Benefits of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise on albuminuria in diabetic and non-diabetic Japanese populations.

BACKGROUND: Albuminuria is a biomarker for chronic kidney disease and an independent predictor of cardiovascular and all-cause mortality. A recent meta-analysis concluded that these risks increase with urinary albumin concentration, even when below the microalbuminuria threshold. Thus, minimizing urinary albumin may be a valuable therapeutic goal regardless of disease status. METHODS: We investigated the benefits and safety of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise for reducing albuminuria in 295 normoalbuminuric or microalbuminuric Japanese adults, including 30 with type 2 diabetes mellitus (T2DM), 104 with metabolic syndrome (MS), and 145 with hypertension (HT). RESULTS: In the study population, the urinary albumin:creatinine ratio (UACR) was reduced significantly (ΔUACR -3.8 ± 16.8 mg/g, P < 0.001) with no change in estimated glomerular filtration rate (eGFR) (ΔeGFR -0.4 ± 7.4 mL/min/1.73 m(2), P = 0.343). The reduction in UACR was associated with decreased fasting plasma glucose (P < 0.05). The UACR was also reduced in the T2DM, MS, and HT groups with no change in eGFR. Reduced UACR was associated with decreased fasting plasma glucose in the MS group and decreased systolic blood pressure in the HT group. The UACR was also reduced in 46 subjects using renin-angiotensin system inhibitors with no change in eGFR. CONCLUSIONS: Our 12-week lifestyle modification program reduced UACR, maintained eGFR, and improved multiple fitness findings in Japanese subjects including T2DM, MS, and HT patients.

Effects of pitavastatin add-on therapy on chronic kidney disease with albuminuria and dyslipidemia.

BACKGROUND: In non-dialysis chronic kidney disease (CKD) patients with dyslipidemia, statin therapy is recommended to prevent cardiovascular complications. Dyslipidemia has been also shown to be an independent risk factor for the progression of CKD. However, it is still unclear whether statin therapy exerts an inhibitory effect on renal deterioration in CKD patients with dyslipidemia. The purpose of the present study was to examine possible therapeutic effects of statin add-on therapy on renal function as well as parameters of lipid and glucose metabolism, arterial stiffness and oxidative stress, in comparison to diet therapy, in CKD patients with dyslipidemia. METHODS: This study was a randomized, open-label, and parallel-group trial consisted of a 12-months treatment period in non-dialysis CKD patients with alubuminuria and dyslipidemia. Twenty eight patients were randomly assigned either to receive diet counseling alone (diet therapy group) or diet counseling plus pitavastatin (diet-plus-statin therapy group), to achieve the LDL-cholesterol (LDL-C) target of <100 mg/dl. RESULTS: The statin treatment by pitavastatin was well tolerated in all of the patients without any significant adverse events and the average dose of pitavastatin was 1.0 ± 0.0 mg daily after treatment. After the 12-months treatment period, LDL-C was significantly lower in the diet-plus-statin therapy group compared with the diet therapy group (diet vs diet-plus-statin: LDL-C, 126 ± 5 vs 83 ± 4 mg/dL, P < 0.001). On the other hand, the diet-plus-statin therapy did not significantly reduce albuminuria or delay the decline in eGFR compared with the diet therapy, and there was no relationship between the change in LDL-C and the change in eGFR or albuminuria. However, diet therapy as well as diet-plus-statin therapy exerted similar lowering effects on the pentosidine levels (diet therapy group, baseline vs 12 months: 40 ± 4 vs 24 ± 3 ng/mL, P = 0.001; diet-plus-statin therapy, 46 ± 7 vs 34 ± 6 ng/mL, P = 0.008). Furthermore, the results of multivariate regression analysis indicated that the change in pentosidine was a significant contributor to the change in eGFR (ß = -0.536, P = 0.011). CONCLUSIONS: Although statin add-on therapy did not show additive renal protective effects, the diet therapy as well as the diet-plus-statin therapy could contribute to the reduction in plasma pentosidine in CKD patients with albuminuria and dyslipidemia.

High protein weight loss diets in obese subjects with type 2 diabetes mellitus.

