Association between social network and dietary variety among community-dwelling older adults.

OBJECTIVE: Social networks are critical social health factors for older adults. This study examined the association between social networks and dietary variety among community-dwelling older adults. DESIGN: A cross-sectional study, using the dietary variety score (DVS) developed for older Japanese people to assess dietary variety and the Lubben Social Network Scale (LSNS-6) to assess social networks. SETTING: N City, H Prefecture, Japan. PARTICIPANTS: Community-dwelling older adults aged ≥ 65 years (n 1229). RESULTS: The LSNS-6 score in the low DVS group was lower than that in the middle and high DVS groups (12·2 ± 5·6 v. 13·4 ± 5·4 and 14·4 ± 5·7, P < 0·001). The population of social isolation (LSNS-6, < 12) in the low DVS group was higher than that in the middle and high DVS groups (43·5 % v. 35·8 % and 31·0 %, P = 0·005). Multivariate linear regression analysis showed that the LSNS-6 score was positively correlated with DVS (standardised coefficient, 0·092; P = 0·002). Social isolation was also significantly associated with a low DVS in the multivariate-adjusted logistic analysis model (OR, 1·30; 95 % CI 1·00, 1·68; P = 0·048). Stratified analysis results revealed the LSNS-6 and DVS were significantly associated in participants with the following characteristics: younger age (< 75 years), women and those living with someone. CONCLUSIONS: Social networks were associated with dietary variety; social isolation was related to poor dietary variety among community-dwelling older adults. An association between social networks and dietary variety was observed among young-old older adults, women and those living with someone.

Social contact impacts physical activity and sedentary behavior among older adults in Japan due to COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has adversely affected social contact and physical activity. This study investigated the correlation between physical activity, social contact, and sedentary time among adults aged 65 years and above during the COVID-19 pandemic. METHODS: This study was conducted in N City, H Prefecture, Japan. The authors randomly selected 4,996 adults, aged 65 years and above (mean age 74.1 ± 6.1 years), living in N City, and survey forms were distributed by mail in mid-August 2020. Altogether, 1,925 participants were included in this study. The survey comprised questions concerning the participants' sex, height, weight, age, smoking and drinking habits, living arrangements, social contact assessments, physical activity levels, and sedentary time. Moreover, linear regression analysis was utilized to investigate the associations between the variables. RESULTS: The reported median physical activity was 1272 metabolic equivalent of task-min/week (interquartile range 528-2628), and the reported median sedentary time was 360 min/week (interquartile range 240-600). COVID-19 "somewhat," "quite a lot," or "completely" hindered the frequency of in-person contact with friends among 75.5% of the respondents and hampered the frequency of virtual contact with friends among 38.8% of the respondents. Physical activity was associated significantly with in-person contact indicators: "interaction with friends" (B = -0.111; 95%CI: -0.187, -0.035; p = 0.004) and "social participation" (B = -0.163; 95%CI: -0.248, -0.079; p < 0.001). These associations remained significant for both multivariate analysis Models 1 (sex and age) and 2 (addition of body mass index [BMI], alcohol use, smoking, living alone, and the number of illnesses to Model 1). Additionally, sedentary time was significantly associated with the social contact variable of "interaction with friends" (B = 0.04; 95%CI: 0.016, 0.064; p = 0.001). This association remained significant in both multivariate analysis models. CONCLUSIONS: Significant associations were confirmed between reduced social contact, decreased physical activity, and more sedentary behavior among older adults due to COVID-19. Hence, continuous monitoring and support for social activities among susceptible older adults in extraordinary circumstances are essential.

Lower dietary variety is associated with worse sleep quality in community-dwelling elderly Japanese women.

BACKGROUND AND OBJECTIVES: Sleep disturbance is a common health problem in the elderly population. We examined the association between dietary variety and subjective sleep quality in community-dwelling elderly Japanese women. METHODS AND STUDY DESIGN: This cross-sectional study recruited 160 community-dwelling elderly women aged ≥65 years. Subjective sleep quality and dietary variety were assessed by Pittsburgh Sleep Quality Index (PSQI) and dietary variety score (DVS), respectively. DVS was calculated from the eating frequency of 10 food groups. Sleep disturbance was defined as PSQI score of ≥6. RESULTS: The DVS in subjects with sleep disturbance was significantly lower than that of those without the disturbance (4.1±2.1 vs 5.3±2.1, p<0.01). In the multivariable regression model, the PSQI score was negatively correlated with the DVS score in age-adjusted model (standardized coefficient; -0.234, p<0.01). In the further adjusted model that included depression levels, the negative association between PSQI score and DVS score was retained (standardized coefficient; -0.211, p<0.05). Among 10 food groups comprising DVS, the eating frequency of soybean and soybean products was the determinant of sleep disturbance in the stepwise liner regression analysis. In the further model that contained DVS, DVS was the independent determinant of sleep disturbance, while the eating frequency of soybean and soybean products was excluded. CONCLUSIONS: A worse sleep quality was associated with lower DVS in elderly Japanese women. Diet comprising various food groups was better for sleep quality than consuming only a particular food in the elderly.

