Activity In Chronic Kidney Disease Research Articles

Impaired 11[beta]-hydroxysteroid dehydrogenase type 2 activity in chronic kidney disease disrupts 11-oxygenated androgen biosynthesis

Impaired 11[beta]-hydroxysteroid dehydrogenase type 2 activity in chronic kidney disease disrupts 11-oxygenated androgen biosynthesis

Erythropoietin Effect on Complement Activation in Chronic Kidney Disease.

The complement system is an important part of innate immunity. Despite its known protective role, the complement system may contribute to increased inflammation and tissue injury in cases where its balanced activation is disrupted. The kidneys have been shown to be largely affected by complement dysregulation. The aim of the present study was to investigate the effect of erythropoietin administration, on the complement system, in chronic kidney disease patients. The study involved 20 patients with CKD who received erythropoietin and measurements of levels of complement factors C3a and C5a and complement regulatory proteins (CregPs) CD55, CD46, and CD59. An increase in serum C3a and C5a levels was observed in response to EPO therapy. The increase in C3a was statistically significant (p < 0.05) and concurrent with a statistically significant decrease in CD55 in CD4+ T cells (p < 0.05) and B cells (p < 0.05) and CD59 levels in CD4+ and CD8+ T cells (p < 0.05) at completion of EPO therapy compared with healthy controls. The above observations demonstrate that EPO induces complement activation in patients undergoing EPO therapy with a simultaneous restriction of CRegPs expression, thus possibly allowing the uncontrolled complement activation, which may contribute to tissue injury and disease progression.

Fitwalking: A New Frontier for Kidney Patients – A Center’s Experience

Introduction: Physical inactivity is common in patients with chronic kidney disease (CKD) and is an important modifiable risk factor for mortality, morbidity, and reduced quality of life. The present single-centre pilot study evaluated the possibility of performing structured physical exercise using a specific walking model, Fitwalking, in a population of patients with CKD and, according to the American College of Rheumatology guidelines, also in a population with immuno-rheumatological disease. Methods: Patients were recruited from nephrology, haemodialysis, peritoneal dialysis, transplantation, and immuno-rheumatology outpatient clinics. After general and functional clinical evaluation and exercise prescription at the Department of Sports Medicine, we performed scientifically proven tests on CKD (6-min walk test and sit-to-stand test), before and after the Fitwalking technique training course, and again after 6 and 12 months, evaluated its effectiveness and identify any critical issues. Results: We enrolled 80 patients (41 males, 51.2%), with a mean age of 53 ± 12 years; the clinical data showed statistically significant improvements in systolic, average, and differential blood pressure, average speed, and physical strength. Participants also adapted to muscle fatigue, experienced a reduction in BMI with stable lean mass and reduced fat mass, and reported improved perceptions of physical and mental health, and quality of life. Conclusion: All enrolled patients successfully completed the process. A specific prescription was used that provided health education and allowed for the implementation of structured physical activity that could be performed safely and independently even after the training period. The activity was sustainable thanks to the training of in-house medical and nursing staff, demonstrating that it is possible to overcome this type of barrier to physical activity in CKD and in immuno-rheumatological patients.

The role of hypoxia in chronic kidney disease: a nuanced perspective.

This review critically examines the role of hypoxia in chronic kidney disease (CKD). While traditionally viewed as detrimental, recent insights suggest a more nuanced understanding of hypoxia's role during renal disease. Emerging evidence challenges the traditional view that hypoxia is universally harmful in CKD context. We review here the recent evidence about hypoxia and HIF activation in CKD. We also discuss the effect of hypoxia on the renal tissue, and the relative inhibition of different HIF isoforms. Recent advancements in therapies, such as HIF prolyl hydroxylase inhibitors (HIF-PHIs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors seem to target the HIF pathway. These drugs impact anemia associated with CKDbut also renoprotection, hinting at a more complex interplay between hypoxia, HIF activation, and renal health. A certain level of hypoxia and specific HIF pathway activation, especially HIF-α, can be beneficial in CKD progression. Therapeutic strategies targeting HIF stabilization, such as with HIF-PHIs and SGLT2 inhibitors, offer promising avenues for enhancing renal protection. Future investigations should aim at better understanding the precise effects on HIF pathway and optimize their clinical application to improve outcomes for CKD patients.