BACKGROUND AND AIM: Diets where carbohydrate has been partially exchanged for protein have shown beneficial changes in persons with type 2 diabetes but no studies have enrolled people with albuminuria. We aim to determine if a high protein to carbohydrate ratio (HPD) in an energy reduced diet has a beneficial effect on metabolic control and cardiovascular risk factors without negatively affecting renal function. METHOD AND RESULTS: Adult, overweight participants with type 2 diabetes, with albuminuria (30-600 mg/24 h or an albumin-to-creatinine ratio of 3.0-60 mg/mmol), and estimated GFR of >40 ml/min/1.73 m(2) were enrolled. Participants were randomized to an HPD or an SPD. Protein:fat:carbohydrate ratio was 30:30:40% of energy for the HPD and 20:30:50% for the SPD. Main outcomes were renal function, weight loss, blood pressure, serum lipids and glycaemic control. We recruited 76 volunteers and 45 (35 men and 10 women) finished. There were no overall changes in renal function at 12 months and no significant differences in weight loss between groups (9.7 ± 2.9 kg and 6.6 ± 1.4 kg HPD and SPD group respectively; p = 0.32). Fasting blood glucose decreased significantly with no treatment effect. The decrease in HbA1c differed between treatments at 6 months (HPD -0.9 vs. SPD -0.3%; p = 0.039) but not at 12 months. HDL increased significantly with no treatment effects. There were no changes in LDL or blood pressure overall but DBP was lower in the HPD group (p = 0.024) at 12 months. CONCLUSION: Weight loss improved overall metabolic control in this group of well controlled participants with type 2 diabetes regardless of diet composition.

Low-protein diet improves blood and urinary glucose levels and renal manifestations of diabetes in C57BLKS-db/db mice.

PURPOSE: Dietary protein content is related clinically to the development of diabetic nephropathy. Here, we investigated how dietary protein content (12-24 % energy) within the range used by humans affected renal manifestations including the expressions of genes involved in the renin-angiotensin (RA) system in control and diabetic mice. Moreover, we examined the effects of dietary protein content on HbA1c and urinary glucose. METHODS: Control (CT) and leptin receptor-deficient obese (db) mice, 5 weeks old, were fed the diets below. Under ad libitum conditions, mice were fed 12, 18, and 24 % energy from protein (L-, M-, and H-diets) for 8 weeks. Under pair-feeding conditions, db mice were supplied H-diet (db-Hp) to the equivalent energy to that consumed by db-L mice. Renal manifestations and values related to glucose and insulin were examined biochemically and pathologically. RESULTS: Under ad libitum conditions, db mice consumed food and water dose dependently of the dietary protein content, although they were consumed similarly by CT mice. CT-L mice showed lower urinary albumin and kidney weight, in association with lower mRNA levels of angiotensinogen and renin, than CT-H mice. Under pair-feeding conditions, db-L mice showed a lower ratio of kidney/body weight, HbA1(C), and urinary glucose, and a higher ß-cell distribution rate in the pancreas than db-Hp mice. CONCLUSIONS: Low-protein intake in the range used by humans may relieve renal manifestations through the suppressed expression of genes in the renal RA system of CT mice. On the other hand, in db mice, low-protein intake improved hyperglycemia and the renal manifestations of diabetes.

Dietary Acid Load and Relationship with Albuminuria and Glomerular Filtration Rate in Individuals with Chronic Kidney Disease at Predialysis State.

The Western diet, characterized by excessive consumption of animal protein and reduced intake of vegetables and fruits, is also rich in sulfur, chlorine, and organic acids, which are the main sources of dietary acid load. A relationship between dietary acid load, renal function, and progression of chronic kidney disease has been demonstrated. Dietary modifications seem to contribute to a reduction in dietary acid load, and are associated with improved outcomes in individuals with chronic kidney disease (CKD). The aim of this paper was to review the existing evidence concerning the association between dietary acid load and renal function in nondialyzed individuals with CKD. A systematic review was conducted by gathering articles in electronic databases (MEDLINE/PubMed, Scopus, and Web of Science) from January 2018 to May 2021. Dietary acid load and GFR and/or albuminuria were analyzed. A total of 1078 articles were extracted, of which 5 met the inclusion criteria. Only one study found no statistically significant associations between the study variables. The remaining showed a negative association between dietary acid load and renal function. This systematic review confirmed the existence of an association between dietary acid load and renal function, with a high dietary acid load contributing to a decreased renal function.

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.

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.

The effects of dietary patterns on urinary albumin excretion: results of the Dietary Approaches to Stop Hypertension (DASH) Trial.

