells: intracellular ATP, biomarker release and pathological finding, each as a percentage of control (n = 3), for a test compound, approved compounds A and B and cisplatin. Individual data points and p-values are shown.
Figure 1. Species-specific responses in human and rat proximal tubule (PT) cells. Intracellular ATP, biomarker release and pathological finding in human (left) and rat (right) PT cells, shown as a percentage of control (n = 3). Conditions: media control; a test compound and two approved compounds (A and B), each at three concentrations; and cisplatin. Statistical comparisons are annotated on each chart.
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Renal uptake and accumulation

Investigate megalin- and cubilin-mediated uptake

The proximal tubule reclaims filtered proteins and peptides through receptor-mediated endocytosis involving megalin and cubilin at the apical membrane. Some drug modalities, including peptides and oligonucleotides, anti-infectives, proteins and biologics, and radioligand and radiopharmaceutical therapies, can engage these pathways, resulting in intracellular accumulation that may affect cell function or contribute to renal injury.

Why the model matters

Assessment of receptor-mediated uptake depends on retaining the relevant cellular machinery. FarneBio’s primary proximal tubule cells are cultured under conditions designed to retain megalin and cubilin expression, supporting the investigation of receptor-mediated internalisation and intracellular accumulation.

Uptake can also be assessed alongside nephrotoxicity endpoints, helping investigate the relationship between cellular exposure and injury.

From donor kidney to uptake data

Model preparation

  1. Two species

    • Human donor
    • Mouse

    One platform: human donor and mouse. Choose your species combination.

  2. Fresh isolation

    Isolated directly from fresh tissue and never passaged.

  3. Cell culture inserts

    Megalin and cubilin expression preserved

    Advanced culture and media conditions maintain the cells’ differentiated phenotype.

  4. Compound dosing

    • Peptides and oligonucleotides
    • Anti-infectives
    • Proteins and biologics
    • Radioligand and radiopharmaceutical therapies

    Compounds are applied to the compartment of interest (apical, basolateral or both).

Testing and readout

  1. Receptor-mediated uptake

    Apical (lumen)Clathrin-coatedpitCoated vesicleAccumulationReceptorsrecycleEndosomeLysosomeProximal tubule cell
    • Ligand
    • Megalin
    • Cubilin
    4°C control

    Separates surface binding from internalisation.

    Inhibition

    Receptor inhibition; supports receptor-mediated uptake.

    Temperature and inhibition controls support the conclusion that uptake is mediated by megalin and cubilin.

  2. Readout

    Accumulation

    Uptake inside the cells

    Injury Optional

    Measures of cell health and function

    Accumulation can be assessed in parallel with readouts of toxicity.

  3. Data reporting

    • Human
    • Mouse

    Cross-species comparisons to support translation to in vivo data.

Case studies

Investigating renal uptake and safety liabilities

FarneBio’s proximal tubule models can help drug-development teams investigate receptor-mediated uptake, assess injury-associated responses, and compare how antibody-fragment constructs influence renal payload accumulation.

Case study · Human proximal tubule cells

Assessing renal uptake and injury in human cells

For compounds with potential to accumulate in the kidney, understanding uptake is only part of the picture. Drug-development teams also need to assess potential effects on renal cell health. This study illustrates how FarneBio’s human proximal tubule model can be used to investigate uptake mechanisms and measure injury-associated responses within a coordinated study.

A · The uptake machinery is present

Western blotting detected megalin and cubilin in freshly isolated and cultured human proximal tubule cells, confirming expression of key receptors involved in proximal tubule uptake.

B–C · Uptake function can be tested

Albumin uptake was reduced at 4°C and in the presence of megalin-cubilin inhibitors, supporting temperature-dependent, receptor-mediated internalisation.

D · Injury-associated effects can also be measured

Polymyxin B, which is taken up by endocytosis, decreased intracellular ATP and increased kidney injury biomarker release at higher concentrations, showing that cell health and injury readouts capture complementary effects.

