Method for predicting the risk of incidence of chronic kidney disease

A method according to any one of the preceding claims, wherein the sample is selected from the group comprising blood sample, a serum sample, a plasma sample, a cerebrospinal fluid sample, a saliva sample and a urine sample or an extract of any of the aforementioned samples.

A method according to any of the preceding claims, wherein the Pro-Enkephalin concentration and/or the concentration of other substances found in the bodily fluid is measured in non-fastening or fastening subjects.

A method according to any of the preceding claims, wherein the level of Pro-Enkephalin or fragments thereof is determined by an immunoassay

A method for predicting the risk of incidence of chronic kidney disease as defined in any of the preceding claims, wherein the Pro-Enkephalin fragment comprises an amino acid sequence as defined in any of the sequences depicted in SEQ ID NOs:

• 1 to 14.

A method according to any of the preceding claims, wherein the Pro-Enkephalin fragment comprises Pro-Enkephalin A 119-159 (SEQ ID NO:

• 6) or a fragment thereof.

A method for predicting the risk of incidence of chronic kidney disease as defined in any of the preceding claims, wherein said method is performed at least once at time-point t0 and optionally at least one or more subsequent time-point(s) (t1 . . . tn) to monitor the risk development of incidence of chronic kidney disease.

A method for predicting the risk of incidence of chronic kidney disease as defined in any of the preceding claims, wherein a bodily fluid of a subject with a Pro-Enkephalin level above a certain threshold level, is classified as having an elevated risk for development of CKD, wherein the threshold associated with an elevated risk for development of CKD is between 30 and 80 pmol/L, more preferably between 35 and 60 pmol/L, even more preferably between 40 and 50 pmol/L, most preferred between 41 and 49 pmol/L.

A method according to any of the preceding claims, wherein the level of Pro-Enkephalin or fragments thereof of at least 5 amino acids, or at least of 6 amino acids, or at least of 7 amino acids, or at least of 8 amino acids, or at least of 9 amino acids, or at least of 10 amino acids, or at least of 12 amino acids is determined by using a binder to Pro-Enkephalin or fragments thereof of at least 5 amino acids, or of at least 6 amino acids, or of at least 7 amino acids, or of at least 8 amino acids, or of at least 9 amino acids, or of at least 10 amino acids, or of at least 12 amino acids.

A method according to any of the preceding claims, wherein a binder is used that specifically binds to Pro-Enkephalin or a fragment thereof, preferably selected from the group comprising an antibody, an antibody fragment or a non-Ig-Scaffold binding to Pro-Enkephalin or fragments thereof.

A method according to any of the preceding claims, wherein said threshold is <41 pmol/L and indicates a low risk of incidence of chronic kidney disease, a range of 41-49 indicates a medium risk of incidence of chronic kidney disease, and a threshold of >49 pmol/L indicates a high risk of incidence of chronic kidney disease.

A method according to any of the preceding claims, wherein an assay is used comprising two binders that bind to two different regions within the region of Pro-Enkephalin that is amino acid 133-140 (SEQ ID NO. 13) and amino acid 152-159 (SEQ ID No. 14) wherein each of said regions comprises at least 4 or 5 amino acids.

A method according to any of the preceding claims, wherein the assay sensitivity is <15 pmol/L.

A method according to any of the preceding claims, further comprising performing a step of selecting suitable therapeutic or preventive measures, when the level Pro-Enkephalin or fragments thereof is above a threshold, preferably a threshold between 30 and 80 pmol/L, more preferably between 35 and 60 pmol/L, even more preferably between 40 and 50 pmol/L, most preferred between 41 and 49 pmol/L.

A method according to any of the preceding claims, wherein said determination of Pro-Enkephalin or fragments thereof is performed more than once in order to monitor the risk of development of the incidence of chronic kidney disease.

A method according to any of the preceding claims, wherein said method is performed to stratify said subjects into risk groups.

A point-of-care device for performing a method according to any of the preceding claims, wherein said point of care device comprises at least one antibody or antibody fragment directed to amino acid 133-140 (SEQ ID No. 13) and/or amino acid 152-159 (SEQ ID NO. 14).

A kit for performing a method according to any of the preceding claims, comprising a point of care device, wherein said point of care device comprises at least one antibody or antibody fragment directed to either amino acid 133-140 (SEQ ID No. 13) or amino acid 152-159 (SEQ ID NO. 14).