Physical activity of patients with chronic kidney disease

Introduction: The main causes of chronic kidney disease (CKD) are diabetic and hypertensive nephropathy. The incidence of civilization diseases is increasing, which also indirectly affects the increase in the incidence of CKD. The patient's therapy after the diagnosis should include the care of a multi-specialist therapeutic team that will remove as many restrictions as possible in everyday functioning and ensure a high quality of life. In addition to the selection of individual renal replacement therapy, i.a. physical rehabilitation. Despite the fact that in the course of chronic kidney disease physical activity is impaired by numerous pathophysiological processes, the patient should be encouraged to undertake physical activity in order to reduce the risk of death due to cardiovascular diseases, as well as to eliminate many other adverse health effects of the disease. The following paper aims to analyze the impact of physical activity on CKD patients and the pathophysiological causes of low physical activity in this group of patients and the possibility of implementing rehabilitation as an element of comprehensive therapy.&#x0D; Aim of the study: To review the current literature on the physical activity of patients with chronic kidney disease&#x0D; Materials and Methods: A review of the publications available in PubMed, using the key words „chronic kidney disease”, „psychical activity in chronic kidney disease”, physical activity”, „kidney failure”, „dialysis”, „renal rehabilitation”, „quality of life”

Effects of long-term tubular HIF-2α overexpression on progressive renal fibrosis in a chronic kidney disease model

Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 μg/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogenactivated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD. [BMB Reports 2023; 56(3): 196-201].

Kidney tubular transcription co-activator, Yes-associated protein 1 (YAP), controls the expression of collecting duct aquaporins and water homeostasis

Final urine volume and concentration are defined by water reabsorption through the water channel proteins aquaporin (AQP)-2, -3 and -4 in the collecting duct. However, the transcriptional regulation of these AQPs is not well understood. The Hippo/Yes-associated protein 1 (YAP) pathway plays an important role in organ size control and tissue homeostasis. When the Hippo pathway including the Mst1/Mst2 kinases is inhibited, YAP is activated and functions as a transcription co-activator. Our previous work revealed a pathological role of tubular YAP activation in chronic kidney disease, but the physiological role of YAP in the kidney remains to be established. Here, we found that tubule-specific Yap knockout mice showed increased urine output and decreased urinary osmolality. Decreases in Aqp2, -3 and -4 mRNA and protein abundance in the kidney were evident in Yap knockout mice. Analysis of Mst1/Mst2 double knockout and Mst1/Mst2/Yap triple knockout mice showed that expression of Aqp2 and Aqp4 but not Aqp3 was dependent on YAP. Furthermore, YAP was recruited to the promoters of the Aqp2 and Aqp4 genes and stimulated their transcription. Interestingly, YAP was found to interact with transcription factors GATA2, GATA3 and NFATc1. These three factors promoted Aqp2 transcription in a YAP dependent manner in collecting duct cells. These three factors also promoted Aqp4 transcription whereas only GATA2 and GATA3 enhanced Aqp3 transcription. Thus, our results suggest that YAP promotes Aqp2 and Aqp4 transcription, interacts with GATA2, GATA3 and NFATc1 to control Aqp2 expression, while Aqp-2, -3 and -4 exploit overlapping mechanisms for their baseline transcriptional regulation.

Relationship between patient activation and self-efficacy among patients undergoing hemodialysis: a cross-sectional study

BackgroundPatient activation in chronic kidney disease (CKD) is increasingly being prioritized and considered a quality metric in CKD. Given the importance of patients’ activation in improving the quality of chronic disease care, this study aimed to assess patients’ activation levels and its relationship with self-efficacy among patients undergoing hemodialysis.MethodsIn this cross-sectional study, a total of 180 patients undergoing maintenance hemodialysis were selected by random sampling from the largest hemodialysis center (dialysis center of Emam Reza hospital, Tabriz) in Iran. Data were collected by demographics, patient activation measure, and chronic kidney disease self-efficacy (CKD-SE) scale from March to May 2021. Collected data were analyzed using SPSS software (ver. 26) using ANOVA, t-test, Pearson correlation coefficient, and multiple regression tests.ResultsThe majority of the participants (35%) were at level 1 of activation and only 28.9% of the individuals were at level 4. According to the results, the mean score of self-efficacy in patients undergoing hemodialysis (in a possible range of 0–10) was 5.50 ± 1.45. Multiple regression analysis showed that factors including self-efficacy, educational level, and marital status were significant predictors of change in patient activation (R2 = 0.85, adjusted R2 = 0.66, p < 0.001). The results showed that self-efficacy was the main predictor of patient activation (β = 0.49, p < 0.001).ConclusionAccording to the result, improving the patients' self-efficacy could improve the patient's activation. Moreover, patients with lower educational level reported the lower activation score; therefore, health care providers should improve the knowledge of patients with lower educational level, encourage them to be more active in their health care, and help them in providing more tailored strategies to improve the quality of care more efficiently. Furthermore, Measuring patients' activation level at admission to the dialysis unit is recommended for all patients undergoing hemodialysis.

Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls.

The nuclear factor erythroid 2-related factor 2 (Nrf2) protects the cell against oxidative damage. The Nrf2 system comprises a complex network that functions to ensure adequate responses to redox perturbations, but also metabolic demands and cellular stresses. It must be kept within a physiologic activity range. Oxidative stress and alterations in Nrf2-system activity are central for chronic-kidney-disease (CKD) progression and CKD-related morbidity. Activation of the Nrf2 system in CKD is in multiple ways related to inflammation, kidney fibrosis, and mitochondrial and metabolic effects. In human CKD, both endogenous Nrf2 activation and repression exist. The state of the Nrf2 system varies with the cause of kidney disease, comorbidities, stage of CKD, and severity of uremic toxin accumulation and inflammation. An earlier CKD stage, rapid progression of kidney disease, and inflammatory processes are associated with more robust Nrf2-system activation. Advanced CKD is associated with stronger Nrf2-system repression. Nrf2 activation is related to oxidative stress and moderate uremic toxin and nuclear factor kappa B (NF-κB) elevations. Nrf2 repression relates to high uremic toxin and NF-κB concentrations, and may be related to Kelch-like ECH-associated protein 1 (Keap1)-independent Nrf2 degradation. Furthermore, we review the effects of pharmacological Nrf2 activation by bardoxolone methyl, curcumin, and resveratrol in human CKD and outline strategies for how to adapt future Nrf2-targeted therapies to the requirements of patients with CKD.

Use of Physiologically Based Pharmacokinetic Modeling to Evaluate the Impact of Chronic Kidney Disease on CYP3A4-Mediated Metabolism of Saxagliptin.

We characterized the impact of chronic kidney disease (CKD) on the cytochrome P450 (CYP) 3A4–mediated metabolism of saxagliptin to its metabolite, 5‐hydroxysaxagliptin, using a physiologically based pharmacokinetic (PBPK) model. A PBPK model of saxagliptin and its CYP3A4 metabolite, 5‐hydroxysaxagliptin, was constructed and validated for oral doses ranging from 5 to 100 mg. The observed ratios of area under the plasma concentration–time curve (AUC) and maximum plasma concentration (Cmax) between healthy subjects and subjects with CKD were compared with those predicted using PBPK model simulations. Simulations were performed with virtual CKD populations having decreased CYP3A4 activity (ie, 64%‐75% of the healthy subjects’ CYP3A4 abundance) and preserved CYP3A4 activity (ie, 100% of the healthy subjects’ CYP3A4 abundance). We found that simulations using decreased CYP3A4 activity generally overpredicted the ratios of saxagliptin AUC and Cmax in CKD compared with those using preserved CYP3A4 activity. Similarly, simulations using decreased CYP3A4 activity underpredicted the ratio of 5‐hydroxysaxagliptin AUC in moderate and severe CKD compared with simulations using preserved CYP3A4 activity. These findings suggest that decreased CYP3A4 activity in CKD underpredicts saxagliptin clearance compared with that observed clinically. Preserving CYP3A4 activity in CKD more closely estimates saxagliptin clearance and 5‐hydroxysaxagliptin exposure changes observed in vivo. Our findings suggest that there is no clinically meaningful impact of CKD on the metabolism of saxagliptin by CYP3A4. Since saxagliptin is not a highly sensitive substrate and validated probe for CYP3A4, this work represents a case study of a CYP3A4 substrate‐metabolite pair and is not a generalization for all CYP3A4 substrates.

First snapshot on behavioral characteristics and related factors of patients with chronic kidney disease in South Korea during the COVID-19 pandemic (June to October 2020).

