Canadian randomized trial of hemoglobin maintenance to prevent or delay left ventricular mass growth in patients with CKD.

BACKGROUND: This randomized clinical trial is designed to assess whether the prevention and/or correction of anemia, by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease, would delay left ventricular (LV) growth. Study design and sample size calculations were based on previously published Canadian data. METHODS: One hundred seventy-two patients were randomly assigned. The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin (Hgb) level targets of 12.0 to 14.0 g/dL (120 to 140 g/L). The control/delayed treatment group had Hgb levels of 9.0 +/- 0.5 g/dL (90 +/- 5 g/L) before therapy was started: target level was 9.0 to 10.5 g/dL (90 to 105 g/L). Optimal blood pressure and parathyroid hormone, calcium, and phosphate level targets were prescribed; all patients were iron replete. The primary end point is LV growth at 24 months. RESULTS: One hundred fifty-two patients were eligible for the intention-to-treat analysis: mean age was 57 years, 30% were women, 38% had diabetes, and median glomerular filtration rate was 29 mL/min (0.48 mL/s; range, 12 to 55 mL/min [0.20 to 0.92 mL/s]). Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline. Erythropoietin therapy was administered to 77 of 78 patients in the treatment group, with a median final dose of 2,000 IU/wk. Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk. There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index (LVMI) from baseline to 24 months, which was 5.21 +/- 30.3 g/m2 in the control/delayed treatment group versus 0.37 +/- 25.0 g/m2 in the treatment group. Absolute mean difference between groups was 4.85 g/m2 (95% confidence interval, -4.0 to 13.7; P = 0.28). Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL (127.5 g/L in treatment group versus 11.46 g/dL [114.6 g/L] in control/delayed treatment group; P = 0.0001). LV growth occurred in 20.1% in the treatment group versus 31% in the control/delayed treatment group (P = 0.136). In patients with a stable Hgb level, mean LVMI did not change (-0.25 +/- 26.7 g/m2), but it increased in those with decreasing Hgb levels (19.3 +/- 28.2 g/m2; P = 0.002). CONCLUSION: This trial describes disparity between observational and randomized controlled trial data: observed and randomly assigned Hgb level and LVMI are not linked; thus, there is strong evidence that the association between Hgb level and LVMI likely is not causal. Large randomized controlled trials with unselected patients, using morbidity and mortality as outcomes, are needed.

Tinzaparin reduces health care resource use for anticoagulation in hemodialysis.

Anticoagulation is required during hemodialysis to prevent thrombus formation within the extracorporeal circuit. The low-molecular-weight heparin tinzaparin is more expensive than unfractionated heparin (UFH) in Canada but more convenient to administer. We conducted a time-and-motion study to test the hypothesis that tinzaparin may reduce nursing time and total health care costs compared with UFH. Data on health care resource use associated with anticoagulation during hemodialysis for chronic renal failure were collected at an academic hospital in Quebec. Nursing time was recorded for 8 nurses performing 16 dialysis sessions for 4 patients receiving tinzaparin and 4 receiving UFH (2 dialysis sessions per patient). Nurses had ≥ 1 year of experience supervising hemodialysis. We estimated total annual costs of nursing time and health care resources (anticoagulants, medical supplies, and laboratory testing) associated with anticoagulation. In sensitivity analyses, drug costs were varied ± 30% of their base-case values. Estimated annual nursing times per patient were 0.8 vs. 11.5 hours in the first year and 0.6 vs. 10.2 hours in subsequent years for tinzaparin vs. UFH, respectively. Annual drug costs per patient were CAD 898.56 for tinzaparin and 546.75 for UFH. Estimated total annual costs were CAD 1061.03 vs. 1012.71 in the first year and CAD 917.75 vs. 895.23 in subsequent years for tinzaparin vs. UFH, respectively. Use of tinzaparin was cost saving relative to UFH if tinzaparin price was reduced 30%. Most of the price differential between tinzaparin and UFH is offset by substantial time savings to nephrology nurses.

A nurse-coordinated model of care versus usual care for stage 3/4 chronic kidney disease in the community: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: It is unclear how to optimally care for chronic kidney disease (CKD). This study compares a new coordinated model to usual care for CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A randomized trial in nephrology clinics and the community included 474 patients with median estimated GFR (eGFR) 42 ml/min per 1.73 m(2) identified by laboratory-based case finding compared care coordinated by a general practitioner (controls) with care by a nurse-coordinated team including a nephrologist (intervention) for a median (interquartile range [IQR]) of 742 days. 32% were diabetic, 60% had cardiovascular disease, and proteinuria was minimal. Guided by protocols, the intervention team targeted risk factors for adverse kidney and cardiovascular outcomes. Serial eGFR and clinical events were tracked. RESULTS: The average decline in eGFR over 20 months was -1.9 ml/min per 1.73 m(2). eGFR declined by ≥4 ml/min per 1.73 m(2) within 20 months in 28 (17%) intervention patients versus 23 (13.9%) control patients. Control of BP, LDL, and diabetes were comparable across groups. In the intervention group there was a trend to greater use of renin-angiotensin blockers and more use of statins in those with initial LDL >2.5 mmol/L. Treatment was rarely required for anemia, acidosis, or disordered mineral metabolism. Clinical events occurred in 5.2% per year. CONCLUSIONS: Patients with stage 3/4 CKD identified through community laboratories largely had nonprogressive kidney disease but had cardiovascular risk. Over a median of 24 months, the nurse-coordinated team did not affect rate of GFR decline or control of most risk factors compared with usual care.

Cost-effectiveness analysis of a randomized trial comparing care models for chronic kidney disease.

BACKGROUND AND OBJECTIVES: Potential cost and effectiveness of a nephrologist/nurse-based multifaceted intervention for stage 3 to 4 chronic kidney disease are not known. This study examines the cost-effectiveness of a chronic disease management model for chronic kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cost and cost-effectiveness were prospectively gathered alongside a multicenter trial. The Canadian Prevention of Renal and Cardiovascular Endpoints Trial (CanPREVENT) randomized 236 patients to receive usual care (controls) and another 238 patients to multifaceted nurse/nephrologist-supported care that targeted factors associated with development of kidney and cardiovascular disease (intervention). Cost and outcomes over 2 years were examined to determine the incremental cost-effectiveness of the intervention. Base-case analysis included disease-related costs, and sensitivity analysis included all costs. RESULTS: Consideration of all costs produced statistically significant differences. A lower number of days in hospital explained most of the cost difference. For both base-case and sensitivity analyses with all costs included, the intervention group required fewer resources and had higher quality of life. The direction of the results was unchanged to inclusion of various types of costs, consideration of payer or societal perspective, changes to the discount rate, and levels of GFR. CONCLUSIONS: The nephrologist/nurse-based multifaceted intervention represents good value for money because it reduces costs without reducing quality of life for patients with chronic kidney disease.