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High Level of Fasti...
High Level of Fasting Plasma Proenkephalin-A Predicts Deterioration of Kidney Function and Incidence of CKD
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- Schulz, Christina-Alexandra (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
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- Christensson, Anders (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Ericson, Ulrika (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
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- Almgren, Peter (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Kardiovaskulär forskning - hypertoni,Diabetes - Cardiovascular Disease,Lund University Research Groups,Cardiovascular Research - Hypertension,Skåne University Hospital
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- Hindy, George (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
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- Nilsson, Peter M (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Struck, Joachim (author)
- Sphingotec GmbH
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- Bergmann, Andreas (author)
- Waltraut Bergmann Foundation
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- Melander, Olle (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital
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- Orho-Melander, Marju (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2017
- 2017
- English 13 s.
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In: Journal of the American Society of Nephrology: JASN. - 1046-6673. ; 28:1, s. 291-303
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Abstract
Subject headings
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- High levels of proenkephalin-A (pro-ENK) have been associated with decreased eGFR in an acute setting. Here, we examined whether pro-ENK levels predict CKD and decline of renal function in a prospective cohort of 2568 participants without CKD (eGFR>60 ml/min per 1.73 m2) at baseline. During a mean follow-up of 16.6 years, 31.7% of participants developed CKD. Participants with baseline pro-ENK levels in the highest tertile had significantly greater yearly mean decline of eGFR (Ptrend<0.001) and rise of cystatin C (Ptrend=0.01) and creatinine (Ptrend<0.001) levels. Furthermore, compared with participants in the lowest tertile, participants in the highest tertile of baseline pro-ENK concentration had increased CKD incidence (odds ratio, 1.51; 95% confidence interval, 1.18 to 1.94) when adjusted for multiple factors. Adding pro-ENK to a model of conventional risk factors in net reclassification improvement analysis resulted in reclassification of 14.14% of participants. Genome-wide association analysis in 4150 participants of the same cohort revealed the strongest association of pro-ENK levels with rs1012178 near the PENK gene, where the minor T-allele associated with a 0.057 pmol/L higher pro-ENK level per allele (P=4.67x10-21). Furthermore, the T-allele associated with a 19% increased risk of CKD per allele (P=0.03) and a significant decrease in the instrumental variable estimator for eGFR (P<0.01) in a Mendelian randomization analysis. In conclusion, circulating plasma pro-ENK level predicts incident CKD and may aid in identifying subjects in need of primary preventive regimens. Additionally, the Mendelian randomization analysis suggests a causal relationship between pro-ENK level and deterioration of kidney function over time.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- Cross-Sectional Studies
- Enkephalins/blood
- Fasting/blood
- Female
- Glomerular Filtration Rate
- Humans
- Incidence
- Kidney/physiopathology
- Male
- Middle Aged
- Predictive Value of Tests
- Prospective Studies
- Protein Precursors/blood
- Renal Insufficiency, Chronic/blood
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Schulz, Christin ...
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Christensson, An ...
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Ericson, Ulrika
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Almgren, Peter
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Hindy, George
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Nilsson, Peter M
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Struck, Joachim
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Bergmann, Andrea ...
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Melander, Olle
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Orho-Melander, M ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Urology and Neph ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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Journal of the A ...
- By the university
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Lund University