Diagnosis and/or prognosis of renal dysfunction

Patent metadata

Field	Value
Publication number	US-10267807-B2
Application number	US-93759309-A
Country	US
Kind code	B2
Filing date	Apr 21, 2009
Priority date	Apr 21, 2008
Publication date	Apr 23, 2019
Grant date	Apr 23, 2019

Abstract

The present invention relates to a method for diagnosing and/or prognosing renal dysfunction. The method comprises the steps of: —(a) determining the level of an anti-inflammatory cytokine present in a urine sample from a subject prior to physical trauma, prior to a hypotensive event, prior to sepsis, and/or prior to septic shock syndrome; (b) determining the level of the anti-inflammatory cytokine present in a urine sample from the subject following physical trauma, following or during a hypotensive event, following or during sepsis, and/or following or during septic shock syndrome; (c) calculating the difference between the level of the anti-inflammatory cytokine determined in step a) from the level of the anti-inflammatory cytokine determined in step b), and (d) providing a diagnosis and/or prognosis on the basis of a comparison between the difference calculated in step c) and the difference calculated in step c) when steps a) and b) are practiced on a control group.

First claim

The invention claimed is:

1. A method for the prognosis of renal dysfunction by detecting a difference in the level of an anti-inflammatory cytokine present in a urine sample from a subject prior to a planned physical trauma and following the planned physical trauma, said method comprising:
a) obtaining a urine sample from a human subject prior to the planned physical trauma;
b) detecting the anti-inflammatory cytokine present in the urine sample obtained in step a), wherein the anti-inflammatory cytokine is selected from the group consisting of IL-1ra, TNFsr1 and TNFsr2 and any combination thereof;
c) obtaining a urine sample from a human subject within 48 hours following the planned physical trauma;
d) detecting the anti-inflammatory cytokine present in the urine sample obtained in step c), wherein the anti-inflammatory cytokine is selected from the group consisting of IL-1ra, TNFsr1 and TNFsr2 and any combination thereof;
e) calculating the difference in the levels of the anti-inflammatory cytokine determined in step b) and step d), wherein those subjects that present with a difference calculated in step e) that is smaller than the difference calculated in step e) when steps b) and d) are practiced on a control group, are at greater risk of developing renal dysfunction relative to the control group, wherein the control group consists of individuals who do not have renal dysfunction on the fifth day following the planned physical trauma; and
f) applying therapeutic measures to treat or obviate impending renal dysfunction, wherein the therapeutic measures to treat or obviate impending renal dysfunction are selected from maintaining supra-normal blood pressure, ensuring adequate tissue oxygen delivery, administration of steroids, renal replacement therapy, dialysis or any combination thereof.

2. The method as claimed in claim 1 , wherein the renal dysfunction is acute renal dysfunction.

3. The method as claimed in claim 1 , wherein the urine sample analyzed in step c) is obtained from the subject between 2 hours and 48 hours following the planned physical trauma.

4. The method of claim 1 further comprising the steps of:
f) detecting the level of one or more additional anti-inflammatory cytokines present in a urine sample from the subject prior to the planned physical trauma;
g) detecting the level of one of more additional anti-inflammatory cytokines present in a urine sample from the subject following the planned physical trauma; and
h) calculating the difference between the level of the one or more additional anti-inflammatory cytokines determined in step f) from the level of the anti-inflammatory cytokines determined in step g) wherein those subjects that present with a difference calculated in step h) that is smaller than the difference calculated in step h) when steps f) and g) are practiced on a control group, are at greater risk of developing renal dysfunction relative to the control group, wherein the control group consists of individuals who do not have renal dysfunction on the fifth day following the planned physical trauma.

5. The method as claimed in claim 1 , further comprising the steps of:
a′″) detecting the level of one or more pro-inflammatory mediator present in a urine sample from a subject prior to the planned physical trauma, wherein the one or more pro-inflammatory mediator is IL-18 or neutrophil gelatinase-associated lipocalin (NGAL);
b′″) detecting the level of one or more pro-inflammatory mediator present in a urine sample from the subject following the planned physical trauma;
c′″) calculating the difference between the level of the one or more pro-inflammatory mediator determined in step a′″) from the level of the one or more additional pro-inflammatory mediator determined in step b′″); and
d′″) comparing the difference calculated in step c′″) and the difference calculated in step c′″) when steps a′″) and b′″) are practiced on a control group, wherein there is an increased risk of developing renal dysfunction when the difference between the pre- and post-event proinflammatory cytokine level for a test group is greater than that experienced by the control group.

6. The method as claimed in claim 1 , wherein when the cytokine is IL-1ra, and the difference calculated in step e) when steps a) and b) are practiced on a control group is 35000 or more pg of IL-1ra in one ml of urine greater than the difference calculated in step e), the subject is at greater than normal risk of developing renal dysfunction.

7. A method for the prognosis of renal dysfunction by detecting a difference in the level of an anti-inflammatory cytokine present in a urine sample from a subject prior to surgery and following the syndrome surgery, said method comprising:
a) obtaining a urine sample from a human subject prior to the surgery;
b) detecting the anti-inflammatory cytokine present in the urine sample obtained in step a), wherein the anti-inflammatory cytokine is selected from the group consisting of IL-1ra, TNFsr1 and TNFsr2 and any combination thereof;
c) obtaining a urine sample from a human subject within 48 hours following the surgery;
d) detecting the anti-inflammatory cytokine present in the urine sample obtained in step c), wherein the anti-inflammatory cytokine is selected from the group consisting of IL-1ra, TNFsr1 and TNFsr2 and any combination thereof;
e) calculating the difference in the levels of the anti-inflammatory cytokine determined in step b) and step d), wherein those subjects that present with a difference calculated in step e) that is smaller than the difference calculated in step e) when steps b) and d) are practiced on a control group, are at greater risk of developing renal dysfunction relative to the control group, wherein the control group consists of individuals who do not have renal dysfunction on the fifth day following the surgery; and
f) applying therapeutic measures to treat or obviate impending renal dysfunction, wherein the therapeutic measures to treat or obviate impending renal dysfunction are selected from maintaining supra-normal blood pressure, ensuring adequate tissue oxygen delivery, administration of steroids, renal replacement therapy, dialysis or any combination thereof.

Assignees

• Mcbride William Thomas
• Armstrong Marilyn
• Belfast Health And Social Care Trust
• Univ Belfast

Inventors

• Mcbride William Thomas
• Armstrong Marilyn

Classifications

• G01N33/6863 Primary

  Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors · CPC title

• G01N2333/7151

  for tumor necrosis factor [TNF]; for lymphotoxin [LT] · CPC title

• G01N2333/545

  IL-1 · CPC title

• G01N2800/347

  Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy · CPC title