Clonal Hematopoiesis of Indeterminate Potential Is Common in Patients on Hemodialysis

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon characterized by the clonal expansion of hematopoietic stem cells harboring somatic mutations in genes such as DNMT3A, TET2, and ASXL1. Its prevalence increases with age and has been reported in approximately 10% of the general population over the age of 70. Recent studies suggest that CHIP is associated with various chronic inflammatory conditions, cardiovascular disease (CVD), and an increased risk of stroke. Furthermore, CHIP has been implicated in the progression of chronic kidney disease (CKD), raising concerns about its impact on patients with advanced CKD. Despite accumulating evidence linking CHIP to CKD progression, the prevalence and clinical significance of CHIP in patients undergoing dialysis remain unclear. The aim of this study is to determine the prevalence of CHIP in patients receiving maintenance hemodialysis. Methods: Peripheral blood samples were collected from maintenance hemodialysis patients attending a single center. Genomic DNA was extracted from leukocyte fractions, and targeted sequencing was performed using a custom error-corrected panel covering 17 CHIP-associated genes known to impact cardiovascular function. Clinical data were also obtained from electronic medical records and integrated for analysis. Results: Using a variant allele frequency (VAF) cutoff of 0.005, CHIP was detected in 77.1% of hemodialysis patients. Among the affected genes, TET2, DNMT3A, and TP53 were the most frequently mutated. The prevalence of CHIP increased with age and peaked in patients in their 70s; however, older CHIP carriers may have been more susceptible to dropout due to death. Comparative analysis revealed that erythropoiesis-stimulating agent (ESA) resistance anemia was significantly more common in the CHIP-positive group (p < 0.01). Conclusion: This study suggests that the prevalence of clonal hematopoiesis is remarkably high in patients undergoing hemodialysis. Consistent with previous reports, CHIP frequency increased with age. Importantly, CHIP was significantly associated with erythropoiesis-stimulating agent (ESA) resistance anemia, indicating its potential clinical relevance in anemia management. These findings underscore the need for further prospective studies to determine the impact of CHIP on long-term prognosis and complication risks in the dialysis population.

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Journal
Journal of the American Society of Nephrology
Published
2025-10-01
DOI
https://doi.org/10.1681/asn.20253bngtmx1
Primary Topic
Hemoglobinopathies and Related Disorders
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article
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article

Clonal Hematopoiesis of Indeterminate Potential Is Common in Patients on Hemodialysis

Shoichi Maruyama, Kazuhiro Furuhashi, Keita Hattori
Journal of the American Society of Nephrology
Hemoglobinopathies and Related Disorders
article

Clonal Hematopoiesis of Indeterminate Potential Is Common in Patients on Hemodialysis

Shoichi Maruyama, Kazuhiro Furuhashi, Keita Hattori
article en

Abstract

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon characterized by the clonal expansion of hematopoietic stem cells harboring somatic mutations in genes such as DNMT3A, TET2, and ASXL1. Its prevalence increases with age and has been reported in approximately 10% of the general population over the age of 70. Recent studies suggest that CHIP is associated with various chronic inflammatory conditions, cardiovascular disease (CVD), and an increased risk of stroke. Furthermore, CHIP has been implicated in the progression of chronic kidney disease (CKD), raising concerns about its impact on patients with advanced CKD. Despite accumulating evidence linking CHIP to CKD progression, the prevalence and clinical significance of CHIP in patients undergoing dialysis remain unclear. The aim of this study is to determine the prevalence of CHIP in patients receiving maintenance hemodialysis. Methods: Peripheral blood samples were collected from maintenance hemodialysis patients attending a single center. Genomic DNA was extracted from leukocyte fractions, and targeted sequencing was performed using a custom error-corrected panel covering 17 CHIP-associated genes known to impact cardiovascular function. Clinical data were also obtained from electronic medical records and integrated for analysis. Results: Using a variant allele frequency (VAF) cutoff of 0.005, CHIP was detected in 77.1% of hemodialysis patients. Among the affected genes, TET2, DNMT3A, and TP53 were the most frequently mutated. The prevalence of CHIP increased with age and peaked in patients in their 70s; however, older CHIP carriers may have been more susceptible to dropout due to death. Comparative analysis revealed that erythropoiesis-stimulating agent (ESA) resistance anemia was significantly more common in the CHIP-positive group (p < 0.01). Conclusion: This study suggests that the prevalence of clonal hematopoiesis is remarkably high in patients undergoing hemodialysis. Consistent with previous reports, CHIP frequency increased with age. Importantly, CHIP was significantly associated with erythropoiesis-stimulating agent (ESA) resistance anemia, indicating its potential clinical relevance in anemia management. These findings underscore the need for further prospective studies to determine the impact of CHIP on long-term prognosis and complication risks in the dialysis population.

Journal of the American Society of NephrologyVol. 36(10S)
Aichi Prefectural University (JP)
Openalex Percentile: Top 58%
Hemoglobinopathies and Related Disorders
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