Haemoglobin and haematocrit targets for the anaemia of chronic renal disease.
BACKGROUND
Anaemia affects 60-80% of patients with renal impairment, reduces quality of life and is a risk factor for early death. Treatment options are blood transfusion, erythropoietin (EPO) alpha or beta and darbepoetin alfa. Recently higher haemoglobin (Hb) and haematocrit targets have been widely advocated because of positive data from observational studies. However, higher targets may lead to access thrombosis and hypertension and are costly.


OBJECTIVE
This review assesses the benefits and harms of low (Hb </= 100 g/L or HCT </= 30%) and high (Hb > 100 g/L or HCT > 30%) targets in pre- and post-dialysis patients receiving any treatment for anaemia.


METHODS
We searched The Cochrane Renal Group specialised register (September 2002), Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 - September 2002), EMBASE (1988 - September 2002) and reference lists of retrieved articles.


METHODS
Randomised controlled trials (RCTs) and quasi-RCTs comparing low Hb/HCT targets (Hb</- 100 g/L) with high Hb/HCT targets (Hb > 100 g/dL) in patients with anaemia of chronic renal disease.


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


RESULTS
Fifteen trials were identified in which 2096 patients were included. Twelve trials (673 patients) compared placebo with EPO and three trials (1423 patients) compared two doses of EPO. Hb values of 100 g/L (obtained with low EPO doses) were associated with lower mortality compared to Hb values of 140 g/L or more (obtained with high EPO doses) in the population with chronic renal disease and cardiovascular impairment (two trials, 1379 patients: RR 0.82; 95% CI 0.68 to 0.99). Lower targets obtained with a placebo resulted in an increased risk for seizures (four trials, 219 patients: RR 5.25; 95% CI 1.13 to 24.34) as compared to higher targets reached with EPO treatment. Finally, there was a reduced risk for hypertensive episodes with lower Hb targets reached with a placebo as compared to higher targets reached with EPO (six trials, 387 patients: RR 0.50; 95% CI 0.33 to 0.76). Quality of life was not adequately evaluated in the studies.


CONCLUSIONS
Lower Hb targets of 100 g/L were associated with a lower risk of death in the population with cardiovascular impairment and chronic renal disease as compared to Hb 140 g/L. Lower Hb targets (Hb < 100 g/L) were also significantly associated with an increased risk for seizures and a reduced risk of hypertension compared to Hb > 100 g/L. There is a need of more adequately powered, well-designed and reported trials in this area. In particular, randomised controlled trials comparing the benefits and harms of low (Hb < 100 g/L) versus intermediate (Hb 130 g/L) and high (Hb 140 g/L) targets in the pre-dialysis population with chronic renal disease are necessary. In fact, there is a large deficiency of trials in the pre-dialysis population. The new trials should focus on hard outcomes and also look at outcomes which were previously not studied adequately, such as seizures and quality of life, which is to be assessed with validated measures.
Strippoli
G F
GF
Centre for Kidney Research, Cochrane Renal Group, Locked Bag 4001, Children's Hospital at Westmead, Westmead, NSW, Australia, 2145. gfmstrippoli@katamail.com
Manno
C
C
Schena
F P
FP
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