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Nutrition therapy is considered as the basis for prevention and management of chronic kidney disease (CKD), throughout the three-tier prevention strategies of CKD. The primary objective is to delay the disease progression, correct metabolic disorders, and improve the outcomes of CKD. Low protein diet has been recognized as an important therapeutic measure in CKD, but the quantity, quality and source of protein are always the points of contention. Recently, both domestic and foreign guidelines have been updated on the amount of protein intake. In addition to quantity, attention has been paid to the type and diversity of proteins. With the rise of plant-based food consumption and the concept of vegetarian diet, the scientific community began to review the benefits of plant protein again, and a plant-based diet is recommend extensively. Whether the plant-based dietary pattern is also suitable for CKD patients who need a low-protein diet, and whether it could meet the nutritional needs of CKD patients are hot topics, this article reviews the recent progress of these research hotspots.
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ABSTRACT Introduction: Chronic Kidney disease (CKD) patients have a high prevalence of cardiovascular mortality, and among the risk factors are dyslipidemia and obesity, common findings in the early stages of CKD. The aim of this study was to evaluate the effects of low protein diet (LPD) on the lipid and anthropometric profile in non-dialysis CKD patients. Methods: Forty CKD patients were studied (20 men, 62.7 ± 15.2 years, glomerular filtration rate (GFR) 26.16 ± 9.4 mL/min/1.73m2). LPD (0.6g/kg/d) was prescribed for six months and, biochemical and anthropometric parameters like body mass index (BMI), waist circumference and body fat mass (assessed by dual X-ray absorptiometry - DXA) were evaluated before and after six months with LPD. Results: After six months of nutritional intervention, patients presented reduction on BMI (from 28.1 ± 5.6 to 27.0 ± 5.3 Kg/m2, p = 0.001), total cholesterol (from 199.7 ± 57.1 to 176.0 ± 43.6mg/dL, p = 0.0001), LDL (from 116.2 ± 48.1 to 97.4 ± 39.1 mg/dL, p = 0,001) and uric acid (from 6.8 ± 1.4 to 6.2 ± 1.3 mg/dL, p = 0.004). In addition, GFR values were increased from 26.2 ± 9.5 to 28.9 ± 12.7mL/min (p = 0.02). The energy, proteins, cholesterol and fiber intake were reduced significantly. Conclusion: LPD prescribe to non-dialysis CKD patients for six months was able to improve some cardiovascular risk factors as overweight and plasma lipid profile, suggesting that LPD can be also an important tool for protection against cardiovascular diseases in these patients.
RESUMO Introdução: Pacientes com Doença Renal Crônica (DRC) possuem alta prevalência de mortalidade cardiovascular e, dentre os fatores de risco, encontram-se alterações no perfil lipídico e excesso de peso, que são achados comuns na DRC. O objetivo deste estudo foi avaliar os efeitos da dieta hipoproteica sobre o perfil antropométrico e lipídico de pacientes com DRC em tratamento conservador. Métodos: Foram estudados 40 pacientes com DRC (20 homens, 62,7 ± 15,2 anos, e Taxa de Filtração Glomerular (TFG) de 26,2 ± 9,4 mL/min/1,73m2). Os pacientes receberam prescrição de dieta hipoproteica (0,6g/kg/d) e parâmetros bioquímicos e antropométricos como índice de massa corporal (IMC), circunferência da cintura (CC) e percentual de gordura corporal (GC) avaliado por absorciometria com raio-x de dupla energia (DXA), foram analisados antes e após 6 meses de intervenção. Resultados: Os pacientes apresentaram após 6 meses, redução do IMC (de 28,1 ± 5,6 para 27,0 ± 5,3Kg/m2, p = 0,001), colesterol total (de 199,7 ± 57,1 para 176,0 ± 43,6mg/dL, p = 0,0001), LDL (de 116,2 ± 48,1 para 97,4 ± 39,1 mg/dL, p = 0,001) e ácido úrico (de 6,8 ± 1,4 para 6,2 ± 1,3 mg/dL, p = 0,004) e, aumento da TFG de 26,2 ± 9,5 para 28,9 ± 12,7mL/min (p = 0,02). Houve redução significativa na ingestão de energia e proteínas, bem como de colesterol e fibras. Conclusão: A intervenção com dieta hipoproteica para pacientes com DRC em tratamento conservador por seis meses foi capaz de melhorar alguns fatores de risco cardiovascular, como o excesso de peso e o perfil lipídico plasmático, sugerindo que a dieta hipoproteica, além de outros benefícios pode também ser importante ferramenta para a proteção de doenças cardiovasculares nesses pacientes.
