METHOD OF DETERMING EXCRETION OF SODIUM AND OTHER ANALYTES

• US 20090157328A1
• Filed: 12/12/2008
• Published: 06/18/2009
• Est. Priority Date: 12/14/2007
• Status: Active Grant

• Current Assignee: Cornell University
• Original Assignee: Cornell University
• Inventors: Gerber, Linda M., Mann, Samuel J.
• Granted Patent: US 9,128,168 B2
• Time in Patent Office: Days
• US Class Current: 702/19
• CPC Class Codes: G01N 33/493 urine
• CPC Class Codes: G01N 33/70 involving creatine or creatinine
• CPC Class Codes: G01R 33/44 using nuclear magnetic resonance [NMR] G01R33/24, G01R33/62 take precedence
• CPC Class Codes: Y10T 436/147777 Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
• CPC Class Codes: Y10T 436/173845 Amine and quaternary ammonium

Abstract

Methods and kits of the invention are useful for calculating 24-hour excretion of sodium without the need to collect urine for 24 hours.

Claims

1. A method of determining a subject'"'"'s 24-hour urinary excretion of an analyte from a single sample of the subject'"'"'s urine, comprising:

measuring the analyte concentration in the single urine sample;

measuring creatinine concentration in the single urine sample;

using the subject'"'"'s age, gender, race, weight, muscle mass, lean body mass, muscle mass, adiposity, physical activity, or a combination thereof, to select a normalized 24-hour creatinine excretion value from an array of normalized 24-hour creatinine excretion values, wherein each normalized 24-hour creatinine excretion value is an estimated mean of observed 24-hour urine creatinine concentrations for a population of persons of similar age, gender, race, weight, muscle mass, lean body mass, muscle mass, adiposity, and/or physical activity; and

using the normalized 24-hour creatinine excretion value, the measured analyte concentration, and the measured creatinine concentration to determine the 24-hour urinary excretion of analyte for the subject.

2. The method of claim 1, wherein the analyte is sodium chloride, albumin, catecholamine, calcium, methylmalonic acid, zinc, magnesium, n-terminal telopeptide (NTx) or a combination thereof.

3. The method of claim 1, wherein the 24-hour urinary excretion of analyte for the subject is determined by identifying the subject'"'"'s 24-hour analyte excretion from an array of 24-hour urinary analyte excretion values that vary depending upon values for normalized 24-hour creatinine excretion, analyte concentration, and creatinine concentration.

4. The method of claim 1, wherein the 24-hour urinary excretion of the analyte for the subject is determined using the following formula:

$\frac{\begin{array}{c}\mathrm{sample}<br><br>\left[\mathrm{analyte}\right]\times <br><br>\\ \mathrm{normalized}<br><br><br><br>24<br><br><br><br>\mathrm{hr}<br><br><br><br>\mathrm{creatinine}<br><br><br><br>\mathrm{value}\end{array}}{\mathrm{sample}\left[\mathrm{creatinine}\right]}=\mathrm{subject}\text{'}"\text{'}"\text{'}<br><br>s<br><br><br><br>24<br><br>\text{-}<br><br>\mathrm{hr}<br><br><br><br>\mathrm{analyte}<br><br><br><br>\mathrm{excretion}<br><br>$

wherein;

sample [analyte] is the measured concentration of analyte in the subject'"'"'s single urine sample;

sample [creatinine] is the measured concentration of creatinine in the subject'"'"'s single urine sample;

normalized creatinine value is the normalized 24-hour creatinine excretion value; and

subject'"'"'s 24-hour analyte excretion is the determined amount of analyte excreted by the subject over 24 hours.

5. The method of claim 1, wherein the subject'"'"'s gender, race and weight are used to select the normalized 24-hour creatinine excretion value from the array of normalized 24-hour creatinine excretion values.

6. The method of claim 1, wherein each normalized 24-hour creatinine excretion value is an estimated mean (from regression analysis) of observed 24-hour urine creatinine concentrations for a population of persons of similar gender, race, and weight.

7. The method of claim 1, wherein the single urine sample is obtained approximately half-way through the subject'"'"'s waking cycle, and several hours after a significant meal.

8. The method of claim 1, wherein the single urine sample is obtained in late afternoon or early evening, before the evening meal.

