Smaller nadroparin dose reductions required for patients with renal impairment: A multicenter cohort study

Background: Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15–29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment. 

Aims: To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment. 

Methods: A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression. 

Results: 770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65–359 and 68-168 IU/kg in eGFR 15–29, 30–60 and > 60 ml/min/1.73m², respectively. In eGFR 15–29 and 30-60 ml/min/1.73m², doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min. 

Conclusion: We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m², which are achieved by smaller dose reductions.