. 2025 Apr 9;36(9):1764-1774.

doi: 10.1681/ASN.0000000680.

Clonal Hematopoiesis of Indeterminate Potential and Progression of CKD

Caitlyn Vlasschaert¹, Yang Pan², Jianchun Chen³, Elvis Akwo³, Varun Rao², James E Hixson⁴, Michael Chong^{5

6

7}, Md Mesbah Uddin⁸, Zhi Yu^{8

9}, Mengdi Jiang³, Fenfen Peng³, Shirong Cao³, Yinqiu Wang³, Do-Kyun Kim⁴, Adriana M Hung³, Jing He³, Manjula Kurella Tamura¹⁰, Debbie L Cohen¹¹, Jiang He¹², Changwei Li¹², Zeenat Bhat¹³, Panduranga Rao¹³, Dawei Xie¹⁴, Alexander G Bick¹⁵, Bryan Kestenbaum¹⁶, Guillaume Paré^{5

6

7

17}, Michael J Rauh¹⁸, Adeera Levin¹⁹, Pradeep Natarajan^{8

9}, James P Lash², Ming-Zhi Zhang³, Raymond C Harris Jr³, Cassianne Robinson-Cohen³, Matthew B Lanktree^{5

20}, Tanika N Kelly²; Chronic Renal Insufficiency Cohort (CRIC) Study Investigators

Collaborators, Affiliations

Collaborators

Chronic Renal Insufficiency Cohort (CRIC) Study Investigators:
Amanda H Anderson, Lawrence J Appel, Jing Chen, Laura M Dember, Alan S Go, Mahboob Rahman, Vallabh O Shah, Mark L Unruh

Affiliations

¹ Department of Medicine, Queen's University, Kingston, Ontario, Canada.
² Division of Nephrology, Department of Medicine, College of Medicine, University of Illinois Chicago, Chicago, Illinois.
³ Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
⁴ Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston School of Public Health, Houston, Texas.
⁵ Population Health Research Institute, Hamilton, Ontario, Canada.
⁶ Thrombosis and Atherosclerosis Research Institute, David Barley Cardiac, Vascular and Stroke Research, Hamilton, Ontario, Canada.
⁷ Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁸ Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
⁹ Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts.
¹⁰ Division of Nephrology, Stanford University School of Medicine, Palo Alto, California.
¹¹ Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
¹² Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.
¹³ Department of Internal Medicine, Division of Nephrology, University of Michigan Health System, Ann Arbor, Michigan.
¹⁴ Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
¹⁵ Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
¹⁶ Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington, Seattle, Washington.
¹⁷ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
¹⁸ Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada.
¹⁹ Division of Nephrology, Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
²⁰ Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

PMID: 40202794
PMCID: PMC12416945 (available on 2026-09-01)
DOI: 10.1681/ASN.0000000680

Clonal Hematopoiesis of Indeterminate Potential and Progression of CKD

Caitlyn Vlasschaert et al. J Am Soc Nephrol. 2025.

. 2025 Apr 9;36(9):1764-1774.

doi: 10.1681/ASN.0000000680.

Authors

Collaborators

Chronic Renal Insufficiency Cohort (CRIC) Study Investigators:
Amanda H Anderson, Lawrence J Appel, Jing Chen, Laura M Dember, Alan S Go, Mahboob Rahman, Vallabh O Shah, Mark L Unruh

Affiliations

¹ Department of Medicine, Queen's University, Kingston, Ontario, Canada.
² Division of Nephrology, Department of Medicine, College of Medicine, University of Illinois Chicago, Chicago, Illinois.
³ Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
⁴ Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston School of Public Health, Houston, Texas.
⁵ Population Health Research Institute, Hamilton, Ontario, Canada.
⁶ Thrombosis and Atherosclerosis Research Institute, David Barley Cardiac, Vascular and Stroke Research, Hamilton, Ontario, Canada.
⁷ Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁸ Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
⁹ Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts.
¹⁰ Division of Nephrology, Stanford University School of Medicine, Palo Alto, California.
¹¹ Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
¹² Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.
¹³ Department of Internal Medicine, Division of Nephrology, University of Michigan Health System, Ann Arbor, Michigan.
¹⁴ Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
¹⁵ Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
¹⁶ Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington, Seattle, Washington.
¹⁷ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
¹⁸ Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada.
¹⁹ Division of Nephrology, Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
²⁰ Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

