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Clinical Epidemiology
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Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease

Caitlyn Vlasschaert, Amy J.M. McNaughton, Michael Chong, Elina K. Cook, Wilma Hopman, Bryan Kestenbaum, Cassianne Robinson-Cohen, Jocelyn Garland, Sarah M. Moran, Guillaume Paré, Catherine M. Clase, Mila Tang, Adeera Levin, Rachel Holden, Michael J. Rauh and Matthew B. Lanktree
JASN May 2022, 33 (5) 985-995; DOI: https://doi.org/10.1681/ASN.2021060774
Caitlyn Vlasschaert
1Department of Medicine, Queen’s University, Kingston, Ontario, Canada
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Amy J.M. McNaughton
2Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Michael Chong
3Population Health Research Institute (PHRI), Hamilton, Ontario, Canada
4David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
5Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
6Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
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Elina K. Cook
2Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Wilma Hopman
1Department of Medicine, Queen’s University, Kingston, Ontario, Canada
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Bryan Kestenbaum
7Department of Medicine, University of Washington, Seattle, Washington
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Cassianne Robinson-Cohen
8Department of Medicine, Vanderbilt University, Nashville, Tennessee
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Jocelyn Garland
1Department of Medicine, Queen’s University, Kingston, Ontario, Canada
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Sarah M. Moran
1Department of Medicine, Queen’s University, Kingston, Ontario, Canada
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Guillaume Paré
3Population Health Research Institute (PHRI), Hamilton, Ontario, Canada
4David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
5Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
6Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
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Catherine M. Clase
9Department of Medicine, McMaster University, Hamilton, Ontario, Canada
10St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada
11Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
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Mila Tang
12St. Paul’s Hospital, Vancouver, British Colombia, Canada
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Adeera Levin
13Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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Rachel Holden
1Department of Medicine, Queen’s University, Kingston, Ontario, Canada
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Michael J. Rauh
2Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
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Matthew B. Lanktree
3Population Health Research Institute (PHRI), Hamilton, Ontario, Canada
9Department of Medicine, McMaster University, Hamilton, Ontario, Canada
10St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada
11Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
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Significance Statement

Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of clonal leukocytes caused by acquired somatic mutations in myeloid stem/progenitor cells, occurs in 10%–15% of the general population aged 65 years or older. This proinflammatory condition appears causally associated with cardiovascular disease and death. The authors found that 43 of 172 (25%) individuals with advanced CKD had CHIP. Those with CHIP had a 2.2-fold greater risk of kidney failure over 5 years of follow-up and were more likely to have complications of CKD (including anemia) compared with those without CHIP. More research, including studies in animal models, is needed to understand the relationship between CHIP and CKD. CHIP-related inflammation might offer a novel therapeutic target for those with CHIP and CKD.

Abstract

Background Clonal hematopoiesis of indeterminate potential (CHIP) is an inflammatory premalignant disorder resulting from acquired genetic mutations in hematopoietic stem cells. This condition is common in aging populations and associated with cardiovascular morbidity and overall mortality, but its role in CKD is unknown.

Methods We performed targeted sequencing to detect CHIP mutations in two independent cohorts of 87 and 85 adults with an eGFR<60 ml/min per 1.73m2. We also assessed kidney function, hematologic, and mineral bone disease parameters cross-sectionally at baseline, and collected creatinine measurements over the following 5-year period.

Results At baseline, CHIP was detected in 18 of 87 (21%) and 25 of 85 (29%) cohort participants. Participants with CHIP were at higher risk of kidney failure, as predicted by the Kidney Failure Risk Equation (KFRE), compared with those without CHIP. Individuals with CHIP manifested a 2.2-fold increased risk of a 50% decline in eGFR or ESKD over 5 years of follow-up (hazard ratio 2.2; 95% confidence interval, 1.2 to 3.8) in a Cox proportional hazard model adjusted for age, sex, and baseline eGFR. The addition of CHIP to 2-year and 5-year calibrated KFRE risk models improved ESKD predictions. Those with CHIP also had lower hemoglobin, higher ferritin, and higher red blood cell mean corpuscular volume versus those without CHIP.

Conclusions In this exploratory analysis of individuals with preexisting CKD, CHIP was associated with higher baseline KFRE scores, greater progression of CKD, and anemia. Further research is needed to define the nature of the relationship between CHIP and kidney disease progression.

  • chronic inflammation
  • anemia
  • macrophages
  • clonal hematopoiesis
  • clone cells
  • hematopoiesis
  • cohort studies
  • chronic renal insufficiency
  • Copyright © 2022 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 33 (5)
Journal of the American Society of Nephrology
Vol. 33, Issue 5
May 2022
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Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease
Caitlyn Vlasschaert, Amy J.M. McNaughton, Michael Chong, Elina K. Cook, Wilma Hopman, Bryan Kestenbaum, Cassianne Robinson-Cohen, Jocelyn Garland, Sarah M. Moran, Guillaume Paré, Catherine M. Clase, Mila Tang, Adeera Levin, Rachel Holden, Michael J. Rauh, Matthew B. Lanktree
JASN May 2022, 33 (5) 985-995; DOI: 10.1681/ASN.2021060774

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Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease
Caitlyn Vlasschaert, Amy J.M. McNaughton, Michael Chong, Elina K. Cook, Wilma Hopman, Bryan Kestenbaum, Cassianne Robinson-Cohen, Jocelyn Garland, Sarah M. Moran, Guillaume Paré, Catherine M. Clase, Mila Tang, Adeera Levin, Rachel Holden, Michael J. Rauh, Matthew B. Lanktree
JASN May 2022, 33 (5) 985-995; DOI: 10.1681/ASN.2021060774
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Keywords

  • chronic inflammation
  • anemia
  • macrophages
  • clonal hematopoiesis
  • clone cells
  • hematopoiesis
  • cohort studies
  • chronic renal insufficiency

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