BackgroundThe recent novel coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented changes in behavior. We evaluated the current status of precautionary behavior and physical activity in chronic kidney disease (CKD) patients during the COVID-19 pandemic.MethodsA population of CKD patients (n = 306) registered in the Study on Kidney Disease and Environmental Chemicals (SKETCH, Clinical Trial No. NCT04679168) cohort recruited from June 2020 to October 2020 was included in the study. We conducted a questionnaire survey related to risk perception of COVID-19, precautionary behavior, and physical activity.ResultsThere were 187 patients (61.1%) with estimated glomerular filtration rate of <45 mL/min/1.73 m2. This population showed a higher degree of risk perception for COVID-19 than the general population. Age was the most significant determinant of risk perception among CKD patients. During the pandemic, social distancing and hygiene-related behavior were significantly increased (p < 0.001). The frequency of exercise was decreased only in those who took regular exercise, without diabetes, or with a lower Charlson comorbidity index (CCI) (p < 0.001), with no change among the other groups. Socioeconomic status and comorbidities significantly affected behavioral characteristics regardless of the category. Education and income were significantly associated with precautionary behaviors such as staying at home and hand sanitizer use. Patients with higher CCI status significantly increased frequency of exercise (adjusted odds ratio, 2.10; 95% confidence interval, 1.01–4.38).ConclusionCKD patients showed higher risk perception with active precautionary behavioral changes than the general population. Healthcare providers should be aware of the characteristics to comprise precautionary behavior without reducing physical activity.

Skeletal muscle metabolic responses to physical activity are muscle type specific in a rat model of chronic kidney disease

Chronic kidney disease (CKD) leads to musculoskeletal impairments that are impacted by muscle metabolism. We tested the hypothesis that 10-weeks of voluntary wheel running can improve skeletal muscle mitochondria activity and function in a rat model of CKD. Groups included (n = 12–14/group): (1) normal littermates (NL); (2) CKD, and; (3) CKD-10 weeks of voluntary wheel running (CKD-W). At 35-weeks old the following assays were performed in the soleus and extensor digitorum longus (EDL): targeted metabolomics, mitochondrial respiration, and protein expression. Amino acid-related compounds were reduced in CKD muscle and not restored by physical activity. Mitochondrial respiration in the CKD soleus was increased compared to NL, but not impacted by physical activity. The EDL respiration was not different between NL and CKD, but increased in CKD-wheel rats compared to CKD and NL groups. Our results demonstrate that the soleus may be more susceptible to CKD-induced changes of mitochondrial complex content and respiration, while in the EDL, these alterations were in response the physiological load induced by mild physical activity. Future studies should focus on therapies to improve mitochondrial function in both types of muscle to determine if such treatments can improve the ability to adapt to physical activity in CKD.

Role of angiotensin-converting enzyme inhibitors in reducing cardiovascular and cerebral complications in chronic kidney disease: focus perindopril

In the development of renocardial relationships in chronic kidney disease, an important role is given to the activation of the renin-angiotensin-aldosterone system (RAAS), as the main component of the progression and development of cardiovascular complications..The presented review is devoted to the analysis of modern scientific data on the effect of high RAAS activity in chronic kidney disease on the course and prognosis of cardiovascular complications, as well as the protective capabilities of angiotensin-converting enzyme inhibitors, in particular perindopril. The results of scientific research on the role of the RAAS in the progression of chronic kidney disease are summarized. Data on chronic kidney disease as a risk factor for cardiovascular and cerebral complications are presented. Attention is focused on the possibilities of prolonging the pre-dialysis period of chronic kidney disease when using angiotensin-converting enzyme inhibitors. The role of perindopril as a lipophilic angiotensin-converting enzyme inhibitor with a high affinity for tissue RAAS was emphasized in reducing cardiovascular and cerebral risk in chronic kidney disease.

Interrelationship of inflammatory biomarkers with ambulatory heart rate phenotypes in a cohort of Nigerian chronic kidney disease patients compared with controls; findings from symbolic study