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Humans , Male , Female , Middle Aged , Cholesterol/blood , Diet, Protein-Restricted , Body Size , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/therapy , Conservative Treatment , Triglycerides/bloodABSTRACT
Objective To explore the effects of long-term low-protein intake on nonspecific inflammatory responses in the liver and T lymphocytes in the spleen in middle-aged and older mice and underlying mechanisms.Methods Fourteen month-old female KM(Kunming)mice were randomly divided into the control group,the low-protein group,the high-protein group and the high-protein + rapamycin group.Additionally,Two month-old female KM mice served as the adult group and were fed regular chow.Animals in the high-protein + rapamycin group received injections of rapamycin intraperitoneally once every two days.Animals were sacrificed at the end of 3 months.Liver histology slices were prepared for the examination of pathological changes and detection of the expression of CD68 and mTOR(the mechanistic target of rapamycin).Spleen lymphocyte suspensions were prepared to count the percentages of CD4+ T and CD8+ T cells.Results Compared with the control group,the low-protein group and the high-protein-+-rapamycin group in histology slides showed regularly arranged hepatocytes,no obvious sinus hepaticus expansion and only mild time-related changes.Moreover,compared with the control group,the low-protein and high-protein + rapamycin groups were associated with increased percentages of CD4+T and CD8 + T cells in the spleen(all P＜ 0.05)and decreased expression of CD68 in the liver(P＜0.05),though the levels of mTOR were similar among the groups.Conclusions Long-term low-protein intake has beneficial effects in mitigating the reduction of T lymphocytes in the spleen and slowing age-related structural and nonspecific inflammatory changes in the liver,possibly through downregulation of the expression of the mTOR protein.
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Diet therapy is considered as the basic treatment of chronic kidney disease (CKD),and its primary goals are improving metabolic disorder,relieving symptoms and prevent complications,hence to retard renal function lost of CKD patients.However,there have been controversies about the results of clinical studies on nutritional treatment for CKD.This article reviews the effectiveness,safety and compliance of low-protein diet (LPD) for CKD patients,and related clinical management strategies.The article also recommends the feasible diet scheme to provide a reference of clinical LPD therapy for patients with CKD.
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Objective To explore the impacts of 75％ low-protein diet intake during gestation on fetal growth restriction (FGR) rat model establishment.Methods Thirty-eight pregnant Sprague-Dawley rats were included into the study.At first,five pregnant rats were fed with sufficient normal diet with protein content of 22％.Their daily food consumption was recorded and taken as the basis to determine daily feed consumption of 75％ low-protein group (protein content 9.2％).In order to ensure that each group finally had at least ten pregnant rats to deliver,there were 11 rats assigned to the control group (pregnant rats fed with sufficient normal diet,protein content was 22％),13 to the low-protein group (pregnant rats fed with low protein diet,protein content was 9.2％,but the food consumption was the same as control group) and 14 to the 75％ lowprotein group (pregnant rats fed with low-protein diet,protein content was 9.2％,the food consumption was 75％ of the control group).All female rats were fed with sufficient normal diet after delivery.The body weight,overall weight gain during gestation,the mortality rate and the non-delivery rate of pregnant rats were compared.The third day's newborn weight after birth,FGR incidence and the mortality rate within three days after birth of newborns were also compared.One way analysis of variance,LSD-t test,independent sample t-test and Chisquare test were used as statistical methods.Results (1) The body weight of pregnant rats:There was no significant difference in body weight among the three groups at gestational day 0,3 and 6.On day 9,body weight of 75％ low-protein group [(271.9±8.4) g] and low-protein group [(274.1 ±7.8) g] were significantly lower than that of the control group [(287.2± 18.7) g] (t=2.514 and 2.170,both P＜0.05),but there was no significant difference between the former two groups.On Day 12,body weight of 75％ low-protein group [(275.7 ± 