Asymmetric Dimethylarginine Contributes to the Impaired Response to Erythropoietin in CKD-Anemia.

Erythropoietin-resistant anemia is associated with adverse cardiovascular events in patients with ESRD, but the underlying mechanism remains unclear. Here, we evaluated the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In 54 patients with advanced CKD, erythrocyte but not plasma ADMA levels independently associated with low hemoglobin values, although levels of both types of ADMA were elevated compared with those in healthy volunteers. Furthermore, erythrocyte ADMA level associated with the erythropoietin resistance index in patients receiving a weekly injected dose of erythropoiesis-stimulating agents standardized for hemoglobin levels and body weight, whereas it correlated with the erythropoietin demand index (plasma erythropoietin units divided by the hemoglobin value) in patients not receiving erythropoiesis-stimulating agents. Compared with sham-operated controls, wild-type mice with 5/6 subtotal nephrectomy (Nx), a remnant kidney model with advanced CKD, had decreased hemoglobin, hematocrit, and mean corpuscular volume values but increased erythrocyte and plasma ADMA and plasma erythropoietin levels. In comparison, dimethylarginine dimethlaminohydrolase-1 transgenic (DDAH-1 Tg) mice, which efficiently metabolized ADMA, had significant improvements in all of the values except those for erythropoietin after 5/6 Nx. Additionally, wild-type Nx mice, but not DDAH-1 Tg Nx mice, had reduced splenic gene expression of erythropoietin receptor and erythroferrone, which regulates iron metabolism in response to erythropoietin. This study suggests that erythrocyte ADMA accumulation contributes to impaired response to erythropoietin in predialysis patients and advanced CKD mice via suppression of erythropoietin receptor expression.

Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage.

Mitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology of a variety of renal diseases, such as CKD, AKI, and steroid-resistant nephrotic syndrome. Antioxidant therapies are being investigated, but clinical outcomes have yet to be determined. Recently, we reported that a newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level and survival of fibroblasts from patients with mitochondrial disease. MA-5 modulates mitochondrial ATP synthesis independently of oxidative phosphorylation and the electron transport chain. Here, we further investigated the mechanism of action for MA-5. Administration of MA-5 to an ischemia-reperfusion injury model and a cisplatin-induced nephropathy model improved renal function. In in vitro bioenergetic studies, MA-5 facilitated ATP production and reduced the level of mitochondrial reactive oxygen species (ROS) without affecting activity of mitochondrial complexes I-IV. Additional assays revealed that MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane. In Hep3B cells, overexpression of mitofilin increased the basal ATP level, and treatment with MA-5 amplified this effect. In a unique mitochondrial disease model (Mitomice with mitochondrial DNA deletion that mimics typical human mitochondrial disease phenotype), MA-5 improved the reduced cardiac and renal mitochondrial respiration and seemed to prolong survival, although statistical analysis of survival times could not be conducted. These results suggest that MA-5 functions in a manner differing from that of antioxidant therapy and could be a novel therapeutic drug for the treatment of cardiac and renal diseases associated with mitochondrial dysfunction.

L-Carnitine Supplementation Improves Self-Rating Depression Scale Scores in Uremic Male Patients Undergoing Hemodialysis.

BACKGROUND: Depression is highly prevalent in uremic patients undergoing hemodialysis (HD). We previously found that low free-carnitine levels are associated with depression severity in male patients undergoing HD. However, whether L-carnitine supplementation improves the depression state in male patients undergoing HD remains unclear. METHODS: Sixteen male patients undergoing HD were orally administered 900 mg L-carnitine daily or intravenously administered 1000 mg L-carnitine immediately after undergoing HD for 3 months. The depression state and various types of carnitine levels were evaluated using the self-rating depression scale (SDS) and tandem mass spectrometry, respectively, at baseline and 3 months after treatment. RESULTS: L-carnitine supplementation significantly increased serum levels of free and other acylcarnitine types, associated with improved SDS scores in male patients undergoing HD. Univariate analysis revealed that low baseline butyryl- and isovaleryl-/2-methylbutyryl-carnitine levels were significantly correlated with SDS scores after treatment. Multiple regression analysis revealed that butyryl-carnitine levels were a sole independent predictor of SDS scores after treatment (r2 = 0.533). CONCLUSION: L-carnitine supplementation for 3 months improved the depression state in uremic male patients undergoing HD. Thus, low butyryl-carnitine levels may predict the clinical response to L-carnitine supplementation in male patients undergoing HD and who have mild depression.

