Drug Therapy in Patients With Chronic Renal Failure

Anticoagulation in Renal Failure Is Safe and Effective Hartmann et al presented important principles of drug therapy in patients with renal failure. However, concrete individual recommendations regarding anti coagulation given in the article have to be corrected. Uremic bleeding disorder simultaneously combines bleeding risk with procoagulatory activity and increased risk of thrombosis. Especially patients with severe renal failure (GFR <30 mL/min) present with increased cardiovascular morbidity and mortality. Then any type of anticoagulation incurs an increased risk of hemorrhage and requires critical selection of the anti coagulatory drug using appropriate dosage and laboratory monitoring. Patients with severe renal failure are usually not represented in study populations, even for the newer oral anticoagulants. Low molecular weight heparins have notably improved the options for anticoagulation compared with unfractionated heparin and vitamin K antagonists. The articles’ conclusion, not to use enoxaparin in patients with GFR <60 mL/min, is wrong. Enoxaparin is the low molecular weight heparin that has been most extensively studied for all stages of renal failure and is explicitly licensed for a GFR<30 mL/min with clear recommendations how to adapt the dosage. Suggesting tinzaparin as an alternative in this context is not reasonable. As assessed by permeation chromatography, enoxaparin is the low molecular weight heparin with the highest content of defined oligomers, whereas tinza parin to a substantial extent resembles unfractionated heparin (1). The wording of accumulation “in a deep compartment” in the article remains an enigma. In acute coronary syndrome, using enoxaparin yields a mortality advantage without increasing hemorrhageassociated complications, even in severe renal failure (2, 3). Mahe et al did not observe more hemorrhagic complications in the referenced study for enoxaparin than for tinzaparin, although the dosage of enoxaparin had not been adequately adjusted in some cases and not adapted according to laboratory monitoring. The IRIS study investigated tinzaparin versus unfractionated heparin in venous thrombosis and found a higher mortality for tinzaparin in patients with renal failure who were older than 70. DOI: 10.3238/arztebl.2011. 0112a Antithrombotic Prophylaxis and Therapy in Renal Failure The authors postulate a “deep compartment” for enoxaparin. This is surprising in view of a distribution volume of some 5 liters and monophasic elimination (compare product information). Because of the structural differences of low molecular weight heparins, the pharmacokinetics of each low molecular weight heparin should be examined individually (1). Such substance specific studies in renal failure have been published for enoxaparin for a long time and have resulted in different dosage recommendations (1, 2, product information). Unfortunately, all this was ignored in the review article. For this reason, the article’s conclusions directly contradict the national and international licensing status of enoxaparin (for example, the US Food and Drug Administration [FDA]’s or the German Federal Institute for Drugs and Medical Devices [BfArM]’s). After repeated subcutaneous administration of the prophylactic dose (40 mg) in patients with a creatinine clearance <30 mL/min enoxaparin, the area under the plasma concentration time curve (AUC) is increased by an average of 65%. Because of this, the prophylactic dose in patients with severely restricted renal function, according to the existing risk of thromboembolism should not be higher than 20 mg or 30 mg. After administration of the therapeutic dose (1 mg/mg KG b.d.) in severely impaired renal function, the AUC has been Drug Therapy in Patients With Chronic Renal Failure