Dietary counseling, meal patterns, and diet quality in patients with type 2 diabetes mellitus with/without chronic kidney disease.

BACKGROUND: Aim to this study is to investigate the association of Dietary Counseling, Meal Patterns, and Diet Quality (DietQ) in Patients with Type 2 Diabetes Mellitus (T2DM) with/without chronic kidney disease (CKD) in primary healthcare. METHODS: Cross-sectional study acquired data on dietary counseling and meal patterns by direct interview with a food-frequency questionnaire and one 24-h food-recall. The Healthy Eating Index (HEI) was used to classify DietQ ["good" DietQ (GDietQ, score ≥ 80) and "poor" DietQ (PDietQ, score < 80)]. PARTICIPANTS/SETTING: This study included 705 patients with T2DM: 306 with normal kidney function; 236 with early nephropathy, and 163 with overt nephropathy (ON). STATISTICAL ANALYSES PERFORMED: Multivariate linear-regression models for predicting HEI and χ2 tests for qualitative variables and one-way ANOVA for quantitative variables were employed. Mann-Whitney U and independent Student t were performed for comparisons between GDietQ and PDietQ. RESULTS: Only 18 % of the population was classified as GDietQ. Patients with ON and PDietQ vs. with GDietQ received significantly less dietary counseling from any health professional in general (45 % vs 72 %, respectively), or from any nutrition professional (36 % vs. 61 %, respectively). A better HEI was significantly predicted (F = 42.01; p = 0.0001) by lower HbA1C (ß -0.53, p = 0.0007) and better diet diversity (ß 8.09, p = 0.0001). CONCLUSIONS: Patients with more advanced stages of CKD had less nutritional counseling and worse dietary patterns, as well as more frequent PDietQ. Our findings reinforce the need for dietitians and nutritionists in primary healthcare to provide timely nutritional counseling.

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.

Dietary resistant starch enhances immune health of the kidney in diabetes via promoting microbially-derived metabolites and dampening neutrophil recruitment.

BACKGROUND: Dietary-resistant starch is emerging as a potential therapeutic tool to limit the negative effects of diabetes on the kidneys. However, its metabolic and immunomodulatory effects have not yet been fully elucidated. METHODS: Six-week-old db/db mice were fed a diet containing 12.5% resistant starch or a control diet matched for equivalent regular starch for 10 weeks. db/m mice receiving the control diet were utilised as non-diabetic controls. Freshly collected kidneys were digested for flow cytometry analysis of immune cell populations. Kidney injury was determined by measuring albuminuria, histology, and immunohistochemistry. Portal vein plasma was collected for targeted analysis of microbially-derived metabolites. Intestinal histology and tight junction protein expression were assessed. RESULTS: Resistant starch limited the development of albuminuria in db/db mice. Diabetic db/db mice displayed a decline in portal vein plasma levels of acetate, propionate, and butyrate, which was increased with resistant starch supplementation. Diabetic db/db mice receiving resistant starch had a microbially-derived metabolite profile similar to that of non-diabetic db/m mice. The intestinal permeability markers lipopolysaccharide and lipopolysaccharide binding protein were increased in db/db mice consuming the control diet, which was not seen in db/db mice receiving resistant starch supplementation. Diabetes was associated with an increase in the kidney neutrophil population, neutrophil activation, number of C5aR1+ neutrophils, and urinary complement C5a excretion, all of which were reduced with resistant starch. These pro-inflammatory changes appear independent of fibrotic changes in the kidney. CONCLUSIONS: Resistant starch supplementation in diabetes promotes beneficial circulating microbially-derived metabolites and improves intestinal permeability, accompanied by a modulation in the inflammatory profile of the kidney including neutrophil infiltration, complement activation, and albuminuria. These findings indicate that resistant starch can regulate immune and inflammatory responses in the kidney and support the therapeutic potential of resistant starch supplementation in diabetes on kidney health.

Adherence to a Mediterranean diet is associated with a lower risk of diabetic kidney disease among individuals with hyperglycemia: a prospective cohort study.

