Compositions and systems for renal function determination

Abstract

The present disclosure relates to systems and methods for determining the renal glomerular filtration rate or assessing the renal function in a patient in need thereof. The system includes a computing device, a power supply, one or more sensors, and at least one tracer agent that fluoresces when exposed to electromagnetic radiation. The electromagnetic radiation is detected using the sensors, and the rate in which the fluorescence decreases in the patient is used to calculate the renal glomerular filtration rate in the patient.

What is claimed is: 
     
         1 . A system for determining a real-time glomerular filtration rate (GFR) in a patient in need thereof, said system comprising:
 a computing device, and   one or more sensor heads operatively coupled to said computing device,   wherein the computing device is configured to record over a measurement time window one or more measurements of spectral energy sent from the sensor heads before and/or after administration of a tracer agent to the patient ;   wherein the tracer agent is configured to emit spectral energy when exposed to electromagnetic radiation;   wherein the computing device determines the GFR of said patient 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 the body surface area of the patient;   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; and   wherein the fit to the data starts after equilibration of the tracer agent within or between fluid compartments of the patient.   
     
     
         2 . The system of  claim 1 , wherein the computing device further correlates a decrease in spectral energy emitted by the tracer agent over a measurement time window to the GFR of said patient. 
     
     
         3 . The system of  claim 1 , wherein the tracer agent is a compound of Formula I 
       
         
           
           
               
               
           
         
         wherein each of X 1  and X 2  is independently —CO 2 R 1 , —CONR 1 R 2 , —CO(AA) or —CONH(PS); 
         each of Y 1  and Y 2  is independently selected from the group consisting of —NR 1 R 2  and 
       
       
         
           
           
               
               
           
         
         Z 1  is a single bond, —CR 1 R 2 —, —O—, —NR 1 —, —NCOR 1 —, —S—, —SO—, or —SO 2 —; 
         each of R 1  to R 2  are independently selected from the group consisting of H, —CH 2 (CHOH) a H, —CH 2 (CHOH) a CH 3 , —CH 2 (CHOH) a CO 2 H, —(CHCO 2 H) a CO 2 H, —(CH 2 CH 2 O) c H, —(CH 2 CH 2 O) c CH 3 , —(CH 2 ) a SO 3 H, —(CH 2 ) a SO 3   − , —(CH 2 ) a SO 2 H, —(CH 2 ) a SO 2   − , —(CH 2 ) a NHSO 3 H, —(CH 2 ) a NHSO 3   − , —(CH 2 ) a NHSO 2 H, —(CH 2 ) a NHSO 2   − , —(CH 2 ) a PO 4 H 3 , —(CH 2 ) a PO 4 H 2   − , —(CH 2 ) a PO 4 H 2− , —(CH 2 ) a PO 4   3− , —(CH 2 ) a PO 3 H 2 , —(CH 2 ) a PO 3 H − , and —(CH 2 ) a PO 3   2− ; 
         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; and 
         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. 
       
     
     
         4 . The system of  claim 1 , wherein the tracer agent is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         5 . A method for assessing renal function in a patient in need thereof by determining a real-time glomerular filtration rate (GFR) of the patient, the method comprising:
 recording one or more measurements of spectral energy emitted by a tracer agent over a measurement time window, wherein the tracer agent is administered to the patient and is configured to emit spectral energy when exposed to electromagnetic radiation; and   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 the body surface area of the patient;   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; and   wherein the fit to the data starts after equilibration of the tracer agent within or between fluid compartments of the patient.   
     
     
         6 . The method of  claim 5 , further comprising correlating a decrease in spectral energy emitted by the tracer agent over a measurement time window to the GFR of said patient. 
     
     
         7 . The method of  claim 5 , wherein one or more method steps are performed via a computing device. 
     
     
         8 . The method of  claim 5 , wherein a baseline signal measured prior to tracer agent administration is subtracted from the spectral energy data prior to or in conjunction with applying the fit. 
     
     
         9 . The method of  claim 5 , further comprising reporting the GFR. 
     
     
         10 . The method of  claim 5 , wherein the method steps of recording and calculating are each performed more than once. 
     
     
         11 . The method of  claim 10 , wherein the method steps of recording and calculating are each performed every 15 minutes for a period in a range of 12 hours to 24 hours. 
     
