Low-Protein Diets Could Be Effective and Safe in Elderly Patients with Advanced Diabetic Kidney Disease.

Low-protein diets (LPDs) seem to improve metabolic complications of advanced CKD, thus postponing kidney replacement therapy (KRT) initiation. However, the nutritional safety of LPDs remains debatable in patients with diabetic kidney disease (DKD), especially in the elderly. This is a sub-analysis of a prospective unicentric interventional study which assessed the effects of LPD in patients with advanced DKD, focusing on the feasibility and safety of LPD in elderly patients. Ninety-two patients with DKD and stable CKD stage 4+, proteinuria >3 g/g creatininuria, good nutritional status, with confirmed compliance to protein restriction, were enrolled and received LPD (0.6 g mixed proteins/kg-day) supplemented with ketoanalogues of essential amino acids for 12 months. Of the total group, 42% were elderly with a median eGFR 12.6 mL/min and a median proteinuria 5.14 g/g creatininuria. In elderly patients, proteinuria decreased by 70% compared to baseline. The rate of kidney function decline was 0.1 versus 0.5 mL/min-month before enrolment. Vascular events occurred in 15% of cases, not related to nutritional intervention, but to the severity of CKD and higher MAP. LPDs seem to be safe and effective in postponing KRT in elderly patients with advanced DKD while preserving the nutritional status.

Low Protein Diet Reduces Proteinuria and Decline in Glomerular Filtration Rate in Advanced, Heavy Proteinuric Diabetic Kidney Disease.

Low protein diet (LPD) seems beneficial in ameliorating the complications of chronic kidney disease (CKD), in reducing proteinuria and the decline in kidney function, thus postponing the need for kidney replacement therapy (KRT). However, this type of intervention was less investigated in diabetic kidney disease (DKD). This is a single-center, prospective, interventional study that aims to assess the efficacy of reducing proteinuria and the rate of decline in the estimated glomerular filtration rate (eGFR). Patients with advanced DKD (stable proteinuria > 3 g/g and eGFR < 30 mL/min) with a good nutritional status and accepting a LPD were evaluated for inclusion. Ninety-two of the 452 screened patients (66% males, median age 61 years, proteinuria 4.8 g/g creatininuria, eGFR 11.7 mL/min/1.73 m2) completed the study. Intervention consisted of LPD supplemented with ketoanalogues of essential amino acids (KA) along with conventional nephroprotective therapy. Efficacy parameters were the variation in proteinuria and in eGFR from baseline to the end of the study. Proteinuria decreased 3-fold, and the rate of decline in eGFR decreased 5-fold in the intervention phase. No patient initiated KRT or died. LPD supplemented with KA seems effective in safely postponing KRT by reducing proteinuria and the decline in kidney function in advanced DKD.

Adherence to the Mediterranean Diet Improves Fatty Acids Profile in Pediatric Patients with Idiopathic Nephrotic Syndrome.

The fatty acid profiles of patients with idiopathic nephrotic syndrome (INS) are different from that of healthy controls, even during remission, revealing an increase of the pro-inflammatory omega 6 series. It is still unknown whether the concomitance of nephrotic syndrome affects the potential positive effects of the Mediterranean diet on the levels of omega 3 and 6 fatty acids. We performed a cross-sectional study to evaluate the association between the adherence to the Mediterranean diet and fatty acid profile in 54 children with INS. The dietary habits were assessed through the validated Kidmed questionnaire. Patients with higher adherence had lower levels of linoleic acid and total omega-6. Moreover, a negative correlation between proteinuria and the anti-inflammatory omega-3 series was found. In conclusion, patients with INS with proteinuria and low adherence to the Mediterranean diet have an imbalance in the omega-6/omega-3 ratio that may benefit from following the Mediterranean diet.

The Forgotten Antiproteinuric Properties of Diuretics.

BACKGROUND: Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration. SUMMARY: Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.

Quality or Quantity of Proteins in the Diet for CKD Patients: Does "Junk Food" Make a Difference? Lessons from a High-Risk Pregnancy.

