Response to: “Clonal Hematopoiesis of Indeterminate Potential and Diabetic Kidney Disease: A Nested Case-Control Study”

Vlasschaert, Caitlyn; Rauh, Michael J.; Lanktree, Matthew B.

doi:10.1016/j.ekir.2022.06.022

Cited by 5 publications

(3 citation statements)

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“…However these studies were limited by small sample sizes and had important differences in CHIP variant assessment and classification. 24…”

Section: Introductionmentioning

confidence: 99%

“…However these studies were limited by small sample sizes and had important differences in CHIP variant assessment and classification. 24 In this study, we first examine the prospective associations between CHIP and CKD progression events in four large CKD cohorts, totaling 6,216 individuals: the Chronic Renal Insufficiency Cohort (CRIC), the African American Study of Kidney Disease (AASK), subjects with CKD from the BioVU biorepository, and the Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT). We then use Mendelian randomization as an orthogonal method to assess the contribution of CHIP to eGFR decline.…”

Section: Introductionmentioning

confidence: 99%

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Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression

Vlasschaert,

Pan,

Chen

et al. 2024

Preprint

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BackgroundClonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other thanDNMT3A(non-DNMT3ACHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes.MethodsIn this study, we examined the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients (total N = 5,772). The primary outcome was a composite of 50% kidney function decline or kidney failure. The slope of eGFR decline was examined as a secondary outcome. Mendelian randomization techniques were then used to investigate potential causal effects of CHIP on eGFR decline. Finally, kidney function was assessed in adenine-fed CKD model mice having received a bone marrow transplant recapitulatingTet2-CHIP compared to controls transplanted wild-type bone marrow.ResultsAcross all cohorts, the average age was 66.4 years, the average baseline eGFR was 42.6 ml/min/1.73m2, and 24% had CHIP. Upon meta-analysis, non-DNMT3ACHIP was associated with a 59% higher relative risk of incident CKD progression (HR 1.59, 95% CI: 1.02-2.47). This association was more pronounced among individuals with diabetes (HR 1.29, 95% CI: 1.03-1.62) and with baseline eGFR ≥ 30 ml/min/1.73m (HR 1.80, 95% CI: 1.11-2.90). Additionally, the annualized slope of eGFR decline was steeper among non-DNMT3ACHIP carriers, relative to non-carriers (β -0.61 ± 0.31 ml/min/1.73m2, p = 0.04). Mendelian randomization analyses suggested a causal role for CHIP in eGFR decline among individuals with diabetes. 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.ConclusionNon-DNMT3ACHIP is a potentially targetable novel risk factor for CKD progression.

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“…However these studies were limited by small sample sizes and had important differences in CHIP variant assessment and classification. 24…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression

Vlasschaert,

Pan,

Chen

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Active campaigns for some of these individual medically relevant emoji, such as the anatomical kidney, stomach, and liver have received substantial support from relevant societies and require ongoing attention . However, to establish a standardized set of medically relevant emoji, it is crucial for medical societies and relevant organizations to not only endorse individual emoji but also come together to agree on a comprehensive set of symbols that are universally recognized and understood.…”

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confidence: 99%