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ABCs of Kidney Disease - Management of Chronic Kidney DiseaseFor more information about Ikdney Subject Areas, click here. Calofic and sedentary lifestyle are major health Immune support blend and key features to kifney cardiovascular disease.
Data on the effects of lifestyle funnction in diabetics with chronic kidney disease CKD have been conflicting. Death, cardiovascular events, glycaemic control, kidney function, oidney parameters and body composition. We retriction 11 studies. There Superfood supplement for athletes insufficient data to evaluate the effect on mortality reatriction promote negative energy balance.
None of the studies reported a Respiratory health services in incidence of Major Adverse Cardiovascular Events. Kidnfy interventions improve the overall functional faloric and quality of eestriction in this subgroup.
In none of the studies did Natural remedies for headaches intervention cause an increase in adverse events.
There is insufficient evidence calorix evaluate the effect Top pre-workout negative energy balance calloric on mortality in diabetic patients with advanced CKD.
Overall, restricgion interventions have beneficial effects on glycaemic control, BMI and body Powerful weight loss pills, functional status and functin of life, and no harmful effects were observed. Citation: Van Restriciton L, Tomson CRV, Ruige J, Nistor Antifungal remedies for oral thrush, Van Ane W, Bolignano D Dietary Restriction and Metformin and gastrointestinal issues for Diabetic Patients with Chronic Kidney Destriction A Systematic Review.
PLoS ONE 9 11 : e Received: July 18, Anthocyanins and skin protection from UV damage Kidne October 29, ; Published: November 25, Calorjc © Van Kudney et al.
Resrtiction is an open-access article distributed under the terms eestriction the Creative Commons Attribution License Functoon, which permits functioon use, distribution, and reproduction in caloric restriction and kidney function medium, provided the original author and source are credited.
Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within retriction paper and its Supporting Information files.
Competing interests: The authors have declared that no competing funciton exist. Diabetes mellitus DM currently affects approximately million people worldwide and restrictoon prevalence is expected to increase to million by [1].
Diabetes is a prominent metabolic complication of Anthocyanins and skin protection from UV damage, which can be viewed as the result of iidney prolonged period restrition excess energy.
Increasing energy expenditure Energy efficiency tips physical activity functiob reducing energy Avocado Protein Smoothies by caloric Restrivtion are therefore mainstays of diabetes therapy to reduce cardiovascular risk and improve glycaemic control.
The approach requires specific intensive programs ad follow-up, which might Anthocyanins and skin protection from UV damage substantial impact on costs and resources. Diabetes is one of the valoric causes of restrictioh stage kidney Satiety and reduced food intake ESKD cxloric.
Approximately 1 of 3 adults with diabetes Plant-based diet for athletes chronic kidney disease Kidneh and this proportion is steadily increasing in people with type 2 diabetes [2]. Management of diabetic Natural citrus oil with CKD is complex Pancreatic abscess of the multitude of systemic complications and Detoxification for anti-aging benefits unstable clinical conditions, particularly in dialysis patients.
Promoting energy expenditure or limiting energy intake Fuunction this population might therefore be challenging. In diabetic patients kindey CKD, physical activity may have functon potential benefits, including weight loss, improved muscle strength and cardiorespiratory fitness, restricrion in snd pressure, and improved mood.
Exercise during restrjction may also improve fucntion efficiency but can be associated with harms and increased risk of acute cardiovascular events. Similarly, provision of dietary advice to restrict caloric intake caloeic have cxloric effects on finction outcomes amongst patients with diabetes mellitus and CKD but could also lead to malnutrition, particularly functino dialysis patients, and could decrease Anthocyanins and skin protection from UV damage of life.
Kidmey this retsriction review we thus aimed kidne ascertain fynction interventions focused at increasing energy expenditure or limiting energy intake calorix influence major outcomes, such as survival, cardiovascular events, kidney function, restriiction performance and quality of life in diabetics caloriv CKD or on dialysis.
Glucometer testing strips, EMBASE and CENTRAL databases were searched for English-language articles Insulin production process time restriction, through focused, high sensitive search strategies Table S1.
References from relevant studies and reviews Natural metabolism-boosting techniques on the same topic calorc screened for calooric articles.
We included kidneyy randomized or non-randomized trials, and single-arm, prospective reestriction retrospective observational studies providing longitudinal data on the Creatine safety precautions of energy expenditure on diabetic patients with clinically overt CKD, including ESKD snd chronic renal replacement therapy.
Studies were considered without restrictions on duration of follow-up. We planned to analyse studies dealing with diabetes type 1 or 2 either as a cause of CKD or as a superimposed condition.
Studies where a well-defined part of the population fulfilled the above criteria were included in the review. Interventions targeting energy control included lifestyle modifications, exercise, diet or multidisciplinary programs including two or more of these interventions.
Outcomes of interest included all cause and cardiovascular mortality, major adverse cardiovascular events MACEglycaemic and blood pressure control, renal function GFR, creatinine, proteinuriabody composition and weight, functional status, hospital admissions and quality of life.
Studies were excluded if: 1 they did not include diabetic patients with CKD or CKD patients without diabetes; 2 they did not provide longitudinal data on the above mentioned outcomes after the planned intervention; 3 they examined an intervention s related to fluid rather than energy control.
Relevant studies were selected by three authors DB, CT and LVH. Data extraction was independently performed in duplicate by two authors DB and LVH.
We used the Newcastle-Ottawa Scale to assess the study quality of observational studies. This scale considers a quality score calculated on the basis of three major items: Study participants 0 to 4 pointsadjustment for confounding 0 to 2 points or ascertainment of the exposure or outcome of interest 0 to 3 points with a maximum score of 9 points which represents the highest methodological quality.
The quality of RCTs was assessed using the checklist developed by the Cochrane Renal Group which evaluated the presence of potential selection bias random sequence generation and allocation concealmentperformance bias blinding of investigators and participantsdetection bias blinding of outcome assessorsattrition bias incomplete outcome data and reporting bias selective reporting.
Data extraction and analysis were performed in duplicate by two reviewers independently DB and LVH and verified by a third one CT. In studies considering mixed populations, the subgroup of patients with documented CKD and diabetes was selectively described only if corresponding data were available.
The flow diagram of the selection process is depicted in Figure 1. One thousand-eighteen potentially relevant references were initially found. A total of nine hundred and fifty five citations were excluded because of search overlap, because they dealt with population without the inclusion criteria or because they did not contain original research.
