Kidney Week

Abstract: SA-PO0209

Use of Molecularly Targeted Cancer Medications and Kidney Health

Session Information

• Onconephrology: MGRS, HSCT, Electrolytes, RCC, and More
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1700 Onconephrology

Authors

• Ziolkowski, Susan, Stanford University, Stanford, California, United States

Susan Ziolkowski, MD, MS, FASN

• Long, Jin, Stanford University, Stanford, California, United States

Jin Long, PhD

• Zhong, Yutong, Stanford University, Stanford, California, United States

Yutong Zhong, MS

• Morgan-Cooper, Hannah, Stanford Health Care Corporation, Palo Alto, California, United States

Hannah Morgan-Cooper, MSc

• Wakelee, Heather, Stanford University, Stanford, California, United States

Heather Wakelee, MD

• Khaki, Ali Raza, Stanford University, Stanford, California, United States

Ali Raza Khaki, MD, MS

• Riaz, Fauzia, Stanford University, Stanford, California, United States

Fauzia Riaz, MD, MHS

• Leonard, Mary B., Stanford University, Stanford, California, United States

Mary B. Leonard, MD, MS

• Anand, Shuchi, Stanford University, Stanford, California, United States

Shuchi Anand, MD, MS

Background

Oral molecularly targeted cancer medications are widely used. Product labels describe an increase in serum creatinine (sCr), potentially due to reversible inhibition of tubular creatinine secretion, rather than acute kidney injury. Whether these medications are associated with progressive decline in kidney dysfunction with continued daily use is unknown.

Methods

Since center retrospective cohort study using electronic health record data of adult patients receiving cyclin dependent kinase 4/6 (CDK 4/6i), poly ADP ribose polymerase (PARPi), and specific drugs within tyrosine kinases inhibitor (TKI) subgroups that are associated with an acute change in sCr handling. We defined progressive kidney dysfunction as a sustained >30% decline in eGFR or reaching end-stage kidney disease over two years. To account for a potentially reversible rise in sCr at drug start, our baseline eGFR was the mean value from days 1-60 after drug start. We used cox proportional hazards regression models to determine the hazard of progressive kidney dysfunction for each drug class compared with propensity score matched cohorts without cancer. Subgroup analyses excluded patients without a >20% increase in sCr at drug start and without exposure to potentially nephrotoxic chemotherapy or immunotherapy during the study period.

Results

Among 5,015 patients in the treated cohort, median age was 62 (25^th-75^th percentile 51-72) years and mean baseline eGFR prior to drug start was 87 (SD 23) ml/min/1.73m². The overall incidence and rate of progressive kidney dysfunction was higher in the treated cohort than in propensity matched cohorts of patients without cancer [44 versus 38 per 1000 person-years; HR 1.4 (95% CI:1.2-1.6]. Rates of kidney dysfunction were higher among patients treated with CDK 4/6i [HR 1.9 (95% CI: 1.4-2.6)], EGFRi [HR 1.8 (1.2–2.5)], VEGFRi [HR 2.1 (1.6–2.7)], and BRAFi [1.9 (1.1–3.3)], compared with controls. These higher rates persisted in patients without >20% increase in sCr at drug start and without exposure to chemotherapy or immunotherapy.

Conclusion

We observed higher incidence and relative rate for kidney dysfunction among patients treated with specific molecularly targeted anti-cancer medications, compared with matched cancer-free patients, and after accounting for risk factors and early increase in sCr.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025tbk58j9p