Anticoagulant use in patients with chronic renal impairment.

Patients with renal failure have an increased risk of both thrombotic and bleeding complications. A number of antithrombotic drugs undergo renal clearance. Therefore, estimation of renal function is necessary when prescribing these drugs to patients with renal dysfunction. Pharmacokinetic and clinical data in patients with chronic renal impairment are limited for several anticoagulants, and adequate administration information is often absent. Dose adjustment of anticoagulants may be indicated when the creatinine clearance falls below 30 mL/min. Unfractionated heparin, argatroban, and vitamin K antagonists generally do not require dose adjustment with renal dysfunction. However, smaller doses of warfarin may be required to achieve a particular target international normalized ratio. Close monitoring of anticoagulation is recommended when argatroban or high doses of unfractionated heparin are administered in patients with severe chronic renal impairment. Low-molecular weight heparins, danaparoid sodium, hirudins, and bivalirudin all undergo renal clearance. Lower doses and closer anticoagulation monitoring may be advisable when these agents are used in patients with chronic renal failure. We recommend that fondaparinux sodium and ximelagatran (not yet licensed) be avoided in the presence of severe renal impairment and be used with caution in patients with moderate renal dysfunction. While acknowledging the lack of pharmacokinetic data, this review provides specific recommendations for the use of anticoagulants in patients with chronic renal impairment.

Defining conditions that lead to the retention of water: the importance of the arterial sodium concentration.

BACKGROUND: A water diuresis occurs when a large volume of water is ingested rapidly. Nevertheless, water conservation is required to provide a source of water for evaporative heat dissipation throughout the day. Therefore, the objective was to define conditions that permit the retention of ingested water. METHODS: Volunteers collected urine q2h plus an overnight specimen; water loading was conducted after overnight food and water restriction; paired arterialized and venous blood samples were analyzed. RESULTS: When 20 mL water/kg was consumed in <15 minutes, the peak urine flow rate was 11 +/- 0.6 mL/min. The volume of water retained after water intake stopped, and when the urine was hyperosmolar, correlated directly with the daily excretion of sodium plus potassium (r(2)= 0.63). The plasma sodium concentration (P(Na)) was 4.0 +/- 0.5 mmol/L lower in arterialized than paired venous blood 30 to 40 minutes after water ingestion began (P < 0.01). In preliminary studies, the smallest water load consumed in 15 minutes that would reproducibly cause a water diuresis was defined in each subject. This same acute water load was retained, however, if it contained 150-mmol/L fructose, but not glucose, or if it was consumed slowly (sipping). The arterialized P(Na) was not significantly lower than in paired venous samples when water was sipped. CONCLUSION: A large fall in arterialized and not venous P(Na) best reflected the signal to induce a water diuresis. Although a very large water load can induce a water diuresis, smaller water loads can be retained for future heat dissipation.

Evolution of naturally acquired hepatitis B immunity in the long-term hemodialysis population.

BACKGROUND: Although the natural history of vaccination-induced hepatitis B virus (HBV) antibodies (Abs) is becoming clearer, little is known about naturally acquired immunity. Some assume that these patients never lose their Abs. METHODS: To document the natural history of HBV immunity, we prospectively followed up all naturally immune patients initiating hemodialysis (HD) therapy at St Michael's Hospital (Toronto, Canada). Patients presenting with Ab to hepatitis B surface antigen (HBsAb) who had no history of vaccination had a core Ab level measured to confirm natural immunity. When HBsAb titer decreased to less than 10 IU/L, patients were administered a single dose of 40 microg of Engerix B vaccine (Smith Kline Beecham Pharma Inc, Oakville, Ontario, Canada) intramuscularly as a booster dose. RESULTS: We identified 29 patients beginning HD therapy with natural immunity. Nine patients (30%) subsequently lost immunity (defined as Ab titer decreasing to < 10 IU/L) during follow-up. They were older and had a lower Ab titer at initiation of HD therapy. Four of 5 patients with a low response to the booster dose were 75 years or older. Two patients with a low peak Ab titer after the booster dose again had their Ab titer decrease to less than 10 IU/L after 6 and 10 months. Both patients were switched to intradermal vaccination. All other patients were still immune after a median of 26 months. CONCLUSION: Individuals who are naturally immune against HBV may experience a decrease in Ab titer. Their responses to booster vaccinations varied widely. It is possible that elderly patients with natural immunity require closer surveillance. We provide recommendations for surveillance in these patients.