BACKGROUND: How to manage patients with severe kidney disease in pregnancy is still a matter of discussion, and deciding if and when to start dialysis is based on the specialist's experience and dialysis availability. The effect of toxic substances usually cleared by the kidney may be more severe and readily evident. The review, and related case, underlines the importance of considering the presence of additives in food in delicate conditions, such as CKD pregnancy. The Case: A 39-year-old indigenous woman from a low-resourced area in Mexico was referred to the obstetric nephrology at 25 gestational weeks because of serum creatinine at 3.6 mg/dL, hypertension on low-dose alpha-methyl-dopa, and nephrotic-range proteinuria. Kidney ultrasounds showed small poorly differentiated kidneys; foetal ultrasounds detected a female foetus, normal for gestational age. The patient's baseline protein intake, which was estimated at 1.2-1.3 g/kg/day, was mostly of animal-origin (>70%) poor-quality food ("junk food"). In the proposed diet, protein intake was only slightly reduced (1.0-1.2 g/kg/day), but the source of proteins was changed (only 30% of animal origin) with attention to food quality. A remarkable decrease in BUN was observed, in concomitance with adequate dietary follow-up, with rapid rise of BUN when the patient switched temporarily back to previous habits. A healthy female baby weighing 2,460 g (11th centile for gestational age) was delivered at 37 gestational weeks. Discussion and Literature Review: While data on patients with chronic kidney disease are scant, the long list of contaminants present in food, especially if of low quality, should lead us to reflect on their potential negative effect on kidney function and make us realize that eating healthy, unprocessed "organic" food should be encouraged, in delicate conditions such as pregnancy and breastfeeding and for young children, in particular when kidney function is failing. The case herein described gave us the opportunity to reflect on the importance of diet quality and on the potential risks linked to food additives, many of which, including phosphates and potassium, are not declared on food labels, while others, including dyes, antioxidants, thickeners, emulsifiers, and preservatives, are qualitatively, but not quantitatively, reported.

Efficacy of low-protein diet in diabetic nephropathy: a meta-analysis of randomized controlled trials.

PURPOSE: We aimed to systematically assess the efficacy of low-protein diet preventing progression of diabetic nephropathy based on randomized controlled trials (RCTs). METHODS: A systematic and electronic search was conducted. Initial searches of literature updated to September 2018 were made using the following databases including CNKI, VIP, Wanfang, Cochrane, PubMed, and Embase using the index words for qualified RCTs. Additional searches were performed to identify linked literature sources. Data of RCTs on low-protein diet versus control diet, efficacy analysis of kidney function, nutritional status or proteinuria were extracted. Random effects model and fixed effects model were applied to combine the data which were further analyzed by Chi-squared test and I2tests. The main outcomes were then analyzed through the use of relative risks (RR), mean difference (MD) and its 95% confidence interval (95% CI). RESULTS: Twenty articles were included in the present meta-analysis with a total of 690 patients in the low-protein diet group (LPD) and a total of 682 patients in the control group. Moderate to strong evidence indicated that LPD was significantly effective for decreasing the urinary albumin excretion rate (SMD:0.62, 95%CI:0.06-1.19) and proteinuria (SMD:0.69, 95%CI:0.22-1.16) versus the control group. No statistical difference, however, was found in glycosylated hemoglobin (SMD:0.17, 95%CI:-0.18-0.51), serum creatinine (SMD:0.20, 95%CI:-0.26-0.66), as well as glomerular filtration rate (SMD:0.21, 95%CI:-0.29-0.71) between the two groups. CONCLUSION: The current meta-analysis reveals an effective role of low-protein diet in improving diabetic nephropathy. However, the small number of involved patients may limit the accuracy of results. High-quality RCTs with a larger sample size in the future are required to confirm the current findings.

Dietary intake of cod protein beneficially affects concentrations of urinary markers of kidney function and results in lower urinary loss of amino acids in obese Zucker fa/fa rats.

Obesity increases the risk for developing kidney disease, and protection of kidneys through changes in diet should be investigated. Fish intake has been associated with reduced risk of developing kidney disease; therefore, we wanted to investigate whether cod protein intake could prevent or delay the development of kidney damage in an obese rat model that spontaneously develops proteinuria and focal segmental glomerulosclerosis. The aim of the study was to investigate any effects of cod protein intake on established markers of kidney function, amino acid composition, protein utilisation and growth in obese Zucker fa/fa rats in the early stage of decreased renal function. Male obese Zucker fa/fa rats (HsdOla:Zucker-Lepr) were fed cod muscle proteins in an amount corresponding to 25 % of dietary protein, with the remaining protein from a casein/whey mixture (COD diet). A control group was fed a diet with a casein/whey mixture as the only protein source (CAS diet). The intervention started when rats were 9-10 weeks old, and the rats were fed these diets for 4 weeks. At the end of the study, rats fed the COD diet had lower urine concentration of cystatin C, T-cell immunoglobulin mucin-1 (TIM-1), amino acids, carbamide, uric acid and ammonium and higher concentrations of creatine, trimethylamine N-oxide, 1-methylhistidine and 3-methylhistidine, lower kidney concentration of TIM-1 and showed better growth when compared with the CAS group. To conclude, cod protein may have the potential to delay the development of kidney damage in young obese Zucker rats and to improve protein utilisation and growth.

