Kidney Week

Abstract: TH-PO1088

Association Between Multiple Clonal Hematopoiesis of Indeterminate Potential Mutations and CKD Progression in a Japanese Population: A Biobank Japan Cohort Study

Session Information

• CKD: Epidemiology, Risk Factors, and Other Conditions
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Mochida, Yasuhiro, Shonan Kamakura Sogo Byoin, Kamakura, Kanagawa Prefecture, Japan

Yasuhiro Mochida

• Salybekov, Amankeldi, Shonan Kamakura Sogo Byoin, Kamakura, Kanagawa Prefecture, Japan

Amankeldi Salybekov, MD, PhD

• Ishioka, Kunihiro, Shonan Kamakura Sogo Byoin, Kamakura, Kanagawa Prefecture, Japan

Kunihiro Ishioka, MD

• Oka, Machiko, Shonan Kamakura Sogo Byoin, Kamakura, Kanagawa Prefecture, Japan

Machiko Oka, MD

• Moriya, Hidekazu, Shonan Kamakura Sogo Byoin, Kamakura, Kanagawa Prefecture, Japan

Hidekazu Moriya, MD

• Ohtake, Takayasu, Shonan Kamakura Sogo Byoin, Kamakura, Kanagawa Prefecture, Japan

Takayasu Ohtake, MD, PhD

• Hidaka, Sumi, Shonan Kamakura Sogo Byoin, Kamakura, Kanagawa Prefecture, Japan

Sumi Hidaka, MD, PhD

• Matsuda, Koichi, Tokyo Daigaku, Bunkyo, Tokyo, Japan

Koichi Matsuda, MD, PhD

• Kobayashi, Shuzo, Shonan Kamakura Sogo Byoin, Kamakura, Kanagawa Prefecture, Japan

Shuzo Kobayashi, MD, PhD

Background

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition involving somatic mutations in hematopoietic stem cells. Although a few studies have suggested an association between CHIP and chronic kidney disease (CKD), the clinical impact of multiple CHIP mutations on kidney outcomes remains unclear.

Methods

We conducted a cohort study of 5,588 Japanese individuals aged 60–84 years with preserved kidney function (eGFR ≥60 mL/min/1.73 m²) enrolled in the Biobank Japan project. CHIP mutations were identified using targeted sequencing of 23 driver genes with a variant allele frequency ≥2%. Participants were categorized into three groups based on CHIP mutation count: none, single, or multiple (≥2). The primary outcome was a composite renal event, defined as a ≥40% decline in eGFR, end-stage kidney disease, or renal-related death. Secondary outcomes included cardiovascular, hematologic malignancy-related, and all-cause death. Cox proportional hazards models were applied to evaluate associations, adjusting for demographic, clinical, and laboratory covariates.

Results

CHIP mutations were found in 1,033 patients (18.5%), including 151 (2.7%) with multiple mutations. Over a median follow-up of 10 years, 1,224 individuals (21.9%) experienced a composite renal event. The incidence was significantly higher in the multiple mutation group (adjusted HR 2.21, 95% CI: 1.58–3.08). Among CHIP genes, DNMT3A and TET2 were most frequently mutated, but RUNX1 showed the strongest association with renal events (HR 50.2, 95% CI: 12.3–204.7). In terms of secondary outcomes, multiple CHIP mutations were significantly associated with hematologic malignancy-related death (HR 3.85, 95% CI: 2.37–6.27) and all-cause mortality (HR 1.46, 95% CI: 1.11–1.91), while the association with cardiovascular mortality was not statistically significant (HR 1.72, 95% CI: 0.97–3.04, p = 0.06).

Conclusion

Our findings demonstrate that multiple CHIP driver mutations are independently associated with an increased risk of CKD progression, death from hematologic malignancy, and all-cause mortality. These results suggest that the CHIP mutational burden may serve as a useful biomarker for identifying elderly individuals at high risk for kidney function decline and adverse outcomes.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.202590kajrj5