Maternal exposure to high-fat and high-fructose diet evokes hypoadiponectinemia and kidney injury in rat offspring.

BACKGROUND: Maternal exposure to overnutrition during fetal development contributes to metabolic and renal damage in offspring. Adiponectin plays a protective role against obesity-related renal injury. However, role of adiponectin in renal injury of offspring exposed to maternal overnutrition remains unknown. We addressed the issue. METHODS: Female Sprague-Dawley rats were fed either a standard (N) or a high-fat and high-fructose (HFF)-diet for 6 weeks before mating, and kept each diet during the gestation and lactation period. After 4 weeks postpartum, all the offspring were fed N diet, and followed by 12 weeks. Kidney weight, urinary albumin excretion, blood pressure, and blood chemistry, including adiponectin and malondialdehyde, a marker of oxidative stress, were evaluated in the offspring. RESULTS: Compared with N-offspring, serum adiponectin levels of 1-day- and 4-week-old HFF-offspring were significantly lower, the latter of which was inversely associated with malondialdehyde. Kidney weight was significantly decreased in 1-day-old HFF-offspring, whereas increased in 4-week-old HFF-offspring. Urinary albumin excretion levels of HFF-offspring at 8, 12, and 16-week old were significantly higher than those of N-offspring at the same age, whose levels at 16-week old were inversely correlated with plasma adiponectin. Compared with N-offspring, HFF-offspring at 16-week old exhibited glomerulosclerosis, hyperglycemia, and high mean blood pressure associated with reduced podocin and increased transforming growth factor-ß1 expression in the kidneys. CONCLUSIONS: Our present study suggests that exposure to maternal HFF-diet during fetal and early postnatal development induces hypoadiponectinemia in offspring, which might cause renal injury and metabolic derangements later in life.

Oral L-carnitine supplementation increases trimethylamine-N-oxide but reduces markers of vascular injury in hemodialysis patients.

OBJECTIVES: Food or supplement-derived L-carnitine is changed to trimethylamine (TMA) by interstinal microbiota, which is further metabolized to trimethylamine-N-oxide (TMAO), being involved in the promotion of atherosclerosis in animal models. Meanwhile, carnitine deficiency has played a role in accelerated atherosclerosis in hemodialysis (HD) patients. However, effects of oral L-carnitine supplementation on circulating levels of TMAO and markers of vascular injury and oxidative stress in patients on HD remain unclear. In this study, we addressed the issue. METHODS: Thirty-one HD patients with carnitine deficiency were treated with oral L-carnitine (900 mg/d) for 6 months. At baseline and after treatment, clinical variables including circulating levels of carnitine fractions, TMA, TMAO, advanced glycation end products (AGE), soluble forms of intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and malondialdehyde (MDA) were measured. RESULTS: Oral L-carnitine supplementation significantly increased total, free, acyl carnitine, and plasma TMA and TMAO levels, whereas it decreased markers of vascular injury and oxidative stress such as sICAM-1, sVCAM-1, and MDA levels. TMA and TMAO levels at baseline were correlated with each other, and free carnitine was independently associated with TMAO levels. Furthermore, change in AGE values from baseline ([INCREMENT]AGE) was positively correlated with [INCREMENT]sICAM-1 (P = 0.043) and was a sole independent determinant of [INCREMENT]sICAM-1 (R = 0.133, P = 0.043). CONCLUSIONS: This study demonstrated that although oral L-carnitine supplementation was associated with increased TMAO levels, it might be beneficial on vascular injury in patients on HD. Vasculoprotective properties of L-carnitine supplementation in HD patients might be ascribed partly to its inhibitory actions on AGE.

Asymmetric dimethylarginine accumulates in the kidney during ischemia/reperfusion injury.

