SERUM HYALURONAN CONCENTRATIONS REFLECT GLOMERULAR ENDOTHELIAL INJURY DURING ANTI-VEGF TREATMENT

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Abstract Title *

SERUM HYALURONAN CONCENTRATIONS REFLECT GLOMERULAR ENDOTHELIAL INJURY DURING ANTI-VEGF TREATMENT

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Co-author 1

Tomoko Mizaki mizaki.tomoko@gmail.com Aichi Medical University Department of Pharmacy Nagakute Japan *

Co-author 2

Yasuhiko Ito yasuito@aichi-med-u.ac.jp Aichi Medical University Department of Nephrology and Rheumatology Nagakute Japan -

Co-author 3

Takashi Iwata iwata.takashi.970@mail.aichi-med-u.ac.jp Aichi Medical University Oncology Center Nagakute Japan -

Co-author 4

Shogo Nakano nakano.shougo.876@mail.aichi-med-u.ac.jp Aichi Medical University Department of Breast and Endocrine Surgery Nagakute Japan -

Co-author 5

Naoto Sassa sassa@aichi-med-u.ac.jp Aichi Medical University Department of Urology Nagakute Japan -

Co-author 6

Akihito Kubo kuboa@aichi-med-u.ac.jp Aichi Medical University Oncology Center Nagakute Japan -

Co-author 7

Takayuki Nakayama nakayama.takayuki.005@mail.aichi-med-u.ac.jp Aichi Medical University Department of Clinical Laboratory Nagakute Japan -

Co-author 8

Akimasa Asai asai.akimasa.002@mail.aichi-med-u.ac.jp Aichi Medical University Department of Nephrology and Rheumatology Nagakute Japan -

Co-author 9

Makoto Yamaguchi yamaguchi.makoto.231@mail.aichi-med-u.ac.jp Aichi Medical University Department of Nephrology and Rheumatology Nagakute Japan -

Co-author 10

Takuji Ishimoto takuji.ishimoto@aichi-med-u.ac.jp Aichi Medical University Department of Nephrology and Rheumatology Nagakute Japan -

Co-author 11

Hideyuki Mishima mishima.hideyuki.960@mail.aichi-med-u.ac.jp Aichi Medical University Oncology Center Nagakute Japan -

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

Renal dysfunction associated with anticancer drugs may interfere with subsequent treatment. Anticancer therapeutics that target the vascular endothelial growth factor (VEGF) pathway are widely used to treat various cancers. However, they can cause vascular endothelial injury, including thrombotic microangiopathy and proteinuria. Hyaluronan is a component of the glycocalyx of endothelial cells in blood vessels. This study investigates whether serum hyaluronan concentration could reflect glomerular endothelial damage during anti-VEGF therapy.

Methods

A total of 275 patients scheduled to receive chemotherapy were enrolled in this study. Serum hyaluronan concentrations and urine protein-to-creatinine ratios (UPCRs) were assessed in 148 patients before they received chemotherapy, including anti-VEGF therapy. Hyaluronan and UPCR were evaluated at the beginning of anti-VEGF treatment and six months later, as well as when UPCR reached 0.5 g/g creatinine or renal dysfunction occurred.

Results

The serum hyaluronan concentration increased in 43% of patients who were treated with anti-VEGF therapy, and this increase correlated with UPCR. Changes in serum hyaluronan levels preceded changes in proteinuria levels. Patients who had normal proteinuria levels initially, but subsequently developed increased proteinuria and elevated serum hyaluronan levels, had significantly higher hyaluronan levels before receiving anti-VEGF therapy. In cases of nephrotic syndrome, such as membranous nephropathy due to podocyte injury, serum hyaluronan concentrations were not elevated. Serum hyaluronan levels were affected by sex, age, estimated glomerular filtration rate (eGFR), liver fibrosis, and gastric cancer.

Conclusion

Serum hyaluronan concentrations reflect glomerular endothelial injury and enable the earlier detection of renal injury than UPCR does during anti-VEGF treatment. Proper assessment requires serial measurements in individuals. Further studies in a larger cohort are warranted.

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