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Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort
G Pernod1, J-L Bosson, D Golshayan
1DBPC, Hemostasis Unit, GREPI EA, CHU Grenoble, France.
Insights
Cardiovascular disease (CVD) is a major concern for end-stage renal disease (ESRD) patients. This study identified previous CVD events, high homocysteine, and MTHFR genotype as key risk factors for future cardiovascular events in dialysis patients.
Area of Science:
- Nephrology
- Cardiology
- Genetics
Background:
- Cardiovascular disease (CVD) is the leading cause of mortality in end-stage renal disease (ESRD) patients.
- Traditional CVD risk factors inadequately explain the high prevalence of CVD in ESRD.
- Non-traditional cardiovascular risk markers are increasingly recognized in this population.
Purpose of the Study:
- To investigate the relationship between CVD and phenotypic and genotypic risk markers in incident dialysis patients.
- To identify predictive factors for cardiovascular events in patients initiating chronic dialysis.
- To assess the impact of baseline risk markers on cardiovascular morbidity and mortality.
Main Methods:
- Prospective cohort study of 279 incident dialysis patients (Diamant Alpin Dialysis Cohort Study).
- Determination of phenotypic and genotypic parameters at dialysis initiation.
- Monitoring of patients over 2 years for cardiovascular events (morbidity and mortality).
Main Results:
- A total of 82 cardiovascular events occurred, with 26 deaths from CVD.
- Previous cardiovascular events were strong predictors of future events (HR 2-3.9).
- Elevated lipoprotein(a) and total plasma homocysteine (>30 micromol/l) were independent predictors of CV events.
- In patients with homocysteine < 30 micromol/l, the MTHFR 677TT genotype predicted CV events (HR 2.5).
Conclusions:
- Patients with ESRD initiating dialysis who have a history of CVD, elevated homocysteine, or the MTHFR 677TT genotype are at high risk.
- These findings highlight specific phenotypic and genotypic markers for risk stratification in ESRD patients.
- Early identification and management of these risk factors may improve cardiovascular outcomes in dialysis patients.
Abstract:
Cardiovascular disease (CVD) remains the major cause of death in patients with end-stage renal disease (ESRD). Traditional risk factors do not explain the high prevalence of CVD in this population, and other non-traditional cardiovascular (CV) risk markers have now been described. Therefore, the potential relationship between CVD and phenotypic and genotypic risk markers was investigated prospectively in incident dialysis patients cohort. The 279 patients (244 on hemodialysis, 35 on peritoneal dialysis) within the Diamant Alpin Dialysis Cohort Study were investigated. Phenotypic and genotypic parameters were determined at dialysis initiation, patients monitored over a 2-year period, and CV events (morbidity and mortality) recorded. Globally, 82 CV events occurred and 26 patients (9.3%) died from CVD, whereas 28 (10%) died from non-CV causes. Previous CV events were strongly predictive of CV events occurrence, whatever patients had had one (hazard ratio (HR) 2, 95% confidence intervals (CI) 1.1-3.5) or more (HR 3.9, 95% CI 2.1-7.1) CV accidents before starting dialysis. Both lipoprotein(a) (HR 1.67, 95% CI 1-2.5) and total plasma homocysteine at cutoff 30 micromol/l (HR 1.7, 95% CI 1.1-2.8) were independent predictors of CV events outcome. In the subgroup of patients with homocysteine < 30 micromol/l, methylenetetrahydrofolate reductase (MTHFR) TT was the sole biological parameter predictive of CV event outcome (HR 2.5, 95% CI 1.1-10, P = 0.03). ESRD patients who enter chronic dialysis with a previous CV event, high total homocysteinemia levels, or MTHFR 677TT genotype must be considered at high risk of incident CV events.
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