Why it matters

Rather than measuring uptake alone, researchers can test whether uptake is functionally active and assess injury-associated responses in human proximal tubule cells. This combined view can help teams characterise renal uptake and evaluate potential safety liabilities during compound assessment.

Swipe sideways to see the full figure.

Panels A to D from human proximal tubule cells. A: Western blot of megalin (LRP2) and cubilin (CUBN), with vinculin shown in each sample, in freshly isolated cells, cultured cells and lung fibroblasts as a negative control. B: bar chart of FITC-albumin uptake at 37°C and 4°C. C: bar chart of albumin uptake with and without inhibitors. D: bar charts of intracellular ATP and biomarker release after polymyxin B at increasing concentrations.
Figure 2. Renal uptake and injury-associated readouts in human proximal tubule (PT) cells. (A) Cultured PT cells retain the receptors required for endocytosis. Western blot showing expression of megalin (LRP2) and cubilin (CUBN), the key receptors for PT protein uptake, in freshly isolated and cultured cells. Neither receptor is detected in lung fibroblasts, which serve as a negative control. Vinculin confirms protein is present in all samples. (B) FITC-albumin uptake at 37°C relative to 4°C; dotted line indicates the binding reference. (C) FITC-albumin uptake at 37°C with or without megalin-cubilin inhibitors, normalised to the no-inhibitor condition. (D) Intracellular ATP and kidney injury biomarker release following 24-hour polymyxin B (PmB) exposure, expressed as a percentage of control. Statistical comparisons are indicated on the plots.
Case study · Mouse proximal tubule cells

Assessing how constructs influence renal payload uptake

When developing antibody-fragment constructs, understanding their effect on renal payload uptake can help identify potential kidney accumulation liabilities. This study used FarneBio’s mouse proximal tubule model to compare radiolabelled payload accumulation with and without two bispecific antibody-fragment constructs.

A–B · Functional uptake controls

Mouse proximal tubule cells were cultured on cell culture inserts, with transepithelial electrical resistance used to confirm barrier integrity. Albumin uptake was reduced at 4°C and by megalin-cubilin inhibitors, supporting functional, receptor-mediated uptake.

C · Constructs increase apical payload accumulation

Both bispecific antibody-fragment constructs significantly increased apical accumulation of the radiolabelled payload compared with payload alone. Basolateral accumulation remained low, with no clear differences between treatments.

Why it matters

The model enables researchers to compare how candidate constructs influence payload accumulation in renal proximal tubule cells. By identifying construct-associated increases in uptake, it can help teams investigate potential kidney accumulation liabilities and inform construct selection and further safety assessment.

Swipe sideways to see the full figure.

Panels A to C from mouse proximal tubule cells. A: bar chart of FITC-albumin uptake at 37°C and 4°C. B: bar chart of albumin uptake with and without inhibitors. C: bar charts of intracellular accumulation of a radiolabelled payload after apical and basolateral exposure, alone or with bispecific antibody-fragment construct A or B.
Figure 3. Albumin uptake controls and radiolabelled payload accumulation in mouse proximal tubule (PT) cells. (A) Cell-associated FITC-albumin at 37°C relative to the 4°C condition, with the dotted line indicating the binding reference. (B) Cell-associated FITC-albumin at 37°C in the absence or presence of megalin-cubilin inhibitors, expressed as a percentage of the no-inhibitor condition. (C) Intracellular accumulation of radiolabelled payload after apical or basolateral exposure, alone or in combination with bispecific antibody-fragment construct A or B, in mouse PT cells cultured on cell culture inserts. Statistical comparisons are indicated on the apical plot.
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Cross-species comparison studies

Compare renal responses across human and preclinical species

Species differences can influence compound uptake and renal injury responses. We compare human proximal tubule models with relevant preclinical species using aligned study protocols and endpoints, helping identify species-dependent findings and interpret preclinical results alongside human-cell data.

Species available by study type
Study typeSpecies available
NephrotoxicityHuman donor, rat, mouse and dog
Receptor-mediated uptakeHuman donor and mouse

For an example of a human–rat comparison, see the nephrotoxicity case study.

