Hans Furuland

The use of pretransplant erythropoietin to normalize hemoglobin levels has no deleterious effects on renal transplantation outcome

Background. The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. Methods. A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90–120 g/liter) to a normal level (135–160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. Results. Preoperative Hb levels were 143±17 and 121±14 g/liter in the two groups, respectively (P <0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P <0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. Conclusions. EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function.

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-α 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×s (p<0.001). Blood viscosity standardized to a hematocrit level of 45% and a plasma viscosity of 1.31 mPa×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/m2 (p<0.05). The total peripheral resistance index increased from 3270±985 to 4013±1046 (dyn×s/cm5)m2 (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.

Effect of switching from subcutaneous to intravenous administration of epoetin-alpha in haemodialysis patients: results from a Swedish multicentre survey.

Objective In 2002, many haemodialysis patients were switched from subcutaneous (s.c.) to intravenous (i.v.) administration of epoetin-α following reports of antibody formation and development of pure red-cell aplasia in patients treated via the s.c. route. We evaluated the possible effect of this change in the route of administration on haemoglobin (Hb) levels and epoetin-α requirements. Material and methods This retrospective survey involved 223 haemodialysis patients from 25 Swedish centres. Variables were recorded before and after a mean period of 213 days (range 89–297 days) after the change in the route of administration. Results The mean epoetin-α do had to be increased from 159±104 to 185±122 U/kg/week (p<0.0001) to maintain a constant Hb level (121±12 vs 120±11 g/l). Plasma ferritin, albumin, C-reactive protein, iron, iron transferrin saturation and body mass index remained constant. The relative increase in epoetin-α dose was negatively correlated with the s.c. dose prior to the switch (R=–0.3; p<0.0001), with the most pronounced dose increases occurring in patients who received a low s.c. dose. Conclusions A switch from s.c. to i.v. administration of epoetin-α in haemodialysis patients was accompanied by an increase in the mean dose requirement of 15%. This increase may be less pronounced in patients receiving high s.c. doses prior to the switch.

Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure

Abstract Aims: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients. Materials and methods: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management. Results: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (£110), and associated net monetary benefit (£10,679 at £20,000 per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy. Limitations: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves. Conclusions: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.

Perspectives on clinical use of bioimpedance in hemodialysis: focus group interviews with renal care professionals

BackgroundInadequate volume control may be a main contributor to poor survival and high mortality in hemodialysis patients. Bioimpedance measurement has the potential to improve fluid management, but several dialysis centers lack an agreed fluid management policy, and the method has not yet been implemented. Our aim was to identify renal care professionals’ perceived barriers and facilitators for use of bioimpedance in clinical practice.MethodsQualitative data were collected through four focus group interviews with 24 renal care professionals: dieticians, nephrologists and nurses, recruited voluntarily from a nation-wide selection of hemodialysis centers, having access to a bioimpedance-device. The participants were connected to each other and a moderator via equipment for telemedicine and the sessions were recorded. The interviews were semi-structured, focusing on the participants’ perceptions of use of bioimpedance in clinical practice. Thematic content analysis was performed in consecutive steps, and data were extracted by employing an inductive, interactive, comparative process.ResultsSeveral barriers and facilitators to the use of bioimpedance in clinical practice were identified, and a multilevel approach to examining barriers and incentives for change was found to be applicable to the ideas and categories that arose from the data. The determinants were categorized on five levels, and the different themes of the levels illustrated with quotations from the focus groups participants.ConclusionsDeterminants for use of bioimpedance were identified on five levels: 1) the innovation itself, 2) the individual professional, 3) the patient, 4) the social context and 5) the organizational context. Barriers were identified in the areas of credibility, awareness, knowledge, self-efficacy, care processes, organizational structures and regulations. Facilitators were identified in the areas of the innovation’s attractiveness, advantages in practice, and collaboration. Motivation, team processes and organizational capacities appeared as both barriers and facilitators.