More than 30% of attrition during drug development is related to renal toxicity. Further, the prevalence of acute kidney injury due to drug toxicity in clinical practice is as a high as 18-27% (van Meer, 2014). Although, kidney function is routinely assessed during preclinical safety evaluations, nephrotoxicity remains a primary reason for discontinuation at all phases of drug development (Fuchs 2011). Because nephrotoxicity may affect one or more kidney cell types, the identification and evaluation of potential nephrotoxic effects is a challenging endeavor for pharmaceutical scientists.
For these reasons, new tools (e.g., cell- and biomarker-base assays) are playing an increasingly important role in the early identification of nephrotoxic effects (Huang, 2014). While animal models remain an integral part of the overall safety assessment of new drugs, advancement in these new tools is important because: 1) there exist well-known limitations to the translation of animal safety data to humans, and 2) there is an impetus for researchers to adhere to the principles of the 3Rs which advocate for Replacement, Reduction and Refinement of animals.
The availability of additional tools can improve a researcher’s ability to identify and assess the potential for an investigational drug to have nephrotoxic effects earlier in the drug development process. Earlier identification of nephrotoxic effects allows for pharmaceutical scientists to determine possible risk in humans before advancing to the clinical testing phase. Preclinical prediction of nephrotoxicity reduces the time and expense of drug development and increases the chance for clinical trial success, ultimately resulting in safe and efficacious drugs for patients.
The kidney plays an important role in the metabolism of exogenous compounds. Thus, primary human kidney cells that are cultured directly from organ tissue provide a great model for the evaluation of potential nephrotoxic effects from investigational new drugs (Li 2017). As compared to primary cell lines from other species (e.g., Cai 2009) or even human immortalized cell lines (Van der Hauwaert 2014), primary human kidney cells can better model metabolic pathways. Indeed, it has been reported that primary proximal tubule kidney cell cultures (a common target of toxic compounds (e.g., Havasi 2016)), and not immortalized cell lines, showed the most similarities with kidney tissue based on transcript profiling, and it was concluded that primary kidney cells are the most relevant in vitro model for investigating the potential nephrotoxic effects of new drugs (Van der Hauwaert 2014). Some researchers are also incorporating proximal tubule kidney cells on microchips for nephrotoxicity evaluations since these can better model the structural, mechanical, transport, absorptive, and physiological properties of the human kidney (Wilmer 2016; Jang 2013).
Prior to initiating a study with human primary kidney cells, researchers should conduct due diligence to identify a supplier that is reliable, has an established organ procurement network, and is experienced in providing high-quality cell lines. Novabiosis is a leading provider of several cryopreserved human cells from multiple organ types for research applications, drug discovery, and drug development. They offer a wide selection of primary human kidney cells from normal, healthy donors, including Glomerular Endothelial Cells, Kidney Cortical Cells, Kidney Mesangial Cells, Kidney Proximal Tubule Cells, and Kidney Podocytes. Primary human kidney cells are ideal to study renal function, fibrosis, inflammation, metabolism, and nephrotoxicity, and can be used to model or measure drug response.
Using primary human kidney cells during preclinical safety assessments may help identify potential nephrotoxic effects early in the drug development process so that pharmaceutical scientists can assess the potential risk to humans and subsequently develop plans to mitigate the toxicity or abandon the compound altogether.