A nutraceutical diet based on Lespedeza spp., Vaccinium macrocarpon and Taraxacum officinale improves spontaneous feline chronic kidney disease.

Chronic kidney disease is characterized by structural and/or functional impairment of one or both kidneys persisting for more than 3 months. In cats, chronic kidney disease can frequently occur in animals aged over 9 years with an incidence of approximately 10%. Thirty-four client-owned, neutered cats, suffering from stage II-III chronic kidney disease and diagnosed according to the International Renal Interest Society guidelines were randomly assigned to receive either a control diet (n = 17) or a nutraceutical diet (ND; n = 17) for 90 days. Both diets were commercialized for management of CKD symptoms. The diets were identical except that the ND contained tablets that consisted of 60-80% hydrolysed proteins, 20-40% minerals and active substances, that are, Lespedeza spp. 0.0588%, Vaccinium macrocarpom 0.0371%, and Taraxacum officinale 0.0231%. No adverse effects were reported during this study. Both diets resulted in an improvement in CKD symptoms. After a 90-day evaluation, creatinine, blood urea nitrogen, total proteins, and aspartate aminotransferase significantly decreased in cats that received the ND. A significant decrease was also observed in urine turbidity score, color score, and total proteins in cats that received the ND. We have found that a ND based on Lespedeza spp., Vaccinium macrocarpon, and Taraxacum officinale improves key indicators of renal failure in cats affected by chronic kidney disease.

Efficacy of low-protein diet for diabetic nephropathy: a systematic review of randomized controlled trials.

BACKGROUND: A low-protein diet (LPD) is believed to be beneficial in slowing the progression of kidney disease. It is reported that low protein diet can improve protein, sugar and lipid metabolism, and reduce the symptoms and complications of renal insufficiency. However, there has been controversial regarding the effects of protein restriction on diabetic nephropathy (DN). OBJECTIVE: To investigate the efficacy of LPD on renal function in patients with type 1 or 2 DN by meta-analysis of randomized controlled trials (RCTs). DESIGN: PubMed, MEDLINE, EMBASE and China National Knowledge Infrastructure databases were searched. Eleven randomized controlled trials met the inclusion criteria, of which 10 were English and 1 was Chinese. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was a change in proteinuria. Random-effects models were used to calculate the standardized mean difference (SMD) and the corresponding 95% confidence intervals (CI). Subgroup analyses were also performed. RESULTS: Our research indicated that LPD was not associated with a significant improvement in GFR (1.59 ml · min-1 · 1.73 m-2, 95% CI -0.57, 3.75, I2 = 76%; p = 0.15). This effect was consistent across the subgroups regardless of type of diabetes, course of diabetes and intervention period. Our results also showed that there was no significant difference on improvement of proteinuria in patients of LPD and those in normal-protein diet groups (- 0.48, 95%CI-1.70, 0.74, I2 = 94%, p = 0.44). Subgroup analysis revealed that LPD resulted in increased excretion of proteinuria in patients with type 2 diabetes (1.32, 95% CI 0.17, 2.47, I2 = 86%, p = 0.02). CONCLUSION: The present research showed that LPD was not significantly associated with improvement of renal function in patients with either type 1 or 2 diabetic nephropathy. Although these results do not completely eliminate the possibility that LPD is beneficial for patients with diabetic nephropathy, it does not seem to be significant benefit to renal function.

Pregnancy, Proteinuria, Plant-Based Supplemented Diets and Focal Segmental Glomerulosclerosis: A Report on Three Cases and Critical Appraisal of the Literature.

