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 < 60 mL/min/1.73 m2 were assessed. Results During a median follow-up of 11 (range, 7.81-13.57) years, 500 cases of new-onset eGFR < 60 mL/min/1.73 m2 occurred. The population had a mean eGFR decline of 0.96 ± 0.92 mL/min/1.73 m2 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/1.73 m2 per year) and higher risk for new-onset eGFR < 60 mL/min/1.73 m2 (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.
Bibliographical noteFunding Information:
Support: The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission; and the Municipality of Rotterdam. The measurement of ADAMTS13 was financially supported by Baxalta Innovations GmbH , now part of Shire, Vienna, Austria through an unrestricted grant. Dr Dehghan is supported by Netherlands Organization for Scientific Research (NWO) grant (veni, 916.12.154) and the Erasmus University Rotterdam Fellowship. Dr Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd) , Metagenics Inc , and AXA . Nestlé Nutrition (Nestec Ltd), Metagenics Inc, and AXA had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript.
- ADAMTS13 activity
- disease progression
- eGFR trajectory
- estimated glomerular filtration rate (eGFR)
- kidney disease
- prothrombotic factors
- von Willebrand factor (vWF)
- von Willebrand factor protease