BACKGROUND: Dietary studies designed to decrease the urinary albumin excretion rate (AER) typically reduce protein by increasing lower protein plant foods and decreasing higher protein animal products. STUDY DESIGN: We evaluated AER while increasing protein intake in the Dietary Approaches to Stop Hypertension (DASH) Trial (randomized, parallel group, 8 week controlled feeding). SETTING & PARTICIPANTS: 378 individuals without diabetes with prehypertension or stage I hypertension. INTERVENTION: The DASH diet, 18% energy from protein, emphasizes, among other features, low-fat dairy products; and the fruit/vegetable (FV) and control diets, each with 15% energy from protein. OUTCOME: AER. MEASUREMENTS: We measured AER by using immunoassay and covariates at baseline and after 8 weeks. RESULTS: Baseline AER had a geometric mean value of 4.0 +/- 0.2 (SE) mg/24 h. In 285 participants with baseline AER less than 7 mg/24 h, AER was unchanged by diet treatment (geometric mean, 2.5 +/- 0.2 mg/24 h in the control diet, 3.0 +/- 0.2 mg/24 h in the FV diet, and 2.8 +/- 0.2 mg/24 h in the DASH diet). Conversely, in 93 participants with baseline AER of 7 mg/24 h or greater, end-of-feeding AER was lower in the FV diet (6.6 +/- 1.0 mg/24 h) than in the control (11.4 +/- 1.8 mg/24 h; P = 0.01) or DASH diets (11.7 +/- 1.6 mg/24 h; P = 0.005). The DASH and control diets were not different (P = 0.9). LIMITATIONS: Long-term AER change not studied. CONCLUSIONS: The decrease in AER after 8 weeks occurred in only those with high-normal baseline AER in the FV diet, in a pattern distinct from the blood pressure decrease. The DASH diet did not increase AER despite a 3% increase in energy from protein.

Enhanced Therapeutic Potency of Nanoemulsified Garlic Oil Blend Towards Renal Abnormalities in Pre-diabetic Rats.

The therapeutic potency of ultrasonic nanoemulsified garlic oil blend using a non-ionic surfactant (Tween 80) was assessed on pre-diabetic Wistar rats with microalbuminuria. The pre-diabetic condition was induced in male albino Wistar rats by supplementing high-fat diet. The prolonged period of the pre-diabetic state caused renal dysfunctioning, which was indicated by microalbuminuria. Treatment of pre-diabetic rats with nanoemulsified garlic oil blend significantly ameliorated the lipid profile (p < 0.001), urinary albumin (p < 0.01), microprotein (p < 0.001), urinary triglycerides (p < 0.01), serum triglycerides (p < 0.01), serum albumin (p < 0.05), and protein levels (p < 0.01) in comparison to treatment of pre-diabetic rats with garlic oil blend or atorvastatin. Similarly, histopathological investigations indicated a remarkable attenuation in the mesangial expansion and proliferation, glomerular and tubular basement membrane thickening, and the tubular lipid deposits on administering nanoemulsified garlic oil blend than garlic oil blend or atorvastatin. Moreover, nanoemulsified garlic oil blend significantly promoted renal podocin gene expression by 3.98-fold (p < 0.001) and attenuated increased urinary podocin level by 2.92-fold (p < 0.01). Thus, our study affirms that the efficacy of garlic oil blend was augmented upon nanoemulsification, which substantially ameliorated the renal abnormalities observed in the pre-diabetic condition than garlic oil blend or atorvastatin.

Long-term effect of a chicken-based diet versus enalapril on albuminuria in type 2 diabetic patients with microalbuminuria.

