MDRD Feasibility Study A 1989.

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 25 to 80 mL/min/1.73 m2 with age 18 to 75 years and showing progressive decline in GFR; dietary protein intake ≥ 0.9 g/kg/d Number: low protein diet group (10); normal protein diet group (11) Mean age ± SD: 44.8 ± 12.3 years Sex M/F: 15/6 Exclusion criteria: doubtful compliance; pregnancy; body weight < 80% or > 160% of standard body weight; proteinuria > 10 g/d; renal artery stenosis; urinary tract obstruction; DM requiring insulin; kidney transplant; chronic medical conditions; immunosuppressive agents, NSAIDs
Interventions	Low protein diet Prescribed protein diet: 0.575 g protein/kg/d Calculated protein intake: 0.85 ± 0.03 g/kg/d Normal protein diet Prescribed protein diet: 1.2 g protein /kg/d Calculated protein intake: 1.04 ± 0.04 g/kg/d Co‐interventions Antihypertensive medications, phosphate binders
Outcomes	Slope of GFR decline over time (rate of change of GFR) by renal clearance of I‐125 Iothalamate Death (all causes) Number reaching ESKD Malnutrition
Notes	Third group (9), which received very low protein diet, not included in analyses Data on deaths not separated between patient 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; 4 patients lost to follow‐up
Selective reporting (reporting bias)	High risk	No report of numbers in each group 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