Safety assessments for drug-induced kidney injury

Category: ciPTEC, Research

Safety assessments for drug-induced kidney injury

Obtaining mechanistic insights on adverse effects in the kidney during clinical trials is challenging. 

We are going to show you how you can perform confident safety assessments on observed drug-induced kidney injury with our ciPTEC cell models. Just like we did with researchers at Biomarin, GSK, and AstraZeneca

As a researcher, it’s your job to understand adverse effects through mechanistic insights that allow you to determine the exact toxic potential, or to determine whether the risk is limited as compared to the benefits of the drug. 

It will be your results and insights that determine the course towards a successful market introduction.


Evaluating the risks

For example, the development of anti-sense oligonucleotides as therapeutic intervention for genetic diseases is associated with proximal tubular dysfunction and presented with proteinuria. 

This adverse effect was observed both in animal and clinical studies performed by BioMarin. Moreover, the effect seemed to be reversible when treatment was arrested and the toxicological importance was considered to be limited. 

Obviously, such observation demands further mechanistic investigations in order to fully understand the risks and pave the way for a confident and successful market introduction.


Getting answers

In case of the proximal tubule dysfunction as presented here, we’ll need to answer;

  • Which mechanism is responsible for the reversible nature of the clinical proteinuria? and,… 
  • Is the drug exposure leading to a relevant toxicological risk? 

The better you’re able to address these questions, the better your insights will be to determine the risks, and the bigger the impact your research will have. 

Therefore, arming yourself with a highly reliable and accurate renal cell model like ciPTEC is essential.


BioMarin results

ciPTEC was used by BioMarin to address these questions in the case of antisense oligonucleotide therapy in the treatment of Duchenne’s muscular dystrophy. 

Due to the high resemblance of ciPTEC with the in vivo situation and intact transporter capacity, we could demonstrate the uptake of the drug in ciPTEC. The drug competed with uptake of proteins that are normally taken up by the proximal tubule cells. 

This observation explained the mechanism behind the clinical observations: drug competition in the proximal tubule cells resulted in elevated levels of proteins ending up in the urine of treated animals and patients. 

Last but not least, our in vitro assays with drugs exposed to ciPTEC did not lead to a toxic response, underscoring the limited toxicological importance of the observations and so provided confidence to continue clinical studies towards market introduction. This study was published by Janssen MJ et al, Mol Ther Nucleic Acids 2019

ciPTEC is a valuable tool to help you understand the mechanism of toxicity observed in clinical trials and provide a platform to make an informed decision on the continuation of the drug development process.


If you would like to try ciPTEC yourself you can contact us: here. 

  • Assay ready cryopreserved aliquots 
  • Fully differentiated and pre-qualified
  • For instant use, no cultivation required
  • Improved reproducibility by homogeneous cell banks

If you have questions then please feel free to reply to this email. We are happy to help.


Coming up: Fail fast, without losing your next blockbuster

We’ll unpack that in our next blogpost. 

Martijn & Errol



If you would like to read more about the use of ciPTEC, here are three publications we think you’ll like: