| Milovanova et al., 2018 [3]
| [2]
| 5/6 nephrectomy rats |
|
| RCT |
| n = 42 in LPD + KA vs. LPD n = 37 |
| Non-diabetic CKD 3B–4 |
| NPD: 22% protein |
| vs. |
| LPD: 6% protein |
| vs. |
| LPD + KAs: 5% protein plus 1% KA |
|
| LPD (0.6 g/kg of body weight/day, comprising 0.3 g of vegetable protein and 0.3 g of animal protein, phosphorus content ≤ 800 mg/day and calories: 34–35 kcal/kg/day) vs. LPD + KA: 0.6 g/kg of body weight/day |
| 24 weeks |
|
|
| 14 months |
| ↓ muscle atrophy |
| ↑ activities of mitochondrial electron transport chain complexes and mitochondrial respiration, |
| ↓ muscle oxidative damage |
|
| ↑ eGFR (29.1 L/min/1.73 m ↑body weight |
|
2 vs. 26.6) |
| ↓SBP |
| ↑BMI and muscle body mass |
| NO change in albumin levels |
| No change in lipids parameters |
| ↓ phosphate, FGF23, and PTH levels ↑Klotho levels and phosphate binder uses |
| ↑bicarbonates levels |
|
| Ca-Ketoeucine |
|
| Similar protein intake in both group |
| Long follow up |
|
| Liu et al., 2018 [9]
| [8]
|
| 101 |
|
| Di Iorio et al., 2018 [20]
| [19]
| KKAy mice, an early type 2 DN model |
|
| RCT, crossover trial |
| CKD stages 3B–4 |
| Group A1: 3 months of FD, 6 months of VLPD + KA, 3 months of FD and 6 months of MD |
| Group B: 3 months of FD, 6 months of MD, 3 months of FD and 6 months of VLPD + KA. |
| n = 30 in each group |
| NPD: 22% protein |
| vs. |
| LPD: 6% protein |
| vs. |
| LPD + KAs: 5% protein plus 1% KA |
|
| 12 weeks |
|
| ↓ proteinuria |
| FD: proteins 1 g/kg body weight (bw)/day (animal proteins 50–70 g/day, vegetal proteins 15–20 g/day), energy 30–35 kcal/bw/day, calcium (Ca) 1.1–1.3 g/day, phosphorus (P) 1.2–1.5 g/day, sodium (Na) 6 g/day and potassium (K) 2–4 g/day. |
| MD: proteins 0.7–0.8 g/kg bw/day (animal proteins 30–40 g/day, vegetal proteins 40–50 g/day), energy 30–35 kcal/bw/day, Ca 1.1–1.3 g/day, P 1.2–1.5 g/day, Na 2.5–3 g/day and K 2–4 g/day. |
| VLPD + KA: proteins 0.3–0.5 g/kg bw/day (animal proteins 0 g/day, vegetal proteins 30–40 g/day), energy 30–35 kcal/bw/day, Ca 1.1–1.3 g/day, P 0.6–0.8 g/day, Na 6 g/day, K 2–4 g/day plus a mixture of KA |
| ↓ mesangial proliferation and oxidative stress |
| 6 months |
| ↑ serum albumin and body weight |
| No difference in creatinine and GFR |
|
| ↓ SBP |
| No change in creatinuria |
| ↓proteinuria |
| ↓ phosphate, FGF23, and PTH levels |
| ↑bicarbonates levels |
| ↑Hg levels |
| ↓protein carbamylation |
|
| Sodium intake and phosphore intake was reduce in VLDP + KA group |
|
| Ca-Ketophénylalanine |
|
10]
| [9] |
| Garneata et al., 2016 [21]
|
| 68 |
|
|
[20]
| 3/4 nephrectomy rats |
|
| RCT |
| CKD stage 4–5, |
| proteinuria < 1 g/24 h |
| n = 207 |
| NPD: 18% protein |
| vs. |
| LPD: 6% protein |
| vs. |
| LPD + KAs: 5% protein plus 1% KA |
|
| 12 weeks |
|
| LPD = 0.6 g protein/kg per day |
| vs. |
| VLPD + KA = vegetarian diet, 0.3 g protein/kg per day + KA |
|
| 15 months |
| ↓ proteinuria |
| ↓ intrarenal RAS activation. |
| ↓ transforming growth factor-β1 in the mesangial cells |
|
| ↓ RRT initiation or a >50% reduction in the initial GFR (13% in KA+LDP vs. 42% in LPD reached the primary composite efficacy point i.e., RRT initiation or a >50% reduction in the initial GFR) |
| ↓CRP |
| ↑bicarbonates levels |
| ↓uric acid |
| ↓ phosphate, FGF23 and PTH levels and phosphate binder uses |
| No difference in proteinuria |
| No difference of death and CV events |
| No difference of albumin, BMI |
| No change in lipids parameters |
| Ca-Ketovaline |
|
| 86 |
|
| Zhang et al., 2016 [ |
|
| Long follow up |
| Large effective |
| Only 14% of patients screened was included |
|
| Zhang et al., 2015 [11]
| [10]
|
| Di Iorio et al., 2012 [22]
| [21]
| 5/6 nephrectomy rats |
|
|
| RCT, crossover trial |
| eGFR < 55 and > 20 mL/min/1.73 m 2 |
| Group A: VLDP + KA during the first week and LPD during the second week |
| Group B: LPD during the first week and a VLPD + KA during the second week. |
| n = 16 in each group |
| NPD: 11 g/kg/day protein |
| vs. |
| LPD: 3 g/kg/day protein |
| vs. |
| LPD + KAs: 3 g/kg/day protein which including 5% protein plus 1% KA |
|
| LPD = 0.6 g protein/kg per day |
| 24 weeks |
|
vs. VLPD + KA = 0.3 g protein/kg per day + KA |
| ↑ body weight, gastrocnemius muscle mass |
| ↓ autophagy marker in muscle |
| No difference of inflammation markers |
|
| 1 week |
|
| ↓ phosphate (−12%), FGF23 (−33.5) |
| No change on calcium |
| a post hoc of this study, ↓ indoxyl sulfate [ 23]
| [ 22 ]
| ↑bicarbonates levels |
|
| Short exposition |
|
| Ca-Hydroxy-dl-methionine |
|
| Wang et al., 2014 [12]
| [11]
|
| Di Iorio et al., 2009 [24 |
| 59 |
|
]
| [23]
| 5/6 nephrectomy rats |
|
|
| RCT, crossover trial |
| eGFR < 55 and > 20 mL/min |
| Group A: VLDP + KA during 6 month and a LPD during 6 month |
| Group B: LPD during 6 month and a VLDP + KA during 6 month. |
| n = 16 in each group 32 patients |
| NPD: 22% protein |
| vs. |
| LPD: 6% protein |
| vs. |
| LPD + KAs: 5% protein plus 1% KA |
|
| LPD = 0.6 g protein/kg per day |
| vs. |
| VLPD + KA = 0.3 g protein/kg per day + KA |
| 24 weeks |
|
| 6 months |
| ↑improved protein synthesis and increased related mediators such as phosphorylated Akt in the muscle |
| ↓ protein degradation and proteasome activity in the muscle |
|
| ↓proteinuria and AGE |
|
| Open label |
| Phosphor intake was different and lower in VLDP+ KA |
|
| l-Lysine monoacetate |
|
| 105 |
|
| Gao et al., 2010 [13]
| [12]
|
| Menon et al., 2009 [25]
| [24]
| 5/6 Nephrectomy rats |
|
|
| Post hoc study of MDRD study B |
| NPD: 22% protein |
| vs. |
| LPD: 6% protein |
| vs. |
| LPD + KAs: 5% protein plus 1% KA |
|
CKD stage 4 nondiabetic |
| n = 255 |
|
| LPD = 0.6 g protein/kg per day |
| vs. |
| VLPD + KA = 0.3 g protein/kg per day + KA |
| 24 weeks |
|
| 10.2 years |
| ↓ proteinuria, glomerular sclerosis, and tubulointerstitial fibrosis |
| ↑renal function |
| ↑ body weight and albumin |
| ↓ lipid and protein oxidative products |
|
|
| No delay progression to kidney failure |
| ↑the risk of death. |
|
| Long follow up without intervention -Observance and protein intake was not monitored during the follow up |
|
| l-Threonine |
|
| Gao et al., 2011 [14]
| [13]
|
| 53 |
|
| 5/6 Nephrectomy rats |
|
| Teplan et al., 2008 [4]
| [3]
|
| RCT, double-blind placebo |
| CKD stage 4 |
| n = 111 |
| NPD: 22% protein |
| vs. |
| LPD: 6% protein |
| vs. |
| LPD + KAs: 5% protein plus 1% KA |
|
| LDP: 0.6 g protein/kg per day |
| vs. |
| LPD + KA: 0.6 g protein/kg per day + KA |
| 6 months |
|
| 36 months |
| ↑ body weight and albumin |
|
| ↓ADMA ↑ Kruppel-like factor-15, a transcription factor shown to reduce fibrosis |
|
| ↓ BMI and visceral body fat in obese patients |
| ↓proteinuria |
|
| l-Tryptophan |
|
↓ glycated hemoglobin |
| ↓LDL-cholesterol |
|
| Mean BMI was > 30 kg/m2 at the inclusion |
| Long follow up |
| No difference of protein intake |
| Using a placebo |
|
| Maniar et al., 1992 [15]
| [14]
|
| 23 |
|
| Mircescu et al., 2007 [26]
| [25]
| 5/6 Nephrectomy rats |
|
| RCT |
| eGFR <30 mL/min/1.73 m 2, nondiabetic |
| n = 53 |
| NPD: 16% casein |
| vs. |
| LPD + EAA: 6% casein + EAA |
| vs. |
| LPD + KAs: 6% casein + KA |
|
| VLPD + KA =0.3 g/kg vegetable proteins + KA |
| 3 months |
|
| vs. |
| LPD =0.6 g/kg/d) |
| No difference on body weight |
| No difference on proteinuria vs. LDP + EAA but reduction vs. NPD |
|
| 48 weeks |
| ↓ creatinemia, proteinuria, glomerular sclerosis, and tubulointerstitial fibrosis vs. NPD but no difference vs. LPD + EAA |
| ↑survival vs. NPD but no difference vs. LPD + EAA |
|
| ↑bicarbonates levels |
| ↑calcium levels and ↓ phosphate |
| lower percentages of patients in group I required renal replacement therapy initiation (4% vs. 27%). |
| No change of rate of eGFR and proteinuria |
| l-Histidine |
|
| 38 |
|
| No change in SBP |
|
| Open label |
|
| Laouari et al., 1991 [16]
| [15]
|
| Gennari et al., 2006 [27]
| [26]
| 5/6 Nephrectomy rats |
|
|
| Post hoc study of MDRD study |
| NPD: 12% casein |
| l-Tyrosine |
|
| 30 |
|