Raising haemoglobin (red blood cell) levels above 133 g/L in people with heart and kidney disease does not reduce mortality, and may even increase it

Having too few red blood cells (anaemia) makes a person feel tired and unwell. Blood transfusions or drugs can be given to increase red blood cell levels (haemoglobin). Having too many red blood cells can lead to blockages in catheters and other vascular access for patients on dialysis. It can also cause high blood pressure. This review of clinical studies found that increasing haemoglobin to high levels lowered the chance of a person having a seizure, but increased blood pressure. Haemoglobin levels above 133 g/L did not reduce the risk of death in people with heart and kidney disease.

Authors' conclusions: 

There was no significant difference in the risk of death for low (< 120 g/L) versus higher Hb targets (>133 g/L). Lower Hb targets were significantly associated with an increased risk for seizures but a reduced risk of hypertension. In general study quality was poor. There is a need for more adequately powered, well-designed and reported trials. Trials should be pragmatic, focusing on hard end-points (mortality, ESKD, major side effects) or outcomes which were previously not studied adequately (e.g. seizures, quality of life).

Read the full abstract...
Background: 

Anaemia affects 60% to 80% of patients with chronic kidney disease (CKD) reduces quality of life and is a risk factor for early death. Treatment options are blood transfusion, erythropoietin (EPO) and darbepoetin alfa. Recently higher haemoglobin (Hb) and haematocrit (HCT) targets have been widely advocated because of positive associations with improved survival and quality of life from observational studies.

Objectives: 

To assess the benefits and harms of different Hb or HCT targets in CKD patients receiving any treatment for anaemia.

Search strategy: 

We searched The Cochrane Renal Group's specialised register, Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library) MEDLINE (from 1966), EMBASE (from 1980) and reference lists of retrieved articles.

Selection criteria: 

Randomised controlled trials (RCTs) and quasi-RCTs comparing different Hb/HCT targets in patients with the anaemia of CKD.

Data collection and analysis: 

Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and results expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with 95% confidence intervals (CI).

Main results: 

Twenty two trials (3707 patients) were included. Hb ≥ 133 g/L was not associated with a reduction in the risk of all-cause mortality compared with 120 g/L in dialysis and pre-dialysis patients. In pre-dialysis patients, there was a significantly lower end of treatment creatinine clearance with Hb < 120 g/L compared to > 130 g/L (MD -4.17, 95% CI -6.33 to -2.02) but no significant difference in the risk of end-stage kidney disease (ESKD) (RR 1.05, 95% CI 0.50 to 2.22). Lower Hb targets resulted in an increased risk for seizures (RR 5.25, 95% CI 1.13 to 24.34) and a reduced risk of hypertensive episodes (RR 0.50, 95% CI 0.33 to 0.76). There were no significant differences in the risk of vascular access thrombosis.

Share/Save