OBJECTIVE: In short-term studies, the replacement of red meat in the diet with chicken reduced the urinary albumin excretion rate (UAER) and improved lipid profile in type 2 diabetic patients with diabetic nephropathy. The present study sought to assess these effects over a long-term period, comparing the effects of a chicken-based diet (CD) versus enalapril on renal function and lipid profile in microalbuminuric type 2 diabetic patients. DESIGN: This was a randomized, open-label, controlled clinical trial with a follow-up of 1 year. SETTING: The trial involved outpatients with type 2 diabetes attending a clinic of the Division of Endocrinology at a tertiary-care hospital. PATIENTS: Twenty-eight microalbuminuric patients completed the study and were evaluated. INTERVENTIONS: Patients were randomized to an experimental diet (CD plus active placebo) or to treatment with enalapril (10 mg/day plus usual diet). MAIN OUTCOME MEASURES: The main outcome measure was UAER (according to immunoturbidimetry). Blood pressure, anthropometric indices, and compliance were also evaluated monthly. The glomerular filtration rate ((51)Cr-EDTA), and lipid, glycemic, and nutritional indices, were measured at baseline and quarterly. RESULTS: The UAER was reduced after CD (n = 13; from 62.8 [range, 38.4 to 125.1] to 49.1 [range, 6.2 to 146.5] microg/min; P < .001) and after enalapril (n = 15; from 55.8 [range, 22.6 to 194.3] to 23.1 [range, 4.0 to 104.9] microg/min; P < .001), and this was already significant at month 4. The reduction in UAER after CD (32%; 95% confidence interval, 6.7% to 57.6%) and after enalapril treatment (44.7%; 95% confidence interval, 28.3% to 61.1%; P = .366) were not significantly different. CONCLUSIONS: The CD and the angiotensin-converting enzyme inhibitor enalapril promoted a similar reduction of UAER in patients with type 2 diabetes and microalbuminuria in a 12-month follow-up period.

[Effect of a personalized diet in the metabolic control and renal function of patients with type 2 diabetes]. / Efecto de la dieta personalizada en el control metabólico y función renal de pacientes con diabetes tipo 2.

OBJECTIVE: to evaluate a personalized diet customize for present comorbidity, on metabolic control indicators and renal function. METHODS: a non-randomized clinical trial was conducted during a three-month period in a group of patients with microalbuminuria and in a group with macroalbuminuria. The patients received personalized dietary counseling customize to their comorbidity (obesity, hypertension, and dislypidemia). The effect of the diet was measured through metabolic control variables: body mass index (BMI), waist circumference, fasting glucose levels, glycated hemoglobin (HbA(1))c and lipids profile; the renal function variables were: glomerular filtration rate (GFR) and urine albumin excretion (UAE). Statistical analysis was done with t-paired test. RESULTS: thirty-nine patients were included (21 women and 18 men). After the intervention, the weight and waist circumference had significantly decreased (p = 0.01); the fasting glucose levels and HbA(1)c were significantly lower (p = 0.001). The HDL-cholesterol increased significantly (p = 0.009); UAE decreased significantly in patients with micro and macroalbuminuria; 123.0 +/- 73.4 to 105.3 +/- 61.3 mg/24-h; p = 0.040 and 1482.7 +/- 1200.6 to 1093.5 +/- 601.8 mg/24-h; p = 0.02. The GFR increased in both groups: 68.9 +/- 35.4 to 74.7 +/- 41.6 mL/min, p = 0.04; and 62.2 +/- 26.6 to 68.5 +/- 25.3 mL/min, p = 0.02. CONCLUSIONS: the dietary intervention improved the metabolic control and renal function in type 2 diabetes patients with comorbidity.

Dietary Salt Restriction in Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: A clear evidence on the benefits of reducing salt in people with chronic kidney disease (CKD) is still lacking. Salt restriction in CKD may allow better control of blood pressure (BP) as shown in a previous systematic review while the effect on proteinuria reduction remains poorly investigated. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the effects of low versus high salt intake in adult patients with non-dialysis CKD on change in BP, proteinuria and albuminuria. RESULTS: Eleven RCTs were selected and included information about 738 CKD patients (Stage 1⁻4); urinary sodium excretion was 104 mEq/day (95%CI, 76⁻131) and 179 mEq/day (95%CI, 165⁻193) in low- and high-sodium intake subgroups, respectively, with a mean difference of −80 mEq/day (95%CI from −107 to −53; p <0.001). Overall, mean differences in clinic and ambulatory systolic BP were −4.9 mmHg (95%CI from −6.8 to −3.1, p <0.001) and −5.9 mmHg (95%CI from −9.5 to −2.3, p <0.001), respectively, while clinic and ambulatory diastolic BP were −2.3 mmHg (95%CI from −3.5 to −1.2, p <0.001) and −3.0 mmHg (95%CI from −4.3 to −1.7; p <0.001), respectively. Mean differences in proteinuria and albuminuria were −0.39 g/day (95%CI from −0.55 to −0.22, p <0.001) and −0.05 g/day (95%CI from −0.09 to −0.01, p = 0.013). CONCLUSION: Moderate salt restriction significantly reduces BP and proteinuria/albuminuria in patients with CKD (Stage 1⁻4).

