Title: A Randomized, Controlled Trial of Early Versus Late Initiation of Dialysis
Date Posted: June 28, 2010
Authors: Cooper BA, Branley P, Bulfone L, et al., on behalf of the IDEAL Study Investigators.
Citation: N Engl J Med 2010;Jun 27:[Epub ahead of print].
Study Question:
What is the influence of the timing of the initiation of maintenance dialysis on survival among patients with chronic kidney disease?
Methods:
The Initiating Dialysis Early and Late (IDEAL) study investigators randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (eGFR) between 10.0-15.0 ml/min/1.73 m2 of body-surface area (calculated with the use of the Cockcroft–Gault equation) to planned initiation of dialysis when the eGFR was 10.0-14.0 ml/min (early start) or when the eGFR was 5.0-7.0 ml/min (late start). The primary outcome was death from any cause.
Results:
Between July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60-2.23) in the early-start group and 7.40 months (95% CI, 6.23-8.27) in the late-start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the eGFR was above the target of 7.0 ml/min, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late-start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83-1.30; p = 0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis).
Conclusions:
The authors concluded that planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes.
Perspective:
In this study involving patients with chronic kidney disease, early initiation of dialysis had no significant effect on the rate of death from any cause or on cardiovascular events, infectious events, or complications of dialysis. The results suggest that with careful clinical management of chronic kidney disease, dialysis can be delayed for some patients until the GFR drops below 7.0 ml/min or until more traditional clinical indicators for the initiation of dialysis are present. It should be noted that the majority of the patients assigned to the late-start group did not commence dialysis at the level of GFR defined in the protocol, and the mean difference in eGFR was only 2.2 ml/min. However, there was a difference of 6 months between the groups in the start time for dialysis, reflecting the critical importance of close clinical follow-up if dialysis is to be delayed.
Author(s): Debabrata Mukherjee, M.D., F.A.C.C.
Title: Acquired von Willebrand Syndrome After Continuous-Flow Mechanical Device Support Contributes to a High Prevalence of Bleeding During Long-Term Support and at the Time of Transplantation
Date Posted: June 30, 2010
Authors: Uriel N, Pak SW, Jorde UP, et al.
Citation: J Am Coll Cardiol 2010;Jun 30.
Study Question:
What is the prevalence and mechanism of bleeding events in patients receiving left ventricular assist device (LVAD) support?
Methods:
This was a retrospective study of 79 HeartMate II (HM II) patients who underwent implantation between 2004 and 2009. Bleeding was defined as the need for transfusion >7 days after device insertion. Transfusion at heart transplantation was compared with that in Heart-Mate XVE patients.
Results:
Some 44.3% of HM II patients had bleeding episodes at 112 ± 183 days after LVAD implantation, with 50% experiencing an event within 2 months. Gastrointestinal bleeding was the most frequent event. At the index event, the INR averaged 1.67 ± 0.53, and the platelet count was 237 ± 119 x 109/L. Comparison of the transfusion requirements at heart transplantation of 35 HM II patients with 62 HeartMate XVE patients demonstrated twice the transfusion requirements in HM II patients (packed red blood cells, 6.3 ± 0.8 U vs. 3.8 ± 0.5 U; platelets, 12.5 ± 5.4 U vs. 8.6 ± 6.4 U; fresh frozen plasma, 9.6 ± 4.9 U vs. 4.9 ± 3.6 U; and cryoprecipitate, 4.3 ± 3.6 U vs. 2.2 ± 3.5 U; p < 0.05 for all). High molecular weight von Willebrand factor (VWF) multimers were measured in 31 HM II patients and were reduced in all patients; 18 of these 31 (58%) patients had bleeding.
Conclusions:
Patients with the HM II had a high incidence of bleeding events during device support and at heart transplantation. HM II patients had reduced high molecular weight VWF multimers.
Perspective:
Bleeding complications are high in patients receiving LVAD support, especially in continuous-flow devices that require anticoagulation. This study supports previous observations that an acquired hemostatic defect involving reduced VWF multimers may contribute to bleeding events in patients with HM II devices. This is presumably related to enhanced proteolysis of hemostatic VWF multimers triggered by shear stress, a hypothesis previously proposed to explain increased bleeding in patients with severe aortic stenosis. If these findings are confirmed in larger trials, measurement of VWF multimers may prove useful in guiding anticoagulant and antiplatelet therapy in patients receiving LVAD support, to reduce bleeding complications.
Author(s): Daniel T. Eitzman, M.D., F.A.C.C.