A portable fiberoptic ratiometric fluorescence analyzer provides rapid point-of-care determination of glomerular filtration rate in large animals

Abstract

Measurement of the glomerular filtration rate (GFR) is the gold standard for precise assessment of kidney function. A rapid, point-of-care determination of the GFR may provide advantages in the clinical setting over currently available assays. Here we demonstrate a proof of principle for such an approach in a pig and dogs, two species that approximate the vascular access and GFR results expected in humans. In both animal models, a sub-millimeter optical fiber that delivered excitation light and collected fluorescent emissions was inserted into a peripheral vein (dog) or central venous access (pig) by means of commercial intravenous catheters. A mixture of fluorescent chimeras of a small freely filterable reporter and large non-filterable plasma volume marker were infused as a bolus, excited by light-emitting diodes, and the in vivo signals detected and quantified by photomultiplier tubes in both species in less than 60 min. Concurrent standardized 6-h iohexol plasma kidney clearances validated the accuracy of our results for both physiologic and a chronic kidney disease setting. Thus, our ratiometric technique allows for both measurement of plasma vascular volume and highly accurate real-time GFR determinations, enabling clinical decision making in real time.

Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

“…Iohexol clearance has been used in critically ill patients but as mentioned above, is laborious and time consuming 36,37 . Finally, fibreoptic ratiometric fluorescence analysis has shown promise for the measurement of GFR in large animals but awaits validation in human clinical settings 38 .…”

Targeting Endogenous Repair Pathways after AKI

“…14 The renal tubular compartment is the most commonly injured target in various settings of AKI. There are multiple markers available to evaluated tubular dysfunction, such as albuminuria, small molecular weight proteinuria, renal glycosuria, impaired tubular acidification, and decreased urinary concentrating function.…”

The first decade of using multiphoton microscopy for high-power kidney imaging

“…The Molitoris group established the ratiometric measurement of glomerular filtration function using various GFR and plasma markers (61,64,65). Their work ultimately resulted in the development of a novel, clinically useful diagnostic approach for the rapid quantification of GFR, for example, in acute kidney injury (60).…”