gms | German Medical Science

Background: In clinical practice, kidney function is most commonly assessed by calculation of glomerular filtration rate (eGFR) based on measurement of serum creatinine concentrations (SCr). In addition to passive filtration in the glomerulus, creatinine is actively secreted into the proximal tubule by several renal transport proteins such as OCT2, OAT2 and MATE1/2K. Various drugs that are inhibitors of these transporters (e.g., CDK4/6-inhibitors) can cause a significant increase in SCr without altering kidney function. This may result in misinterpretations of the calculated eGFR values. Therefore, clinicians need to be informed by Summaries of Product Characteristics (SmPCs) for adequate decision-making. The aim of our study was the compilation of a comprehensive list of drugs that cause an increase in SCr through transporter inhibition, i.e., a pseudo-worsening of kidney function, followed by the analysis of the quality of information provided in German and US SmPCs on this topic.

Materials and Methods: Through literature research, the UCSF-FDA Transportal database and 2022/2023 EMA and FDA approvals, we identified putative drug substrates and inhibitors of renal creatinine transporters. By reviewing relevant literature and the SmPCs of the identified putative drug substrates and inhibitors, we compiled a list of drugs that can lead to pseudo-worsening of kidney function due to inhibition of renal creatinine transport. Subsequently, we reviewed the German and US SmPCs of these drugs and ranked their quality of information based on a self-developed ranking system concerning information provided about transporter interaction and influence on SCr levels.

Results: We identified 514 drugs that were substrates and/or inhibitors of renal creatinine transport proteins. Of these, we identified 30 drugs, primarily oral antitumor drugs (56.7%, 17/30) that cause an increase in SCr without altering kidney function. By reviewing a total of 51 SmPCs from Germany and the USA of these drugs, we found that only 12 SmPCs (23.5%, 12/51) contained adequate information and provided information about the transporter interaction, the increase in SCr and action recommendations for treating physicians.

Conclusion: Unrecognized pseudo-worsening of kidney function due to inhibition of renal creatinine secretion can lead to severe clinical consequences, such as unnecessary treatment discontinuation. Our analysis showed that the information provided in SmPCs on this topic is insufficient, posing an avoidable risk for medication safety.