Mircescu 2007.

Study characteristics
Methods	Study design: open‐label, parallel RCT Study duration: 15 January 2004 to 15 February 2005 Study follow‐up period: 60 weeks with a 12‐week baseline phase
Participants	Country: Romania Setting: single centre Relevant health status: adults with eGFR 30 mL/min/1.73 m2 by MDRD formula; stable kidney function for at least 12 weeks before enrolment (reduction in eGFR ≤ 4 mL/min/year); well controlled arterial pressure; proteinuria < 1 g/g urinary creatinine; good nutritional status (SGA A/B; serum albumin > 35 g/L); anticipated good compliance with the prescribed diet Number: very low protein diet (27); low protein diet (26) Mean age ± SD (years): very low protein diet (55 ± 12.7); low protein diet (53.6 ± 11.0) Sex M/F: very low protein diet (17/10); low protein diet (15/11) Other relevant information: not reported Exclusion criteria: poorly controlled arterial pressure (> 145/85 mmHg); comorbid conditions (DM, heart failure, active hepatic disease, digestive diseases with malabsorption, inflammation/anti‐inflammatory therapy); uraemic complications (pericarditis, polyneuropathy); feeding inability (anorexia, nausea)
Interventions	Very low protein diet Prescribed protein diet: 0.3 g/kg/day vegetable protein + keto‐analogues/essential amino acids (Ketosteril 1 capsule/5 kg of ideal body weight/day) Calculated protein intake at 48 weeks: 0.32 ± 0.07g/kg/day Low protein diet Prescribed protein intake: 0.6 g/kg/day (including high biological value proteins) Calculated protein intake 48 weeks: 0.59 ± 0.08 g/kg/day Total recommended energy intake: 30 kcal/kg/day Co‐interventions All received calcium and water soluble vitamin supplementation as required Serum ferritin < 200 ng/mL: 100 mg IV iron sucrose weekly 200 to 400 ng/mL: 100 mg IV iron sucrose every other week 400 to 500 ng/mL: 100 mg IV iron sucrose monthly > 500 ng/mL: iron administration stopped
Outcomes	Death (all causes) ESKD and commencement of dialysis Change in GFR by MDRD formula Adverse events
Notes	Dietary compliance was assessed weekly for the first month, every 4 weeks for the next 8 weeks and every 12 weeks thereafter Funding source: "C‐reactive protein, and parathyroid hormone, as well as logistics for the transportation of blood samples to the central laboratory, were supported by F. Hoffmann‐LaRoche. No other financial support was received by any of the authors"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information to permit judgement
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	eGFR calculated from SCr using MDRD formula. Based on 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	Low risk	"RRT initiation was decided by the Ethical Committee of the Hospital considering the clinical and biochemical status of the patient (...). Members of the Committee were unaware of which arm the patient had been assigned to"
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants accounted for
Selective reporting (reporting bias)	Low risk	All reviews prespecified outcomes mentioned
Other bias	Unclear risk	Insufficient information to permit judgement