BACKGROUND: Type 2 diabetes is associated with a variety of complications, including micro- and macrovascular complications, neurological manifestations and poor wound healing. Adhering to a Mediterranean Diet (MED) is generally considered an effective intervention in individuals at risk for type 2 diabetes mellitus (T2DM). However, little is known about its effect with respect to the different specific manifestations of T2DM. This prompted us to explore the effect of MED on the three most significant microvascular complications of T2DM: diabetic retinopathy (DR), diabetic kidney disease (DKD), and vascular diabetic neuropathies (DN). METHODS: We examined the association between the MED and the incidence of these microvascular complications in a prospective cohort of 33,441 participants with hyperglycemia free of microvascular complications at baseline, identified in the UK Biobank. For each individual, we calculated the Alternate Mediterranean Diet (AMED) score, which yields a semi-continuous measure of the extent to which an individual's diet can be considered as MED. We used Cox proportional hazard models to analyze hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics, lifestyle factors, medical histories and cardiovascular risk factors. RESULTS: Over a median of 12.3 years of follow-up, 3,392 cases of microvascular complications occurred, including 1,084 cases of diabetic retinopathy (DR), 2,184 cases of diabetic kidney disease (DKD), and 632 cases of diabetic neuropathies (DN), with some patients having 2 or 3 microvascular complications simultaneously. After adjusting for confounders, we observed that higher AMED scores offer protection against DKD among participants with hyperglycemia (comparing the highest AMED scores to the lowest yielded an HR of 0.79 [95% CIs: 0.67, 0.94]). Additionally, the protective effect of AMED against DKD was more evident in the hyperglycemic participants with T2DM (HR, 0.64; 95% CI: 0.50, 0.83). No such effect, however, was seen for DR or DN. CONCLUSIONS: In this prospective cohort study, we have demonstrated that higher adherence to a MED is associated with a reduced risk of DKD among individuals with hyperglycemia. Our study emphasizes the necessity for continued research focusing on the benefits of the MED. Such efforts including the ongoing clinical trial will offer further insights into the role of MED in the clinical management of DKD.

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.

Nutritional Strategies against Diabetic Nephropathy: Insights from Animal Studies and Human Trials.

Diabetic nephropathy (DN), defined as continuously elevated urinary albumin and a diminished estimated glomerular filtration rate, is a serious complication of both type 1 diabetes and type 2 diabetes and is the main cause of end-stage kidney disease. Patients with end-stage renal disease require chronic kidney dialysis and/or a kidney transplantation. Research highlights the role of diet in modulating specific signaling pathways that are instrumental in the progression of DN. Nutrient-sensitive pathways, affected by nutritional compounds and dietary components, offer a novel perspective on the management of DN by influencing inflammation, oxidative stress, and nutrient metabolism. Animal models have identified signaling pathways related to glucose metabolism, inflammation responses, autophagy, and lipid metabolism, while human population studies have contributed to the clinical significance of designing medical and nutritional therapies to attenuate DN progression. Here, we will update recent progress in research into the renoprotective or therapeutic effects of nutritional compounds, and potential nutrition-modulated pathways.

Effects of dietary intervention on diabetic nephropathy: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials.

Objective: To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). Methods: We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN incidence. The literature was searched via PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as "high", "moderate", "low" or "very low" quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories. Results: We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles. Moderate-quality evidence suggested that probiotic supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in DN patients. Low-quality evidence indicated that probiotic supplementation significantly improved the serum creatinine concentration, urinary albumin-creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low-quality evidence suggested that a salt restriction diet could significantly improve the creatinine clearance rate (CrCl) in patients with DN. Low-quality evidence suggested that vitamin D supplementation could significantly improve the UACR in patients with DN. In addition, low-quality evidence has indicated that soy isoflavone supplementation could significantly improve BUN, FBG, total cholesterol (TC), triglyceride (TG) and LDL-C levels in patients with DN. Furthermore, low-quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low-quality evidence suggested that supplementation with antioxidant vitamins could significantly improve the serum creatinine concentration, systolic blood pressure, and HbA1c level in patients with DN. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence. Conclusion: Moderate to low amounts of evidence suggest that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, or salt-restricted diets may significantly improve clinical outcomes in patients with DN. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024512670.

Nutrient quality in dietary therapy for diabetes and diabetic kidney disease.

Dietary therapy is crucial for diabetes care with the aim of preventing the onset and progression of diabetes and its complications. The traditional approach to dietary therapy for diabetes has primarily focused on restricting the intake of the three major nutrients and rigorously controlling blood glucose levels. However, advancements in nutritional science have shown that within the three major nutrients - carbohydrates, proteins and lipids - there exist multiple types, each with distinct impacts on type 2 diabetes and its complications, sometimes even showing conflicting effects. In light of this, the present review shifts its focus from the quantity to the quality of the three major nutrients. It aims to provide an overview of how the differences in nutrient quality can influence onset and progression of type 2 diabetes and diabetic kidney disease, highlighting the diverse effects and, at times, contradictory impacts associated with each nutrient type.