Chronic kidney disease (CKD) is increasingly recognized in pregnant patients. Three characteristics are associated with a risk of preterm delivery or small for gestational age babies; kidney function reduction, hypertension, and proteinuria. In pregnancy, the anti-proteinuric agents (ACE-angiotensin converting enzyme-inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for their potential teratogenicity, and there is no validated approach to control proteinuria. Furthermore, proteinuria usually increases as an effect of therapeutic changes and pregnancy-induced hyperfiltration. Based on a favourable effect of low-protein diets on proteinuria and advanced CKD, our group developed a moderately protein-restricted vegan-vegetarian diet tsupplemented with ketoacids and aminoacids for pregnant patients. This report describes the results obtained in three pregnant patients with normal renal function, nephrotic or sub-nephrotic proteinuria, and biopsy proven diagnosis of focal segmental glomerulosclerosis, a renal lesion in which hyperfiltration is considered of pivotal importance (case 1: GFR (glomerular filtration rate): 103 mL/min; proteinuria 2.1 g/day; albumin 3.2 g/dL; case 2: GFR 86 mL/min, proteinuria 3.03 g/day, albumin 3.4 g/dL; case 3: GFR 142 mL/min, proteinuria 6.3 g/day, albumin 3.23 g/dL). The moderately restricted diet allowed a stabilisation of proteinuria in two cases and a decrease in one. No significant changes in serum creatinine and serum albumin were observed. The three babies were born at term (38 weeks + 3 days, female, weight 3180 g-62th centile; 38 weeks + 2 days, female, weight 3300 g-75th centile; male, 38 weeks + 1 day; 2770 g-8th centile), thus reassuring us of the safety of the diet. In summary, based on these three cases studies and a review of the literature, we suggest that a moderately protein-restricted, supplemented, plant-based diet might contribute to controlling proteinuria in pregnant CKD women with focal segmental glomerulosclerosis. However further studies are warranted to confirm the potential value of such a treatment strategy.

Keto-supplemented Low Protein Diet: A Valid Therapeutic Approach for Patients with Steroid-resistant Proteinuria during Early-stage Chronic Kidney Disease.

BACKGROUND AND OBJECTIVES: Low protein diets supplemented with keto acid (sLPD) are recommended for patients with stage 3-5 chronic kidney disease (CKD). This study assessed whether sLPD is beneficial for patients with steroid-resistant proteinuria during early-stage CKD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A 1-year randomized controlled trial was conducted from 2010 to 2012. In this study, 108 proteinuric patients who were steroid-resistant were assigned to a sLPD group (0.6 g/kg/d with 0.09 g/kg/d keto acids) or a normal protein diet group (NPD, 1.0 g/kg/d). Estimated dietary protein intake, urinary protein excretion, remission rate, renal function, nutritional status, and blood pressure were measured. RESULTS: Baseline characteristics were comparable between the sLPD group (47 patients) and the NPD group (49 patients). Urinary protein excretion significantly decreased in sLPD compared to NPD in months 6, 9, and 12 (P<0.05). Proteinuria reduction was higher in sLPD than in NPD (P<0.001) at the end of the study. Complete remission and partial remission rates were higher in sLPD than in NPD. Serum albumin and pre-albumin levels were higher in sLPD than in NPD in months 9 and 12 (P<0.05). Serum total cholesterol and triglyceride levels declined more significantly in sLPD than in NPD (P<0.01) at the end of the study. There were no differences in nutritional status, renal function, hemoglobin, or blood pressure between the two groups. CONCLUSIONS: sLPD is both nutritionally safe and beneficial, providing nephroprotective effects for early-stage CKD patients with steroid-resistant proteinuria.

Impact of phosphorus restriction and vitamin D-substitution on secondary hyperparathyroidism in a proteinuric mouse model.

BACKGROUND/AIMS: Since the discovery of FGF23, secondary hyperparathyroidism (SHPT) in renal disease has been considered to result primarily from phosphorus retention rather than vitamin D deficiency. However, the impact of phosphorus restriction and vitamin D supplementation on SHPT is still ill defined. METHODS: We investigated the development of SHPT in a doxorubicin-induced proteinuric mouse model and tested different treatment strategies including a low phosphorus diet and substitution with native or active vitamin D in 129 S1/SvImJ wild-type mice. RESULTS: Development of SHPT at day 30 was strongly related to the magnitude of induced proteinuria. In mice with a proteinuria <100 mg/mg creatinine, SHPT was mild (PTH increase 2.4-fold), and serum levels of FGF23, phosphate and urea remained almost stable, whereas mice with heavy proteinuria (>100 mg/mg creatinine) developed marked SHPT (PTH increase 10.1-fold) accompanied by massive increase in FGF23 (27.0-fold increase), hyperphosphatemia (1.8-fold increase), renal failure (7.3-fold urea increase) and depletion of both 25-OH vitamin D and 1,25-OH vitamin D. Substitution with native or active vitamin D was unable to suppress SHPT, whereas a low-phosphorus diet (Pi content 0.013%) completely suppressed SHPT in mice with both mild and heavy proteinuria. CONCLUSIONS: The development of SHPT resulted from phosphate retention in this proteinuric model and could completely be suppressed with a low-phosphorus diet.

