title: Rethinking CKD Evaluation: Should We Be Quantifying Basal or Stimulated GFR to Maximize Precision and Sensitivity?
abstract: Chronic kidney disease (CKD) is an increasing clinical problem. Although clinical risk factors and biomarkers for the development and progression of CKD have been identified, there is no commercial surveillance technology to definitively diagnose and quantify the severity and progressive loss of glomerular filtration rate (GFR) in CKD. This has limited the study of potential therapies to late stages of CKD when FDA-registerable events are more likely. Because patient outcomes, including the rate of CKD progression, correlate with disease severity and effective therapy may require early intervention, being able to diagnose and stratify patients by their level of decreased kidney function early on is key for translational progress. In addition, renal reserve, defined as the increase in GFR following stimulation, may improve the quantification of GFR based solely on basal levels. Various groups are developing and characterizing optical measurement techniques using new minimally invasive or noninvasive approaches for quantifying basal and stimulated kidney function. This development has the potential to allow widespread individualization of therapy at an earlier disease stage. Therefore, the purposes of this review are to suggest why quantifying stimulated GFR, by activating renal reserve, may be advantageous in patients and to review fluorescent technologies to deliver patient-specific GFR.
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indiana Center for Biological Microscopy, Rouderbush VA, Indianapolis, IN. Electronic address: bmolitor@iu.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology; D004044:Dietary Proteins / Q000378:metabolism; D018450:Disease Progression; D061345:Early Medical Intervention; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005452:Fluoresceins; D005919:Glomerular Filtration Rate; D006801:Humans; D007444:Inulin / Q000031:analogs & derivatives; D007668:Kidney / Q000000981:diagnostic imaging; D009844:Oligosaccharides; D061848:Optical Imaging; D010953:Plasma Volume; D019275:Radiopharmaceuticals; D051436:Renal Insufficiency, Chronic / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D012720:Severity of Illness Index; D016284:Technetium Tc 99m Pentetate
chemical_list: D015415:Biomarkers; D004044:Dietary Proteins; C584353:FITC-inulin; D005452:Fluoresceins; D009844:Oligosaccharides; D019275:Radiopharmaceuticals; C576250:fluorescein-isothiocyanate sinistrin; D007444:Inulin; D003404:Creatinine; D016650:Fluorescein-5-isothiocyanate; D016284:Technetium Tc 99m Pentetate
keywords: 2-compartment GFR model; FDA registration; Renal reserve; chronic kidney disease (CKD); diabetic nephropathy; early detection; estimated GFR; filtration marker; fluorescent GFR determinations; glomerular filtration rate (GFR); hyperfiltration; kidney disease progression; measured GFR; one-compartment GFR model; plasma volume; renal function; review; serum creatinine; surrogate marker; therapeutic success