Hemorheological and hemodynamic changes in predialysis patients after normalization of hemoglobin with epoetin-alpha.

OBJECTIVE: Changes in blood viscosity and total peripheral resistance may contribute to increased blood pressure during partial correction of renal anemia with erythropoietin. An increase in hemoglobin level is followed by decreases in cardiac output and left ventricular mass. We examined how normalization of hemoglobin in predialysis patients affects both hemorheological and hemodynamic variables. MATERIAL AND METHODS: Twelve moderately anemic predialysis patients (hemoglobin 115.9+/-7.8 g/l) received epoetin-alpha with the aim of achieving a normal hemoglobin level (135-160 g/l). Hemorheological variables were measured using rotational viscometry. Cardiac index was determined by means of Doppler echocardiography. RESULTS: After 48 weeks, the hematocrit level had increased from 37.9%+/-3.0% to 47.0%+/-3.1% (p<0.0001). Blood viscosity increased from 3.84+/-0.33 to 4.59+/-0.4 mPa x s (p<0.001). Blood viscosity standardized to a hematocrit level of 45% and a plasma viscosity of 1.31 mPa x s did not change. Plasma viscosity, erythrocyte aggregation tendency and erythrocyte fluidity remained unchanged. The cardiac index decreased from 2.64+/-0.57 to 2.19+/-0.72 l/min/m(2) (p<0.05). The total peripheral resistance index increased from 3270+/-985 to 4013+/-1046 (dyn x s/cm(5))m(2) (p<0.05). Blood pressure remained constant, but the amount of antihypertensive medication used increased by 30%. CONCLUSIONS: Hemoglobin normalization in predialysis patients raised blood viscosity and total peripheral resistance due to an increase in hematocrit level, without other consistent hemorheological changes. Antihypertensive therapy had to be increased in many patients to maintain an acceptable blood pressure. The cardiac index was reduced, which may have prevented further development of left ventricular hypertrophy.

Reduced hemodialysis adequacy after hemoglobin normalization with epoetin.

BACKGROUND: Increased hemoglobin (Hb) levels and higher blood viscosity could reduce hemodialyzer clearance. We examined hemodialysis (HD) adequacy after treatment with epoetin alfa aimed at normalizing Hb levels. METHODS: Thirty-three HD patients were randomly allocated to achieve a normal Hb level (135-160 g/L) or a subnormal (control) Hb level of 90-120 g/L. HD adequacy was assessed by Kt/V measurement. RESULTS: In the 24 evaluable patients, Hb levels reached 144 +/- 11 g/L in the normal Hb group (n=10) and 109 +/- 10 g/L in the subnormal group (n=14). Single-pool Kt/V decreased from 1.25 +/- 0.19 to 1.15 +/- 0.13 (p<0.01) in the normal Hb group, but remained constant in the subnormal group (1.26 +/- 0.26 and 1.26 +/- 0.28). CONCLUSIONS: Normalization of Hb with epoetin alfa in HD patients resulted in a slight but statistically significant reduction in Kt/V. Therefore, when Hb is normalized, an increased dialysis dose could be necessary to maintain dialysis adequacy.

Pharmacokinetics and red cell utilization of 52Fe/59Fe-labelled iron polymaltose in anaemic patients using positron emission tomography.

Parenteral iron-polysaccharide complexes are increasingly applied. The pharmacokinetics of iron sucrose have been assessed by our group using positron emission tomography (PET). A single intravenous injection of 100 mg iron as iron (III) hydroxide-polymaltose complex, labelled with a tracer in the form of 52Fe/59Fe, was similarly assessed in six patients using PET for about 8 h. Red cell utilization was followed for 4 weeks. Iron polymaltose was similarly distributed to the liver, spleen and bone marrow. However, a larger proportion of this complex was rapidly distributed to the bone marrow. The shorter equilibration phase for the liver, about 25 min, indicates the minimal role of the liver for direct distribution. Splenic uptake also reflected the reticuloendothelial handling of this complex. Red cell utilization ranged from 61% to 99%. Despite the relatively higher uptake by the bone marrow, there was no saturation of marrow transport systems at this dose level. In conclusion, high red cell utilization of iron polymaltose occurred in anaemic patients. The major portion of the injected dose was rapidly distributed to the bone marrow. In addition, the reticuloendothelial uptake of this complex may reflect the safety of polysaccharide complexes. Non-saturation of transport systems to the bone marrow indicated the presence of a large interstitial transport pool, which might possibly be transferrin.

A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients.

BACKGROUND: Partial correction of renal anaemia with erythropoietin improves quality of life (QoL). We aimed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe. METHODS: 416 Scandinavian patients with renal anaemia [pre-dialysis, haemodialysis (HD) and peritoneal dialysis patients] were randomized to reach a normal haemoglobin of 135-160 g/l (n=216) or a subnormal haemoglobin of 90-120 g/l (n=200) with or without epoetin alfa. Study duration was 48-76 weeks. QoL was measured using Kidney Disease Questionnaires in 253 Swedish dialysis patients. Safety was examined in all patients. RESULTS: QoL improved, measured as a decrease in physical symptoms (P=0.02), fatigue (P=0.05), depression (P=0.01) and frustration (P=0.05) in the Swedish dialysis patients when haemoglobin was normalized. In pre-dialysis patients, diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks. However, the progression rate of chronic renal failure was comparable. In the normal haemoglobin group (N-Hb), 51% had at least one serious adverse event compared with 49% in the subnormal haemoglobin group (S-Hb) (P=0.32). The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ. The mortality rate was 13.4% in the N-Hb group and 13.5% in the S-Hb group (P=0.98). Mortality decreased with increasing mean haemoglobin in both groups. CONCLUSIONS: Normalization of haemoglobin improved QoL in the subgroup of dialysis patients, appears to be safe and can be considered in many patients with end-stage renal disease.

Enalapril Treatment in a Patient With Impaired Renal Function and Intolerance to Captopril.

In a 36-year-old woman with malignant hypertension and moderate renal insufficiency from nephrosclerosis normotension was not achieved by the combination of a beta-blocker, a vasodilator, and a loop-diuretic. The angiotensin-converting enzyme (ACE) inhibitor captopril was then added to the therapy. The blood pressure control was good. However, due to adverse reactions, captopril had to be withdrawn. Later on, the patient was successfully treated with enalapril, another ACE inhibitor, without the relapse of any adverse reactions.