Ischemia/reperfusion injury is the leading cause of acute tubular necrosis. Nitric oxide has a protective role against ischemia/reperfusion injury; however, the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in ischemia/reperfusion injury remains unclear. ADMA is produced by protein arginine methyltransferase (PRMT) and is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). Here we examined the kinetics of ADMA and PRMT and DDAH expression in the kidneys of ischemia/reperfusion-injured mice. After the injury, DDAH-1 levels were decreased and renal and plasma ADMA values were increased in association with renal dysfunction. Renal ADMA was correlated with 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress. An antioxidant, N-acetylcysteine, or a proteasomal inhibitor, MG-132, restored these alterations. Infusion of subpressor dose of ADMA exacerbated renal dysfunction, capillary loss, and tubular necrosis in the kidneys of ischemia/reperfusion-injured wild mice, while damage was attenuated in DDAH transgenic mice. Thus, ischemia/reperfusion injury-induced oxidative stress may reduce DDAH expression and cause ADMA accumulation, which may contribute to capillary loss and tubular necrosis in the kidney.

Protective role of JAK/STAT signaling against renal fibrosis in mice with unilateral ureteral obstruction.

Inflammation is involved in renal fibrosis, a final common pathway for kidney diseases. To clarify how JAK/STAT/SOCS system was involved in renal fibrosis, UUO was induced in BALB/c or SOCS3(+/-) mice in the presence or absence of JAK inhibitor-incorporated nanoparticle (pyridine6-PGLA). UUO increased pSTAT3 and subsequently elevated SOCS3 levels in the obstructed kidneys. pSTAT3 levels were further increased in SOCS3(+/-) mice. UUO-induced renal fibrosis was markedly suppressed in SOCS3(+/-) mice, while it was aggravated by pre-treatment with pyridine6-PGLA. Although there were no differences in renal mRNA levels of TGF-ß and collagens between wild and SOCS3(+/-) mice, MMP-2 activity was enhanced in SOCS3(+/-) UUO mice. Activated MMP-2 was completely suppressed by pyridine6-PGLA-pre-treatment. TNF-α one of JAK/STAT activators, increased pSTAT3 levels and subsequently induced MMP-2 activation in proximal tubular cells. These results suggest that JAK/STAT3 signaling may play a role in repair process of renal fibrosis in UUO partly via MMP-2 activation.

Low Dietary Variety Is Associated with Incident Frailty in Older Adults during the Coronavirus Disease 2019 Pandemic: A Prospective Cohort Study in Japan.

BACKGROUND: Stagnation of social activity due to the COVID-19 pandemic probably reduces motivation to maintain a healthy diet. It is important to report on the dietary changes observed in older adults during a period of restriction on outings and to clarify the relationship between dietary variety and frailty. This one-year follow-up study examined the association between frailty and dietary variety during the COVID-19 pandemic. METHODS: Baseline and follow-up surveys were conducted in August 2020 and August 2021, respectively. The follow-up survey was distributed by mail to 1635 community-dwelling older adults aged ≥65 years. Of the 1235 respondents, 1008 respondents who were non-frail at baseline are included in this study. Dietary variety was examined using a dietary variety score developed for older adults. Frailty was assessed using a five-item frailty screening tool. The outcome was frailty incidence. RESULTS: In our sample, 108 subjects developed frailty. A linear regression analysis revealed a significant association between dietary variety score and frailty score (ß, -0.032; 95% CI, -0.064 to -0.001; p = 0.046). This association was also significant in Model 1, adjusted for sex and age, (ß, -0.051; 95% CI, -0.083 to -0.019; p = 0.002) and in a multivariate analysis that added adjustments for living alone, smoking, alcohol use, BMI, and existing conditions to Model 1 (ß, -0.045; 95% CI, -0.078 to -0.012; p = 0.015). CONCLUSIONS: A low dietary variety score was associated with an increased frailty score during the COVID-19 pandemic. The restricted daily routine caused by the COVID-19 pandemic will probably continue to have a long-term effect in terms of reduced dietary variety. Thus, vulnerable populations, such as older adults, might require dietary support.

