1.4 A PROTEOMIC MARKER OF DIABETIC NEPHROPATHY IS ASSOCIATED WITH MORTALITY IN PATIENTS WITH TYPE 2 DIABETES
Background: The urinary proteomic classifier CKD273 has been found to predict diabetic nephropathy development in advance of microalbuminuria. Whether it is also a determinant of mortality and cardiovascular disease in patients with established albuminuria is unknown. Methods: We studied 155 subjec...
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Artery Research |
| Online Access: | https://www.atlantis-press.com/article/125930184/view |
| _version_ | 1818150215799013376 |
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| author | Gemma Currie Sheon Mary Bernt Johan von Scholten Morten Kofod Lindhardt Harald Mischak William Mullen Peter Rossing Christian Delles |
| author_facet | Gemma Currie Sheon Mary Bernt Johan von Scholten Morten Kofod Lindhardt Harald Mischak William Mullen Peter Rossing Christian Delles |
| author_sort | Gemma Currie |
| collection | DOAJ |
| description | Background: The urinary proteomic classifier CKD273 has been found to predict diabetic nephropathy development in advance of microalbuminuria. Whether it is also a determinant of mortality and cardiovascular disease in patients with established albuminuria is unknown.
Methods: We studied 155 subjects with T2D, albuminuria (geometrical mean [IQR]: 85 [34;194] mg/24 hrs), controlled blood pressure (129 ± 16/74 ± 11 mmHg) and preserved renal function (eGFR 88 ± 17 ml/min/1.73 m2). Blood and urine samples were collected for measurement of estimated glomerular filtration rate (eGFR), urine albumin excretion (UAE), N-terminal pro-brain natriuretic peptide (NT-proBNP) and urinary proteomics (capillary electrophoresis coupled to mass spectrometry). Computed tomography imaging was performed to assess coronary artery calcium (CAC) score. Outcome data were collected through national disease registries over a 6 year follow up period.
Results: CKD273 correlated with UAE (r = 0.481, p = <0.001), age (r = 0.238, p = 0.003), CAC score (r = 0.236, p = 0.003), NT-proBNP (r = 0.190, p = 0.018) and eGFR (r = 0.265, p = 0.001). On multiple regression only UAE (β = 0.402, p < 0.001) and eGFR (β = −0.184, p = 0.039) were statistically significant determinants. Twenty participants died during follow-up. CKD273 was a determinant of mortality (log rank [Mantel-Cox] p = 0.004), and retained significance (p = 0.050) after adjustment for age, sex, blood pressure, NT-proBNP and CAC score in a Cox regression model. Neither eGFR nor UAE were determinants of mortality in this cohort.
Conclusions: A multidimensional biomarker can provide information on outcomes associated with its primary diagnostic purpose. Here we demonstrate that the peptidomics-based classifier CKD273 is associated with mortality in albuminuric people with T2D in even when adjusted for other established cardiovascular and renal biomarkers. |
| first_indexed | 2024-12-11T13:19:24Z |
| format | Article |
| id | doaj.art-bd99f756673c4d34998e55af2661b3a6 |
| institution | Directory Open Access Journal |
| issn | 1876-4401 |
| language | English |
| last_indexed | 2024-12-11T13:19:24Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
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| series | Artery Research |
| spelling | doaj.art-bd99f756673c4d34998e55af2661b3a62022-12-22T01:05:55ZengBMCArtery Research1876-44012017-12-012010.1016/j.artres.2017.10.0181.4 A PROTEOMIC MARKER OF DIABETIC NEPHROPATHY IS ASSOCIATED WITH MORTALITY IN PATIENTS WITH TYPE 2 DIABETESGemma CurrieSheon MaryBernt Johan von ScholtenMorten Kofod LindhardtHarald MischakWilliam MullenPeter RossingChristian DellesBackground: The urinary proteomic classifier CKD273 has been found to predict diabetic nephropathy development in advance of microalbuminuria. Whether it is also a determinant of mortality and cardiovascular disease in patients with established albuminuria is unknown. Methods: We studied 155 subjects with T2D, albuminuria (geometrical mean [IQR]: 85 [34;194] mg/24 hrs), controlled blood pressure (129 ± 16/74 ± 11 mmHg) and preserved renal function (eGFR 88 ± 17 ml/min/1.73 m2). Blood and urine samples were collected for measurement of estimated glomerular filtration rate (eGFR), urine albumin excretion (UAE), N-terminal pro-brain natriuretic peptide (NT-proBNP) and urinary proteomics (capillary electrophoresis coupled to mass spectrometry). Computed tomography imaging was performed to assess coronary artery calcium (CAC) score. Outcome data were collected through national disease registries over a 6 year follow up period. Results: CKD273 correlated with UAE (r = 0.481, p = <0.001), age (r = 0.238, p = 0.003), CAC score (r = 0.236, p = 0.003), NT-proBNP (r = 0.190, p = 0.018) and eGFR (r = 0.265, p = 0.001). On multiple regression only UAE (β = 0.402, p < 0.001) and eGFR (β = −0.184, p = 0.039) were statistically significant determinants. Twenty participants died during follow-up. CKD273 was a determinant of mortality (log rank [Mantel-Cox] p = 0.004), and retained significance (p = 0.050) after adjustment for age, sex, blood pressure, NT-proBNP and CAC score in a Cox regression model. Neither eGFR nor UAE were determinants of mortality in this cohort. Conclusions: A multidimensional biomarker can provide information on outcomes associated with its primary diagnostic purpose. Here we demonstrate that the peptidomics-based classifier CKD273 is associated with mortality in albuminuric people with T2D in even when adjusted for other established cardiovascular and renal biomarkers.https://www.atlantis-press.com/article/125930184/view |
| spellingShingle | Gemma Currie Sheon Mary Bernt Johan von Scholten Morten Kofod Lindhardt Harald Mischak William Mullen Peter Rossing Christian Delles 1.4 A PROTEOMIC MARKER OF DIABETIC NEPHROPATHY IS ASSOCIATED WITH MORTALITY IN PATIENTS WITH TYPE 2 DIABETES Artery Research |
| title | 1.4 A PROTEOMIC MARKER OF DIABETIC NEPHROPATHY IS ASSOCIATED WITH MORTALITY IN PATIENTS WITH TYPE 2 DIABETES |
| title_full | 1.4 A PROTEOMIC MARKER OF DIABETIC NEPHROPATHY IS ASSOCIATED WITH MORTALITY IN PATIENTS WITH TYPE 2 DIABETES |
| title_fullStr | 1.4 A PROTEOMIC MARKER OF DIABETIC NEPHROPATHY IS ASSOCIATED WITH MORTALITY IN PATIENTS WITH TYPE 2 DIABETES |
| title_full_unstemmed | 1.4 A PROTEOMIC MARKER OF DIABETIC NEPHROPATHY IS ASSOCIATED WITH MORTALITY IN PATIENTS WITH TYPE 2 DIABETES |
| title_short | 1.4 A PROTEOMIC MARKER OF DIABETIC NEPHROPATHY IS ASSOCIATED WITH MORTALITY IN PATIENTS WITH TYPE 2 DIABETES |
| title_sort | 1 4 a proteomic marker of diabetic nephropathy is associated with mortality in patients with type 2 diabetes |
| url | https://www.atlantis-press.com/article/125930184/view |
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