Clyne 1992

Methods	Study design: RCT Study duration: NS
Participants	Setting: Karolinska Hospital and Danderyd Hospitals Country: Sweden Stage of CKD: eGFR < 25 mL/min/1.73 m² Number: epoetin beta (12), no treatment (10) Mean age ± SD (years): epoetin beta (46 ± 12), no treatment (53 ± 15) Sex (M/F): epoetin beta (6/6), no treatment (5/3) Other characteristics: HCT ≤ 28% Exclusion criteria: RRT; diabetes; angina or prior acute myocardial infarction; platelet count of > 500 x 109/L; epilepsy; treatment with cytotoxic agents; hormone preparations or immunosuppressants; poorly controlled hypertension; and deficiency of folic acid or vitamin B12
Interventions	Treatment group Epoetin beta Starting at 300 U/kg body weight/wk IV to achieve HCT > 30% for 3 months Control group No treatment for 3 months Iron supplementation Oral or IV
Outcomes	Primary study outcome Exercise capacity (symptomatically limited exercise test) Kidney function (GFR and renal plasma flow) Outcome extracted for meta‐analysis Hypertension (new or increased doses of blood pressure medication during follow‐up)
Notes	Funding: NS Trial registration: not applicable Contact with study authors for additional information: not contacted
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	"Open randomised parallel‐group study"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	High risk	Attrition was 1/12 (8%) in the epoetin beta arm and 2/10 (20%) in the control arm. As this was > 10% overall this was judged to be high risk
Selective reporting (reporting bias)	High risk	Major cardiovascular outcomes were not available
Other bias	Low risk	None apparent