Risk factors for thromboembolic events in individuals with dialysis-dependent chronic kidney disease

A recent study has shown that it is reasonable to avoid sudden fluctuations in hemoglobin levels and maintain transferrin saturation (TSAT) levels at or above 30%, rather than escalating the dosage of roxadustat. The findings of the study were published in the journal Advances in Therapy.

Thromboembolic events in patients receiving roxadustat were investigated through a combined analysis of four phase 3 trials, including PYRENEES, HIMALAYAS, SIERRAS, and ROCKIES, both prior to and following the twelfth week. Cox regression analyses were used to explore the baseline risk factors for thromboembolic events. The association between thromboembolic events and laboratory parameters that were last known before the event was explored through nested case-control studies using matched case-control pairs.

Among the 2354 patients studied, 1026 thromboembolic events were observed in 568 patients. Baseline risk factors identified included hemodialysis versus peritoneal dialysis, race, high high-sensitivity C-reactive protein, advanced age ≥ 65 years, a history of thromboembolism, cardiovascular disease, or diabetes. Univariate case-control analyses indicated that a high hemoglobin rate of rise (≥ 0.5 g/dL/week; OR 2.09; 95% CI 0.98-4.46) showed a potential increase in the risk of thromboembolic events before week twelve, while a high rate of hemoglobin decline was linked to events after week 12 (< - 0.5 g/dL/week; OR 3.73; 95% CI 1.68-8.27) in comparison to steady levels of hemoglobin (ranging from ≥ - 0.1– < 0.1 g/dL/week).

Multivariate case-control analyses demonstrated that a low last known hemoglobin level (< 10 g/dL: adjusted OR 1.91; 95% CI 1.04-3.50; versus ≥ 12 g/dL) and low last known transferrin saturation (TSAT < 10%: adjusted OR 3.78; 95% CI 1.71-8.39; versus ≥ 30%) before event onset were associated with events after week twelve. An increased dose of roxadustat was correlated with thromboembolic events in patients whose last known transferrin saturation was less than 30%, while no correlation was observed in patients with transferrin saturation of 30% or higher.

The above study demonstrated that among several risk factors associated with thromboembolic events, it is suitable to avoid abrupt changes in hemoglobin levels and keep TSAT levels at or above 30% instead of increasing the dosage of roxadustat.