10.7) g] and low protein group [(285.1 ± 12.5) g] were significantly lower than that of the control group [(306.4±29.7) g] (t=3.262 and 2.218,both P＜0.05),and the difference between the former two groups was also statistically significant (t=2.098,P＜0.05).Before delivery,body weight of 75％ low-protein group,low protein group and control group were (300.4±14.1) g,(317.0±16.3) g and (372.9±19.1) g,respectively with statisticall significance (F=64.219,P＜0.05).The overall weight gain during pregnancy for 75％low-protein group,low-protein group and control group was (61.6± 19.8) g,(81.8±21.6) g and (139.3± 12.0) g,respectively.The difference among the three groups was statistically significant (F=55.863,P＜0.05).(2) The mortality rates of pregnant rats for 75％ low-protein group,low-protein group and control group were 3/14,2/13 and 1/11 respectively without significant difference (P＞0.05).Neither was the non-delivery rate within 30 days (embryonic resorption) for the three groups (1/14,1/13,0/11,P＞0.05).(3) The numbers of pups were 101 in 75％ low-protein group,104 in low-protein group and 107 in control group.The newborn mortality rate within three days after birth was 28.7％ (29/101) in 75％ tow-protein group and 23.0％ (24/104)in low-protein group,with were significantly higher than that of the control group (7.5％,8/107) (x2=16.022and 9.976,both P＜0.05),but there was no significant difference between groups.The third day's newborn weight after birth for 75％ low-protein group,low-protein group and control group were (6.3 ±0.8) g,(6.9±0.9) g and (8.1 ±0.9) g,the difference was statistically significant (F=90.602,P＜0.05).FGR incidence for 75％ low-protein group was 55.6％ (40/72),which was significantly higher than that of the low-protein group (28.8％,23/80) and the control group (5.0％,5/99) (x2=11.220,54.834 and 18.833 all P＜0.05).Conclusion 75％ low-protein diet feeding during pregnancy is an ideal method to induce FGR rat model with high FGR incidence,whereas and low mortality rates of pregnant rats,the fetuses and newborns.
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Objective To observe the mitochondrial damage associated with protein-energy wasting of skeletal muscle in diabetic kidney disease (DKD) model of Goto-Kakizaki(GK) rats and evaluate the effects of low-protein diet supplemented with α-keto acids on muscle wasting.Methods Forty-five male 24-week-age GK rats were randomly divided into three groups,normal protein diet group (NPD),low-protein diet group (LPD) and LPD +or-keto group (Keto).Fifteen gender and age matched Wistar rats were served as control group (CTL).The living condition of GK rats was observed and the weight was measured once a week.Urine albumin,serum glucose,creatinine and urea nitrogen were measured at 24,32,40,48 week age.Soleus muscle was observed to calculate the muscle size and the percentage of Ⅰ and Ⅱ type muscle fiber with software after SDH and NADH staining at 48-week-age.Tissue ultrastructure was observed under the transmission electron microscopy.The activity of citrate synthase was detected by spectrophotometer.Expression of mitochondrial DNA was examined by Q-PCR.Results Compared with the CTL group,NPD,LPD and Keto groups had lower body weight,higher urine albumin,higher serum creatinine and urea nitrogen (P ＜ 0.05).The crosssectional area of muscle fibers was larger in CTL group.Compared with CTL group,the muscle fiber was partly broken,the mitochondrial morphology was obviously changed,the percentage of type Ⅱmuscle fiber was increased significantly (P ＜ 0.05),and the activity of citrate synthase and the number of mitochondrial DNA were decreased significantly in NPD,LPD and Keto groups (P ＜ 0.05).In Keto group,muscle wasting was improved compared with NPD and LPD group (P ＜ 0.05),the crosssectional area of soleus muscle increased and the percentage of type Ⅱ muscle fiber decreased,levels of urine albumin,semm creatinine and urea nitrogen decreased (P ＜ 0.05).Under transmission electron microscopy,the muscle fiber of keto group was intact and mitochondiral morphology was close to that of CTL group.The activity of citrate synthase and number of mitochondiral DNA were higher as compared to CTL group (P ＜ 0.05).There were no significant differences between NPD and LPD group.Conclusions In DKD condition,protein degradation in the skeletal muscle is accelerated,mitochondrion is swelling,the number of mitochondrial DNA is decreased and mitochondrial function is impaired.Low-protein diet supplemented with α-keto acids can improve mitochondrial damage and muscle wasting induced by DKD.
