Canadian randomized trial of hemoglobin maintenance to prevent or delay left ventricular mass growth in patients with CKD.
ABSTRACT 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.
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.
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).
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.
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ABSTRACT: In predialysis patients, the optimal treatment choices for controlling haemoglobin (Hb) are unknown, because targeting high Hb levels has negative effects-poorer survival-but possible positive effects as well-better health-related quality of life (HRQOL). Moreover, these effects may be different in specific subgroups (e.g. young versus elderly). In the PREPARE-2 follow-up study, incident predialysis patients were included (2004-2011) when referred to 1 of the 25 participating Dutch outpatient clinics. HRQOL was assessed at 6-month intervals with the short form-36 (SF-36) questionnaire [physical/mental summary measure and eight subscales (range 0-100)]. A linear mixed model was used to associate Hb [<11, ≥11 to <12 (reference), ≥12 to <13 and ≥13 g/dL] with HRQOL, stratified by prescription of anaemia medication (erythropoietin-stimulating agent (ESA)/iron) and age (young: <65 years and elderly: ≥65 years). Only elderly patients (n = 214) not prescribed ESA/iron and with a high Hb (≥13 versus ≥11 to <12 g/dL) had a statistically significant (P < 0.05) and/or clinically relevant (>3-5 points) higher physical [11.9, 95% confidence interval (CI) 1.7, 22.2] and mental (6.4, 95% CI -1.7, 14.6) summary score. High Hb was not associated with a higher HRQOL in elderly patients who were prescribed ESA/iron. However, only young patients (n = 157) prescribed ESA/iron and with a high Hb (≥13 versus ≥11 to <12 g/dL) had a higher physical (8.9, 95% CI 2.1, 15.8) and mental (6.2, 95% CI -0.4, 12.8) summary score. The association of Hb levels with HRQOL differs by age and use of ESA/iron medication on predialysis care. Therefore, medical care should aim for shared decision-making regarding the appropriate Hb target leading to more individualized care.Nephrology Dialysis Transplantation 02/2014; · 3.37 Impact Factor
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ABSTRACT: Background: The effect of anemia correction on kidney function in chronic kidney disease (CKD) patients remains unclear. As 19-40% of patients with CKD receive an erythropoiesis-stimulating agent (ESA), this is a potentially important consideration. Summary: We conducted a systematic review and meta-analysis of randomized trials to January 1, 2014 in adult patients with CKD stages 1 to 4. Selection criteria for studies: randomized controlled trials of at least 2 months duration. Patients were allocated to ESA versus placebo, no treatment, or different ESA doses with the purpose of achieving a higher versus a lower hemoglobin target. The analyzed outcomes were the need for renal replacement therapy, doubling of serum creatinine, change in GFR (ml/min), mortality and withdrawal of treatment due to adverse events. A total of 19 trials (n = 8,129 participants with CKD stage 1-4) were reviewed. There was no difference in the risk of end-stage kidney disease (RR, 0.97 [CI 0.83-1.20], 17 trials, 8,104 participants), change in GFR (Mean Difference [MD] -0.45 [-2.21, 1.31], 9 trials, 1,848 participants) or withdrawal of treatment due to adverse events (RR, 1.18 [CI 0.77-1.81], 10 trials, n = 1,958 participants) for patients at higher hemoglobin (Hb) targets. Furthermore, no statistically significant differences in mortality (Risk Ratio [RR] 1.10 [CI 0.90-1.35], 16 trials, n = 8,082 participants) were observed. Key Messages: There is no evidence that ESA treatment affects renal function in patients with CKD. Use of these agents should not therefore be influenced by considerations about influencing CKD progression. © 2014 S. Karger AG, Basel.American Journal of Nephrology 10/2014; 40(3):263-279. · 2.65 Impact Factor
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ABSTRACT: MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. MicroRNAs are present in the blood in a remarkably stable form and have emerged as potential diagnostic markers in patients with cardiovascular disease. Our study aimed to assess circulating miR-133a levels in MHD patients and the relation of miR-133a to cardiac hypertrophy.PLoS ONE 10/2014; 9(10):e103079. · 3.53 Impact Factor