Locatelli 1989.

Methods	Study design: parallel RCT Study duration of study: April 1984 to May 1985 Study follow‐up period: 2 years
Participants	Country: Italy Setting: multicentre (21 sites) Patients with CKD aged 18 to 65 years; GFR < 60 mL/min/1.73 m2 Number (randomised/completed): low protein diet group (226/165); normal protein diet group (230/146) Mean age, range (years): all participants (48.5; range 18 to 65) Sex M/F: all participants (247/209) Exclusion criteria: variation in SCr > 100% in 3 month preliminary observation period; nephrotic syndrome (proteinuria > 3g/24 h, serum albumin < 25 g/L); acute obstruction of urinary tract; acute infectious disease; systemic illness (malignancy/ autoimmune disease); disease necessitating drugs that might affect underlying kidney disease; previous surgery of the GI tract; body weight < 45 kg and > 90 kg
Interventions	Low protein diet group Prescribed protein intake: 0.6 g protein/kg/d Calculated protein intake: 0.72 g/kg/d Normal protein diet group Prescribed protein intake: 1.0 g protein/kg/d Calculated protein intake: 0.9 g/kg/d Co‐interventions Antihypertensive medications, phosphate binders, vitamins, bicarbonate No patient received vitamin D or ACEi
Outcomes	Number requiring dialysis or doubling of baseline SCr Fall in GFR measured by CrCl Body weight
Notes	True difference in protein intake < 0.4 g protein/kg/d, estimated to be 0.18 g/kg/d based on urinary urea nitrogen analysis and 0.3 g/kg/d based on diet records Events recorded at 24 months from the start of study Information on numbers requiring dialysis provided by Professor Locatelli Funding source: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Block randomisation‐ blocks of 4, 1/1 ratio performed at study headquarters "
Allocation concealment (selection bias)	Low risk	Central randomisation
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 and unlikely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias): Need to start dialysis Need to start dialysis	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	High risk	31.7% lost by final follow up
Selective reporting (reporting bias)	High risk	Not all reviews pre‐specified outcomes mentioned. No weights, no adverse events
Other bias	Unclear risk	Insufficient information to permit judgement