Risk of VTE Increases with Albuminuria in Patients with Normal eGFRs

There is an increase in the risk of venous thromboembolism (VTE) in patients with chronic kidney disease (CKD) with elevated albuminuria or with low estimated glomerular filtration rate (eGFR). However, according to David Massicotte-Azarniouch, MD, and colleagues, it is unclear whether the increased risk of VTE associated with albuminuria differs by level of kidney function.

Noting that clarifying the individual and combined contributions of albuminuria and kidney function would be of use in accurately determining the risk of VTE and identifying appropriate prophylactic therapies for patients at risk, the researchers utilized a large population-based database to examine the association of VTE events in patients by albuminuria and eGFR. Results were reported in the American Journal of Kidney Diseases [2017;70(6):826-833].

The final analytic cohort included 694,956 adults in Ontario, Canada, from 2002 to 2012. Patients were stratified according to albumin-creatinine ratio (ACR). Those with higher urine ACRs were older, more likely to be male, and had lower eGFRs. They also had lower income status and more comorbid conditions (diabetes mellitus, hypertension, stroke, hemorrhage, cardiac disease, chronic obstructive pulmonary disease, and liver disease). Further, VTE-specific risk factors, including recent surgery, remote/active cancer, and lower-extremity fracture, were all more common in patients with higher ACRs. Utilization of healthcare (determined by visits to the emergency department and family or general physician visits) were higher in that patient population, as well.

In total, there were 15,180 VTE events during the study period. The proportion of VTEs increased with heavier albuminuria: ACR <30 mg/g: 2.0%; ACR 30 to 300 mg/g: 2.9%; ACR >300 mg/g: 3.1%. There were 248 VTE events in patients with eGFR 15 to 29 mL/min/1.73 m2. Median time to VTE event was 3.7 years; median time to VTE or death was 3.7 years. Median times to death, end-stage renal disease, or end of study were 5.3, 4.2, and 6.4 years, respectively.

When examined as continuous variables, in fully adjusted models that included an ACR ´ eGFR interaction term (P<.001) for both ACR and eGFR, ACR and eGFR were independently associated with VTE. The subdistribution hazard ratio (HR) increased 0.1% per 1-mg/g greater urine ACR. The subdistribution HR decreased 0.4% per 1-mL/min/1.73 m2 in greater eGFR. The interaction for ACR ´ eGFR was highly significant (P<.0001); ACR was an effect modifier on the association of eGFR and VTE.

The researchers examined whether the VTE risk was consistent in ACR categories across categories of eGFR. With higher albuminuria there was a steeper risk in the adjusted subdistribution HR for VTE with eGFR of 120 mL/min/1.73 m2 compared with eGFR of 30 mL/min/1.73 m2. The subdistribution HR at eGFR of 120 mL/min/1.73 m2 and ACR of 500 mg/g was 2.05 (95% confidence interval [CI], 1.74-2.41), whereas at eGFR of 30 mL/min/1.73 m2 and ACR of 500 mg/g, the subdistribution HR was 1.42 (95% CI, 1.24-1.62). There was no substantial change in the risk for VTE with a higher ACR at eGFR of 30 mL/min/1.73 m2 (ACR of 0 m/g: subdistribution HR, 1.26; 95% CI, 1.20-1.33); ACR of 500 mg/g: subdistribution HR, 1.42 (95% CI, 1.24-1.62).

The researchers cited some limitations to the findings, including the observational design of the study that limits the establishment of causality, the inability to specifically examine the cause for declines in kidney function or albuminuria, sensitivity of only 75%, determining eGFR and ACR based on clinical indication rather than population-level screening, and lack of information on medication use in the study population.

“In conclusion, CKD, defined as reduced eGFR and/or albuminuria, is a significant independent risk factor for the development of VTE. The albuminuria-associated risk for VTE changes depending on level of eGFR. In patients with normal kidney function, higher ACR is associated with much larger increase in risk for VTE compared with patients with reduced kidney function. Given the high prevalence, morbidity, and mortality of both CKD and VTE, developing prevention strategies for VTE events in at-risk patients through the use of evidence-based screening tools could decrease the incidence and population-level impact of VTE,” the researchers said.

Takeaway Points

  1. Researchers conducted a population-based cohort study to examine the risk of venous thromboembolism (VTE) due to combined effects of eGFR and albuminuria.
  2. Among a study population of 694,956 adults, 15,180 VTE events (2.2%) occurred throughout the study period 2002-2012.
  3. Albuminuria increased the risk for VTE in patients with normal eGFRs, compared with patients with lower eGFRs.