Kidney Week

Abstract: PUB192

Elevated Serum Syndecan-1 and Altered Glomerular CD34 May Indicate Glomerular Endothelial Injury in Gemcitabine-Induced Thrombotic Microangiopathy

Session Information

• Publication Only

Category: Onconephrology

• 1600 Onconephrology

Authors

• Sakai, Masato, Sugita Genpaku Memorial Obama Municipal Hospital, Obama, Fukui, Japan

Masato Sakai, MD

• Watanabe, Yuki, Sugita Genpaku Memorial Obama Municipal Hospital, Obama, Fukui, Japan

Yuki Watanabe, PhD

• Usada, Ayumu, Sugita Genpaku Memorial Obama Municipal Hospital, Obama, Fukui, Japan

Ayumu Usada, MD

• Matsumura, Yuichiro, Sugita Genpaku Memorial Obama Municipal Hospital, Obama, Fukui, Japan

Yuichiro Matsumura, DrMed

• Yamaguchi, Aina, Sugita Genpaku Memorial Obama Municipal Hospital, Obama, Fukui, Japan

Aina Yamaguchi, MD, PhD

• Masuda, Takahiro, Jichi Medical University, Shimotsuke, Tochigi, Japan

Takahiro Masuda, MD, PhD

• Okada, Hideshi, Gifu University Graduate School of Medicine, Gifu, Japan

Hideshi Okada, MD, PhD

• Yoshida, Haruyoshi, Sugita Genpaku Memorial Obama Municipal Hospital, Obama, Fukui, Japan

Haruyoshi Yoshida, MD, PhD

Introduction

Administration of gemcitabine (GEM) in advanced cancer frequently complicates renal insufficiency by thrombotic microangiopathy (TMA). Recently, serum syndecan-1 (SDC-1), a marker of endothelial glycocalyx injury, has been studied in systemic inflammation and critical illness. However, current evidence on glomerular endothelial injury remains limited.

Case Description

A 64 year old woman was diagnosed with advanced pancreatic cancer on February 202X. From April 202X, she received a cumulative GEM dose of 11,300 mg over months. She showed edema at 7 months and then hypertension at 9 months. At 10 months, GEM was discontinued with laboratory data of Hb 6.6 g/dL, serum haptoglobin <10 mg/dL, increases of serum creatinine (sCr) 1.77 mg/dL, LDH 722 U/L and D-dimer 5.8 μg/mL, and urinary protein 5.38 g/g creatinine. In renal biopsy, 16/22 non-globally-sclerosed glomeruli showed tuft swelling, subendothelial widening and severe glomerular basement membrane (GBM) thickening with irregular double contour, associated with fibrin thrombi. Electron microscopy study supported the diagnosis of TMA. Immunoenzyme staining using anti-CD34 antibody reactive to endothelial cell showed disrupted normal linear pattern with fragmented, granular and attenuated staining in most glomeruli, suggesting severe endothelial injury. Serum SDC-1 showed a moderate increase of 54.6 ng/mL (healthy control: median 19.3 ng/mL, IQR 13.7-27.5 ng/mL) at the last GEM treatment and remained elevated 47.0 ng/mL at discharge 2 months later, while hypertension and proteinuria improved with diuretics despite persistently elevated sCr levels.

Discussion

Glomerular CD34 staining was severely disrupted and serum SDC-1 was moderately elevated, as we have recently observed in a case of ramucirumab-induced glomerular microangiopathy, in which GBM thickening was less prominent.