Pseudo-Worsening of Kidney Function

Letters to the Editor regarding the article Onconephrology: The Significance of Renal Function for the Development, Diagnosis, and Treatment Of Cancer by Susanne Delecluse, Fridtjof Harder, Frieder Keller, Martin Zeier, and Stefanie Zschäbitz in issue 24/2024

In addition to PARP inhibitors, which are mentioned in the article (1), a multitude of further, especially oral, anti-tumor drugs can trigger pseudo-worsening of kidney function (2). In our view, it is crucial that this fact is emphasized since unawareness of this effect may lead to unnecessary dose reductions, interruptions, or even the discontinuation of antitumor treatments. Pseudo-worsening of kidney function is a drug-triggered increase in serum creatinine concentrations with a corresponding decrease in estimated glomerular filtration rates (eGFR) with sustained kidney function. The cause is the inhibition of the transporter-mediated renal creatinine secretion. This can be determined by means of alternative methods—for example, by measuring cystatin-C. For the CKD4/6 inhibitors abemaciclib, palbociclib, and ribociclib this seems to be a class effect. This effect has been described, for example, for abemaciclib in a study of healthy volunteers and is listed in the pertinent German Summary of Product Characteristics (2). Further oral antitumor drugs that can trigger pseudo-worsening of kidney function include cabozantinib, crizotinib, and selpercatinib (2, 3, 4).

In a recent analysis (2) we found 30 drugs that can cause pseudo-worsening of kidney function, 17 of which have antineoplastic or immunomodulatory properties. Unfortunately, only one quarter of the pertinent Summaries of Product Characteristics is unequivocal and sufficiently meaningful for routine clinical practice (2). In 119 further medications that cause an increase in serum creatinine, the data for the unequivocal differentiation of actual kidney injury and pseudo-worsening of kidney function is insufficient (2). Because of this evidence and the possible clinical consequences, we recommend using a creatinine-independent method, such as cystatin C measurement, in any relevant worsening of kidney function during treatment with oral antitumor drugs before making oncological medication-related therapeutic decisions.

DOI: 10.3238/arztebl.m2025.0021

Prof. Dr. med. Martin F. Fromm, Michael I. Sponfeldner,
Prof. Dr. phil. nat. Frank Dörje, Dr. rer. biol. hum. Katja Gessner,
Pauline Dürr, Dr. rer. biol. hum. Lisa Cuba, Julia Schwanfelder

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen

Conflict of interest statement

MFF received third-party funding from German Cancer Aid, the BMBF (the Federal Ministry of Research, Technology and Space), the BMG (the Federal Ministry of Health), the Dr August and Dr Anni Lesmüller Foundation, as well as Boehringer Ingelheim und Heidelberg Pharma Research. He received consultancy honoraria from Boehringer-Ingelheim.

FD received third-party funding from German Cancer Aid, the BMG, and the Dr August and Dr Anni Lesmüller Foundation.

KG received a honorarium for a CME event from Roche Pharma.

The remaining authors declare that no conflict of interest exists.

References

1. Delecluse S, Harder F, Keller F, Zeier M, Zschäbitz S: Onconephrology: The significance of renal function for the development, diagnosis, and treatment of cancer. Dtsch Arztebl Int 2024; 121: 793–9

2. Sponfeldner MI, Andrikyan W, Maas R, Fromm MF: Pseudo-worsening of kidney function due to inhibition of renal creatinine secretion: Quality of information provided in prescribing information/SmPC. Clin Pharmacol Ther 2024; 116: 1259–68

3. Chen MF, Harada G, Liu D, et al.: Brief report: Tyrosine kinase inhibitors for lung cancers that inhibit MATE-1 can lead to “false” decreases in renal function. J Thorac Oncol 2024; 19: 153–9

4. Izzedine H, Bouderlique E, Besse B: Selpercatinib and pseudo-decreases in kidney function. N Engl J Med 2024; 390: 1241–3