9. The method of claim 1, wherein the single urine sample is obtained by the subject at home or work, the concentrations are measured by the subject at home and the subject'"'"'s 24-hour urinary analyte excretion is determined by the subject at home or work.

10. The method of claim 1, wherein the single urine sample is obtained by the subject, the concentrations are measured by a health care professional and the subject'"'"'s 24-hour urinary analyte excretion is determined by a health care professional.

11. The method of claim 1, wherein measurement of the analyte concentration and/or the creatinine concentration is quantitative.

12. The method of claim 1, wherein measurement of the analyte concentration and/or the creatinine concentration is semi-quantitative.

13. The method of claim 1, wherein measurement of the analyte concentration and/or the creatinine concentration yields a numerical value or a range of numerical values.

14. The method of claim 1, wherein the determined 24-hour urinary excretion of analyte for the subject is a numerical value or a range of numerical values.

15. The method of claim 1, wherein the determined 24-hour urinary excretion of analyte for the subject is an indication that the 24-hour urinary excretion of analyte for the subject is low, medium or high.

16. The method of claim 1, wherein the analyte concentration is measured using amperometry, fluorimetry, spectrometry, nuclear magnetic resonance, atomic emission spectrometry, atomic absorption spectrometry, gravimetry, titrimetry, colorimetry, enzyme linked immunosorbant assay (ELISA), high pressure liquid chromatography (HPLC), spectrometry, colorimetry, gas chromatography, mass spectrometry, enzymatic assay, electrophoretically or a combination thereof.

17. The method of claim 1, wherein the analyte concentration and/or the creatinine concentration are measured without the use of a laboratory instrument.

18. The method of claim 1, wherein the analyte concentration and/or the creatinine concentration in the subject'"'"'s urine are measured using a dipstick.

19. The method of claim 18, wherein measurement of the analyte concentration and/or the creatinine concentration with a dipstick yields a numerical value.

20. The method of claim 18, wherein measurement of the analyte concentration and/or the creatinine concentration with a dipstick yields a colorimetric readout.

21. The method of claim 1, wherein the array of normalized 24-hour creatinine excretion values is calculated using either of the following formulae:

y=1150 mg−

407.4 mg(if female)+(5.7)(weight in pounds)−

88 mg(if white) 

 

I

y=654 mg−

537.3 mg(if female)+(7.3)(weight in pounds)−

59.3 mg(if white) 

 

II

wherein y is a normalized 24-hr creatinine excretion value in milligrams.

22. A method of determining a subject'"'"'s 24-hour urinary excretion of sodium from a single sample of the subject'"'"'s urine, comprising:

measuring chloride concentration in the single urine sample;

measuring creatinine concentration in the single urine sample;

using the subject'"'"'s age, gender, race, weight, muscle mass, lean body mass, muscle mass, adiposity, physical activity, or a combination thereof, to select a normalized 24-hour creatinine excretion value from an array of normalized 24-hour creatinine excretion values, wherein each normalized 24-hour creatinine excretion value is an estimated mean of observed 24-hour urine creatinine concentrations for a population of persons of similar age, gender, race, weight, muscle mass, lean body mass, muscle mass, adiposity, and/or physical activity; and

using the normalized 24-hour creatinine excretion value, the measured chloride concentration, and the measured creatinine concentration to determine the 24-hour urinary excretion of sodium for the subject.

23. The method of claim 22, wherein the 24-hour urinary excretion of sodium for the subject is determined by identifying the subject'"'"'s 24-hour sodium excretion from an array of 24-hour urinary sodium excretion values that vary depending upon values for normalized 24-hour creatinine excretion, chloride concentration, and creatinine concentration.

24. The method of claim 22, wherein the 24-hour urinary excretion of sodium for the subject is determined using the following formula:

$\frac{\begin{array}{c}\mathrm{sample}<br><br>\left[\mathrm{chloride}\right]\times <br><br>\\ \mathrm{normalized}<br><br><br><br>24<br><br><br><br>\mathrm{hr}<br><br><br><br>\mathrm{creatinine}<br><br><br><br>\mathrm{excretion}<br><br><br><br>\mathrm{value}\end{array}}{\mathrm{sample}\left[\mathrm{creatinine}\right]}=\mathrm{subject}\text{'}"\text{'}"\text{'}<br><br>s<br><br><br><br>24<br><br>\text{-}<br><br>\mathrm{hr}<br><br><br><br>\mathrm{sodium}<br><br><br><br>\mathrm{excretion}<br><br>$

wherein;

sample [chloride] is the measured concentration of chloride in the subject'"'"'s single urine sample;

sample [creatinine] is the measured concentration of creatinine in the subject'"'"'s single urine sample;

normalized creatinine value is the normalized 24-hour creatinine excretion value; and

subject'"'"'s 24-hour sodium excretion is the determined amount of sodium excreted by the subject over 24 hours.