Case reports were also excluded as the information was regarded as too fragmentary. Two articles were added by additional sources. A total of eleven studies was therefore reviewed in detail and included in the review.
The main characteristics of these studies are summarized in Table 1. Six studies were randomized controlled trials [3][4][5][6][7][8]one was a non-randomized controlled trial [9]three were prospective uncontrolled studies [10][11][12] and one was a retrospective study [13].
The number of participants included in each study ranged from 4 [10] to [6]. The severity of renal function impairment was variable. MacLaughlin [9] included patients with CKD stage 3 to 5.
In Matsuoka [13] and Castaneda [3] all participants had CKD but the severity was not specified. The study of Sigal [6] excluded participants with a serum creatinine above 2. Two studies [7][10] focused on hemodialysis patients.
The prevalence, type and duration of diabetes, as well as glycaemic control, differed between studies. Castaneda [3] selected type-2 diabetics with a disease history of at least 3 years and a mean HbA1c of 8.
Patients studied by Sigal [6] had type 2 diabetes of at least 6 months of duration, mean HbA1c was between 6. All patients of Solerte [11] were obese type 1 or 2 diabetics, mean HbA1c was not specified. In Saiki [12] all patients had diabetes type 1 or 2 with a mean HbA1c of 7. In the study of Matsuoka [13] all the participants had diabetes with no further specification of the type or severity.
The mean HbA1c was 6. Thirty-two and forty-one percent of the participants in the study of Maclaughlin [9] and Chen [4]respectively, were diabetics of either type.
All studies excluded participants with any unstable clinical condition such as heart disease, cancer or rapidly progressive kidney disease. Five studies [3][5][6][10][13] involved physical exercise to improve energy balance.
Three studies examined the effects of a dietary intervention [8][11][12]which consisted respectively of an energy reduction of kcal per day and protein content adjusted to 1 to 1. In one study the participants got a combined dietary and aerobic exercise programme, in combination with behavioural therapy and a pharmacological intervention [9].
In two other studies [4][7] the intervention consisted of exercise advice and counselling. The study quality of RCTs was variable. In Sigal [6]central randomization was used, with allocation concealment before randomization and block sizes varied randomly between 4 and 8.
In Tawney [7]patients were randomized to the intervention or control group with a frequency matching strategy based on age group 18 to 44, 45 to 64, and 65 years or oldersex, diabetes as cause of ESRD, and ethnicity. Data on random sequence generation and allocation concealment were not provided in any of the other RCTs included.
In Sigal [6]to permit blinding of the research coordinator, the personal trainer rather than the research coordinator handled the randomization visit. Performance and detection bias were high in the remaining RCTs which were all not blinded. Reporting bias was low in all studies as all the outcomes defined were reported.
The general quality of observational studies was low to moderate. None of the studies reviewed included patient survival as a study outcome. In the study of Tawney [7]three deaths occurred in the group receiving the physical rehabilitation program vs.
one in the control group but no details were available on whether these deaths were related to the intervention.
None of the studies reviewed were specifically designed to evaluate MACEs as a study outcome. In the paper of Castaneda [3]three patients in the resistance exercise group had a minor episode of angina pectoris, of which one was hospitalised. One subject in the aerobic exercise group in the study of Sigal [6] was diagnosed with angina pectoris without need for hospitalisation.
Morales [8] reported no changes in mean serum creatinine or creatinine clearance after a dietary intervention with energy intake reduction of kcal per day and limited protein intake.
This can be explained by loss of muscle mass or reduced intake of proteins since the value is an estimated GFR based on serum creatinine. There were 3 transplants in the weight management program group 2 live related donor kidney transplants, 1 cadaveric donor kidney transplant and 1 transplant in the usual-care group live related donor kidney transplant.
Conversely, no significant changes in eGFR were reported by Leehey [5] after an aerobic exercise intervention. In the retrospective cohort study of Matsuoka [13]maintenance of a physical active daily life did not affect progression to dialysis. Aerobic exercise regimens during and between hemodialysis sessions had no effect on serum creatinine levels or dialysis dose required [10].
In Morales [8]hour proteinuria was significantly reduced at the end of the study in subjects undergoing a diet program as compared with the control group 1. Conversely, no significant changes in this parameter were noticed after exercise or counselling interventions [5][13].
As compared with no exercise, resistance exercise significantly reduced mean HbA1c 7. Two small studies showed that low intensity aerobic exercise did not influence the mean blood glucose [10] or mean HbA1c [5]. Another larger study found that exercise advice alone without supervision or control of the exercise did not alter mean blood glucose levels [4].
: Caloric restriction and kidney function| Can Calorie Restriction Improve Progressive Kidney Function Decline? | Conversely, high Calogic exerts a protective effect on survival [18][19]. Obesity Studies September 15 Main Text. Received : 15 October Tomobe, K. |
| Patient eligibility | Caloric restriction Csloric -mediated organ restrictuon caloric restriction and kidney function been shown to be extremely efficient in wnd models of kirney kidney injury AKI. The Guideline Development Group Creatine benefits explained that restrictiln consists restrictoon Henk Bilo, Prediabetes resources Bolignano, Louis Coentrao, Cecile Couchoud, Adrian Liver Health Awareness Campaign, Christiane Drechsler, Johan Ad Sutter, David Calorlc, Luigi Gnudi, Kitty Caloric restriction and kidney function, James Restrictiin, Olle Heimburger, Hakan Nacak, Caloric restriction and kidney function Soler, Charlie Tomson, Wim Van Biesen, Liesbeth Van Huffel, Steven Van Laecke, Laurent Weekers, Andrzej Wiecek. Findings of this study showed that regular moderate-intensity exercise before induction of AKI reduces injury, inflammation and oxidative stress following AKI and also leads to less reduction in SIRT1 in those with previous exercise compared to those without exercise. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. Ibrahim A, Al-Hizab FA, Abushouk AI, Abdel-Daim MM. There is insufficient evidence to evaluate the effect of negative energy balance interventions on mortality in diabetic patients with advanced CKD. Zhaleh F, Amiri F, Mohammadzadeh-Vardin M, Bahadori M, Harati MD, Roudkenar MH, et al. |