     
         12 . The method of  claim 5 , wherein the tracer agent is a compound of Formula I 
       
         
           
           
               
               
           
         
         wherein each of X 1  and X 2  is independently —CO 2 R 1 , —CONR 1 R 2 , —CO(AA) or —CONH(PS); 
         each of Y 1  and Y 2  is independently selected from the group consisting of —NR 1 R 2  and 
       
       
         
           
           
               
               
           
         
         Z 1  is a single bond, —CR 1 R 2 —, —O—, —NR 1 —, —NCOR 1 —, —S—, —SO—, or —SO 2 —; 
         each of R 1  to R 2  are independently selected from the group consisting of H, —CH 2 (CHOH) a H, —CH 2 (CHOH) a CH 3 , —CH 2 (CHOH) a CO 2 H, —(CHCO 2 H) a CO 2 H, —(CH 2 CH 2 O) c H, —(CH 2 CH 2 O) c CH 3 , —(CH 2 ) a SO 3 H, —(CH 2 ) a SO 3   − , —(CH 2 ) a SO 2 H, —(CH 2 ) a SO 2   − , —(CH 2 ) a NHSO 3 H, —(CH 2 ) a NHSO 3   − , —(CH 2 ) a NHSO 2 H, —(CH 2 ) a NHSO 2   − , —(CH 2 ) a PO 4 H 3 , —(CH 2 ) a PO 4 H 2   − , —(CH 2 ) a PO 4 H 2− , —(CH 2 ) a PO 4   3− , —(CH 2 ) a PO 3 H 2 , —(CH 2 ) a PO 3 H − , and —(CH 2 ) a PO 3   2− ; 
         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; and 
         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. 
       
     
     
         13 . The method of  claim 5 , wherein the tracer agent is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof 
     
     
         14 . A computing device configured to determine a real-time glomerular filtration rate (GFR) in a patient in need thereof, said computing device comprising:
 a memory; and   a processor communicatively coupled to the memory,   wherein the computing device is configured to operatively couple to one or more sensor heads; and   wherein the processor is programmed to:   record one or more measurements of spectral energy sent from the sensor heads before and/or after administration of a tracer agent to the patient over a measurement time window, wherein the tracer agent is configured to emit spectral energy when exposed to electromagnetic radiation;   determine the GFR of said patient 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 the body surface area of the patient; and   determine the rate constant 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, wherein the fit to the data starts after equilibration of the tracer agent between vascular and extravascular body spaces of the patient.   
     
     
         15 . The computing device of  claim 14 , wherein the processor is further programmed to correlate a decrease in spectral energy emitted by the tracer agent over a measurement time window to the GFR of said patient. 
     
     
         16 . The computing device of  claim 14 , wherein the operative coupling between the computing device and the one or more sensor heads is a direct or indirect mechanical, electrical, and/or communication connection. 
     
     
         17 . The computing device of  claim 14 , further comprising a display device communicatively coupled to the processor. 
     
     
         18 . The computing device of  claim 14 , further comprising a user interface communicatively coupled to the processor. 
     
     
         19 . The computing device of  claim 14 , wherein the tracer agent is a compound of Formula I 
       
         
           
           
               
               
           
         
         wherein each of X 1  and X 2  is independently —CO 2 R 1 , —CONR 1 R 2 , —CO(AA) or —CONH(PS); 
         each of Y 1  and Y 2  is independently selected from the group consisting of —NR 1 R 2  and 
       
       
         
           
           
               
               
           
         
         Z 1  is a single bond, —CR 1 R 2 —, —O—, —NR 1 —, —NCOR 1 —, —S—, —SO—, or —SO 2 —; 
         each of R 1  to R 2  are independently selected from the group consisting of H, —CH 2 (CHOH) a H, —CH 2 (CHOH) a CH 3 , —CH 2 (CHOH) a CO 2 H, —(CHCO 2 H) a CO 2 H, —(CH 2 CH 2 O) c H, —(CH 2 CH 2 O) c CH 3 , —(CH 2 ) a SO 3 H, —(CH 2 ) a SO 3   − , —(CH 2 ) a SO 2 H, —(CH 2 ) a SO 2   − , —(CH 2 ) a NHSO 3 H, —(CH 2 ) a NHSO 3   − , —(CH 2 ) a NHSO 2 H, —(CH 2 ) a NHSO 2   − , —(CH 2 ) a PO 4 H 3 , —(CH 2 ) a PO 4 H 2   − , —(CH 2 ) a PO 4 H 2− , —(CH 2 ) a PO 4   3− , —(CH 2 ) a PO 3 H 2 , —(CH 2 ) a PO 3 H − , and —(CH 2 ) a PO 3   2− ; 
         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; and 
         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. 
       
     
     
         20 . The computing device of  claim 14 , wherein the tracer agent is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.