PMID: 40202794
PMCID: PMC12416945 (available on 2026-09-01)
DOI: 10.1681/ASN.0000000680

Abstract

Key Points:

Non-DNMT3A clonal hematopoiesis of indeterminate potential was associated with CKD progression in a meta-analysis of 5654 individuals with CKD.
In an adenine-induced CKD mouse model, Tet2-clonal hematopoiesis of indeterminate potential was linked to lower GFR, increased kidney inflammation, tubular injury, and fibrosis.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. CHIP has been associated with incident AKI and kidney function decline in the general population, particularly mutations in CHIP genes other than DNMT3A (termed non-DNMT3A CHIP). Previous studies of CHIP in individuals with CKD had limited sample sizes and conflicting findings.

Methods: We examined CHIP and CKD progression in four CKD cohorts (N=5654): the Chronic Renal Insufficiency Cohort, the African American Study of Kidney Disease, individuals with CKD from the BioVU biorepository, and the Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events. Primary outcomes were incident CKD progression (50% eGFR decline or kidney failure) and eGFR slope over time. In addition, kidney function and pathology were assessed in a Tet2-CHIP mouse model of CKD induced by dietary adenine.

Results: Across all cohorts, the average age was 66±11 years, with an average baseline eGFR of 43±15 ml/min per 1.73 m², and 24% had CHIP. After meta-analysis, non-DNMT3A CHIP was associated with a 64% higher relative risk of incident CKD progression (hazard ratio, 1.64; 95% confidence interval, 1.00 to 2.68), with the strongest effect observed in individuals with baseline eGFR 30–60 ml/min per 1.73 m² (hazard ratio, 1.85; 95% confidence interval, 1.18 to 2.90). Non-DNMT3A CHIP carriers also exhibited a faster eGFR decline (β, −0.62±0.28 ml/min per 1.73 m² per year; P = 0.03). In a dietary adenine mouse model of CKD, Tet2-CHIP was associated with lower GFR as well as greater kidney inflammation, tubular injury, and tubulointerstitial fibrosis.

Conclusions: Non-DNMT3A CHIP was associated with CKD progression among individuals with CKD. Furthermore, Tet2-CHIP mouse models support a causal role in kidney injury.

Keywords: CKD; chronic inflammation; genetic kidney disease; immunology.

PubMed Disclaimer

Conflict of interest statement

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/F162.

Update of

Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression.
Vlasschaert C, Pan Y, Chen J, Akwo E, Rao V, Hixson JE, Chong M, Uddin MM, Yu Z, Jiang M, Peng F, Cao S, Wang Y, Kim DK, Hung AM, He J, Tamura MK, Cohen DL, He J, Li C, Bhat Z, Rao P, Xie D, Bick AG, Kestenbaum B, Paré G, Rauh MJ, Levin A, Natarajan P, Lash JP, Zhang MZ, Harris RC, Robinson-Cohen C, Lanktree MB, Kelly TN; CRIC Study Investigators. Vlasschaert C, et al. medRxiv [Preprint]. 2024 Jun 20:2024.06.19.24309181. doi: 10.1101/2024.06.19.24309181. medRxiv. 2024. Update in: J Am Soc Nephrol. 2025 Apr 09;36(9):1764-1774. doi: 10.1681/ASN.0000000680. PMID: 38946975 Free PMC article. Updated. Preprint.

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Clonal Hematopoiesis of Indeterminate Potential and Progression of CKD

Collaborators

Affiliations

Clonal Hematopoiesis of Indeterminate Potential and Progression of CKD

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Update of

References

Grants and funding

LinkOut - more resources

Research Materials

Miscellaneous