Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease
The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying th...
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| Published in | Journal of clinical medicine Vol. 8; no. 7; p. 1034 |
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| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
MDPI
15.07.2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2077-0383 2077-0383 |
| DOI | 10.3390/jcm8071034 |
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| Abstract | The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying the pathogenesis of CKD. We aimed to assess the prognostic value of circulating PON-1 protein and PON lactonase activity on adverse clinical outcomes across various stages and etiologies of CKD. Circulating PON-1 protein levels and PON lactonase activity were measured simultaneously in patients with CKD as well as a cohort of apparently healthy non-CKD subjects. Both circulating PON-1 protein levels and PON lactonase activity were significantly lower in CKD patients compared to the non-CKD subjects. Similarly, across all stages of CKD, circulating PON-1 protein and PON lactonase activity were significantly lower in patients with CKD compared to the non-CKD controls. Circulating PON lactonase activity, but not protein levels, predicted future adverse clinical outcomes, even after adjustment for traditional risk factors. The combination of lower circulating protein levels and higher activity within the CKD subjects were associated with the best survival outcomes. These findings demonstrate that diminished circulating PON lactonase activity, but not protein levels, predicts higher risk of future adverse clinical outcomes in patients with CKD. |
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| AbstractList | The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying the pathogenesis of CKD. We aimed to assess the prognostic value of circulating PON-1 protein and PON lactonase activity on adverse clinical outcomes across various stages and etiologies of CKD. Circulating PON-1 protein levels and PON lactonase activity were measured simultaneously in patients with CKD as well as a cohort of apparently healthy non-CKD subjects. Both circulating PON-1 protein levels and PON lactonase activity were significantly lower in CKD patients compared to the non-CKD subjects. Similarly, across all stages of CKD, circulating PON-1 protein and PON lactonase activity were significantly lower in patients with CKD compared to the non-CKD controls. Circulating PON lactonase activity, but not protein levels, predicted future adverse clinical outcomes, even after adjustment for traditional risk factors. The combination of lower circulating protein levels and higher activity within the CKD subjects were associated with the best survival outcomes. These findings demonstrate that diminished circulating PON lactonase activity, but not protein levels, predicts higher risk of future adverse clinical outcomes in patients with CKD. The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying the pathogenesis of CKD. We aimed to assess the prognostic value of circulating PON-1 protein and PON lactonase activity on adverse clinical outcomes across various stages and etiologies of CKD. Circulating PON-1 protein levels and PON lactonase activity were measured simultaneously in patients with CKD as well as a cohort of apparently healthy non-CKD subjects. Both circulating PON-1 protein levels and PON lactonase activity were significantly lower in CKD patients compared to the non-CKD subjects. Similarly, across all stages of CKD, circulating PON-1 protein and PON lactonase activity were significantly lower in patients with CKD compared to the non-CKD controls. Circulating PON lactonase activity, but not protein levels, predicted future adverse clinical outcomes, even after adjustment for traditional risk factors. The combination of lower circulating protein levels and higher activity within the CKD subjects were associated with the best survival outcomes. These findings demonstrate that diminished circulating PON lactonase activity, but not protein levels, predicts higher risk of future adverse clinical outcomes in patients with CKD.The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying the pathogenesis of CKD. We aimed to assess the prognostic value of circulating PON-1 protein and PON lactonase activity on adverse clinical outcomes across various stages and etiologies of CKD. Circulating PON-1 protein levels and PON lactonase activity were measured simultaneously in patients with CKD as well as a cohort of apparently healthy non-CKD subjects. Both circulating PON-1 protein levels and PON lactonase activity were significantly lower in CKD patients compared to the non-CKD subjects. Similarly, across all stages of CKD, circulating PON-1 protein and PON lactonase activity were significantly lower in patients with CKD compared to the non-CKD controls. Circulating PON lactonase activity, but not protein levels, predicted future adverse clinical outcomes, even after adjustment for traditional risk factors. The combination of lower circulating protein levels and higher activity within the CKD subjects were associated with the best survival outcomes. These findings demonstrate that diminished circulating PON lactonase activity, but not protein levels, predicts higher risk of future adverse clinical outcomes in patients with CKD. |
| Author | Dube, Prabhatchandra Sarsour, Tiana Haller, Steven T. Kleinhenz, Andrew L. James, Richard W. Ghosh, Subhanwita Xie, Yanmei Malhotra, Deepak Kalra, Philip A. Mohammed, Chrysan J. Kennedy, David J. Brewster, Pamela S. Crawford, Erin L. |
| AuthorAffiliation | 2 Department of Internal Medicine, Geneva University Hospital, 1205 Geneva, Switzerland 3 Department of Renal Medicine, Salford Royal Hospital, Stott Lane, Salford, Greater Manchester M6 8HD, UK 1 Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA |
| AuthorAffiliation_xml | – name: 2 Department of Internal Medicine, Geneva University Hospital, 1205 Geneva, Switzerland – name: 1 Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA – name: 3 Department of Renal Medicine, Salford Royal Hospital, Stott Lane, Salford, Greater Manchester M6 8HD, UK |
| Author_xml | – sequence: 1 givenname: Chrysan J. surname: Mohammed fullname: Mohammed, Chrysan J. – sequence: 2 givenname: Yanmei surname: Xie fullname: Xie, Yanmei – sequence: 3 givenname: Pamela S. surname: Brewster fullname: Brewster, Pamela S. – sequence: 4 givenname: Subhanwita orcidid: 0000-0002-0510-2917 surname: Ghosh fullname: Ghosh, Subhanwita – sequence: 5 givenname: Prabhatchandra surname: Dube fullname: Dube, Prabhatchandra – sequence: 6 givenname: Tiana surname: Sarsour fullname: Sarsour, Tiana – sequence: 7 givenname: Andrew L. surname: Kleinhenz fullname: Kleinhenz, Andrew L. – sequence: 8 givenname: Erin L. orcidid: 0000-0002-4447-5863 surname: Crawford fullname: Crawford, Erin L. – sequence: 9 givenname: Deepak surname: Malhotra fullname: Malhotra, Deepak – sequence: 10 givenname: Richard W. surname: James fullname: James, Richard W. – sequence: 11 givenname: Philip A. surname: Kalra fullname: Kalra, Philip A. – sequence: 12 givenname: Steven T. orcidid: 0000-0002-6919-6342 surname: Haller fullname: Haller, Steven T. – sequence: 13 givenname: David J. orcidid: 0000-0001-5265-0142 surname: Kennedy fullname: Kennedy, David J. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31311140$$D View this record in MEDLINE/PubMed |
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| Keywords | chronic kidney disease clinical outcomes lactonase activity paraoxonase |
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| Title | Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease |
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