Table 2.

Summary of the randomized controlled clinical trials, including more than 200 patients with follow-up > 6 months, investigating the role of protein restricted diets in patients with chronic kidney disease of stages 3 to 5 (not on dialysis).

Author, Year	Aim and Outcome	Sample Characteristics	Main Findings	Comments
Rosman et al., 1984 [41]	Role of protein restriction in retarding CKD progression rate of decline of renal function.	228 pts (15 to 73 years old) GFR 30 to 60 mL/min/1.73 m2 LPD 0.6 g/kg/day vs. UPD GFR ≤ 30 mL/min/1.73 m2 LPD: 0.6 g/kg/day vs. UPD. 2-year follow-up.	The LPD groups showed lower decrease in serum Creatinine over time, whereas the UPD groups showed no changes. The LPD had a lower serum urea during the study when compared to the UPD group.	No changes in body weight and serum albumin were observed during the study in the LPD and UPD groups.
Locatelli et al., 1991 [42]	Role of protein restriction in retarding CKD progression. Renal survival (need for dialysis or doubling serum Creatinine).	456 pts (18–65 years old) GFR < 60 mL/min/1.73 m2 LPD: 0.6 g/kg/day vs. UPD: 1.0 g/kg/day. 2-year follow-up.	Renal survival was a lithe bit higher in the LPD group vs. UPD (p = 0.06). No differences in GFR were observed between the LPD and UPD groups.	Low adherence to the prescribed protein intake in the LPD group. No changes in body weight were observed during the study in the LPD and UPD groups.
Klahr et al., 1994 MDRD, Study 1 [43]	Role of protein restriction and blood pressure control in retarding CKD progression GFR rate of decline.	585 patients (18–70 years old) GFR 55 to 25 mL/min/1.73 m2. BP control level: Usual vs. Low LPD: 0.6 g/kg/day vs. UPD: 1.3 g/kg/day. 2.2-year follow-up	No differences in the rate of GFR decline between protein intake groups and blood pressure groups were observed.	Low adherence to the protein prescribed in LPD and UPD groups. Nutritional status was maintained thru the study in the LPD, UPD and VLPD groups.
Klahr et al., 1994 MDRD, Study 2 [43]	Role of protein restriction and blood pressure control on CKD progression GFR decline.	Study 2: 255 patients (18–70 years old) GFR 24 to 13 mL/min/1.73 m2. BP control level: usual vs. low LPD: 0.6 g/kg/day vs. VLPD: 0.3 g/kg/day plus supplementation of EAA and KA. 2.2-year follow-up	No differences in the average rate of GFR decline between protein and blood pressure groups were observed.	Although not significant, a trend to slower GFR decline was observed in the VLPD vs. the LPD group (p = 0.07).
Cianciaruso et al., 2008 [40]	Role of low protein diet on metabolism Modification in serum urea.	392 patients (Age > 18 years) GRF ≤ 30 mL/min/1.73 m2 LPD: 0.6 g/kg/day vs. UPD: 0.8 g/kg/day. 6 to 18 months follow-up.	No difference in serum urea between LPD and UPD group, but serum urea was lower in patients adherent to LPD. The need for medications was lower in the LPD vs UPD group.	Nutritional status was maintained in the LPD and UPD group.
Garneata et al., 2016 [44]	Role of severe protein restriction in retarding CKD progression. Dialysis start or 50% reduction of eGFR	207 pts median age 54 years eGFR < 30 mL/min/1.73 m2 and proteinuria < 1 g/day. LPD (0.6 g/kg/day) vs. VLPD (0.3 g/kg/day) plus supplementation of EAA and KA. 15-month follow-up	VLPD plus EAA and KA was more effective than LDP in delaying the start of dialysis or avoiding 50% loss of GFR, especially n patients with GFR < 20 mL/min.	Compliance to diet was good, with no changes in nutritional parameters. The randomization occurred in patients previously selected for attitude to dietary restriction during the run-in period.

LPD: Low protein diet; UPD: Usual protein diet; VLPD: Very low protein diet; GFR: Glomerular filtration rate; eGFR: Estimated glomerular filtration rate; BP: Blood pressure; CKD: chronic kidney disease; EAA: essential amino acids, KA: ketoacids.