Use of monomeric and oligomeric flavanols in the dietary management of patients with type 2 diabetes mellitus and microalbuminuria (FLAVA trial): study protocol for a randomized controlled trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2D) are prone to micro- and macro-vascular complications. Monomeric and oligomeric flavanols (MOF) isolated from grape seeds (Vitis vinifera) have been linked to improved endothelial function and vascular health. The aim of this study is to determine the effect of a daily supplementation of 200 mg MOF on renal endothelial function of patients with T2D and microalbuminuria. METHODS/DESIGN: For this double-blind, placebo-controlled, randomized, multicenter trial 96 individuals (ages 40-85 years) with T2D and microalbuminuria will be recruited. Participants will be randomly assigned to the intervention group, receiving 200 mg of MOF daily for 3 months, or to the control group, receiving a placebo. The primary endpoint is the evolution over time in albumin excretion rate (AER) until 3 months of intervention as compared with placebo. Secondary endpoints are the evolution over time in established plasma markers of renal endothelial function-asymmetric dimethylarginine (ADMA), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and von Willebrand Factor (vWF)-until 3 months of intervention as compared with placebo. Mixed modeling will be applied for the statistical analysis of the data. DISCUSSION: We hypothesize that T2D patients with microalbuminuria have a medically determined requirement for MOF and that fulfilling this requirement will result in a decrease in AER and related endothelial biomarkers. If confirmed, this may lead to new insights in the dietary management of patients with T2D. TRIAL REGISTRATION: Nederlands Trial Register, NTR4669 , registered on 7 July 2014.

Ambulatory blood pressure in the dash diet trial: Effects of race and albuminuria.

We evaluated whether low-grade albuminuria or black race modulates ambulatory blood pressure (BP) or nocturnal BP response to the DASH diet. Among 202 adults enrolled in the DASH multicenter trial who were fed the DASH or control diet for 8 weeks, reductions in 24-hour daytime and nighttime SBP and DBP were significantly larger for DASH compared to control. Median changes in nocturnal BP dipping were not significant. Compared to urine albumin excretion of <7 mg/d, ≥7 mg/d was associated with larger significant median reductions in 24-hour SBP (-7.3 vs -3.1 mm Hg), all measures of DBP (24-hour: -5.9 vs -1.8 mm Hg; daytime: -9.9 vs -4.0 mm Hg; nighttime -9.0 vs -2.0 mm Hg), and with increased nocturnal SBP dipping (2.3% vs -0.5%). Black race was associated with larger median reduction in 24-hour SBP only (-5.5 vs -2.4 mm Hg). This analysis suggests greater effect of DASH on ambulatory BP in the presence of low-grade albuminuria.

Dietary low-fat soy milk powder retards diabetic nephropathy progression via inhibition of renal fibrosis and renal inflammation.

SCOPE: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Here, we examined the effect of long-term consumption of a low-fat soy milk powder (LFSMP) on the diabetic kidney structure and function. METHODS AND RESULTS: KKAy mice were fed a casein-, LFSMP-, or high-fat soy mixture powder (HFSMP)-based diet for 4 months. Plasma and urine were subjected to a biochemical assay every 2-4 wk. Renal morphology and protein expression were evaluated by histochemical staining and western blots. Although HFSMP-based diet showed no protective effect on DN. LFSMP-fed mice exhibited lower water intake, urine output, and urinary albumin, and glucose excretion. Furthermore, strong preservation of renal structural proteins and low urinary N-acetyl-beta-d-glucosaminidase activity were observed in LFSMP-fed mice, indicating alleviation of renal injury. LFSMP-fed mice showed a lesser degree of mesangial matrix expansion, of tubulointerstitial fibrosis, and of myofibroblast differentiation. Finally, milder renal inflammation was found in LFSMP-fed mice, as evidenced by a decrease in urinary monocyte chemoattractant protein- 1 excretion and lesser macrophage infiltration into the tubulointerstitium. CONCLUSION: The present data suggests that long-term consumption of LFSMP but not HFSMP retards DN progression via suppressing renal injury, myofibroblast differentiation, and renal macrophage infiltration in diabetic condition.

Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice.

