BACKGROUND Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established. METHODS We randomly assigned 603 patients with an estimated glomerular filtration rate (GFR) of 15.0 to 35.0 ml per minute per 1.73 m 2 of body-surface area and mild-to-moderate anemia (hemoglobin level, 11.0 to 12.5 g per deciliter) to a target hemoglobin value in the normal range (13.0 to 15.0 g per deciliter, group 1) or the subnormal range (10.5 to 11.5 g per deciliter, group 2). Subcutaneous erythropoietin (epoetin beta) was initiated at randomization (group 1) or only after the hemoglobin level fell below 10.5 g per deciliter (group 2). The primary end point was a composite of eight cardiovascular events; secondary end points included left ventricular mass index, quality-of-life scores, and the progression of chronic kidney disease. RESULTS During the 3-year study, complete correction of anemia did not affect the likelihood of a first cardiovascular event (58 events in group 1 vs. 47 events in group 2; hazard ratio, 0.78; 95% confidence interval, 0.53 to 1.14; P = 0.20). Left ventricular mass index remained stable in both groups. The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year, respectively (P = 0.40). Dialysis was required in more patients in group 1 than in group 2 (127 vs. 111, P = 0.03). General health and physical function improved significantly (P = 0.003 and P<0.001, respectively, in group 1, as compared with group 2). There was no significant difference in the combined incidence of adverse events between the two groups, but hypertensive episodes and headaches were more prevalent in group 1. CONCLUSIONS In patients with chronic kidney disease, early complete correction of anemia does not reduce the risk of cardiovascular events. (ClinicalTrials.gov number, NCT00321919.)

Normalization of Hemoglobin Level in Patients with Chronic Kidney Disease and Anemia

KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update

https://escholarship.org/content/qt5w36657n/qt5w36657n.pdf?t=pzxgl5

Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients

https://www.ajkd.org/article/S0272-6386(14)01065-8/pdf

Diabetic Kidney Disease: A Report From an ADA Consensus Conference

282 Summary of Recommendation Statements 283 Chapter 1: Diagnosis and evaluation of anemia in CKD 288 Chapter 2: Use of iron to treat anemia in CKD 292 Chapter 3: Use of ESAs and other agents to treat anemia in CKD 299 Chapter 4: Red cell transfusion to treat anemia in CKD 311 Methods for Guideline Development 317 Biographic and Disclosure Information 324

KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease

Although treating anemia of chronic kidney disease by erythropoiesis-stimulating agents (ESA) may improve survival, most studies have examined associations between baseline hemoglobin values and survival and ignored variations in clinical and laboratory measures over time. It is not clear whether longitudinal changes in hemoglobin or administered ESA have meaningful associations with survival after adjustment for time-varying confounders. With the use of time-dependent Cox regression models, longitudinal associations were examined between survival and quarterly (13-wk averaged) hemoglobin values and administered ESA dose in a 2-yr (July 2001 to June 2003) cohort of 58,058 maintenance hemodialysis patients from a large dialysis organization (DaVita) in the United States. After time-dependent and multivariate adjustment for case mix, quarterly varying administered intravenous iron and ESA doses, iron markers, and nutritional status, hemoglobin levels between 12 and 13 g/dl were associated with the greatest survival. Among prevalent patients, the lower range of the recommended Kidney Disease Quality Outcomes Initiative hemoglobin target (11 to 11.5 g/dl) was associated with a higher death risk compared with the 11.5- to 12-g/dl range. A decrease or increase in hemoglobin over time was associated with higher or lower death risk, respectively, independent of baseline hemoglobin. Administration of any dose of ESA was associated with better survival, whereas among those who received ESA, requiring higher doses were surrogates of higher death risk. In this observational study, greater survival was associated with a baseline hemoglobin between 12 and 13 g/dl, treatment with ESA, and rising hemoglobin. Falling hemoglobin and requiring higher ESA doses were associated with decreased survival. Randomized clinical trials are required to examine these associations.

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Associations Between Changes in Hemoglobin and Administered Erythropoiesis-Stimulating Agent and Survival in Hemodialysis Patients

OBJECTIVE —The optimal target for glycemic control has not been established in diabetic dialysis patients.

RESEARCH DESIGN AND METHODS —To address this question, the national database of a large dialysis organization (DaVita) was analyzed via time-dependent survival models with repeated measures.

RESULTS —Of 82,933 patients undergoing maintenance hemodialysis (MHD) in DaVita outpatient clinics over 3 years (July 2001 through June 2004), 23,618 diabetic MHD patients had A1C measurements at least once. Unadjusted survival analyses indicated paradoxically lower death hazard ratios (HRs) with higher A1C values. However, after adjusting for potential confounders (demographics, dialysis vintage, dose, comorbidity, anemia, and surrogates of malnutrition and inflammation), higher A1C values were incrementally associated with higher death risks. Compared with A1C in the 5–6% range, the adjusted all-cause and cardiovascular death HRs for A1C ≥10% were 1.41 (95% CI 1.25–1.60) and 1.73 (1.44–2.08), respectively ( P 11.0 g/dl). In subgroup analyses, the association between A1C >6% and increased death risk was more prominent among younger patients, those who had undergone dialysis for >2 years, and those with higher protein intake (>1 g · kg−1 · day−1), blood hemoglobin (>11 g/dl), or serum ferritin values (>500 ng/ml).

CONCLUSIONS —In diabetic MHD patients, the apparently counterintuitive association between poor glycemic control and greater survival is explained by such confounders as malnutrition and anemia. All things equal, higher A1C is associated with increased death risk. Lower A1C levels not related to malnutrition or anemia appear to be associated with improved survival in MHD patients.

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Jason Aronovitz

Papers

Associations Between Changes in Hemoglobin and Administered Erythropoiesis-Stimulating Agent and Survival in Hemodialysis Patients

A1C and Survival in Maintenance Hemodialysis Patients