Association between asymmetric dimethylarginine and sarcopenia in community-dwelling older women.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelium nitric oxide synthesis and causes endothelial dysfunction that may be related to sarcopenia. However, the association between ADMA and sarcopenia has not been studied. We evaluated the correlations between plasma ADMA levels and sarcopenia in community-dwelling older women. In total, 144 community-dwelling older women participated in this study. Plasma ADMA levels were measured using a competitive enzyme-linked immunosorbent assay. Skeletal muscle mass, measured in terms of bioimpedance and grip strength, was used to assess sarcopenia. Plasma ADMA levels were significantly higher in participants with sarcopenia than in those without sarcopenia. Through receiver-operating characteristic curve analysis, the cutoff value of plasma ADMA level for sarcopenia was estimated at 0.57 µM. Sarcopenia was significantly more prevalent in participants with higher plasma ADMA levels than in those with lower plasma ADMA levels. According to logistic regression analysis, the crude odds ratio of higher plasma ADMA levels in participants with sarcopenia was 4.57 (95% confidence interval, 1.82-11.47; p = 0.001). Reductions in the skeletal muscle mass index over 2 years were significantly greater in participants with higher plasma ADMA levels. In conclusion, plasma ADMA levels were significantly associated with sarcopenia in community-dwelling older women.

Development of an enzyme-linked immunosorbent assay system for the determination of asymmetric dimethylarginine using a specific monoclonal antibody.

We produced a monoclonal antibody (mAb) against N(G),N(G)-dimethyl-L-arginine (asymmetric dimethylarginine: ADMA), an endogenous competitive inhibitor of nitric oxide synthase (NOS), and developed an enzyme-linked immunosorbent assay (ELISA). The competitive ELISA method using the mAb determined 5 nM-100 nM ADMA, and ADMA levels in human plasma and urine were found to be 0.78 µM and 51.3 µmol/g of creatinine respectively.

Asymmetric dimethylarginine, an endogenous NOS inhibitor, is actively metabolized in rat erythrocytes.

N(G), N(G)-Dimethyl-L-arginine (asymmetric dimethylarginine: ADMA) is an endogenous competitive inhibitor of nitric oxide synthase (NOS). Plasma ADMA concentrations have been reported to increase in connection with diseases associated with an impaired endothelial L-arginine/NO pathway. In this study, we investigated the metabolism of ADMA in circulating blood cell populations to elucidate the regulatory mechanism of elevation of plasma ADMA, a novel risk factor for cardiovascular disease. We found by RT-PCR and Western blot analyses that protein arginine methyltransferase (PRMT)1 and dimethylarginine dimethylaminohydrolase (DDAH)-1, responsible for the biosynthesis and degradation of ADMA respectively, are expressed in erythrocytes (ECs), leukocytes, and platelets. We also identified a major ADMA-containing protein in ECs as catalase, confirmed by GST-pull down assay to bind to PRMT1 in vitro. This is the first report that the ADMA-metabolizing system, including the arginine methylation of proteins and the breakdown of free ADMA, occurs in circulating blood cell-populations, and that catalase in ECs might be a potential protein targeted by PRMT1.

Gastrointestinal digestion and absorption of Pen j 1, a major allergen from Kuruma prawn, Penaeus japonicus.

Tropomyosin had been identified as a major allergen in shrimp. The digestion and absorption of tropomyosin (Pen j 1) from kuruma prawn were investigated by ex vivo, in vitro, and in vivo techniques in order to elucidate the relationship between the allergenicity of the allergen and its gastrointestinal behavior. Pen j 1 transported the Caco-2 monolayer in a dose-dependent manner, and also enhanced the permeability of lucifer yellow, a marker of paracellular transportation, at high concentrations of the allergen. Studies with everted sacs revealed that Pen j 1 was rapidly degraded to small peptides (MW<3.5 kDa) and amino acids by intestinal proteases and absorbed from enterocytes. Furthermore, Pen j 1 orally administered to rats tended to remain in the stomach rather than in the small intestine, after which the allergen moved to the epithelial cells. These observations suggest that Pen j 1 may be absorbed via the gastric mucosa prior to its digestion in the intestines.

Relationship Between Dietary Variety and Frailty in Older Japanese Women During the Period of Restriction on Outings Due to COVID-19.

OBJECTIVES: To investigate the relationship between diet and frailty in community-dwelling older adults during the period of restriction on outings due to novel coronavirus disease 2019 (COVID-19). METHOD: A mail survey targeting adults aged 65 years or older, including questions on sex, age, height, weight, and social participation, was conducted in May 2020. The participants' dietary variety score and frailty score were then calculated. RESULTS: Overall, 322 women aged 65 years or older and who were living in the community were recruited for the study; 253 were finally analyzed. The mean age of the 253 participants was 80.0 ± 6.4 years. The dietary variety score and frailty scores were significantly correlated in the linear regression analysis (ß: -0.224, p < .001). In the multivariate regression analysis, these factors remained significantly correlated in Model 1, which was adjusted for age (ß: -0.229, p < .001), and Model 2, which was adjusted for age, body mass index, and other confounding factors (ß: -0.208, p = .001). DISCUSSION: Diet was correlated with frailty in older adults living in the community during the period of restriction on outings due to COVID-19.

