Efficient monthly subcutaneous administration of darbepoetin in stable CAPD patients.

BACKGROUND: Although subcutaneous administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients is a widely accepted recommendation, the lowest possible frequency of an efficient dosing regimen remains controversial. Darbepoetin alpha, a new erythropoiesis-stimulating protein with a threefold longer serum half-life compared with rHuEPO, has greater in vivo potency and can be administered less frequently to obtain the same biological response. This study assessed the efficacy of darbepoetin administered once monthly in the treatment of anemia in CAPD patients. PATIENTS AND METHODS: In this single-center, prospective cohort study, 11 stable CAPD patients (5 males, 6 females; mean age 68.8 +/- 14.1 years; mean duration on peritoneal dialysis 31.6 +/- 13 months) maintained average hemoglobin and hematocrit levels of 12.09 +/- 1.29 g/dL and 37.29% +/- 3.58%, respectively, while receiving a mean weekly maintenance dose of epoetin alfa of 129 IU/kg. These same patients were assigned to receive the equivalent weekly darbepoetin dose once monthly for 24 consecutive weeks. Hematological response, iron status (transferrin saturation, serum ferritin levels), C-reactive protein (CRP), and the patients' biochemical profiles were evaluated monthly. RESULTS: During the monthly administration of darbepoetin, mean serum levels of Hb and Hct were 12.17 +/- 1.28 g/dL and 37.1% +/- 1.19% respectively. No statistically significant difference was apparent between the previous and monthly dosing values (12.09 +/- 1.29 vs 12.17 +/- 1.28 g/dL, p = 0.769, and 37.29% +/- 3.58% vs 37.1% +/- 1.19%, p = 0.752). Transferrin saturation levels as well as serum ferritin levels also remained unchanged (30.4% +/- 8.6% vs 30.1% +/- 9.4%, NS, and 556 +/- 212 vs 621 +/- 234 ng/mL, respectively, NS). CONCLUSION: These results indicate that darbepoetin alfa can be effectively given subcutaneously at monthly intervals for the treatment of anemia in stable CAPD patients. However, more studies are needed to validate the long-term efficacy of this monthly subcutaneous administration.

Effects of hemodialysis dose on anemia, hypertension, and nutrition.

There is good evidence that by improving dialysis adequacy, morbidity, and mortality of hemodialysis (HD) patients decrease. Dialysis adequacy has also been related to the better control of arterial blood pressure (BP), anemia and improvement of patients' nutritional status. This is a self-control study of 34 HD patients, (23 males, 11 females), aged 52.6 +/- 15.5 years, HD duration 55.9 +/- 61.2 months, referring to the effect of increasing delivered dialysis dose, over a two-year period, on their clinical and laboratory parameters. Delivered HD dose increased statistically significantly: Urea reduction ratio (URR) increased from 52 +/- 8 to 71 +/- 7% and Kt/V from 0.93 +/- 0.19 to 1.55 +/- 0.29 (p < 0.001). Hb increased statistically significantly from 10.4 +/- 1.7 to 11.0 +/- 1.3 g/dL (p < 0.05) while no difference has been noticed in weekly EPO dose. Both systolic and diastolic BP decreased statistically significantly (from 147 +/- 24 to 133 +/- 25mmHg and from 73 +/- 12 to 66 +/- 13 mmHg respectively, p = 0.001). Serum albumin increased from 4.3 +/- 0.4 to 4.6 +/- 0.3g/dL (p = 0.002) and nPCR from 0.93 +/- 0.16 to 1.20 +/- 0.17 (p < 0.001). We conclude that increasing dialysis dose results in both clinical and laboratory improvement regarding hypertension, nutritional status and control of HD patients' anemia.

The Clinical Impact of Increasing the Hemodialysis Dose.

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2-year period, the present self-controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry-weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/Vurea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred-to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)-with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/Vurea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry-weight policy, resulted in improvements in hypertension, nutritional status, and anemia.