25. The method of claim 22, wherein the subject'"'"'s gender, race and weight are used to select the normalized 24-hour creatinine excretion value from the array of normalized 24-hour creatinine excretion values.

26. The method of claim 22, wherein each normalized 24-hour creatinine excretion value is an estimated mean (from regression analysis) of observed 24-hour urine creatinine concentrations for a population of persons of similar gender, race, and weight.

27. The method of claim 22, wherein the single urine sample is obtained approximately half-way through the subject'"'"'s waking cycle, and several hours after a significant meal.

28. The method of claim 22, wherein the single urine sample is obtained in late afternoon or early evening, before the evening meal.

29. The method of claim 22, wherein the single urine sample is obtained by the subject at home or work, the concentrations are measured by the subject at home and the subject'"'"'s 24-hour urinary sodium excretion is determined by the subject at home or work.

30. The method of claim 22, wherein the single urine sample is obtained by the subject, the concentrations are measured by a health care professional and the subject'"'"'s 24-hour urinary sodium excretion is determined by a health care professional.

31. The method of claim 22, wherein measurement of the chloride concentration and/or the creatinine concentration is quantitative.

32. The method of claim 22, wherein measurement of the chloride concentration and/or the creatinine concentration is semi-quantitative.

33. The method of claim 22, wherein measurement of the chloride concentration and/or the creatinine concentration yields a numerical value or a range of numerical values.

34. The method of claim 22, wherein the determined 24-hour urinary excretion of sodium for the subject is a numerical value or a range of numerical values.

35. The method of claim 22, wherein the determined 24-hour urinary excretion of sodium for the subject is an indication that the 24-hour urinary excretion of sodium for the subject is low, medium or high.

36. The method of claim 22, wherein the chloride concentration is measured using amperometry, fluorimetry, spectrometry, nuclear magnetic resonance, atomic emission spectrometry, atomic absorption spectrometry, gravimetry, titrimetry, colorimetry, or a combination thereof.

37. The method of claim 22, wherein the creatinine concentration is measured using enzyme linked immunosorbant assay (ELISA), high pressure liquid chromatography (HPLC), spectrometry, colorimetry, gas chromatography, mass spectrometry, enzymatic assay, electrophoretically or a combination thereof.

38. The method of claim 22, wherein the chloride concentration and/or the creatinine concentration are measured without the use of a laboratory instrument.

39. The method of claim 22, wherein the chloride concentration and/or the creatinine concentration in the subject'"'"'s urine are measured using a dipstick.

40. The method of claim 39, wherein measurement of the chloride concentration and/or the creatinine concentration with a dipstick yields a numerical value.

41. The method of claim 39, wherein measurement of the chloride concentration and/or the creatinine concentration with a dipstick yields a colorimetric readout.

42. The method of claim 22, wherein the array of normalized 24-hour creatinine excretion values is calculated using either of the following formulae:

y=1150 mg−

407.4 mg(if female)+(5.7)(weight in pounds)−

88 mg(if white) 

 

I

y=654 mg−

537.3 mg(if female)+(7.3)(weight in pounds)−

59.3 mg(if white) 

 

II

wherein y is a normalized 24-hr creatinine excretion value in milligrams.

43. A method of improving the accuracy of determining 24-hour urinary excretion of sodium by a subject from a single urine sample, comprising:

measuring creatinine concentration and chloride concentration in a single urine sample obtained from a subject in late afternoon before consuming a meal;

using the subject'"'"'s gender, race and weight to select a normalized 24-hour creatinine excretion value from an array of normalized 24-hour creatinine excretion values, wherein each normalized 24-hour creatinine excretion value in the array is an estimated mean of observed 24-hour urine creatinine concentrations for a population of persons with the subject'"'"'s gender, race and weight; and

determining the subject'"'"'s 24-hour urinary excretion of sodium.