Fibroblast growth factor 23 and the antiproteinuric response to dietary sodium restriction during renin-angiotensin-aldosterone system blockade.

BACKGROUND: Residual proteinuria during renin-angiotensin-aldosterone system (RAAS) blockade is a major renal and cardiovascular risk factor in chronic kidney disease. Dietary sodium restriction potentiates the antiproteinuric effect of RAAS blockade, but residual proteinuria remains in many patients. Previous studies linked high fibroblast growth factor 23 (FGF-23) levels with volume overload; others linked higher serum phosphate levels with impaired RAAS-blockade efficacy. We hypothesized that FGF-23 reduces the capacity of dietary sodium restriction to potentiate RAAS blockade, impairing the antiproteinuric effect. STUDY DESIGN: Post hoc analysis of cohort data from a randomized crossover trial with two 6-week study periods comparing proteinuria after a regular-sodium diet with proteinuria after a low-sodium diet, both during background angiotensin-converting enzyme inhibition. SETTING & PARTICIPANTS: 47 nondiabetic patients with CKD with residual proteinuria (median protein excretion, 1.9 [IQR, 0.8-3.1] g/d; mean age, 50±13 [SD] years; creatinine clearance, 69 [IQR, 50-110] mL/min). PREDICTOR: Plasma carboxy-terminal FGF-23 levels. OUTCOMES: Difference in residual proteinuria at the end of the regular-sodium versus low-sodium study period. Residual proteinuria during the low-sodium diet period adjusted for proteinuria during the regular-sodium diet period. RESULTS: Higher baseline FGF-23 level was associated with reduced antiproteinuric response to dietary sodium restriction (standardized ß=-0.46; P=0.001; model R(2)=0.71). For every 100-RU/mL increase in FGF-23 level, the antiproteinuric response to dietary sodium restriction was reduced by 10.6%. Higher baseline FGF-23 level was a determinant of more residual proteinuria during the low-sodium diet (standardized ß=0.27; P=0.003) in linear regression analysis adjusted for baseline proteinuria (model R(2)=0.71). There was no interaction with creatinine clearance (P interaction=0.5). Baseline FGF-23 level did not predict changes in systolic or diastolic blood pressure upon intensified antiproteinuric treatment. LIMITATIONS: Observational study, limited sample size. CONCLUSIONS: FGF-23 levels are associated independently with impaired antiproteinuric response to sodium restriction in addition to RAAS blockade. Future studies should address whether FGF-23-lowering strategies may further optimize proteinuria reduction by RAAS blockade combined with dietary sodium restriction.

Evaluation of the effects of a therapeutic renal diet to control proteinuria in proteinuric non-azotemic dogs treated with benazepril.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are currently used to control proteinuria in dogs with chronic kidney disease. Renal diets (RDs) have beneficial effects in the management of azotemic dogs, but its role in proteinuric non-azotemic (PNAz) dogs has been poorly documented. HYPOTHESIS: Administration of a RD to PNAz dogs treated with benazepril (Be) improves proteinuria control compared with the administration of a maintenance diet (MD). ANIMALS: Twenty-two PNAz (urine protein/creatinine ratio [UPC] >1) dogs. METHODS: Randomized open label clinical trial design. Dogs were assigned to group-MD (5.5 g protein/100 kcal ME)/Be or to group-RD (3.7 g protein/100 kcal ME)/Be group during 60 days. Dogs with serum albumin (Alb) <2 g/dL received aspirin (1 mg/kg/12 hours). A physical examination, systolic blood pressure (SBP) measurement, complete blood count (CBC), biochemistry panel, urinalysis, and UPC were performed at day 0 (D0) and day 60 (D60). RESULTS: At D0, there were no significant differences between groups in the evaluated variables. During the study, logUPC (geometric mean (95% CI) and SBP (mean±SD mmHg) significantly decreased (paired t-test, P = 0.001) in Group-RD (logUPC(D0) = 3.16[1.9-5.25]; UPC(D60) = 1.20 [0.59-2.45]; SBP(D0) = 160 ± 17.2; SBP(D60) = 151 ± 15.8), but not in Group-MD (UPC(D0) = 3.63[2.69-4.9]; UPC(D60) = 2.14 [0.76-6.17]; SBP(D0) = 158 ± 14.7; SBP(D60) = 153 ± 11.5). However, RM-ANOVA test did not confirm that changes were consequence of dietary modification. Weight and Alb concentration did not change significantly in any group. CONCLUSION AND CLINICAL RELEVANCE: The administration of a RD to PNAz dogs treated with Be might help to control proteinuria and SBP compared with the administration of a MD, without inducing clinically detectable malnutrition, but more studies are warranted.