| Top bar navigation | In addition, DR improves transplant outcomes from young donors by reducing ischemic damage during transplantation van Ginhoven et al. To improve kidney function, a low-calorie or ketogenic diet is recommended for people with obesity accompanied by mild renal insufficiency Bruci et al. Dietary interventions are also recommended for patients with CKD and can ameliorate glomerular filtration rate, lower blood pressure, and serum cholesterol levels, thereby improving health-related quality of life Palmer et al. While the potential of DR to reduce the severity of AKI has been confirmed in experiments with young animals, the largest and most vulnerable group of patients with AKI and CKD is represented by the elderly. The average age of patients with AKI tends to 65 years and steadily decreases every year due to an increase in life expectancy Mehta et al. Accordingly, experimental models should use old animals to consider the structural, functional, and molecular changes observed in kidneys during aging. Aging not only affects the morphology and metabolism of kidney tissue but also worsens ischemic tolerance and increases tissue vulnerability to injury Rosner et al. On the other hand, it has been suggested that life-long DR is most effective in preventing the development of age-related changes in the renal tissue meaning dieting should begin at a young age to protect the old kidney. Indeed, DR started at an early age substantially improved age-associated renal histological abnormalities and survival Bras and Ross, Life-long DR prevented the development of gradually increasing morphological changes in the kidney, such as glomerular lesions, thickening of the basement membrane, and tubular dilatation. Moreover, long-term DR has been proved to significantly extend life span and to ameliorate age-related polycystic kidney disease and CKD Tomobe et al. In rats, DR for 30 months with reduced total calorie intake or protein content retarded the severity of age-related chronic nephropathy Masoro et al. However, some studies have demonstrated that not only life-long DR but also short-term DR protocols are effective against age-associated abnormalities in kidneys. DR initiated in rats of 6 months of age was as effective as food restriction initiated at 6 weeks of age in slowing the progression of chronic nephropathy Maeda et al. Moreover, DR initiated in middle-aged rats, before the onset of significant age-related changes, as well as long-term DR effectively reduced glomerulosclerosis and tubular atrophy, prevented the formation of interstitial fibrosis, thickening of the vascular wall, and the decrease of cytochrome c oxidase expression McKiernan et al. The manifestation of the positive effects of DR even at the debut in adulthood encourages the study of short-term DR protocols due to the great interest in clinical practice which is faced with the complexity of life-long dieting in people. To date, an active investigation of the effects of DR on old animals continues. Transcriptome analysis of renal tissue after life-long DR showed that DR modulates the expression of many genes in old rats and has benefits for kidney function Chen et al. It was found that the expression of 92 genes changed during aging and was reversed by DR for 22 months, including claudin-7, Kim-1, and MMP-7 Chen et al. In addition, the study of the single-cell transcriptional landscape after 9 months of DR revealed significant changes in the expression profile of a large number of genes, including those affecting the process of cellular senescence, stem cell depletion, chronic inflammation, and cell-to-cell communication Ma et al. Adult-onset DR for 6 months also dramatically changed the gene profile, significantly reduced urinary 8-isoprostane and protein carbonyl in the kidney and downregulated inflammatory response pathway Chen et al. The molecular mechanisms of DR in old organisms look similar to young animals. For instance, DR in both young and old rats reduced the pro-inflammatory response from NF-kB and AP-1 and normalized the network of these transcription factors in the renal tissue of old animals Jung et al. Old rats that underwent long-term DR showed higher expression of sirtuin 1 in kidney tissue, a higher degree of autophagy activation, shifted acetylation status of transcriptional growth factors to a more deacetylated state, and an improvement in the functional activity of mitochondria Kume et al. Rats exposed to DR in adulthood had lower levels of renal fibrosis and levels of extracellular matrix proteins type IV collagen and fibronectin Jiang et al. Unsurprisingly, DR affected energy metabolism and mitochondrial functions. The beneficial effects of adult-onset DR manifested in a decreased accumulation of abnormally folded proteins in the kidney mitochondria in old animals McKiernan et al. DR for 3 months in old rats significantly upregulated arginase II activity, which normally regulates urea cycle, polyamine, proline, glutamate synthesis, and production of nitric oxide Majaw and Sharma, Late-onset DR reversed the age-related decline of malate—aspartate shuttle enzymes in the kidneys Goyary and Sharma, The spectrum of mitochondria-associated effects of DR also included as follows: increase in the levels of the anti-apoptotic protein Bcl-X L , normalization of mitochondrial ultrastructure, diminished oxidative stress Cui et al. Note that despite a number of positive changes at the molecular level caused by DR, there are only a few studies that describe the effects of DR on kidney function in AKI. The loss of DR effectiveness during aging is more likely to have a gradual pattern since in month-old rats DR still demonstrated some nephroprotective effect, but to a lesser extent than in young animals Andrianova et al. Most fruitful experimental studies of various DR protocols have been conducted in young animals Singh and Krishan, , while a few studies of DR protection in renal injury have shown a decline in beneficial effects with age Andrianova et al. This raises the question of implementation of DR in clinical practice since elderly people predominate among patients with AKI, so additional studies are needed to improve the effectiveness of DR for the aged kidney. The loss of protective effects of therapeutic methods with age is a significant problem not only for DR but also for other treatment approaches. Earlier, a similar loss of positive impact was described when applying ischemic pre- and postconditioning for kidney and heart of old animals Abete et al. Similarly, in elderly mice, DR did not improved impaired wound healing Reed et al. We hypothesize that the loss of protective properties is a natural and common phenomenon for the majority of therapeutic approaches Jankauskas et al. Thus, not all tissues and systems show improvements during DR with age. For instance, despite the observation that DR ameliorated the state of blood vessels and their response to the vasoconstrictive effect of endothelin-1 in young rats, such positive effects were absent in old rats after short-term DR Amor et al. Moreover, moderate DR stimulated angiogenesis to a very small extent in month-old rats Facchetti et al. The state of the immune system in old animals did not improve during DR either. Insufficient efficiency of DR in old animals is also observed for the hormone levels. In contrast to the leptin level, which decreased during DR in both young and old animals, the adiponectin concentration increased only in young rats Rohrbach et al. Moreover, short-term DR had different effects on lipogenic enzymes in the white adipose tissue of young and old rats demonstrating a reduced adaptation of old animals to a restricted diet Wronska et al. Only life-long DR increased the content of thyroid hormones of rhesus monkeys, whereas short-term DR did not affect the level of thyroid hormones in old animals Roth et al. The observed loss of protective properties of therapies can be partially explained by various age-dependent changes that accumulate in all tissues and affect the functioning and tolerance of organs Rezzani et al. Thus, in the kidney, both structural changes consisting of a decrease in the number of functioning nephrons, degenerative changes in the proximal tubules, glomerulosclerosis, and changes in molecular pathways are observed, e. Aging also leads to significant epigenetic changes at all levels of chromatin and DNA organization López-Otín et al. Significant metabolic shifts accompany aging leading to impaired lipid and carbohydrate metabolism and loss of nutrient-sensing pathways Ehrhardt et al. There are malfunctions in DR-mediated pathways in the elderly including those with IGF-1R, AMPK, sirtuins, and mTOR Bettedi and Foukas, Aging is also associated with cellular senescence, which causes such detrimental phenomena as chronic inflammation Furman et al. The accumulation of senescent cells could lead to greater sensitivity to injury and reduced tissue repair. Endocrine functions are also disrupted with age and the kidneys are no exception Bolignano et al. In particular, the content of the components of the renin-angiotensin system and the levels of aldosterone decrease in blood plasma Yoon and Choi, Although the concentration of erythropoietin in the blood is higher in the elderly compared to the young, there is no pronounced erythropoiesis in response to a drop in hemoglobin levels in elderly Ferrucci et al. The transformation of vitamin D into the active form, which largely occurs in the kidneys, also suffers with aging Armbrecht et al. Despite an increase in the levels of adiponectin in the blood of old organisms, adiponectin-dependent regulation is disrupted and aging is paradoxically associated with the loss of the functionally active isoform of the hormone Gulcelik et al. An important age-related disorder is the deterioration of cellular quality control systems for proteins and organelles. With age, both the dysfunction of the autophagic-lysosomal system Mizushima et al. This inevitably leads to the accumulation of aggregates of misfolded proteins Hipp et al. The accumulation of poorly functioning mitochondria is dangerous for cells as it can cause increased oxidative stress Liguori et al. Changes in the morphology of mitochondria with age have been described for many organisms Sastre et al. Thus, DR is considered a promising approach for the treatment of various age-related diseases, including AKI and CKD. However, some studies reveal a gradual loss of effectiveness of DR with age, which is alarming given the advanced age of patients with AKI and CKD. The adult-onset DR leads to a number of positive changes, but they affect much fewer pathways, so old organisms after DR cannot develop such high improvements and tolerance as young healthy organisms do Figure 1. We postulate that the loss of the nephroprotective properties of DR is part of a natural and general phenomenon inherent in most therapeutic approaches, and this may be due to the accumulation of deleterious changes at the physiological, cellular, and molecular levels during aging. These changes lead to the deterioration of a stress response and reduced adaptation to limited calorie intake. Thereby, the further studies of the DR mechanisms are required to improve the DR effectiveness in elderly organisms. Figure 1. Gradual reduction of the DR protective effects from injuries and age-related changes. In young animals, DR is accompanied by many positive changes, such as enhanced response of nutritional and stress-sensing pathways, metabolic shifts toward lipid utilization and ketone bodies production, autophagy and proteasome activation, improvement in mitochondria functioning, reduced oxidative stress and inflammation, and subsequent resistance to injuries, including ischemic ones. In old animals, DR is associated with a smaller range of positive changes, such as delaying age-related changes and the formation of fibrosis, reducing the number of senescent cells, oxidative stress, and chronic inflammation. NA and EP conceived the manuscript and developed the idea. NA wrote the review. MB and AB helped to collect the data and drafted the manuscript. EP and DZ critically revised and improved the content of the manuscript. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Abete, P. Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats. Heart Circ. doi: PubMed Abstract CrossRef Full Text Google Scholar. Alidadi, M. The effect of caloric restriction and fasting on cancer. Cancer Biol. CrossRef Full Text Google Scholar. Amor, S. Effects of age and caloric restriction in the vascular response of renal arteries to endothelin-1 in rats. Andrianova, N. Mechanisms of age-dependent loss of dietary restriction protective effects in acute kidney injury. Cells Resemblance and differences in dietary restriction nephroprotective mechanisms in young and old rats. Aging 12, — Armbrecht, H. Effect of age on the conversion of hydroxyvitamin D3 to 1,dihydroxyvitamin D3 by kidney of rat. Bettedi, L. Growth factor, energy and nutrient sensing signalling pathways in metabolic ageing. Biogerontology 18, — Boengler, K. Cardioprotection by ischemic postconditioning is lost in aged and STAT3-deficient mice. Bolignano, D. The aging kidney revisited: a systematic review. Ageing Res. Bras, G. Kidney disease and nutrition in the rat. Bruci, A. Very low-calorie ketogenic diet: a safe and effective tool for weight loss in patients with obesity and mild kidney failure. Nutrients Cantó, C. Calorie restriction: is AMPK a key sensor and effector? Physiology 26, — Chen, G. Increased susceptibility of aging kidney to ischemic injury: identification of candidate genes changed during aging, but corrected by caloric restriction. Renal Physiol. Chen, J. Identifying the changes in gene profiles regulating the amelioration of age-related oxidative damages in kidney tissue of rats by the intervention of adult-onset calorie restriction. Rejuvenation Res. Chen, H. Aged kidneys are refractory to ischemic postconditioning in a rat model. Csiszar, A. Circulating factors induced by caloric restriction in the nonhuman primate Macaca mulatta activate angiogenic processes in endothelial cells. A Biol. Cui, J. Age-related changes in the function of autophagy in rat kidneys. Age 34, — Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys. PLoS One 8:e Di Micco, R. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Cell Biol. Dong, D. Oncotarget 8, — Ehrhardt, N. One major strength was the PROBE design, which allowed blinded analyses of outcome variables despite the open design, and at the same time, minimized costs and closely reflected standard clinical practice, which should make the results more easily applicable in routine medical care Changes in considered variables over the follow-up period were consistent and uniformly confirmed the potential beneficial effect of CR on a series of renal and cardiovascular risk factors. The CR-induced negative energy balance results in substantial improvements of several major risk factors for the initiation and progression of CKD in patients with diabetes with abdominal obesity and no evidence of renal involvement. In particular, CR and weight loss, along with amelioration of insulin resistance and other functional and metabolic abnormalities, achieved a significant short-term reduction in the GFR that conceivably reflected amelioration of glomerular hyperfiltration and that resembled the reduction observed after an invasive procedure such as bariatric surgery 8. Long-term randomized clinical trials are needed to assess whether CR may achieve clinically relevant protection against progressive renal function loss and development of nephropathy in the long-term as well as reduce overall patient cardiovascular risk. Clinical trial reg. NCT, clinicaltrials. See accompanying article, p. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. wrote the final version of the manuscript. wrote the study protocol. contributed to data analyses and interpretation. had the original idea. identified, treated, and monitored study participants and contributed to data recording. and G. prescribed CR or SD and monitored compliance to the recommended diets. and L. wrote the first draft. and A. performed the statistical analyses. monitored the study. prepared the database and helped in data handling. performed the GFR measurements and laboratory tests. All of the authors had direct access to original data, critically revised the draft, and approved the final manuscript. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 66, Issue 1. Previous Article Next Article. Research Design and Methods. Article Information. Article Navigation. Obesity Studies September 15 Renal and Systemic Effects of Calorie Restriction in Patients With Type 2 Diabetes With Abdominal Obesity: A Randomized Controlled Trial Piero Ruggenenti ; Piero Ruggenenti. This Site. Google Scholar. Manuela Abbate ; Manuela Abbate. Barbara Ruggiero ; Barbara Ruggiero. Stefano Rota ; Stefano Rota. Matias Trillini ; Matias Trillini. Carolina Aparicio ; Carolina Aparicio. Aneliya Parvanova ; Aneliya Parvanova. Ilian Petrov Iliev ; Ilian Petrov Iliev. Giovanna Pisanu ; Giovanna Pisanu. Annalisa Perna ; Annalisa Perna. Angela Russo ; Angela Russo. Olimpia Diadei ; Olimpia Diadei. Davide Martinetti ; Davide Martinetti. Antonio Cannata ; Antonio Cannata. Fabiola Carrara ; Fabiola Carrara. Silvia Ferrari ; Silvia Ferrari. Nadia Stucchi ; Nadia Stucchi. Giuseppe Remuzzi ; Giuseppe Remuzzi. Corresponding author: Giuseppe Remuzzi, giuseppe. remuzzi marionegri. Luigi Fontana ; Luigi Fontana. Louis, St. Louis, MO. on behalf of the C. Study Group on behalf of the C. Study Group. and M. contributed equally to this research. Diabetes ;66 1 — Article history Received:. Connected Content. A reference has been published: In This Issue of Diabetes. A commentary has been published: Back to the Future: Glomerular Hyperfiltration and the Diabetic Kidney. Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Figure 1. View large Download slide. Table 1 Baseline and 6-month primary and secondary outcome measures in the two study groups. baseline within the same treatment group;. View Large. Table 2 Baseline and 6-month metabolic parameters and daily diet macro- and micronutrients in the two study groups. MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acids. Table 3 Patients with concomitant medications at baseline and at the 6-month follow-up in the two treatment groups. Concomitant medications. Figure 2. Figure 3. Correlation analyses. Multivariable analyses. P value. Table 5 Serious and nonserious adverse in the two treatment groups. CR was also associated with other clinically relevant functional and metabolic effects:. The sponsors had no role in conducting study and reporting the results. Search ADS. Glomerular hyperfiltration in the prediction of nephropathy in IDDM: a year follow-up study. Renal hyperfiltration related to diabetes mellitus and obesity in human disease. Marked association between obesity and glomerular hyperfiltration: a cross-sectional study in an African population. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Overweight, obesity, and the development of stage 3 CKD: the Framingham Heart Study. Metabolically healthy obesity and development of chronic kidney disease: a cohort study. The effects of weight loss on renal function in patients with severe obesity. Tsai AG, Wadden TA. In the clinic: obesity. Ann Intern Med ;ITC—ITC; quiz ITC13— Despite the considerable burden associated with AKI, effective therapeutic and preventive approaches are currently lacking. Since impaired cellular stress-resistance contributes to the development of AKI, preconditioning protocols that augment renal resilience, such as caloric restriction CR , are attractive strategies in the search for organ protection. CR has originally been extensively studied in the context of aging, since it extends lifespan and improves both general and metabolic health across taxa [1]. Recently, it has been shown that CR protects from toxic AKI and renal ischemia-reperfusion injury IRI in rodents []. Limited understanding of the underlying mechanisms has hindered the clinical translation of this immense potential. In this mini-review, we focus on evolutionary conserved molecular mechanisms in response to CR augmenting renal stress-resistance. CR has become of special interest to nephrologists, as it augments renal protection and prevents kidney damage in rodent models of IRI and toxic AKI []. However, CR has not made its way to the clinical setting, partly due to problems regarding feasibility and potential safety concerns. Lack of knowledge regarding normal food and calorie intake especially in elderly multimorbid patients makes trial design complicated. Concealed adherence problems may occur in the CR group due to difficulties regarding food intake surveillance on the one hand. On the other hand, unintended dietary restriction may occur in the control group due to expectations regarding outcome improvement. Additionally, blinding is often difficult in trials examining dietary interventions. Despite the fact that this is enabled when using formula diets, a reduction in caloric intake may easily be noticed by the participants as a consequence of the sensation of hunger. Moreover, recruitment of patients may be limited by lack of motivation to restrict dietary habits before a surgical intervention. Besides, safety concerns, especially in elderly, frail, and severely ill patients, may play a role with prolonged CR [6, 7]. Consequently, developing an increasing knowledge of the underlying molecular mechanisms orchestrating cellular stress-resistance will help to facilitate translation, for example, by identification of targets for pharmacological interventions. Current mechanistic concepts of CR-mediated resilience propose a modulation of several metabolic pathways that will be presented in the following. Improved insulin sensitivity has also been observed to be shared in both genetic and dietary models of longevity and stress-resistance. CR leads to reduced renal levels of Ghr and IGF-1 mRNA and of their associated signaling pathways as well as an elevated expression of antioxidant defense enzymes in the kidney [8]. Furthermore, stress-resistance modulated by CR in renal IRI has been identified to be associated with repression of mammalian target of rapamycin mTOR and AMP-activated protein kinase AMPK activation prior to renal IRI in rodents [9]. mTOR is an evolutionary conserved kinase involved in growth and metabolism which is strongly modulated by nourishment and starvation as well as insulin signaling across taxa. Although there has been profound basic and translational research over the last decades, the role of mTOR in AKI and preconditioning remains controversial. mTOR consists of 2 distinct complexes, the mechanistic target of rapamycin complex 1 mTORC1 and 2 mTORC2 , with different