Methods for renal function determination

A method for determining a glomerular filtration rate (GFR) in a patient in need thereof, said method comprising:

• administering to said patient a compound of Formula I, or a pharmaceutically acceptable salt thereof,
• measuring a concentration of the compound of Formula I in said patient over a measurement time window, wherein the compound of Formula I is configured to emit spectral energy when exposed to electromagnetic radiation, and wherein measuring the concentration of the compound of Formula I comprises transdermally measuring the spectral energy emitted from by the compound of Formula I in said patient over the measurement time window, and
• determining the GFR in said patient based on the measured concentration of the compound of Formula I over the measurement time window;
• wherein in the compound of Formula I,
• each of X1 and X2 is independently —CO2R1, —CONR1R2, —CO(AA) or —CONH(PS);
• each of Y1 and Y2 is independently selected from the group consisting of —NR1R2 and
• Z1 is a single bond, —CR1R2—, —O—, —NR1—, —NCOR1—, —S—, —SO—, or —SO2—;
• each of R1 to R2 are independently selected from the group consisting of H, —CH2(CHOH)aH, —CH2(CHOH)aCH3, —CH2(CHOH)aCO2H, —(CHCO2H)aCO2H, —(CH2CH2O)cH, —(CH2CH2O)cCH3, —(CH2)aSO3H, —(CH2)aSO3−, —(CH2)aSO2H, —(CH2)aSO2−, —(CH2)aNHSO3H, —(CH2)aNHSO3−, —(CH2)aNHSO2H, —(CH2)aNHSO2−,—(CH2)aPO4H3, —(CH2)aPO4H2−, —(CH2)aPO4H2−, —(CH2)aPO43−, —(CH2)aPO3H2, —(CH2)aPO3H−, and —(CH2)aPO32−;
• AA is a single amino acid or a peptide chain comprising two or more amino acids, each amino acid selected from the group consisting of natural and unnatural amino acids, wherein the two or more amino acids of the peptide chain are linked together by peptide or amide bonds and each instance of AA may be the same or different than each other instance;
• PS is a sulfated or non-sulfated polysaccharide chain comprising one or more monosaccharide units connected by glycosidic linkages;
• a is a number from 1 to 10, c is a number from 1 to 100, and each of m and n are independently a number from 1 to 3;
• and
• wherein said patient in need thereof is a human and has at least stage 1 CKD;
• wherein transdermally measuring the spectral energy comprises:
• attaching a sensor on a body of said patient, the body comprising skin, wherein said sensor is configured to generate and deliver electromagnetic radiation to the compound of Formula I, and detect the spectral energy emitted by the compound of Formula I;
• and
• wherein the method is performed using a system that includes the compound of Formula I, the sensor, and a computing device communicatively coupled to the sensor, wherein the computing device determines the GFR by correlating a decrease in the spectral energy emitted by the compound of Formula I over the measurement time window to the GFR of said patient and by calculating a decay parameter associated with renal clearance over the measurement time window, wherein the decay parameter is a rate constant that is directly related to the GFR normalized to a body size metric of the patient, and wherein the rate constant is determined by fitting an exponential function to the spectral energy as a function of time or a linear function to the log of the spectral energy as a function of time.