A simple, safe and effective citrate anticoagulation protocol for the genius dialysis system in acute renal failure.

BACKGROUND: The Genius dialysis system is a close loop dialysis batch system increasingly used as an intermittent hemodialysis device in intensive care units. The aim of this study was to test the safety and feasibility of a regional citrate anticoagulation protocol with respect to acid-base and electrolyte disarrangements in critically ill patients with acute renal failure. A standard heparin anticoagulation protocol served as control. METHODS AND RESULTS: In a cross-over study design, 27 acute renal failure patients were allocated to a citrate- and heparin-anticoagulated dialysis sessions (4-6 h). For citrate anticoagulation, a 4% sodium-citrate solution was infused into the arterial line of the extracorporeal circuit. A low calcium dialysate (1 mmol/l) was used for all dialysis sessions. Citrate dosing was adjusted according to the post-filter ionized calcium concentration (targeted values 0.5-0.7 mmol/l). There was no routine calcium substitution. Heparin anticoagulation was started with a heparin-loading dose followed by an individual, patient-adjusted continuous heparin infusion. Electrolyte disarrangements, namely hypernatremia, hypo- and hypercalcemia did not occur in either group. Although the highest bicarbonate levels were achieved during citrate anticoagulation (p = 0.021 versus heparin) the acid base values remained equilibrated in both groups. Filter longevity was excellent and the targeted dialysis time was achieved in all but 1 patient. Citrate anticoagulation was well tolerated with respect to cardiovascular hemodynamics. CONCLUSIONS: Citrate anticoagulation can be safely and effectively performed during intermittent Genius dialysis. Calcium supplementation is not routinely required.

Metabolic complications during regional citrate anticoagulation in continuous venovenous hemodialysis: single-center experience.

BACKGROUND: Regional anticoagulation with trisodium citrate is an effective form of anticoagulation for continuous renal replacement therapy (CRRT) in patients at a high risk of bleeding. In a prospective, observational study we compared an established regional citrate anticoagulation protocol [Mehta R et al: Kidney Int 1990;38:976-981] versus a standard heparin anticoagulation protocol focusing on acid-base and electrolyte derangements as well as on cost effectiveness. METHODS AND RESULTS: 209 patients were included in the study. In 37 patients, citrate was used as the sole anticoagulant, 87 patients received low-dose heparin plus citrate, and 85 patients received only heparin as anticoagulant. A customized dialysate solution was used for citrate-anticoagulated CRRT (no buffer, no calcium, reduced sodium concentration). Filter life was significantly higher during citrate anticoagulation compared to heparin anticoagulation (80.2 +/- 60 vs. 30.2 +/- 32 h; p < 0.001). No difference was found between citrate and citrate-heparin anticoagulation (p = 0.310). Metabolic alkalosis was observed in more than 50% of patients on citrate anticoagulation. Alkalosis developed within the first 72 h after initiating treatment and could be reversed in almost all cases by increasing the dialysate flow rate. Hypercalcemia was observed in 13 patients on citrate anticoagulation. Patients with impaired liver function were particularly at risk. Systemic hypocalcemia, hypernatremia, and anion gap acidosis were not observed. Citrate anticoagulation was well tolerated hemodynamically. A longer filter life during citrate anticoagulation translated into a significant cost reduction compared to standard heparin anticoagulation (p < 0.01). CONCLUSION: Regional anticoagulation with trisodium citrate in combination with a customized calcium-free dialysate is a safe and effective alternative to a heparin-based anticoagulation regimen.

Pharmacokinetics of valganciclovir and ganciclovir in renal impairment.

BACKGROUND: Valganciclovir is the oral prodrug of ganciclovir. The pharmacokinetics of valganciclovir in patients with renal impairment is not known. Furthermore, it is not known whether there are any pharmacokinetic differences between patients who are positive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) and healthy subjects. METHODS: A total of 44 patients were included-18 with mild, medium, or severe renal impairment; 6 with end-stage renal disease who were on long-term hemodialysis; 8 HIV/CMV-positive patients with normal renal function; and 12 healthy subjects serving as controls. Valganciclovir and ganciclovir serum concentrations were measured after oral administration of 900 mg of valganciclovir. Pharmacokinetic parameters were estimated by means of noncompartmental and compartmental methods. RESULTS: After oral administration of the prodrug valganciclovir, ganciclovir bioavailability was 60% and ganciclovir concentrations were higher (maximum concentration [C(max)], 8.5 microg/mL versus 5.8 microg/mL) and appeared later (time to maximum concentration [T(max)], 4.3 versus 2.0 hours) in patients with severe renal impairment compared with healthy subjects. The elimination half-life (t(1/2)) of ganciclovir was longer in patients with renal failure (t(1/2) of 68.1 hours in patients with end-stage renal disease compared with 3.5 hours in healthy subjects). Ganciclovir clearance was correlated with creatinine clearance (r = 0.975). Hemodialysis removed 50% of ganciclovir. We observed no differences in pharmacokinetics between HIV/CMV-positive patients and healthy subjects. A 2-compartment model with zero-order input and first-order elimination proved to be the most appropriate model for ganciclovir after oral administration of valganciclovir. CONCLUSIONS: The dosage of valganciclovir has to be adjusted to the degree of renal impairment. Dosage adjustment is not necessary for HIV/CMV-positive patients.