Clonal Hematopoiesis and Kidney Function in the ASPREE Cohort

Area of Science:

• Nephrology
• Hematology
• Genetics

Background:

• Clonal hematopoiesis of indeterminate potential (CHIP) is a novel risk factor for nonhematological diseases.
• Existing research on CHIP's association with kidney outcomes is conflicting.

Purpose of the Study:

• To assess the association between CHIP and kidney function in older adults.
• To perform a meta-analysis of published cohorts on CHIP and kidney function decline.

Main Methods:

• Secondary analysis of the ASPREE trial involving 9434 community-dwelling adults >70 years.
• Assessment of baseline kidney function (eGFR, UACR) and longitudinal changes.
• Meta-analysis of published cohorts investigating CHIP and incident kidney function decline.

Main Results:

• No association was found between CHIP (including large or non-DNMT3A CHIP) and baseline kidney function or its decline over 8.4 years in the ASPREE cohort.
• Incident kidney function decline was not increased in this cohort.
• Meta-analysis indicated an increased risk of kidney function decline in non-DNMT3A CHIP, with significant heterogeneity across studies.

Conclusions:

• CHIP, particularly non-DNMT3A CHIP, may be associated with kidney function decline, but findings vary.
• Participant factors like comorbidities may explain heterogeneity in cohort studies.
• Understanding CHIP's role in disease requires considering individual patient characteristics.