The case for a ketogenic diet in the management of kidney disease.

Ketogenic diets have been widely used for weight loss and are increasingly used in the management of type 2 diabetes. Despite evidence that ketones have multiple positive effects on kidney function, common misconceptions about ketogenic diets, such as high protein content and acid load, have prevented their widespread use in individuals with impaired kidney function. Clinical trial evidence focusing on major adverse kidney events is sparse. The aim of this review is to explore the effects of a ketogenic diet, with an emphasis on the pleiotropic actions of ketones, on kidney health. Given the minimal concerns in relation to the potential renoprotective effects of a ketogenic diet, future studies should evaluate the safety and efficacy of ketogenic interventions in kidney disease.

Can Probiotics Supplementation Improve Glycemic and Renal Status in Diabetic Nephropathy? A Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND & AIM: This meta-analysis was performed to quantify the effects of probiotics on renal and glycemic biomarkers among patients with Diabetic Nephropathy (DN). METHODS: Electronic databases were searched on May 10, 2020. All trials that investigated the effect of probiotics on serum glycemic markers (Fasting Plasma Glucose [FPG], Hemoglobin A1C, Insulin, Homeostatic Model Assessment-Insulin Resistance [HOMA-IR], and Quantitative Insulin Sensitivity Check Index [QUICKI]), and renal status markers (Creatinine [Cr], Blood Urea Nitrogen [BUN], and Glomerular Filtration Rate [GFR]) were included. RESULTS: Seven trials that included 340 patients were identified for analysis. The results indicated that probiotics significantly reduced FPG (WMD= -19.08 mg/dl; 95% CI= -32.16, -5.99; P=0.004), HOMA-IR (WMD= -1.88; 95% CI= -3.63, -0.12; P=0.036), and Cr (WMD= -0.18 mg/dl; 95% CI= -0.26, -0.09; P<0.001) levels in DN patients; however, there was no statistically significant change in Hemoglobin A1C, Insulin, QUICKI, BUN, and GFR. CONCLUSION: This meta-analysis supports the potential use of probiotics in the improvement of some glycemic and renal biomarkers in patients with DN.

Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology.

Diabetic kidney disease (DKD) is a critical complication associated with diabetes; however, there are only a few animal models that can be used to explore its pathogenesis. In the present study, we established a mouse model of DKD using a technique based on the Developmental Origins of Health and Disease theory, i.e., by manipulating the embryonic environment, and investigated whether a dietary intervention could ameliorate the model's pathology. Two-cell embryos were cultured in vitro in α-minimum essential medium (MEM; MEM mice) or in standard potassium simplex-optimized medium (KSOM) as controls (KSOM mice) for 48 h, and the embryos were reintroduced into the mothers. The MEM and KSOM mice born were fed a high-fat, high-sugar diet for 58 days after they were 8 weeks old. Subsequently, half of the MEM mice and all KSOM mice were fed a diet containing rice powder (control diet), and the remaining MEM mice were fed a diet containing barley powder (barley diet) for 10 weeks. Glomerulosclerosis and pancreatic exhaustion were observed in MEM mice, but not in control KSOM mice. Renal arteriolar changes, including intimal thickening and increase in the rate of hyalinosis, were more pronounced in MEM mice fed a control diet than in KSOM mice. Immunostaining showed the higher expression of transforming growth factor beta (TGFB) in the proximal/distal renal tubules of MEM mice fed a control diet than in those of KSOM mice. Pathologies, such as glomerulosclerosis, renal arteriolar changes, and higher TGFB expression, were ameliorated by barley diet intake in MEM mice. These findings suggested that the MEM mouse is an effective DKD animal model that shows glomerulosclerosis and renal arteriolar changes, and barley intake can improve these pathologies in MEM mice.

Safety and efficacy of very low carbohydrate diet in patients with diabetic kidney disease-A randomized controlled trial.

INTRODUCTION: There is limited data on the effects of low carbohydrate diets on renal outcomes particularly in patients with underlying diabetic kidney disease. Therefore, this study determined the safety and effects of very low carbohydrate (VLCBD) in addition to low protein diet (LPD) on renal outcomes, anthropometric, metabolic and inflammatory parameters in patients with T2DM and underlying mild to moderate kidney disease (DKD). MATERIALS AND METHODS: This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages. RESULTS: The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p = <0.001) and improvements in body fat percentages. WC was significantly reduced in the VLCBD group, even after adjustments to age, HbA1c, weight and creatinine changes. Both dietary interventions were well received with no reported adverse events. CONCLUSION: This study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.

