Clonal hematopoietic mutations as a predictor of adverse outcomes in cytopenic patients with chronic kidney disease.

Abstract

Purpose: Clonal hematopoiesis (CH) is associated with cardiovascular disease (CVD), inflammation, and increased mortality. However, its prevalence and clinical impact in patients with cytopenia and chronic kidney disease (CKD) remain unclear.

Methods: We conducted a retrospective cohort study of patients with cytopenia and CKD who underwent targeted sequencing to evaluate the association between CH, CKD progression, and overall mortality.

Results: A total of 67 patients were included (mean age 75.7 ± 10.5 years; 58.2% male). Most patients had myelodysplastic neoplasms (MDS) (79.1%), followed by clonal cytopenia of undetermined significance (CCUS) and idiopathic cytopenia of undetermined significance (ICUS) (14.9%). CH was detected in 53.7% of the patients, most commonly involving TET2 (44.4%), DNMT3A (22.2%), and ASXL1 (22.2%). Over a median follow-up of 43.5 months (interquartile range [IQR] 34.3-79.3), CKD progression occurred in 34.3%. The 5-year cumulative incidence of CKD progression tended to be higher in the CH carriers than in the non-carriers (55.4% vs. 31.4%; log-rank p = 0.066). In multivariable Cox analysis, CH remained independently associated with CKD progression (adjusted hazard ratio [HR] 2.83; 95% confidence intervals [CI] 1.03-7.79; p = 0.044). CKD progression was most frequent in patients with MDS and CH (46%), followed by MDS without CH (30%) and CCUS (16%), with no progression in ICUS. Mortality was higher in CH carriers (50.0% vs. 16.1%; p = 0.004) and remained independently associated with CH (adjusted HR 3.90; 95% CI 1.41-10.83; p = 0.009).

Conclusions: CH is common in cytopenic patients with CKD and is independently associated with an increased risk of CKD progression and mortality. The assessment of CH may improve risk stratification and identify high-risk patients with adverse renal and survival outcomes.