MDRD Feasibility B 1989.

Study characteristics
Methods	Study design: parallel RCT Study duration: September 1985 to September 1988 Study follow‐up period: 14 months (mean); range 2 to 22 months
Participants	Country: USA Setting: multicentre (9 sites) CKD with GFR 7.5 to 24 mL/min/1.73 m2; aged 18 to 75 years and showing progressive decline in GFR over 3 months to 3 years; dietary protein intake ≥ 0.9 g/kg/day Number: very low protein diet group (22); low protein diet group (23) Mean age ± SD: 50.4 ± 12.5 years (includes 21 participants treated with a very low protein diet + amino‐acids & not included in analyses) Sex M/F: 25/20 (includes 21 participants treated with a very low protein diet + amino‐acids and not included in analyses) Exclusion criteria: doubtful compliance; pregnancy; body weight < 80% or > 160% of standard body weight; proteinuria > 10 g/day; renal artery stenosis; urinary tract obstruction; DM requiring insulin; kidney transplant; chronic medical conditions; immunosuppressive agents; NSAIDs
Interventions	Very low protein diet Prescribed protein intake: 0.28 g protein/kg/day + keto acid/amino acid mixture (total nitrogen content 28.6 mg/kg/day) Calculated protein intake: 0.5 ± 0.03 g/kg/day Low protein diet Prescribed protein intake: 0.575 g protein/kg/day (range 0.46 to 0.69 g/kg/day) Calculated protein intake: 0.72 ± 0.03 g/kg/day Co‐interventions Antihypertensive medications, phosphate binders, iron supplements
Outcomes	Slope of GFR decline over time by renal clearance of I125 Iothalamate Death (all causes) Number reaching ESKD Malnutrition
Notes	Third group of participants (21) receiving very low protein + amino acids excluded from analyses Data on deaths not separated between groups Funding source: National Institute of Diabetes, Digestive and Kidney Disease and Health Care Finance Administration, NIH, USA
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Random permutated blocks to ensure equal balance of participants assigned to each treatment combination"
Allocation concealment (selection bias)	Low risk	"Centrally administered at data co‐ordination centre through telephone contact"
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not blinded and lack of blinding may influence patient management
Blinding of outcome assessment (detection bias): End or change in GFR End of change in GFR	Low risk	Laboratory measurement (iothalamate clearance) and unlikely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias): Need to start dialysis Need to start dialysis	Low risk	Onset of ESKD endpoint reviewed by Clinical Committee without knowledge of dietary assignment
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants accounted for; 1 patient lost to follow‐up
Selective reporting (reporting bias)	High risk	No report of numbers in each group on death (combined data only). No information on final weights provided
Other bias	Low risk	National Institute of Diabetes, Digestive and Kidney Disease and Health Care Finance Administration, NIH, USA