Dietary fat modification in patients with chronic kidney disease: n-3 fatty acids and beyond.

Replacement of dietary saturated fat with unsaturated fat has been recommended for prevention of cardiovascular disease (CVD) in the general population. Less is known of the health risks in individuals with chronic kidney disease (CKD), of a diet with an unhealthy fat profile, in general characterized by insufficient polyunsaturated fatty acids (PUFA) and excess satu-rated fatty acids (SFA). The dietary intake of PUFA, both the n-3 and n-6 subfamilies, is increasingly gaining attention in CKD, owing to its broad cardioprotective effects. Conversely, dietary SFA may promote CVD in this vulnerable population. This review discusses the potential benefits of dietary fat modification in CKD patients, including plausible effects on renal function, albuminuria, lipoproteins, nutritional status, inflammation, thrombosis and clinical outcomes. Increasing evidence supports the concept that n-3 PUFA might have therapeutic potential in reducing proteinuria in CKD and reducing triglycerides and inflammation in dialysis patients. In addition, emerging evidence suggests that linoleic acid, a major n-6 PUFA derived from vegetable oils, may be beneficial for a number of CVD risk factors. Increased consumption of oily fish as part of plant-based diets with low content of SFA is likely to benefit patients who have CKD, or are at risk of developing CKD. Such recommendations are in line with the concept of a healthy "Mediterranean diet" and are in line with current dietary recommendations for CVD prevention in the community.

Attenuation of the activated mammalian target of rapamycin pathway might be associated with renal function reserve by a low-protein diet in the rat remnant kidney model.

The mammalian target of rapamycin (mTOR), a regulator of cellular protein synthesis and cell growth, plays an important role in the progression of renal hypertrophy and renal dysfunction in experimental chronic kidney disease models. Because the mTOR activity is regulated by nutrients including amino acids, we tested the hypothesis that the renoprotective effect of a low-protein diet (LPD) might be associated with the attenuation of the renal mTOR pathway. In this study, 5/6 nephrectomized rats were fed an LPD or a normal protein diet (NPD), and a number of rats that were fed an NPD received rapamycin (1.0 mg kg⁻¹ d⁻¹), a specific inhibitor of mTOR. After 6 weeks, renal tissue was collected to evaluate the activity of the mTOR pathway and histologic changes. The phosphorylation of p70S6k, a kinase in the downstream of mTOR, was significantly higher in the NPD-fed rats that showed progressive renal dysfunction than in the sham-operated rats (NPD). The LPD attenuated the excessive phosphorylation of p70S6k concomitant with reduced proteinuria and improved renal histologic changes in the 5/6 nephrectomized rats. The effects of the LPD were similar to the effects of rapamycin. The expression of phosphorylated p70S6k was significantly correlated with proteinuria (r² = 0.63, P < .001), the glomerular area (r² = 0.60, P < .001), and the number of phosphorylated Smad2-positive cells in the glomerulus (r² = 0.26, P < .05) of these rats. These results suggest that the preventive effect of an LPD on the progression of renal failure is associated with attenuation of the activated mTOR/p70S6k pathway in the rat remnant kidney model.

