Clonal Hematopoiesis of Indeterminate Potential and Kidney Failure in CKD: An East Asian Cohort Study

Clonal hematopoiesis of indeterminate potential was more prevalent in patients with CKD than the general population. Clonal hematopoiesis of indeterminate potential was associated with a higher risk of kidney failure in patients with CKD across both the Korean and European ancestry populations. Variant allele fraction of clonal hematopoiesis of indeterminate potential‑associated mutations was higher in patients with CKD than those without CKD.

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with inflammation. Although CKD shares these pathophysiological features, the prognostic role of CHIP on CKD progression remains unclear, particularly in underrepresented East Asian populations.

Deep targeted sequencing of CHIP-driving mutations was used to identify the presence of CHIP, defined as variant allele fraction (VAF) ≥2.0%. CHIP prevalence was compared between 175 Korean participants with CKD in the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) cohort and 700 matched general population controls in the Gene-Environmental Interaction and Phenotype (GENIE) cohort. The association between CHIP and kidney failure (KF) risk was evaluated using multivariable Cox regression analysis both in the KNOW-CKD cohort and 232 matched UK Biobank participants with CKD. Furthermore, VAF was compared between CHIP-positive participants in the KNOW-CKD and GENIE cohorts.

The prevalence of CHIP was significantly higher in the KNOW-CKD cohort than in the GENIE cohort (17% versus 11%; P = 0.04). Over a median follow-up of 10.0 years, 66 participants (38%) developed KF in the KNOW-CKD cohort. After multivariable adjustment, CHIP was associated with higher risk of KF (adjusted hazard ratio, 1.90; 95% confidence interval, 1.03 to 3.51). Furthermore, in the UK Biobank, KF occurred in 43 participants (20%) over a median follow-up of 12.9 years and the association of CHIP with higher risk of KF was consistently observed (adjusted hazard ratio, 2.16; 95% confidence interval, 1.15 to 4.03). Furthermore, among CHIP-positive participants, the median VAF of CHIP-associated mutations was significantly higher in participants within the KNOW-CKD cohort compared with healthy controls in the GENIE cohort (7.3% versus 4.4%; P = 0.02).

CHIP is more prevalent in patients with CKD and serves as an independent risk factor of KF. This association is consistently observed across both an underrepresented East Asian cohort and a European cohort, establishing CHIP as a globally relevant risk factor of CKD progression.