Planning a cross-species study?

Discuss your compound, target species and study objectives with our team.

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Custom renal assays

Tailored studies for specific renal research questions

When your research question extends beyond our established assay formats, we can discuss a tailored study design around your compound and objectives, drawing on our renal cell models and experience delivering projects with bespoke functional, biomarker and molecular readouts.

Discuss a custom study →
How we work

From study design to results, in three stages

01
Study design
We work with your team to define the research question, compounds, models, species and endpoints. The study protocol, timeline and cost are agreed before work begins.
02
Study execution
A technical project lead coordinates the study, including compound logistics. We conduct the work to the agreed protocol, with interim updates provided at agreed milestones.
03
Results and discussion
You receive a full data set and project report, with a presentation to discuss the findings and their interpretation in the context of your research objectives, and potential next steps.
Internal quality framework

All studies are conducted in accordance with FarneBio’s internal quality framework, supporting a consistent approach to study execution and data quality.

Publications

The science behind the technology

  • Pye, K., Tasinato, E., Shuttleworth, S., Devlin, C., & Brown, C. (2024). Comparison of the impact of VRP-034 and polymyxin B upon markers of kidney injury in human proximal tubule monolayers in vitro. Antibiotics, 13(6), 530. https://doi.org/10.3390/antibiotics13060530
  • Vriend, J., Pye, K., & Brown, C. (2021). In vitro models for accurate prediction of renal tubular xenobiotic transport in vivo. Current Opinion in Toxicology, 25, 15–22. https://doi.org/10.1016/j.cotox.2020.12.001
  • Bajaj, P., Chung, G., Pye, K., Yukawa, T., Imanishi, A., Takai, Y., Brown, C., & Wagoner, M. P. (2020). Freshly isolated primary human proximal tubule cells as an in vitro model for the detection of renal tubular toxicity. Toxicology, 442, 152535. https://doi.org/10.1016/j.tox.2020.152535
  • Bartels, M., Brown, C., Chung, G., Chan, M., Terry, C., Gehen, S., & Corvaro, M. (2020). Review of the pharmacokinetics and metabolism of triclopyr herbicide in mammals: Impact on safety assessments. Regulatory Toxicology and Pharmacology, 116, 104714. https://doi.org/10.1016/j.yrtph.2020.104714
  • Kumar, V., Yin, J., Billington, S., Prasad, B., Brown, C. D. A., Wang, J., & Unadkat, J. D. (2018). The importance of incorporating OCT2 plasma membrane expression and membrane potential in IVIVE of metformin renal secretory clearance. Drug Metabolism and Disposition, 46(10), 1441–1445. https://doi.org/10.1124/dmd.118.082313
  • Prasad, B., Johnson, K., Billington, S., Lee, C., Chung, G. W., Brown, C. D. A., Kelly, E. J., Himmelfarb, J., & Unadkat, J. D. (2016). Abundance of drug transporters in the human kidney cortex as quantified by quantitative targeted proteomics. Drug Metabolism and Disposition, 44(12), 1920–1924. https://doi.org/10.1124/dmd.116.072066
  • Jenkinson, S. E., Chung, G. W., van Loon, E., Bakar, N. S., Dalzell, A. M., & Brown, C. D. A. (2012). The limitations of renal epithelial cell line HK-2 as a model of drug transporter expression and function in the proximal tubule. Pflügers Archiv – European Journal of Physiology, 464(6), 601–611. https://doi.org/10.1007/s00424-012-1163-2
  • Brown, C. D. A., Sayer, R., Windass, A. S., Haslam, I. S., De Broe, M. E., D’Haese, P. C., & Verhulst, A. (2008). Characterisation of human tubular cell monolayers as a model of proximal tubular xenobiotic handling. Toxicology and Applied Pharmacology, 233(3), 428–438. https://doi.org/10.1016/j.taap.2008.09.018
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Let’s discuss your renal research question

Tell us what you need to understand about your compound. We will help you explore the relevant models, endpoints and study approach.

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