von Willebrand Factor, ADAMTS13 Activity, and Decline in Kidney Function: A Population-Based Cohort Study

Abstract

Background: Altered levels of von Willebrand factor (vWF) and ADAMTS13 can promote thrombosis and disturb blood flow in kidney microcirculations. We investigated the association of serum vWF:ADAMTS13 ratio in relation to decline in kidney function.

Study design: Prospective cohort study.

Setting & participants: 2,479 individuals (mean age, 65.1±5.9 [SD] years; 43% men) from the population-based Rotterdam Study.

Predictors: vWF, ADAMTS13, and vWF:ADAMTS13 ratio.

Outcomes & measurements: Annual decline in estimated glomerular filtration rate (eGFR), halving of eGFR, and new-onset eGFR<60mL/min/1.73m² were assessed.

Results: During a median follow-up of 11 (range, 7.81-13.57) years, 500 cases of new-onset eGFR<60mL/min/1.73m² occurred. The population had a mean eGFR decline of 0.96±0.92mL/min/1.73m² per year. Higher vWF:ADAMTS13 ratio was associated with steeper annual decline in eGFR (difference, -0.06 [95% CI, -0.09 to -0.02] mL/min/1.73m² per year) and higher risk for new-onset eGFR<60mL/min/1.73m² (OR, 1.13; 95% CI, 1.01-1.27). Likewise, higher vWF:ADAMTS13 ratio was associated with higher risk for halving of eGFR (OR, 1.40; 95% CI, 1.02-1.93). After adjustment for cardiovascular risk factors and blood group, effect estimates remained the same.

Limitations: No data available for albuminuria. Participants were classified based on a single measurement of vWF and ADAMTS13.

Conclusions: In this population-based study, we showed that higher vWF:ADAMTS13 ratio is associated with decline in kidney function, suggesting a role of elevated prothrombotic factors in the development and progression of kidney disease.

Keywords: ADAMTS13 activity; disease progression; eGFR trajectory; estimated glomerular filtration rate (eGFR); kidney disease; prothrombotic factors; von Willebrand factor (vWF); von Willebrand factor protease.