functions. mTORC1 is an upstream inhibitor of autophagy and can be inhibited by rapamycin pharmacologically, resulting in lifespan extension and increased stress-resistance in various longevity models [ 10 ]. As mTORC1 has a critical role in sensing nutrients and insulin, it appears reasonable to assume that CR benefits depend on reduced mTORC1 levels, too. Of note, CR does not extend life-span in yeast, worm, and flies with reduced mTORC1 activity suggesting overlapping mechanisms of resilience by CR and mTORC1, such as an increase in autophagy and a decrease in mRNA translation and protein metabolism limiting proteotoxic and oxidative stress [ 10 ]. In contrast, mTORC2 is not affected by rapamycin and contributes to the CR-mediated improvement of insulin sensitivity, but its disruption in an adipose-specific RICTOR knockout mouse inducing insulin resistance does not alter the CR-induced increase in metabolic health and lifespan [ 11 ]. Overall mTOR activity is low in kidney tissue. However, its activity is significantly induced during the reperfusion period after renal IRI in rats, which can reasonably be assumed to be a consequence of the sudden availability of growth factors, amino acids, and adenosine triphosphate [ 12 ]. Inhibition of mTORC1 by rapamycin during reperfusion in renal IRI delays recovery of kidney function in rats and — in line with this finding — is associated with delayed graft function in humans [ 12 ]. Therefore, inhibition of mTOR by CR or rapamycin may be beneficial in renal IRI, for example, by induction of autophagy when applied before damage but appears to impair the natural response to IRI and regeneration [ 13 ]. However, it has to be noted that data on postconditioning by, for example, rapamycin treatment in AKI models are lacking. In contrast to these findings, the beneficial effects of mTOR inhibition appear to be more straightforward in sepsis or cisplatin-induced AKI models in mice and mainly employ the induction of tubular cell autophagy and the alleviation of cell death [ 14, 15 ]. Taken together, the role of mTOR inhibition in nephroprotection and AKI appears to depend on its exact timing as well as the type of damage and may also be subject to species-dependent differences. AMPK signaling is an additional pathway that is closely connected to both mTOR and CR. AMPK is a key regulator of cellular and mitochondrial health, as it serves as an energy sensor regulating cellular metabolism and homeostasis. Additionally, AMPK promotes both mito- and autophagy. Under conditions of CR, mTORC1 is suppressed allowing activation of AMPK and the induction of autophagy. Additionally, activated AMPK suppresses the regulatory-associated protein of mTOR RAPTOR inhibiting mTORC1. AMPK activates its downstream target, the nicotinamide adenine dinucleotide NAD -dependent type III deacetylase sirtuin 1 SIRT1 , by increasing cellular NAD levels. Promoting autophagy by pharmacological inhibition of mTORC1 or activation of AMPK as well as by CR protects from both ischemic and toxic AKI in rodents [ 16 ]. Besides, considering the growing knowledge on the impact of NAD in renal IRI, it will be intriguing to characterize a potential role of CR in this context [ 17 ]. Beyond the impact on mTOR and AMPK signaling described above, CR activates the transsulfuration pathway TSP resulting in the generation of hydrogen sulfide H 2 S , which is associated with anti-inflammation, reduction of reactive oxygen species ROS , and adaptations in lipid metabolism. The TSP-mediated generation of H 2 S by CR is evolutionary conserved across taxa as determined in different longevity models [1]. Furthermore, the endogenous generation of H 2 S has been identified to be essential for CR benefits in a rodent model of hepatic IRI [ 18 ]. Supplementation of the sulfur-containing amino acids SAA methionine and cysteine, mTORC1 activation, or inhibition of the TSP enzyme cystathionine γ-lyase CGL decrease the production of H 2 S and counteract CR-orchestrated stress-resistance in rodents. The SAA methionine and cysteine are metabolized through the TSP. Their restriction results in an elevation of endogenous TSP activity generating H 2 S in the kidney. Besides, dietary restriction of SAA has additionally been widely studied in the context of longevity and age-associated diseases across taxa, as it efficiently augments stress-resistance revealing various shared mechanisms with CR [1]. Of note, H 2 S generation by the gut microbiota in response to a high-SAA diet was recently described to protect from uremic toxicity and disease progression in a rodent CKD model [ 19 ]. In contrast to human tissue including the kidney, liver, and brain, where SAA shortage leads to the endogenous production of H 2 S through the activated TSP, cysteine desulfhydrases in gut bacteria directly convert cysteine to H 2 S, pyruvate, and ammonia explaining these seemingly conflicting observations [ 18, 19 ]. Gut microbiota have been recognized as a central modulator of cardiovascular and renal disease during the last decade. Consequently, the impact of CR on microbiota is expected to be an important aspect. |
| Brief Title:Effect of a Preoperative Calorie Restriction on Renal Function After Cardiac Surgery | Ann Transl Med ;9 12 Accordingly, a weight Role of exercise in maintaining blood sugar levels of mainly fat tissue Restrkction a gain of Thermogenic metabolism enhancement mass, as is obtained with physical restricrion, should be favourable. Anthocyanins and skin protection from UV damage consistently testriction by 1. Assessment per time point showed no significant differences of absolute serum creatinine concentrations between groups throughout the postoperative follow-up Figure 3A. Independent of involved mechanisms, amelioration of the functional and metabolic parameters mentioned above can be seen in the context of an overall amelioration of metabolic syndrome and are expected to translate into a clinically relevant reduction in long-term cardiovascular risk. |
| Introduction | Twelve M old rats had significantly higher renal dysfunction as assessed by 24 h urine protein content The same parameters were also evaluated in 12 M old SD rats on CR 12 M-CR to determine the effect of CR on renal dysfunction and metabolic parameters. Ageing associated fibrotic changes were reduced as evident by PAS staining Figure 1A ; bottom panels. Body weight in 12 M-CR rats The 24 h urine protein content in the 12 M-CR rats Taken together, these results indicate that within the context of the SD rats used in the current study, CR is associated with the reversal of age-related changes in renal dysfunction and altered lipid metabolism. Ageing induced oxidative damage results in activation of the NF-κB signaling pathway ultimately leading to a cytokine storm Indeed, ageing is associated with a pro-inflammatory shift in the vascular cytokine expression profile Given the critical role of the renal artery in renal perfusion 8 , and that ageing is an independent risk factor for both impaired renal function and vascular disorders 9 , we next determined if the expression of pro-inflammatory cytokines increased in the renal artery with ageing, and if such an increase could be reversed by CR. We found ageing significantly increased mRNA expression of the inflammatory cytokines of IL-6, IL-1β , TNF-α , and TGF-β1 in the renal artery Figure 2A. The expression of all four mRNAs was significantly decreased in the 12 M-CR group compared to the 12 M group Figure 2A. ELISA