Haemoglobin and haematocrit targets for the anaemia of chronic kidney disease.
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.


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


METHODS
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. Date of most recent search: April 2006


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


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


RESULTS
Twenty two trials (3707 patients) were included. Hb > or = 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.


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).
Strippoli
G F M
GF
NHMRC Centre for Clinical Research Excellence in Renal Medicine, Cochrane Renal Group, Centre for Kidney Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia. gfmstrippoli@alice.it
Navaneethan
S D
SD
Craig
J C
JC
D000740:Anemia / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D004921:Erythropoietin / Q000627:therapeutic use*; D006400:Hematocrit; D006441:Hemoglobin A / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis; D018570:Risk Assessment
D004921:Erythropoietin; D006441:Hemoglobin A