The development of a near infrared inulin optical probe for measuring glomerular filtration rate

A Hauser-Kawaguchi; M Milne; F Li; T Y Lee; L G Luyt

doi:10.1016/j.ijbiomac.2018.11.034

The development of a near infrared inulin optical probe for measuring glomerular filtration rate

Int J Biol Macromol. 2019 Feb 15:123:255-260. doi: 10.1016/j.ijbiomac.2018.11.034. Epub 2018 Nov 10.

Authors

A Hauser-Kawaguchi¹, M Milne², F Li³, T Y Lee⁴, L G Luyt⁵

Affiliations

¹ Department of Chemistry, Western University, London, Ontario, Canada.
² Cancer Research Laboratory Program, Lawson Health Research Institute and London Regional Cancer Program, London Health Sciences Center, London, Ontario, Canada.
³ Department of Medical Biophysics, Western University, London, Ontario, Canada; Robarts Research Institute, Western University, London, Ontario, Canada.
⁴ Department of Medical Biophysics, Western University, London, Ontario, Canada; Robarts Research Institute, Western University, London, Ontario, Canada; Department of Medical Imaging, Western University, London, Ontario, Canada.
⁵ Department of Chemistry, Western University, London, Ontario, Canada; Cancer Research Laboratory Program, Lawson Health Research Institute and London Regional Cancer Program, London Health Sciences Center, London, Ontario, Canada; Department of Medical Imaging, Western University, London, Ontario, Canada; Department of Oncology, Western University, London, Ontario, Canada. Electronic address: lluyt@uwo.ca.

PMID: 30419331
DOI: 10.1016/j.ijbiomac.2018.11.034

Abstract

The polysaccharide, inulin, is considered the clinical gold standard for measuring glomerular filtration rate (GFR), an assessment of kidney filtering capacity and renal function, and therefore, is a prognostic indicator of chronic kidney disease (CKD). The classic method of measuring GFR is laborious, tedious and invasive. Therefore, estimated GFR (eGFR) has become the favoured measurement, but unfortunately suffers in its accuracy. Here, we describe the development of a near infrared dye-labeled inulin, Cy7.5-inulin conjugate, for use as an optical probe to accurately and non-invasively measure GFR in patients by transcutaneous pulse dye densitometer (TPDD). We have characterized the modifications made to inulin and the dye-polysaccharide conjugate by a number of analytical techniques and demonstrated that it is stable under experimental in vivo conditions. To this end, the probe has been successfully used in a pig model to accurately measure GFR non-invasively.

Keywords: Conjugation chemistry; Glomerular filtration rate; Inulin; Polysaccharide; Transcutaneous pulse dye densitometer.

MeSH terms

Animals
Creatinine / chemistry
Densitometry
Glomerular Filtration Rate / physiology*
Humans
Inulin / chemistry
Inulin / isolation & purification*
Prognosis
Renal Insufficiency, Chronic / diagnosis*
Renal Insufficiency, Chronic / physiopathology
Swine

Substances

Inulin
Creatinine