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Objective To evaluate the efficacy and safety of short-term restriction of dietary protein intake (DPI) supplemented with α-keto acids on chronic hepatitis B patients complicated with chronic kidney diseases (CKD). Methods A prospective randomized controlled trial was carried out.Seventeen chronic hepatitis B patients with CKD were randomized to either low DPI with α-keto acid-supplemented (sLP) or low DPI (LP) group for 3 months.Low-protein diet (LPD) was individualized with total energy intake 125.52-146.44 kJ·kg-1 ·d-1,and protein intake of 0.6-0.8 g·kg-1·d-1.α-keto acid was supplied in a dosage of 0.1 g·kg-1·d-1.Nutritional indexes were recorded and other clinical indexes were measured to evaluate the efficacy and safety respectively. Results The urine protein excretion level and microalbuminuria were significantly decreased at the end of the observation period in the sLP group compared to the basal value and the LP group [24 h urine protein:baseline (4.52±1.74) g,the 1st month (3.19±1.52) g,the 2nd month (2.19±1.1) g,the 3rd month (1.64±0.77) g,P＜0.05; microalbuminyria:baseline (2855.43±248.03) mg/L,the 1st month (2157.14±218.15) mg/L,the 2nd month (1681.57±146.18) mg/L,the 3rd month (924.29±83.33) mg/L,P＜0.05].No significant difference was found in Scr and eGFR.Nutritional indexes (SGA,serume albumin) were significantly higher at the end of 3 months in the sLP group (P＜0.05).No obvious side-effect occurred. Conclusions Short-term restriction of DPI is safe,and when combined with α-keto acids,can increase serum protein and decrease urine protein excretion in chronic hepatitis B patients complicated with CKD without significant sideeffect.
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Objective To observe the changes of renin-angiotensin system (RAS) in cultured mesangial cells by serum from 3/4 nephrectomized rats feeding with low protein diet and α-keto acid. Methods Thirty male SD rats received 3/4 nephrectomy (Nx) were placed on 18%normal protein diet (NPD,n=10),6% low protein diet(LPD,n=10) or 5% low protein plus 1%α-keto acid diet (LK,n=10) flor 12 weeks.Ten male SD sham-operated rats fed with 18% normal protein diet were used as control (sham group).In addition,mesangial cells were cultured in sera (10%) collected from above animals treated with or without losartan (0.02 mmol/L)for 48 hours.ELISA was applied to detect the level of Ang II,TGF-β1 and fibronectin (FN) in cell medium.Westem blotting was used to determine the protein level of ATI receptor (AT1R)and real-time PCR was used to detect the mRNA level of AT1R,TGF-β1 and FN. Results (1) Nutritional indices including body weight,total protein and albumin had no significant difference in each group. (2) Serum creatinine and 24 h pruteinuria were significantly inceased in nephrectomized groups compared to sham group(P<0.05,respectively).24 h proteinuria was greatly lower in LK group than that in NPD and LPD groups(P<0.05,respectively).(3)LK greatly decteased the level of Ang II[NPD(12.70±0.12)mg/g protein;sham(8.04±0.62)mg/g protein]in supernatant as well as the protein and mRNA expression of AT1R in cultured mesangial cells (P<0.05).(4)NPD serum directly induced higher secretion[FN:sham(20.58±0.46)g/g protein,NPD (39.84±0.06)g/g protein;TGF-β1:sham(10.12±O.56)mg/g protein,NPD(83.85±3.58)mg/g protein] and mRNA expression of FN and TGF-β1 compared with sham group (P<0.05).LPD decreased these increment (P<0.05) and LK showed stronger inhibitory effect (P<0.05). (5)Losartan application sharply reduced FN and TGF-β1 production both in supematant and in mRNA expression in NPD serum treated cells (P<0.05,respectively). Conclusion Low protein diet with α-keto acids supplement directly inhibits the RAS in mesangial cells which may contribute to its beneficial effect on the kidney.