results showed a similar significant increase in serum IL-6 CR significantly decreased secretion of IL-6 Cumulatively, these results show that CR is associated with the reversal of ageing induced expression of mRNA encoding pro-inflammatory cytokines in the renal artery and their serum levels. Given that it has been earlier reported that ageing is associated with an increase in ET-1 expression in renal vasculature, which in turn increases the expression of LOX-1 and results in increased uptake of ox-LDL 17 , 20 , 22 , we next determined if the expression of ET-1 and LOX-1 changed within our model system, and if such changes were affected by CR. We found ageing induced significant increases in Edn1 which encodes ET-1 and Olr1 which encodes LOX-1 mRNA expression in the renal artery of 12 M old rats compared to 2 M old rats Figure 3A. Expression of both Edn1 and Olr1 mRNA was significantly decreased in the renal artery of 12 M-CR rats Figure 3A. Immunoblot analysis revealed significant increases in ET-1 and LOX-1 protein expression in the renal artery of 12 M rats compared to 2 M rats ET 3. CR significantly decreased both ET-1 2. Cumulatively, these results indicate that CR is associated with the inhibition of ageing-induced increases in the expression of ET-1 in the renal artery. Given that the expression of ET-1 increases with ageing, which is reversed by CR, we next asked how CR impacts the expression of ET-1 in the renal artery. The transcription factor NF-E2-related factor 2 Nrf2 plays a central role in mitigating oxidative stress in healthy cells and is inactivated in ageing cells 33 , Oxidative stress mediated activation of NF-κB signaling has been shown to regulate transcription of Edn1 in multiple cell types including endothelial cells 35 - The Edn1 promoter has functional binding elements at position base pairs for NF-κB CR can decrease oxidative stress partially by inducing histone deacetylase and gene repressor sirtuin 1 SIRT1 , which has been shown to decrease the production of ROS 24 , 26 , Immunoblot analysis showed significant increases in phosphorylated P65 7. Phosphorylation of IκBα led to its degradation, releasing P65, which can be phosphorylated and translocated to the nucleus, ultimately resulting in transcriptional upregulation of target genes of the NF-κB signaling pathway Expression of Nrf2 5. However, phosphorylated P65 and IκBα were significantly downregulated, whereas expression of Nrf2 and SIRT1 were upregulated, in the renal arteries of 12 M-CR rats Figure 4. These results cumulatively indicate that ageing mediated activation of ET-1 expression is potentially being mediated by the activation of NF-κB signaling, whereas CR inhibits ET-1 expression both by inactivation of NF-κB signaling and activation of Nrf2-SIRT1. Life expectancy is projected to increase to 91 years for women and 88 years for men by 29 and age related chronic kidney disease is already becoming a serious medical concern associated with ageing 3 , 4 , 7 , 14 , 29 , 40 , Hence it is of paramount importance to define underlying pathogenic mechanisms associated with ageing-induced renal dysfunction and identify potential therapeutic targets. CR, a reduction in calorie intake without malnutrition, is a powerful intervention known for decades to slow down aging and increase lifespan across different species 42 - Given the critical role of the renal arterioles in renal perfusion 8 , and ageing is an independent risk factor for both impaired renal function, the results are potentially applicable to renal dysfunction in ageing. Our results corroborate previous findings that CR can prevent impaired renal function 6. Indeed, inhibition of ET-1 activity by the use of antagonists against its receptors are already in different stages of pre-clinical and clinical studies 8 , 22 , 45 , Our results suggest that CR, alone or in combination with endothelin receptor antagonists, should be tested in pre-clinical studies to test its efficacy in rescuing ageing-induced renal dysfunction. 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The age-associated loss of ischemic preconditioning in the kidney is accompanied by mitochondrial dysfunction, increased protein acetylation and decreased autophagy. Aged kidney: can we protect it? Autophagy, mitochondria and mechanisms of ischemic preconditioning.
Cell Cycle 17, — Jiang, T. Calorie restriction modulates renal expression of sterol regulatory element binding proteins, lipid accumulation, and age-related renal disease. Johnson, S. Subcellular Biochemistry. Harris and V. Korolchuk Springer, Singapore , 49— Google Scholar. Jongbloed, F. Protein and calorie restriction may improve outcomes in living kidney donors and kidney transplant recipients.
A signature of renal stress resistance induced by short-term dietary restriction, fasting, and protein restriction. Jung, K. Effect of short term calorie restriction on pro-inflammatory NF-κB and AP-1 in aged rat kidney.
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van Ginhoven, T. Pre-operative dietary restriction is feasible in live-kidney donors. Cumulatively, these results show that CR is associated with the reversal of ageing induced expression of mRNA encoding pro-inflammatory cytokines in the renal artery and their serum levels.
Given that it has been earlier reported that ageing is associated with an increase in ET-1 expression in renal vasculature, which in turn increases the expression of LOX-1 and results in increased uptake of ox-LDL 17 , 20 , 22 , we next determined if the expression of ET-1 and LOX-1 changed within our model system, and if such changes were affected by CR.
We found ageing induced significant increases in Edn1 which encodes ET-1 and Olr1 which encodes LOX-1 mRNA expression in the renal artery of 12 M old rats compared to 2 M old rats Figure 3A. Expression of both Edn1 and Olr1 mRNA was significantly decreased in the renal artery of 12 M-CR rats Figure 3A.
Immunoblot analysis revealed significant increases in ET-1 and LOX-1 protein expression in the renal artery of 12 M rats compared to 2 M rats ET 3. CR significantly decreased both ET-1 2. Cumulatively, these results indicate that CR is associated with the inhibition of ageing-induced increases in the expression of ET-1 in the renal artery.
Given that the expression of ET-1 increases with ageing, which is reversed by CR, we next asked how CR impacts the expression of ET-1 in the renal artery. The transcription factor NF-E2-related factor 2 Nrf2 plays a central role in mitigating oxidative stress in healthy cells and is inactivated in ageing cells 33 , Oxidative stress mediated activation of NF-κB signaling has been shown to regulate transcription of Edn1 in multiple cell types including endothelial cells 35 - The Edn1 promoter has functional binding elements at position base pairs for NF-κB CR can decrease oxidative stress partially by inducing histone deacetylase and gene repressor sirtuin 1 SIRT1 , which has been shown to decrease the production of ROS 24 , 26 , Immunoblot analysis showed significant increases in phosphorylated P65 7.
Phosphorylation of IκBα led to its degradation, releasing P65, which can be phosphorylated and translocated to the nucleus, ultimately resulting in transcriptional upregulation of target genes of the NF-κB signaling pathway Expression of Nrf2 5. However, phosphorylated P65 and IκBα were significantly downregulated, whereas expression of Nrf2 and SIRT1 were upregulated, in the renal arteries of 12 M-CR rats Figure 4.