Impact of vitamin D on chronic kidney diseases in non-dialysis patients: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Recent studies have supported a role for both newer and more established vitamin D compounds in improving proteinuria, although systematic evaluation is lacking. Furthermore, concerns remain regarding the influence of vitamin D on the progression of renal function. We analyzed the efficacy and safety of vitamin D in non-dialysis patients and compared the use of newer versus established vitamin D compounds by performing a meta-analysis of randomized controlled trials. DESIGN: A literature search of PubMed (1975 to September, 2012), EMBASE.com (1966 to September, 2012) and Ovid EBM Reviews (through September, 2012) was conducted. RESULTS: Eighteen studies were eligible for final inclusion; of these, six explored the effects of vitamin D on proteinuria, twelve studied the effects of supplementation on renal function, and fifteen discussed the incidence of hypercalcemia. Compared to the placebo or no interference, both the newer and established vitamin D sterols reduced proteinuria to a similar extent (RR, 2.00; 95% CI, 1.42 to 2.81). No decrease in the glomerular filter rate was observed (SMD, -0.10; 95%CI, -0.24 to 0.03), and the risk for dialysis initiation was 1.48 (95% CI, 0.54 to 4.03) with vitamin D treatment. Additionally, there was an increased risk of hypercalcemia for patients treated with either newer or established vitamin D compounds as compared with the controls (RR, 4.78; 95% CI, 2.20 to 10.37). The head-to-head studies showed no differences in the effects of either newer or established compounds on proteinuria or the risk of hypercalcemia. No serious adverse events were associated with the administration of vitamin D. CONCLUSIONS: Vitamin D therapy appears to decrease proteinuria and have no negative influence on renal function in non-dialysis patients. But the occurrence of hypercalcemia should be evaluated when vitamin D is provided. No superiority for newer versus established vitamin D analogue is found.

Amelioration of circulating lipoprotein profile and proteinuria in a patient with LCAT deficiency due to a novel mutation (Cys74Tyr) in the lid region of LCAT under a fat-restricted diet and ARB treatment.

Familial lecithin-cholesterol acyltransferase (LCAT) deficiency is a hereditary disease characterized by an abnormal lipid profile, corneal opacity, anemia and progressive renal disease. We report a patient with complete loss of LCAT activity due to a novel lcat gene mutation of Cys74Tyr in the lid region of LCAT protein. Esterification of cholesterol in this patient was disturbed by disruption of a substrate binding loop of Cys50-Cys74 in LCAT protein. She had progressive renal dysfunction, proteinuria, corneal opacity, anemia and an abnormal lipid profile. Her serum lipids showed a significant increase in abnormal lipoproteins at the original position in agarose gel electrophoresis and VLDL-cholesterol, and a severe decrease in serum HDL-cholesterol. Lipoprotein analyzes also revealed the presence of an abnormal midband lipoprotein, and a maturation disturbance of HDL particles. Renal function and proteinuria improved following the adoption of a fat-restricted diet and administration of an angiotensin II receptor blocker. The abnormal lipoproteins also decreased after this treatment.

[Comparison of the effects of alpha-keto/ amino acid supplemented low protein diet and diabetes diet in patients with diabetic nephropathy].

OBJECTIVE: To investigate if a-keto/amino acid supplemented low protein diet can slow down the progression of diabetic nephrophathy in comparison with non-supplemented diabetes diet. METHODS: A prospective, randomized, controlled clinical study was conducted. Twenty three cases of type 2 diabetic nephropathy in IV stage were randomly divided into alpha-keto/amino acid supplemented diet group (trial group) and conventional diabetes diet group (control group), The treatment duration was 52 weeks. 24 h urine protein was measured at 0, 12, 20, 36 and 52 weeks. Before and after the 52 weeks treatment, all the patients received the measurement of glomerular filtration rate (GFR), blood glucose, blood lipids, inflammatory markers, as well as nutritional status. RESULTS: After the treatment for 20, 36, 52 weeks, mean 24 h urine protein decreased significantly in trial groups (P < 0.05), and 24 h urine protein in trial group were significantly decreased (P < 0.05) compared with control group in 20 weeks after treatment. Either in trial group or in control group, GFR remained relatively stable during the observation period. Nutrition status, inflammatory markers, and serum calcium, phosphorus levels between the two groups were no significantly difference. The adverse events experienced by the patients in trial group were similar and consistent with the patients underlying renal diseases. CONCLUSION: Alpha-keto/amino acid can reduce proteinuria more effectively, while improve renal function and nutritional status in diabetic nephropathy patients with well-toleration.