Plasma galectin-3 levels are associated with the risk of incident chronic kidney disease

Casey Rebholz, Elizabeth Selvin, Menglu Liang, Christie M. Ballantyne, Ron C. Hoogeveen, David Aguilar, John W. McEvoy, Morgan Grams, Josef Coresh

Research output: Contribution to journalArticle

Abstract

Galectin-3 has been proposed as a novel biomarker of heart failure and cardiac fibrosis, and may also be associated with fibrosis of other organs such as the kidney. To determine this, we prospectively analyzed data from 9,148 Atherosclerosis Risk in Communities (ARIC) Study participants with measured plasma galectin-3 levels (baseline, visit 4, 1996-98) and without prevalent chronic kidney disease (CKD) or heart failure. We identified 1,983 incident CKD cases through December 31, 2013 over a median follow-up of 16 years. At baseline, galectin-3 was cross-sectionally associated with estimated glomerular filtration rate and urine albumin-to-creatinine ratio; both significant. The results were adjusted for age, sex, race-center, education, physical activity, smoking status, body mass index, systolic blood pressure, anti-hypertensive medication use, history of cardiovascular disease, diabetes, fasting blood glucose, and rs4644 (a single nucleotide polymorphism of galactin-3). There was a significant, graded, and positive association between galectin-3 and incident CKD (quartile 4 vs. 1 hazard ratio: 2.22 [95% confidence interval: 1.89, 2.60]). The association was attenuated but remained significant after adjustment for estimated glomerular filtration rate, urine albumin-to-creatinine ratio, troponin T, and N-terminal pro-brain natriuretic peptide (quartile 4 vs. 1 hazard ratio: 1.75 [95% confidence interval: 1.49, 2.06]), and was stronger among those with hypertension at baseline (significant interaction). Thus, in this community-based population, higher plasma galectin-3 levels were associated with an elevated risk of developing incident CKD, particularly among those with hypertension.

Original languageEnglish (US)
JournalKidney International
DOIs
StateAccepted/In press - 2017

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Galectin 3
Chronic Renal Insufficiency
Glomerular Filtration Rate
Albumins
Creatinine
Fibrosis
Heart Failure
Urine
Confidence Intervals
Blood Pressure
Hypertension
Troponin T
Brain Natriuretic Peptide
Antihypertensive Agents
Chronic Kidney Failure
Single Nucleotide Polymorphism
Blood Glucose
Fasting
Atherosclerosis
Body Mass Index

Keywords

  • Chronic kidney disease
  • Fibrosis
  • Galectin-3
  • Hypertension

ASJC Scopus subject areas

  • Medicine(all)
  • Nephrology

Cite this

Plasma galectin-3 levels are associated with the risk of incident chronic kidney disease. / Rebholz, Casey; Selvin, Elizabeth; Liang, Menglu; Ballantyne, Christie M.; Hoogeveen, Ron C.; Aguilar, David; McEvoy, John W.; Grams, Morgan; Coresh, Josef.

In: Kidney International, 2017.

Research output: Contribution to journalArticle

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abstract = "Galectin-3 has been proposed as a novel biomarker of heart failure and cardiac fibrosis, and may also be associated with fibrosis of other organs such as the kidney. To determine this, we prospectively analyzed data from 9,148 Atherosclerosis Risk in Communities (ARIC) Study participants with measured plasma galectin-3 levels (baseline, visit 4, 1996-98) and without prevalent chronic kidney disease (CKD) or heart failure. We identified 1,983 incident CKD cases through December 31, 2013 over a median follow-up of 16 years. At baseline, galectin-3 was cross-sectionally associated with estimated glomerular filtration rate and urine albumin-to-creatinine ratio; both significant. The results were adjusted for age, sex, race-center, education, physical activity, smoking status, body mass index, systolic blood pressure, anti-hypertensive medication use, history of cardiovascular disease, diabetes, fasting blood glucose, and rs4644 (a single nucleotide polymorphism of galactin-3). There was a significant, graded, and positive association between galectin-3 and incident CKD (quartile 4 vs. 1 hazard ratio: 2.22 [95{\%} confidence interval: 1.89, 2.60]). The association was attenuated but remained significant after adjustment for estimated glomerular filtration rate, urine albumin-to-creatinine ratio, troponin T, and N-terminal pro-brain natriuretic peptide (quartile 4 vs. 1 hazard ratio: 1.75 [95{\%} confidence interval: 1.49, 2.06]), and was stronger among those with hypertension at baseline (significant interaction). Thus, in this community-based population, higher plasma galectin-3 levels were associated with an elevated risk of developing incident CKD, particularly among those with hypertension.",
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AU - Selvin, Elizabeth

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AU - Ballantyne, Christie M.

AU - Hoogeveen, Ron C.

AU - Aguilar, David

AU - McEvoy, John W.

AU - Grams, Morgan

AU - Coresh, Josef

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AB - Galectin-3 has been proposed as a novel biomarker of heart failure and cardiac fibrosis, and may also be associated with fibrosis of other organs such as the kidney. To determine this, we prospectively analyzed data from 9,148 Atherosclerosis Risk in Communities (ARIC) Study participants with measured plasma galectin-3 levels (baseline, visit 4, 1996-98) and without prevalent chronic kidney disease (CKD) or heart failure. We identified 1,983 incident CKD cases through December 31, 2013 over a median follow-up of 16 years. At baseline, galectin-3 was cross-sectionally associated with estimated glomerular filtration rate and urine albumin-to-creatinine ratio; both significant. The results were adjusted for age, sex, race-center, education, physical activity, smoking status, body mass index, systolic blood pressure, anti-hypertensive medication use, history of cardiovascular disease, diabetes, fasting blood glucose, and rs4644 (a single nucleotide polymorphism of galactin-3). There was a significant, graded, and positive association between galectin-3 and incident CKD (quartile 4 vs. 1 hazard ratio: 2.22 [95% confidence interval: 1.89, 2.60]). The association was attenuated but remained significant after adjustment for estimated glomerular filtration rate, urine albumin-to-creatinine ratio, troponin T, and N-terminal pro-brain natriuretic peptide (quartile 4 vs. 1 hazard ratio: 1.75 [95% confidence interval: 1.49, 2.06]), and was stronger among those with hypertension at baseline (significant interaction). Thus, in this community-based population, higher plasma galectin-3 levels were associated with an elevated risk of developing incident CKD, particularly among those with hypertension.

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KW - Fibrosis

KW - Galectin-3

KW - Hypertension

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