Correcting fluorescein isothiocyanate-sinistrin half-life-derived glomerular filtration rate in rats during growth and salt-driven volume expansion.
basic_science · Level V
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- Record sourced from PubMed, PMID 42492854.
- Also identified by DOI 10.1016/j.kint.2026.06.032.
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Abstract
Transcutaneous fluorescein isothiocyanate (FITC)-sinistrin fluorescence enables convenient, minimally invasive estimation of the glomerular filtration rate (GFR) in rodents. However, the commonly used fixed-factor conversions (i.e., GFR/BW conversion factor (21.33)/HL, where HL is sinistrin half-life and BW is body weight) assume the volume of distribution scales proportionally with BW. This assumption can bias GFR estimates when body composition shifts with growth or when extracellular fluid volume expands under high-salt intake. Here, we quantified these errors and developed improved HL-to-GFR conversion methods. Male and female Dahl salt-sensitive rats with chronically implanted venous catheters underwent simultaneous measurements of serum and transcutaneous FITC-sinistrin fluorescence. Serum clearance provided reference GFR and serum-derived HL, and the transcutaneous signal provided transcutaneous HL. In separate cohorts, body composition and extracellular fluid were assessed by Nuclear Magnetic Resonance-Bioimpedance Spectroscopy. A regression of GFR×HL was performed using BW, age, sex, and salt intake. In low-salt fed rats, sex-specific BW-based models explained much of the variability in GFR×HL (females: 97.81×BW<sup>0.385</sup>; males: 203.0×BW<sup>0.855</sup>; BW in kg). Separately, using data from all rats across salt conditions, we derived a salt-dependent conversion to allow for temporal salt effects. The corrected model detected the transient increase in GFR on high salt day 3 that was missed by a fixed factor. GFR scaled sub-linearly with BW (exponent 0.744). Allowing the sinistrin HL-to-GFR conversion to vary with BW and salt condition moderately improves the accuracy of HL-based FITC-sinistrin GFR estimates compared with a single fixed conversion factor and captures the transient GFR increase after salt loading. Sub-linear scaling of GFR supports allometric size adjustment (BW<sup>0.744</sup>) to reduce size dependent bias and better reflect true GFR in growing rats.