Role of dietary modifications in the management of type 2 diabetic complications.

Diabetes is a chronic metabolic disorder with a high rate of morbidity and mortality. Insufficient insulin secretion and insulin action are two major causes for the development of diabetes, which is characterized by a persistent increase in blood glucose level. Diet and sedentary life style play pivotal role in development of vascular complications in type 2 diabetes. Dietary modification is associated with a reprogramming of nutrient intake, which are proven to be effective for the management of diabetes and associated complications. Dietary modifications modulate various molecular key players linked with the functions of nutrient signalling, regulation of autophagy, and energy metabolism. It activates silent mating type information regulation 2 homolog1 (SIRT1) and AMP-activated protein kinase (AMPK). AMPK mainly acts as an energy sensor and inhibits autophagy repressor Mammalian target of rapamycin (mTOR) under nutritional deprivation. Under calorie restriction (CR), SIRT1 gets activated directly or indirectly and plays a central role in autophagy via the regulation of protein acetylation. Dietary modification is also effective in controlling inflammation and apoptosis by decreasing the level of pro-inflammatory cytokines like nuclear factor kappa- beta (NF-kß), tissue growth factor-beta (TGF-ß), tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). It also improves glucose homeostasis and insulin secretion through beta cell regeneration. This indicates calorie intake plays a crucial role in the pathogenesis of type 2 diabetes-associated complications. The present review, emphasizes the role of dietary modifications in diabetes and associated complications.

Therapeutic application of nutraceuticals in diabetic nephropathy: Current evidence and future implications.

Diabetes mellitus (DM) is a common metabolic disease which may cause several complications, such as diabetic nephropathy (DN). The routine medical treatments used for DM are not effective enough and have many undesirable side effects. Moreover, the global increased prevalence of DM makes researchers try to explore potential complementary or alternative treatments. Nutraceuticals, as natural products with pharmaceutical agents, have a wide range of therapeutic properties in various pathologic conditions such as DN. However, the exact underlying mechanisms have not been fully understood. The purpose of this review is to summarize recent findings on the effect of nutraceuticals on DN.

Anti-Inflammatory and Antioxidative Properties of Isoflavones Provide Renal Protective Effects Distinct from Those of Dietary Soy Proteins against Diabetic Nephropathy.

SCOPE: Dietary soy reportedly protects from diabetic nephropathy (DN), but its active components and mechanism of action remain unknown. METHODS AND RESULTS: In this study, KKAy mice are fed three types of diet: Dietary soy isoflavones with soy protein (Soy-IP) diet, reduced isoflavones soy protein (RisoP), and oral administration of isoflavones aglycones (IsoAgc). Albuminuria and glycosuria are decreased only in the soy-IP group. The risoP group show reduced expansion of mesangial matrix and renal fibrosis, the IsoAgc group show renal anti-fibrotic and anti-inflammatory effects; however, these renal pathological changes are repressed in the soy-IP group, suggesting the distinct protective roles of soy protein or isoflavones in DN. The isoflavone genistein has a better inhibitory effect on the inflammatory response and cellular interactions in both mouse tubular cells and macrophages when exposed to high glucose and albumin (HGA). Genistein also represses HGA-induced activator protein 1 activation and reactive oxidases stress generation, accompanied by reduced NADPH oxidase (NOX) gene expression. Finally, diabetic mice show a decrease in lipid peroxidation levels in both plasma and urine, along with lower NOXs gene expression. CONCLUSION: The data elucidate the detailed mechanism by which isoflavones inhibit renal inflammation and provide a potential practical adjunct therapy to restrict DN progression.

Aspartic acid supplementation ameliorates symptoms of diabetic kidney disease in mice.

Diabetic kidney disease (DKD) is among the most common and serious complications of both type 1 and type 2 diabetes. In this study, we used KK/Ta-Ins2Akita (KK-Akita) mice as a model of DKD and KK/Ta (KK) mice as controls to identify novel factors related to the development/progression of DKD. Capillary electrophoresis coupled with mass spectrometry analysis revealed that circulating Asp (l-aspartic acid) levels in diabetic KK-Akita mice tend to be lower than those in control KK mice. Therefore, we evaluated the effect of Asp supplementation to prevent the progression of DKD in KK-Akita mice. Mice were divided into three groups: (a) untreated KK mice (Control group), (b) untreated KK-Akita mice (DKD group), and (c) treated (double-volume Asp diet) KK-Akita mice (Tx group). Kidney sections were stained with fluorescein isothiocyanate-labeled lectins, wheat germ agglutinin (WGA), and anti-endothelial nitric oxide synthase (eNOS) antibody for evaluation of endothelial surface layer (ESL) and NO synthesis. The mesangial area and glomerular size in the DKD group were significantly larger than those in the Control group; however, there was no significant difference in those between the DKD and Tx groups. Albuminuria, the ratio of foot process effacement, and thickness of glomerular basement membrane in the Tx group were significantly lower than those in the DKD group. Furthermore, the expression levels of glomerular WGA and microvascular eNOS in the Tx group improved significantly and approached the level in the Control group. In conclusion, the improvement of albuminuria in the Tx group may be caused by the reduction of oxidative stress in the kidneys, which may lead to the subsequent improvement of glomerular ESL.