44. The method of claim 43, wherein the 24-hour urinary excretion of sodium for the subject is determined using the following formula:

$\frac{\begin{array}{c}\mathrm{sample}<br><br>\left[\mathrm{chloride}\right]\times <br><br>\\ \mathrm{normalized}<br><br><br><br>24<br><br><br><br>\text{-}<br><br>\mathrm{hr}<br><br><br><br>\mathrm{creatinine}<br><br><br><br>\mathrm{excretion}<br><br><br><br>\mathrm{value}\end{array}}{\mathrm{sample}\left[\mathrm{creatinine}\right]}=\mathrm{subject}\text{'}"\text{'}"\text{'}<br><br>s<br><br><br><br>24<br><br>\text{-}<br><br>\mathrm{hr}<br><br><br><br>\mathrm{sodium}<br><br><br><br>\mathrm{excretion}<br><br>$

wherein;

sample [chloride] is the measured concentration of chloride in the subject'"'"'s single urine sample;

sample [creatinine] is the measured concentration of creatinine in the subject'"'"'s single urine sample;

normalized creatinine value is the normalized 24-hour creatinine excretion value; and

the subject'"'"'s 24-hour sodium excretion is the determined amount of sodium excreted by the subject over 24 hours.

45. The method of claim 43, wherein the 24-hour urinary excretion of sodium for the subject is selected from an array of normalized 24-hour creatinine excretion values.

46. A kit for calculating 24-hour excretion of an analyte by a subject, the kit comprising:

(a) a container for holding a single urine sample;

(b) a device for measuring the analyte concentration in the single urine sample;

(c) a device for measuring creatinine concentration in the single urine sample; and

(d) instructions comprising a first nomogram listing normalized 24-hour creatinine excretion values for distinct populations of subjects, where the normalized 24-hour creatinine excretion values vary depending upon the populations'"'"' age, gender, race, weight, lean body mass, muscle mass, adiposity, physical activity, or a combination thereof, and

47. The kit of claim 46, wherein the analyte is sodium chloride, albumin, catecholamine, calcium, methylmalonic acid, zinc, magnesium, n-terminal telopeptide (NTx) or a combination thereof.

48. The kit of claim 46, wherein the analyte is sodium chloride.

49. The kit of claim 48, further comprising a second nomogram listing calculated 24-hour sodium excretion values, where the calculated 24-hour sodium excretion values are derived from the normalized 24-hour urine creatinine excretion value for the subject, the chloride concentration in the single urine sample and the creatinine concentration in the spot urine sample.

50. The kit of claim 46, wherein the devices are titrator dipsticks for calorimetric determination of the concentrations of the analyte and creatinine in the urine sample.

51. The kit of claim 46, wherein the first nomogram is an array or listing of normalized 24-hour creatinine excretion values that vary depending upon the populations'"'"' gender, race, and weight.

52. An article of manufacture comprising an array of normalized 24-hour creatinine excretion values and instructions for converting a subject'"'"'s spot urine analyte concentration and the subject'"'"'s spot creatinine concentration to a normalized 24 hour analyte concentration for the subject.

53. The article of claim 52, wherein the instructions comprise directions for obtaining the analyte concentration and the creatinine concentration.

54. The article of claim 52, further comprising devices for measuring the analyte concentration and the creatinine concentration.

55. The article of claim 52, wherein the array of normalized 24-hour creatinine excretion values is:

White Black White Black Weight males males females females 90 1168 1256 100 1225 1313 110 1689 1777 1282 1370 120 1746 1834 1339 1427 130 1803 1891 1396 1484 140 1860 1948 1453 1541 150 1917 2005 1510 1598 160 1974 2062 1567 1655 170 2031 2119 1624 1712 180 2088 2176 1681 1769 190 2145 2233 1738 1826 200 2202 2290 1795 1883 210 2259 2347 1852 1940 220 2316 2404 1909 1997 230 2373 2461 1966 2054 240 2430 2518 2023 2111 250 2487 2575 2080 2168 260 2544 2632 2137 2225 270 2601 2689 2194 2282 280 2658 2746 2251 2339

56. A computer-readable medium having stored thereon an array of normalized 24-hour creatinine excretion values and a program of instructions executable by a processor to convert a subject'"'"'s urine sample analyte concentration value, and the subject'"'"'s urine sample creatinine concentration to a calculated 24 hour analyte concentration for the subject.