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Methods of prognosis in chronic kidney disease

a kidney disease and prognosis technology, applied in the field of chronic kidney disease prognosis, can solve the problems of difficult to determine patients for whom a kidney transplant may be life-saving, many patients are likely to die, and the outcome and the nature of the link between them are ill-defined, so as to reduce the risk of death and prevent death

Inactive Publication Date: 2012-05-03
ST VINCENTS HOSPITAL SYDNEY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0015](ii) comparing the amount of MIC-1 determined in step (i) with a reference amount of MIC-1 that is an elevated amount of MIC-1 associated with an increased likelihood of death of the subject;such that when the amount of MIC-1 determined in step (i) is greater than or substantially equivalent to the reference amount, the subject has an increased likelihood of death, and when the amount of MIC-1 determined in step (i) is less than the reference amount, the subject has a decreased likelihood of death.
[0027]In a fifth aspect, the present invention provides a method of preventing death or reducing the risk of death in a CKD subject, particularly a CKD subject suffering from end-stage renal disease, comprising treating blood, plasma or serum of said subject so as to remove or inactivate MIC-1 present in said blood, plasma or serum.

Problems solved by technology

Some patients with end-stage renal disease can survive indefinitely on dialysis; however, many patients are likely to die in the absence of a kidney transplant.
However, the contribution of malnutrition and inflammation to disease outcome and the nature of the link between them is ill-defined.
There are currently no reliable prospective methods for determining which patients are likely to die in the absence of a kidney transplant, and it is accordingly difficult to determine patients for whom a kidney transplant may be life saving.

Method used

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  • Methods of prognosis in chronic kidney disease
  • Methods of prognosis in chronic kidney disease

Examples

Experimental program
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Effect test

example 1

Patient Cohorts

Materials and Methods

[0113]Cohorts of incident haemodialysis patients (ie patients that have reached the stage of requiring dialysis but have not yet commenced such treatment) from Sweden (n=98) and established haemodialysis patients from the United States of America (n=381) had serum MIC-1 and C-Reactive Protein (CRP)-4 levels and BMI measured at study entry. Serum CRP-4 (Dade Behring, Inc., Deerfield, Ill., United States of America) was determined as described in Brown et al. (2002a); and serum MIC-1 was determined as described below. Demographic information collected included age, sex, history of cardiovascular disease (CVD), history of diabetes mellitus (DM), height and weight. Additional markers of nutrition, body composition and inflammation were assessed in Swedish patients.

Swedish Cohort

[0114]Swedish patients were incident dialysis patients with end-stage renal disease enrolled in the dialysis program at the Karolinska University Hospital at Huddinge between 1...

example 2

Serum MIC-1 is Related to Subjective Global Nutritional Assessment (SGA) in the Swedish Cohort

[0121]Data regarding the US cohort has previously been published indicating that serum MIC-1 levels are negatively correlated with BMI (Johen et al., 2007). To further study the nutritional changes associated with elevated serum MIC-1 levels, the present applicant analysed data from Swedish patients, from whom nutritional information was available.

Results and Discussion

[0122]The SGA was segregated into normal (SGA=1, n=69) or abnormal (SGA>1, n=27) with data being unavailable for 2 patients. SGA was significantly related with S-creatinine (p=0.0050), BMI (p=0.0051), handgrip strength (p=0.0016 and serum MIC-1 level (p=0.0065). Patients with serum MIC-1 above the median (7430 pg / ml) were significantly more likely to have an abnormal SGA (p=0.0001, chi-square). Serum MIC-1 level above the median was independently associated with SGA in multivariate logistic regression (Table 3). This model wa...

example 3

Serum MIC-1 Level is Related to Nutrition and Markers of Inflammation and Oxidative Damage in the Swedish Cohort

[0124]The relationship between serum MIC-1 levels and circulating markers of inflammation (CRP, fibrinogen) and oxidation (8OHdG), muscle atrophy, BMI and age was examined.

Results and Discussion

[0125]As shown in Table 4, serum MIC-1 level was compared to the levels of circulating markers of inflammation (CRP, fibrinogen), oxidation (8-OHdG) and age in the Swedish population, as these factors may be indicators of mortality in end-stage renal disease. Initial univariate analysis using

[0126]Spearman rank correlation testing demonstrated that serum MIC-1 levels are related to age (ρ=0.252, p=0.0135), CRP (ρ=0.283, p=0.0056), fibrinogen (ρ=0.346, p=0.0018), 8-OHdG (ρ=0.308, p=0.0033) and serum albumin (ρ=−0.211, p=0.0388). Serum MIC-1 level and muscle atrophy did not significantly associate as a continuous variable; however, a strong trend was observed between serum MIC-1 above...

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Abstract

The present invention relates to methods of prognosing the survival of a diseased subject, particularly a subject with chronic kidney disease (CKD), as well as selecting an end-stage renal disease subject for a kidney transplant. The methods involve detecting an elevated amount of macrophage inhibitory cytokine-1 (MIC-1) in a test body sample from the diseased subject. A method of preventing or reducing the risk of death in a CKD subject which involves removing or inactivating MIC-1 present in the blood, plasma or serum of the subject, is also disclosed.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a method of prognosing the survival of a diseased subject. In particular, the invention relates to a method of prognosing the survival of a subject with chronic kidney disease.INCORPORATION BY REFERENCE[0002]This patent application refers to:[0003]International Patent Application No PCT / AU01 / 00456 (WO 01 / 81928);[0004]International Patent Application No PCT / AU2005 / 000525 (WO 2005 / 099746); and[0005]International Patent Application No PCT / AU2008 / 001498 (WO 2009 / 046495); in the following description. The entire content of each of these specifications is herein incorporated by reference.BACKGROUND OF THE INVENTION[0006]Macrophage inhibitory cytokine (MIC)-1 is a transforming growth factor-β (TGF-β) superfamily protein. MIC-1 was originally cloned as macrophage inhibitory cytokine-1 and later identified as placental transforming growth factor-β (PTGF-β), placental bone morphogenetic protein (PLAB), non-steroidal anti-inflammator...

Claims

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Application Information

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IPC IPC(8): A61K33/06A61P13/12G01N33/566
CPCG01N33/6893G01N2800/347A61M1/3624G01N33/6863G01N2333/52G01N2800/52A61P13/12
Inventor BREIT, SAMUEL NORBERTBROWN, DAVID ALEXANDER
Owner ST VINCENTS HOSPITAL SYDNEY
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