Williams 1991.

Study characteristics
Methods	Study design: parallel RCT Duration of study: not reported Study follow‐up period: 1 to 58 months (17.7 months in low protein diet group; 21.4 months in normal protein diet group)
Participants	Country: UK Setting: multicentre (2 sites) CKD with Cr > 150 μmol/L in males and > 130 μmol/L in females; evidence of kidney functional deterioration on > 3 serial measurements of SCr/CrCl over 6 months pre randomisation; adults < 70 years; SCr < 900 μmol/L and phosphate < 2 mmol/L with stable biochemistry Number: low protein diet group (33); normal protein diet group (32) Mean age ± SEM (years): low protein diet group (43 ± 2.3); normal protein diet group (44.5 ± 2.2) Sex M/F: low protein diet group (20/13); normal protein diet group (21/11) Exclusion criteria SCr > 900 μmol/L and/or phosphate > 2 mmol/L; uraemic symptoms; receiving active therapy for underlying kidney disease, malignancy; psychologically unstable or non‐compliant; obese on reducing diet; dietary protein < 0.8 g/kg/day; withdrawn if developed clinical signs of malnutrition
Interventions	Low protein diet group Prescribed protein diet: 0.6 g protein/kg/day Calculated protein intake: 0.69 ± 0.02 g/kg/day Normal protein diet group Prescribed protein intake: > 0.8 g protein/kg/day Calculated protein diet: 1.14 ± 0.05 g/kg/day Daily energy intake: 30 kcal/kg/day Co‐interventions Antihypertensive medications; sodium restriction; vitamin supplements
Outcomes	Number requiring dialysis Number of deaths Change in 24 hr CrCl Slope of reciprocal SCr (1/SCr) over time Weight
Notes	A third group of participants (low phosphorus intake, n = 30) was not kept for analysis Events recorded at 18 months from the start of study Funding source: supported by the Mersey Region Association for Kidney Research
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Pack of numbered cards and random number tables
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
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	Primary outcome (change in CrCl) was a laboratory measure 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	No information provided on criteria for starting dialysis
Incomplete outcome data (attrition bias) All outcomes	High risk	15% (10/65) excluded from calculation of primary outcome of change in CrCl
Selective reporting (reporting bias)	Low risk	Reported on number requiring dialysis, deaths, change in creatinine and weight
Other bias	Unclear risk	Insufficient information to permit judgement

ACEi ‐ angiotensin‐converting enzyme inhibitors; BMI ‐ body mass index; BP ‐ blood pressure; CCB ‐ calcium channel blockers; CKD ‐ chronic kidney disease; CrCl ‐ creatinine clearance; CRP ‐ C‐reactive protein; DM ‐ diabetes mellitus; ESA ‐ erythrocyte stimulating agent; ESKD ‐ end‐stage kidney disease; EPO ‐ erythropoietin; GI ‐ gastrointestinal; (e)GFR ‐ (estimated) glomerular filtration rate; Hb ‐ haemoglobin; MAP ‐ mean arterial pressure; M/F ‐ male/female; MDRD ‐ Modification of Diet in Renal Disease; NSAID ‐ nonsteroidal anti‐inflammatory drugs; RPGN ‐ rapidly progressive glomerulonephritis; SCr ‐ serum creatinine; SD ‐ standard deviation; SGA ‐ Subjective Global Assessment; UPE ‐ urinary protein excretion