We previously demonstrated that polymorphisms in the carnosinase-1 gene (CNDP1) determine the risk of nephropathy in type 2 diabetic patients. Carnosine, the substrate of the enzyme encoded by this gene, is considered renoprotective and could possibly be used to treat diabetic nephropathy (DN). In this study, we examined the effect of carnosine treatment in vivo in BTBR (Black and Tan, BRachyuric) ob/ob mice, a type 2 diabetes model which develops a phenotype that closely resembles advanced human DN. Treatment of BTBR ob/ob mice with 4 mM carnosine for 18 weeks reduced plasma glucose and HbA1c, concomitant with elevated insulin and C-peptide levels. Also, albuminuria and kidney weights were reduced in carnosine-treated mice, which showed less glomerular hypertrophy due to a decrease in the surface area of Bowman's capsule and space. Carnosine treatment restored the glomerular ultrastructure without affecting podocyte number, resulted in a modified molecular composition of the expanded mesangial matrix and led to the formation of carnosine-acrolein adducts. Our results demonstrate that treatment with carnosine improves glucose metabolism, albuminuria and pathology in BTBR ob/ob mice. Hence, carnosine could be a novel therapeutic strategy to treat patients with DN and/or be used to prevent DN in patients with diabetes.

Withdrawal of red meat from the usual diet reduces albuminuria and improves serum fatty acid profile in type 2 diabetes patients with macroalbuminuria.

BACKGROUND: Replacement of red meat in the diet with chicken has reduced the urinary albumin excretion rate (UAER) and serum cholesterol in microalbuminuric type 2 diabetes patients. The effects of withdrawing red meat are unknown in the more advanced stages of diabetic nephropathy. OBJECTIVE: Our objective was to assess the effects of replacing red meat in the usual diet (UD) with chicken (CD) and of consuming a lactovegetarian low-protein diet (LPD) on renal function, fatty acid, and lipid profile in macroalbuminuric type 2 diabetes patients. DESIGN: A crossover controlled trial was conducted in 17 type 2 diabetes patients with macroalbuminuria (24-h UAER > or = 200 microg/min). Each patient followed the UD, CD, and LPD in a random order for 4 wk. After each diet, glomerular filtration rate, UAER, serum fatty acid, lipid profile, glycemic control, anthropometric indexes, and blood pressure were measured. RESULTS: UAER [median CD: 269.4 (range: 111-1128) microg/min; LPD: 229.3 (76.6-999.3) microg/min; UD: 312.8 (223.7-1223.7) microg/min; P < 0.01] and mean (+/-SD) non-HDL cholesterol (CD: 3.92 +/- 0.99 mmol/L; LPD: 3.92 +/- 0.93 mmol/L; UD: 4.23 +/- 1.06 mmol/L; P = 0.042) were lower after CD and LPD than after UD. Compared with the UD, an increase in serum total polyunsaturated fatty acids was also observed (CD: 39.8 +/- 2.6%; LPD: 39.7 +/- 4.4%; UD: 37.3 +/- 3.1%; P = 0.029). CONCLUSION: In macroalbuminuric patients with type 2 diabetes, withdrawing red meat from the diet reduces the UAER.

Determinants of urinary albumin excretion reduction in essential hypertension: A long-term follow-up study.

OBJECTIVE: The objective of the present study was to assess factors related to long-term changes in urinary albumin excretion (UAE) of nondiabetic microalbuminuric (n = 252) or proteinuric hypertensive individuals (n = 58) in a prospective follow-up. METHOD: After enrollment, patients were placed on usual care including nonpharmacological treatment and/or treatment with an antihypertensive drug regime to achieve blood pressure < 135/85 mmHg. Periodic UAE measurements were performed until regression or significant reduction (defined when UAE dropped > 50% from the initial values, plus reduction of UAE to < 30 mg/24 h for microalbuminuric patients and < 300 mg/24 h for proteinuric patients). RESULTS: Among the microalbuminuric patients, 113 (44.8%) significantly reduced UAE after a mean follow-up of 18 months (range 12-69 months), 20.3/100 patients per year. Among the proteinuric patients, 29 (50%) significantly reduced UAE after a mean follow-up of 25 months (range 12-51 months), 20.2/100 patients per year. The baseline glomerular filtration rate, diastolic blood pressure and fasting glucose during follow-up were independent factors related to the regression or significant reduction in a Cox proportional hazard model. Regression of UAE was independently related to initial estimated glomerular filtration rate < or = 60 ml/min per 1.73 m (hazard ratio, 0.57; 95% confidence interval, 0.38-0.86; P = 0.001) and DBP > or = 90 mmHg achieved during the follow-up (hazard ratio, 0.57; 95% confidence interval, 0.38-0.86; P = 0.001), even when adjusted for age, gender, body mass index, fasting glucose, presence of treatment at the beginning of the study and treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers during the follow-up. CONCLUSIONS: The reduction of urinary albumin excretion was linked to the preserved glomerular filtration rate and to adequate blood pressure control.