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Objective To observe the influence of low protein diet with α-keto acid on kidney sclerosis and renin-angiotensin system in renal ablation rats. Methods Chronic renal failure rat model was established by renal ablation in 30 male SD rats,then the animals were randomly assigned to the following diet groups:normal protein group (NPD:18%casein protein),low protein group (LPD:6%casein protein) and supplemented low protein group (LK:5%casein protein+1%α-keto acids).Ten male SD sham-operated rats received 18%casein protein as control.All the rats were killed at the end of the 12th week.Pathologic changes were assessed by PAS staining.Ang II in homogenate and plasma were measured by radioimmunoassay and ELISA respectively.Immunohistochemistry and Western blotting were used to detect the protein expression of TGF-β1,renin and AT1R.Real-time PCR was used to detect the gene expression of renin and ATla,the main subtype of AT1 receptor. Results Body weight,total protein and serum albumin had not significant difference among the four groups(all P>0.05).Serum creatinine and proteinuria of nephrectomized rats were significantly higher compared to the control group (all P<0.05).Proteinuria of the LK group was lower than that of NPD and LPD groups (all P<0.05).Pathological results indicated fibrosis indices were significantly improved after LPD and LK intervention.Expressions of renin,Ang II and AT1R in LK group were significantly lower than those in NPD group (all P<0.05). Conclusions Low protein diet with α-keto acids supplement therapy exhibits renal protective effects of reducing urine protein excretion and improving renal fibrosis,which might be related to the attenuation of local renin-angiotensin system in activity nephrectomized rats.
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Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with C group, the serum cholesterol levels in M and I groups were significantly increased (P<0.05), and the serum phosphorus level in I group was significantly decreased (P<0.05). The levels of serum albumin and serum calcium of all three groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.
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ObjectiveTo observe the influence of different dietary protein intake (DPI) on nitrogen balance and nutritional indices in peritoneal dialysis (PD) patients, and explore the minimal DPI to maintain nitrogen balance.MethodsThirty-four PD patients were randomly divided into group A, B and C with DPI as 1.2, 0.9 and 0.6 g·kg-1·d-1 respectively. All the patients admitted into our hospital and completed a 10-day assessment for nitrogen balance, as well as nutritional status including serum albumin (Alb), pre-albumin at baseline, the 7th and 10th day. ResultsThe DPI of group A, B and C was (1.18±0.05), (0.87±0.02), (0.66±0.03) g·kg-1·d-1, whose differences were significant (P<0.01). The dietary energy intake (DEI) was 129.29 (117.57-133.89), 111.71 (100.42-133.47), 146.86 (128.03-163.18) kJ·kg-1·d-1 respectively. Nitrogen balance was positive in group A, B, C [2.99 (2.15-4.72) g, 1.20(0.59-1.89) g, 0.24 (-0.87-1.27) g]. The BUN decreased at the 7th and 10th day (P<0.01) in group C. The BUN and phosphorus in group A increased, but without significant difference as compared to baseline. No significant differences of nutritional status were found among three groups throughout the trial. ConclusionMinimal DPI 0.65 g·kg-1·d-1 plus the supplement of protein loss in dialysate can maintain the nitrogen balance in peritoneal dialysis patients.
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Objective To investigate the effect of Ketosteril and low protein diet on nutritional status and renal function in patients with chronic kidney disease (CKD). Methods 60 patients with CKD were divided into two groups randomly. The patients were treated with low-protein diet (0.6 g?kg-1?d-1) in control group while the patients was treated with Ketosteril (0.2 g?kg-1?d-1) and low-protein diet (0.6 g?kg-1?d-1) in the test group. The intervention period lasted for 3 months. The body weight, MAC, MAMC and the serum ALB, PA, Tf, BUN and Cr concentrations in the patients were measured. Results Compared with the control group, the body weight, MAC, MAMC were significantly increased in the test group; the serum ALB, PA ,Tf, BUN and Cr concentrations were also improved. Conclusion Combination of Ketosteril and low-protein diet can improve the nutritional status and the kidney function.