Relationship Between Social Activity and Frailty in Japanese Older Women During Restriction on Outings due to COVID-19.

BACKGROUND: This study investigated the relationship between social activities and frailty during the restriction on outings due to COVID-19. DESIGN: A cross-sectional study. SETTING AND SUBJECTS: This study was conducted in City Nishinomiya of Prefecture Hyogo, in Japan. A mail survey was carried out among women aged 65 years or older in May 2020. A population of 293 women aged 65 years or older living in the community was recruited for the study and 213 of them were analyzed. MEASUREMENTS: The survey included questions on sex, age, height, weight, and social activity. Social activity consisted of participation in social organizations and their frequency, as well as frequency of interaction with family and friends. The survey also asked if regular social activity had been impeded by COVID-19. RESULTS: A significant association was found between frailty and hindered interaction with friends (ß: 0.176, p = .014). Multivariate linear regression analysis confirmed that this association was also significant in Model 1 (ß: 0.158, p = .025), and Model 2 (ß: 0.148, p = .034). CONCLUSIONS: No association between being hindered in social activity and frailty was found in older women living in the community during the restriction on outings due to COVID-19.

Urinary sodium-to-potassium ratio and serum asymmetric dimethylarginine levels in patients with type 2 diabetes.

Obesity modifies the association between sodium and potassium intake and blood pressure. However, the impact of obesity on the relationship between the sodium-potassium balance and cardiovascular risk in type 2 diabetes (T2DM) patients remains unclear. We investigated the relationship between the 24-h urinary sodium-to-potassium ratio and serum asymmetric dimethylarginine (ADMA) level, which is a cardiovascular risk factor, in Japanese T2D patients with or without obesity. This cross-sectional study included 243 patients with T2DM who were hospitalized for diabetes education. Urinary sodium-to-potassium ratios were calculated from 24-h urine collection. The subjects were divided into two groups according to their BMIs (<25 and ≥25). The serum ADMA levels positively correlated with the urinary sodium-to-potassium ratios in non-obese patients, but not in obese patients. Multivariate linear regression analyses showed that the serum ADMA levels positively correlated with the urinary sodium-to-potassium ratios after adjustment for other confounders in non-obese patients. This correlation was observed in non-obese patients with hypertension, but not in those without hypertension. Measurement of the pulse wave velocity and intima-media thickness revealed that elevation of the serum ADMA levels was significantly associated with an increase in the degree of atherosclerotic progression in subjects with T2DM. Additionally, an assessment of dietary intake showed that the consumption of dairy products as well as of green and yellow vegetables was negatively associated with urinary sodium-to-potassium ratios in patients with T2DM. In conclusion, elevation of serum ADMA may be positively associated with the urinary sodium-to-potassium ratio in Japanese non-obese patients with T2DM.

RAGE-aptamer attenuates deoxycorticosterone acetate/salt-induced renal injury in mice.

The mineralocorticoid receptor (MR) and its downstream signaling play an important role in hypertensive renal injury. The interaction of advanced glycation end products (AGE) with their receptor (RAGE) is involved in the progression of renal disease. However, the pathological crosstalk between AGE-RAGE axis and MR system in kidney derangement remains unclear. We screened DNA-aptamer directed against RAGE (RAGE-apt) in vitro and examined its effects on renal injury in uninephrectomized deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mice. RAGE, GTP-bound Rac-1 (Rac1), and MR were co-localized in the podocytes of DOCA mice. The deletion of RAGE gene significantly inhibited mesangial matrix expansion and tubulointerstitial fibrosis in DOCA mice, which was associated with the reduction of glomerular oxidative stress, MR, Rac1, and urinary albumin excretion (UAE) levels. RAGE-apt attenuated the increase in carboxymethyllysine (CML), RAGE, nitrotyrosine, Rac1, and MR levels in the kidneys and reduced UAE in DOCA mice. Aldosterone (Aldo) increased nitrotyrosine, CML, and RAGE gene expression in murine podocytes, whereas CML stimulated MR and Rac1 levels, which were blocked by RAGE-apt. The present study indicates the crosstalk between the AGE-RAGE axis and Aldo-MR system, suggesting that RAGE-apt may be a novel therapeutic tool for the treatment of MR-associated renal diseases.