Methionine abrogates the renoprotective effect of a low-protein diet against diabetic kidney disease in obese rats with type 2 diabetes.

Dietary interventions, including a low-protein diet (LPD) and methionine (Met) restriction, have shown longevity, anti-aging and metabolic health effects. We previously reported that the LPD has a renoprotective effect against diabetic kidney disease (DKD) in rats with type 2 diabetes and obesity. However, it is unclear whether the beneficial effect of the LPD is mediated by low-Met intake or how Met is related to the pathogenesis for DKD. We herein show that the addition of Met with the LPD abrogates the beneficial effects induced by the LPD such as anti-oxidative stress, anti-inflammation and anti-fibrosis, in diabetic kidney. Additionally, the increased levels of S-adenosylmethionine (SAM) in renal tubular cells, which are associated with the reduced expression of glycine N-methyltransferase (Gnmt) and non-restricted Met intake, contributes to the activation of mechanistic target of rapamycin complex 1 (mTORC1) and impaired autophagy, in diabetic kidney. Moreover, starvation-induced autophagy was suppressed in renal cortex of Gnmt null mice and amino acid free-induced autophagy was also suppressed by administration of SAM in cultured HK-2 cells. A LPD could exert a renoprotective effect through the suppression of mTORC1 and restoration of autophagy, which is associated with reduced levels of SAM due to low-Met intake, in diabetic kidney.

Are low-carbohydrate diets safe in diabetic and nondiabetic chronic kidney disease?

Diabetes mellitus and obesity both contribute to chronic kidney disease (CKD) and diabetic kidney disease (DKD), and they can accelerate the loss of kidney function. Dietary intake can potentially have wide-reaching effects on the risk of CKD/DKD and their progression by reducing weight and blood pressure, improving glycemic control, reducing hyperfiltration, and modulating inflammation. Low-carbohydrate (LC) diets can reduce weight and improve glycemic control, but the relatively higher protein content also raises concern in CKD/DKD. Empiric evidence supporting the kidney-related benefits or risks of LC diets is needed to understand the balance of these potential harms and benefits for patients with DKD and is the subject of our review.

Effects of dietary protein intake on renal outcome and mortality in patients with advanced diabetic nephropathy.

BACKGROUND: The difficulty of adhering to a low-protein diet is a serious limitation of randomized controlled trials aimed at validating the efficacy of this therapy. In this observational study of patients with diabetic nephropathy, we examined the association of dietary protein intake (DPI) with renal outcome and mortality, taking into account the nutritional status. METHODS: We conducted a single-center historical cohort study of 449 adult Japanese patients with type 2 diabetes and the urinary albumin-to-creatinine ratio of ≥ 300 mg/g or estimated glomerular filtration rate of < 30 mL/min/1.73 m2. DPI was estimated with a formula using nitrogen levels in spot urine and body mass index. Malnutrition was defined as the Geriatric Nutritional Risk Index of ≤ 98. The primary and secondary endpoints were renal replacement therapy (RRT) initiation and mortality before RRT initiation, respectively. The Fine and Gray subdistribution hazard model was used to determine the relative effects of DPI on the respective endpoint. RESULTS: Decreased DPI was associated with lower incidence of RRT with an adjusted hazard ratio of 0.81 (95% confidence interval: 0.72-0.92, p < 0.001). The interaction between DPI and nutritional status with respect to mortality was significant (p interaction = 0.047). Decreased DPI was a risk factor for mortality in patients with malnutrition (p = 0.009) but not in those without malnutrition (p = 0.559). CONCLUSIONS: In patients with type 2 diabetic nephropathy, lower DPI was associated with lower incidence of RRT initiation, suggesting beneficial effects of a low-protein diet on kidneys. Conversely, lower DPI might lead to increased mortality in patients with malnutrition.