These results cumulatively indicate that ageing mediated activation of ET-1 expression is potentially being mediated by the activation of NF-κB signaling, whereas CR inhibits ET-1 expression both by inactivation of NF-κB signaling and activation of Nrf2-SIRT1.
Life expectancy is projected to increase to 91 years for women and 88 years for men by 29 and age related chronic kidney disease is already becoming a serious medical concern associated with ageing 3 , 4 , 7 , 14 , 29 , 40 , Hence it is of paramount importance to define underlying pathogenic mechanisms associated with ageing-induced renal dysfunction and identify potential therapeutic targets.
CR, a reduction in calorie intake without malnutrition, is a powerful intervention known for decades to slow down aging and increase lifespan across different species 42 - Given the critical role of the renal arterioles in renal perfusion 8 , and ageing is an independent risk factor for both impaired renal function, the results are potentially applicable to renal dysfunction in ageing.
Our results corroborate previous findings that CR can prevent impaired renal function 6. Indeed, inhibition of ET-1 activity by the use of antagonists against its receptors are already in different stages of pre-clinical and clinical studies 8 , 22 , 45 , Our results suggest that CR, alone or in combination with endothelin receptor antagonists, should be tested in pre-clinical studies to test its efficacy in rescuing ageing-induced renal dysfunction.
CR improved 24 h urine protein and also serum triglyceride and cholesterol, corroborating previous findings of an intricate relationship between lipid metabolism and ageing in the kidney 47 - ET-1 is an important player in the development of renal disease 51 , as renal arteries are particularly sensitive to it Our results also suggest that ET-1 has direct effects on the renal artery, in regulating the pro-inflammatory factors which are mediated by LOX-1 Given that CR reduced the levels of ET-1 in the renal artery, it is entirely possible that this is one of the mechanisms of CR-mediated rescue of renal function in ageing rats.
It is highly likely that CR induced changes in other tissues such as the fat content, and contributed to reducing inflammation and kidney injury in the ageing rats. Hence, the systemic effect of CR on other organs needs to be investigated in future studies.
Expression of ET-1 is regulated at multiple levels 36 , and whether CR-mediated regulation of ET-1 expression is exclusively regulated by activation of NF-κB signaling in the ageing renal artery remains to be determined. However, the overall upregulation of inflammatory proteins and alterations in lipid metabolism as observed in the current study point to a critical role of NF-κB signaling in ageing associated renal dysfunction.
In addition it remains to be determined how CR increases the expression of Nrf2 and SIRT1, both of which contribute to attenuation of oxidative stress 26 , It might be possible that CR increases glutathione-S-transferase, that in turn, induces SIRT1 and Nrf2 33 , 36 , or the increase may be a feedback regulation of ROS reduced oxidative stress.
It remains to be determined if the decrease in pro-inflammatory cytokines and lipid metabolites observed after CR were due to decreased ET-1 expression. Alternatively, this could be mediated by additional unknown targets that were being modified by CR.
Nonetheless, CR might be a potent alternative to prevent ageing induced renal artery alterations. There major limitation to the current study is that the renal arterioles are the major resistance vessels regulating renal blood flow and glomerular filtration rate, not the renal arteries.
However, due to limitations in the volume of the experimental rats, the renal arterioles of the rats were difficult to separate and obtain, so the renal arteries were used in present study. Reporting Checklist: The authors have completed the ARRIVE reporting checklist.
The authors have no conflicts of interest to declare. Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4. Table 1 Primers sequences Full table. Figure 1 Ageing-induced renal dysfunction and changes in metabolic parameters are inhibited by calorie restriction CR.
A PAS staining of renal tissues obtained from young 2 months-old and aged 12 months-old rats fed ad libitum 2 and 12 M, respectively or under 8 weeks of caloric restriction 12 M-CR SD rats.
Shown are representative images under × magnification scale bars, 50 µM. B Body weight, 24 h urine protein, serum triglyceride, and serum cholesterol in 2, 12 M, and 12 M-CR rats. Figure 2 Ageing-induced induction of pro-inflammatory cytokines in the renal artery can be inhibited by caloric restriction.
Experimental groups were young 2-month-old and aged month-old rats fed ad libitum 2 and 12 M, respectively or under 8 weeks of caloric restriction 12 M-CR. A Expression of the mRNA encoding the pro-inflammatory cytokines IL-6, IL-1β, TNF-α, and TGF-β1 in the renal artery was determined using qRT-PCR.
Data was normalized to GAPDH and expressed relative to expression in the 2 M group. B Quantification of secreted IL-6, IL-1β, TNF-α, and TGF-β1 in blood isolated from tail veins as determined by ELISA.
Figure 3 Expression of ET-1 increases with ageing in the renal artery but is inhibited with caloric restriction. Experimental groups were young 2 months-old and aged 12 months-old rats fed ad libitum 2 and 12 M, respectively or under 8 weeks of caloric restriction 12 M-CR.
A Expression of the Edn1 mRNA, which encodes ET-1 in the renal artery was determined using qRT-PCR. Data were normalized to GAPDH and expressed relative to expression in the 2 M group. B Representative western blot images obtained from one animal from each experimental group showing expression of ET-1 and LOX-1 in the different experimental groups.
β-Actin was used as a loading control. Please refer to Figure S1A for the corresponding uncropped blots. C Quantification of data shown in B.
Figure 4 Caloric restriction-mediated reduction of ET-1 expression in the renal artery potentially occurs via the suppression of NF-κB signaling.
A Representative western blot images obtained from one animal from each experimental group showing the expression of phosphorylated and total P65 and IκBα, Nrf2, and SIRT1 in the different experimental groups.
Anthocyanins and skin protection from UV damage complete functoin of the of the C. Functiln Group can be found in the Supplementary Funcction online. Piero Ruggenenti restrictoon, Manuela AbbateBarbara RuggieroKidneey RotaMatias TrilliniCarolina Aparicio Liver detox for longevity, Aneliya FynctionIlian Petrov IlievGiovanna PisanuAnnalisa PernaAngela RussoOlimpia DiadeiDavide MartinettiAntonio CannataFabiola CarraraSilvia FerrariNadia StucchiGiuseppe RemuzziLuigi Fontanaon behalf of the C. Study Group; Renal and Systemic Effects of Calorie Restriction in Patients With Type 2 Diabetes With Abdominal Obesity: A Randomized Controlled Trial. Diabetes 1 January ; 66 1 : 75—
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