Animal versus plant protein meals in individuals with type 2 diabetes and microalbuminuria: effects on renal, glycemic, and lipid parameters.

OBJECTIVE: To determine, for individuals with type 2 diabetes and microalbuminuria, the effects of 6 weeks of meals containing plant-based protein (PP) versus meals with predominantly animal-based protein (AP) on renal function and secondarily on glycemia, lipid levels, and blood pressure. RESEARCH DESIGN AND METHODS: In a randomized crossover trial, we compared 6 weeks of meals containing only PP with meals containing primarily AP (60% animal, 40% plant) in 17 subjects with type 2 diabetes and microalbuminuria treated with diet and/or oral antidiabetic agents. Protein content was equivalent to the average American diet, and calories provided weight maintenance. Nutrients were equivalent between the two diets. Meals were prepared and packaged by a metabolic kitchen staff and were sent home weekly. At the beginning and end of each 6-week period, subjects were studied for 36 h on a metabolic unit. RESULTS: There were no significant differences between diets for glomerular filtration rate, renal plasma flow, albumin excretion rate, total cholesterol, HDL cholesterol, triglyceride area under the curve (AUC), glucose and insulin AUC, HbA(1c,) blood pressure, or serum amino acids. For both diets, at the end of the treatment periods as compared with baseline, total cholesterol was significantly lower (PP and AP: from 4.75 to 4.34 mmol/l, P < 0.01), HbA(1c) had significantly improved (PP: from 8.1 to 7.5%, P < 0.01; AP: from 7.9 to 7.4%, P < 0.01), and diastolic blood pressure was significantly lower (PP: from 83 to 80 mmHg, P < 0.02; AP: from 82 to 78, P < 0.02). CONCLUSIONS: There is no clear advantage for the recommendation of diets containing only PP rather than diets containing protein that is primarily animal-based for individuals with type 2 diabetes and microalbuminuria. There are, however, potential lipid, glycemic, and blood pressure benefits for following a carefully constructed, weight-maintaining, healthy diet, regardless of protein source.

Reduced albuminuria after dietary protein restriction in insulin-dependent diabetic patients with clinical nephropathy.

Recent clinical investigations have demonstrated that an early restriction of dietary protein intake may reduce the rate of progression of chronic renal failure in humans. In this study the effects of a restricted-protein diet on kidney function in type I diabetic patients with clinical nephropathy were evaluated. Sixteen patients (9 men, 7 women) with mean age 37.1 +/- 9.8 yr, mean duration of diabetes 17.7 +/- 6.6 yr, proteinuria greater than 0.5 g/24 h, and serum creatinine concentration of 0.7-1.9 mg/dl were studied. Patients were randomly divided into two groups. The low-protein diet (LPD) group comprised seven patients who were kept for 4.5 +/- 1 mo on a diet containing 0.71 +/- 0.12 g X kg-1 X day-1 protein. The normal-protein diet (NPD) group comprised nine patients as controls maintained for 11.7 +/- 7 mo on their usual diabetic diet containing 1.44 +/- 0.12 g X kg-1 X day-1 protein. All patients were studied every 1-2 mo. Metabolic control was assessed by evaluation of 5-8 blood glucose determinations/day and by glycosylated hemoglobin, whereas renal function was evaluated by albumin, IgG and beta 2-microglobulin urinary excretion rates, serum creatinine concentration, and creatinine clearance. At each visit, serum concentrations of total protein, albumin, phosphate, calcium, and electrolytes and weight and blood pressure were also measured. A significant reduction (434 +/- 244 to 205 +/- 212 micrograms/min, mean +/- SD) in albumin excretion rate was found in all LPD patients after dietary protein restriction, with a significant reincrease (689 +/- 201 micrograms/min) in the same patients several months after interruption of diet.(ABSTRACT TRUNCATED AT 250 WORDS)