Kidney Week

Abstract: PUB129

Glomerular Endothelial Injury Broadening the Spectrum of Palbociclib-Associated Nephrotoxicity

Session Information

• Publication Only

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Kawata, Yoshihiro, Tomakomai Shiritsu Byoin, Tomakomai, Hokkaido Prefecture, Japan

Yoshihiro Kawata, MD

• Kunishi, Ryosuke, Sapporo Tokushukai Byoin, Sapporo, Hokkaido Prefecture, Japan

Ryosuke Kunishi, MD

• Araki, Makoto, Sapporo Tokushukai Byoin, Sapporo, Hokkaido Prefecture, Japan

Makoto Araki, MD, PhD

• Ogawa, Yayoi, Sapporo Tokushukai Byoin, Sapporo, Hokkaido Prefecture, Japan

Yayoi Ogawa, MD, PhD

• Yanai, Mitsuru, Sapporo Tokushukai Byoin, Sapporo, Hokkaido Prefecture, Japan

Mitsuru Yanai, MD, PhD

Introduction

Palbociclib (PAL), a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has been associated with elevated serum creatinine and acute kidney injury, most attributed to pseudo-AKI due to tubular secretion inhibition or tubulointerstitial injury. Given that PAL has been reported to cause thrombotic microangiopathy (TMA)-like vascular endothelial injury, a similar pathology within the kidney is suspected.

Case Description

A 63-year-old woman with a long treatment history for metastatic breast cancer developed progressive elevation of serum creatinine following initiation of PAL plus letrozole (LET) (from 0.82 to 1.64 mg/dL over approximately 3 months). Renal function continued to deteriorate even after PAL discontinuation (peak creatinine 2.14 mg/dL), prompting referral to our department. Although hepatic metastases were present on MRI, PET-CT demonstrated no viable tumor, making direct tumor-related renal involvement unlikely. Renal biopsy revealed glomerular endothelial injury predominantly characterized by GBM wrinkling and endotheliosis, along with IFTA involving approximately 40% of the cortex, with no immune complex deposition. Following antihypertensive therapy, creatinine declined from 2.14 to 1.76 mg/dL and urinary protein from 2.3 to 1.1 g/gCr. Notably, fundoscopic examination revealed no hypertensive changes, suggesting that chronic hypertensive nephrosclerosis alone was insufficient to explain the observed pathology.

Discussion

Renal biopsy in this case demonstrated a histological pattern dominated by glomerular endothelial injury without immune complex deposition. Although TMA has been reported with PAL, no prior report has described an endothelial injury-predominant renal histology, and this case presents a novel phenotype. Given the potential involvement of endothelial homeostasis disruption including the VEGF pathway, this case challenges the current framework that restricts CDK4/6 inhibitor-related nephrotoxicity to tubular injury alone.