Early versus delayed erythropoietin for the anaemia of end-stage kidney disease

Anaemia (low haemoglobin) is a common complication among people with end-stage kidney disease (ESKD) receiving dialysis treatment. Dialysis treatment removes toxic waste products from the blood when kidneys no longer function. Anaemia treatment is based on the use of manufactured erythropoietin (EPO, a hormone that increases haemoglobin), to improve fatigue and breathlessness which are common symptoms of severe anaemia. It is widely accepted that EPO treatment should be initiated when haemoglobin levels are less than or equal to 10 g/dL (delayed onset). However, it remains unknown if there are clinical benefits or harms when EPO treatment is commenced when haemoglobin levels are greater than 10 g/dL but less than 11 g/dL (early onset).

We conducted this review to try to determine if there are clinical benefits and harms associated with early versus delayed EPO.

We searched the literature to 8 July 2015 but found no studies that investigated early versus delayed EPO for ESKD-related anaemia. Benefits and harms of early versus delayed EPO remain unknown.

Authors' conclusions: 

We found no evidence to assess the benefits and harms of early versus delayed EPO for the anaemia of ESKD.

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Background: 

Anaemia is a common complication in people with chronic kidney disease (CKD) and mainly develops as a consequence of relative erythropoietin (EPO) deficiency. Anaemia develops early in the course of disease and peaks among people with end-stage kidney disease (ESKD). Many types of EPO - also called erythropoiesis-stimulating agents (ESAs) - are used to treat anaemia in people with ESKD.

ESAs have changed treatment of severe anaemia among people with CKD by relieving symptoms and avoiding complications associated with blood transfusion. However, no benefits have been found in relation to mortality rates and non-cardiac fatal events, except quality of life. Moreover, a relationship between ESA use and increased cardiovascular morbidity and mortality in patients with CKD has been reported in studies with fully correcting anaemia comparing with partial anaemia correction. Until 2012, guidelines recommended commencing ESA treatment when haemoglobin was less than 11 g/dL; the current recommendation is EPO commencement when haemoglobin is between 9 and 10 g/dL. However, advantages in commencing therapy when haemoglobin levels are greater than 10 g/dL but less than 11 g/dL remain unknown, especially among older people whose life expectancy is limited, but in whom EPO therapy may improve quality of life.

Objectives: 

To assess the clinical benefits and harms of early versus delayed EPO for anaemia in patients with ESKD undergoing haemodialysis or peritoneal dialysis

Search strategy: 

We searched the Cochrane Kidney and Transplant Specialised Register to 8 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria: 

We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating at the clinical benefits and harms of early versus delayed EPO for anaemia in patients with ESKD undergoing haemodialysis or peritoneal dialysis. Studies comparing EPO with another EPO, placebo or no treatment were eligible for inclusion.

Data collection and analysis: 

It was planned that two authors would independently extract data from included studies and assess risk of bias using the Cochrane risk of bias tool. For dichotomous outcomes (all-cause mortality, cardiovascular mortality, overall myocardial infarction, overall stroke, vascular access thrombosis, adverse effects of treatment, transfusion), we planned to use the risk ratio (RR) with 95% confidence intervals (CI). We planned to calculate the mean difference (MD) and CI 95% for continuous data (haemoglobin level) and the standardised mean difference (SMD) with CI 95% for quality of life if different scales had been used.

Main results: 

Literature searches yielded 1910 records, of these 1534 were screened after duplicates removed, of which 1376 were excluded following title and abstract assessment. We assessed 158 full text records and identified 18 studies (66 records) that were potentially eligible for inclusion. However, none matched our inclusion criteria and were excluded.

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