Abstract Background Inflammatory biomarkers have been identified as strong independent risk factor for cardiovascular events outcome in chronic kidney disease. The positive effect of the autonomic nervous system on inflammatory biomarkers is also being explored. Using the Heart rate as a representative tool for autonomic activity, the exact heart rate metrics in 24 hours associated with increased level of inflammatory activity in chronic kidney disease needs to be assessed among people of African descent. Purpose This study assessed the associations between inflammatory biomarkers and the Heart Rates phenotypes in a population of chronic kidney disease patients compared with controls. Methods All the participants had a 24-hour ambulatory blood pressure monitoring done using SpaceLabs ABPM (Spacelab's Healthcare, Issaquah, WA) which was placed on the non-dominant hand and Cuff sizes were selected after measuring participants' non-dominant arm circumference. Blood samples were analyzed for fasting plasma glucose, lipid profile, electrolytes, urea and creatinine, C - reactive protein (CRP), White cell counts (WBC) and differentials. CRP group was classified as mild, moderate and severe. Heart rate dipping was estimate using formula (1- night time heart rate/daytime heart rate) x100. Normal dipping of heart rate was defined as &amp;gt;10%. Estimated GFR was calculated using CKD-EPI Creatinine Equation and CKD was defined as eGFR&amp;lt;60ml/min/1.73m2. The association between markers of inflammation, heart rate phenotypes and mortality was determined using univariate analysis. Logistic regression model was fitted to determine predictors of all – cause mortality. Results Four hundred and sixty consented participants comprising 231 (50.2%) women, 195 (42.4%) hypertensive without CKD, 98 (21.3%) normotensive and 167 (36.3%) CKD patients with mean age 49.42±13.54 years were analyzed. Compared with controls, greater proportion of CKD patients were non dippers with highest mean White blood cell count, neutrophil counts, and CRP; p&amp;lt;0.05. The mean 24 Hr, daytime and night time heart rate were significantly highest among CKD patients &amp;lt;0.0001. Non-dipping was associated with higher mean WBC, Neutrophils counts, and CRP. Most non-dippers were associated with moderate and severe CRP risk (72.8% vs 27.2%; P&amp;lt;0.0001. Compared with inflammatory markers (CRP), non-dipping status was an independent determinant of all-cause mortality (OR 16.03, CI 2.57–100.1, p=0.003). Conclusion This study highlights a higher prevalence of heart rate non- dipping and inflammatory activities among people with CKD compared with controls. Non dipping status was associated with higher inflammatory activity and higher risk of death. These observations lend some insight into the roles of autonomic nervous system in the pathophysiological mechanisms that implicate inflammatory biomarkers in cardiovascular risk and event outcomes in chronic kidney disease patients. Funding Acknowledgement Type of funding source: Other. Main funding source(s): International society of hypertension

Renal asymmetric dimethylarginine inhibits fibrosis.

Chronic kidney disease (CKD) is a worldwide public health problem that is caused by repeated injuries to the glomerulus or renal tubules. Renal fibrosis commonly accompanies CKD, and it is histologically characterized by excessive deposition of extracellular matrix proteins, such as fibronectin and collagen I, in interstitial areas. Indirect in vivo experimental data suggest that renal asymmetric dimethylarginine (ADMA) exerts antifibrotic activity in CKD. In this study, we aimed to demonstrate that renal ADMA has a direct effect on fibrosis in vivo. Normal saline, ADMA, nonsense control siRNA, Ddah1 siRNA or Ddah2 siRNA was administered into the kidney through the left ureter in a mouse model of unilateral ureteral obstruction (UUO). UUO kidneys were harvested at day 1 or 7. Western blotting was performed to assess the expression of ADMA, DDAH1 and DDAH2 and the expression of fibrotic markers, such as fibronectin, collagen I, α‐smooth muscle actin, phosphorylation of Smad3 and connective tissue growth factor. Masson’s trichrome staining was used to further evaluate renal fibrosis. We observed that intrarenal administration of ADMA increased the renal accumulation of ADMA and attenuated renal fibrosis at days 1 and 7. Knockdown of Ddah1 or Ddah2 increased the amount of ADMA in UUO kidneys and inhibited the expression of fibrotic proteins at days 1 and 7, which was further confirmed by Masson’s staining. Thus, our in vivo data suggest that renal ADMA exerts direct antifibrotic effects in a mouse model of UUO.

Supervised Exercise Intervention and Overall Activity in CKD

IntroductionPatients are often instructed to engage in multiple weekly sessions of exercise to increase physical activity. We aimed to determine whether assignment to a supervised exercise regimen increases overall weekly activity in individuals with chronic kidney disease (CKD).MethodsWe performed a secondary analysis of a pilot randomized 2 × 2 factorial design trial examining the effects of diet and exercise (10%−15% reduction in caloric intake, 3 supervised exercise sessions/wk, combined diet restriction/exercise, and control). Activity was measured as counts detected by accelerometer. Counts data were collected on all days for which an accelerometer was worn at baseline, month 2, and month 4 follow-up. The primary outcome was a relative change from baseline in log-transformed counts/min. Generalized estimating equations were used to compare the primary outcome in individuals in the exercise group and the nonexercise group.ResultsWe examined 111 individuals randomized to aerobic exercise or usual activity (n = 48 in the exercise group and n = 44 controls). The mean age was 57 years, 42% were female, and 28% were black. Median overall adherence over all time was 73%. Median (25th, 75th percentile) counts/min over nonsupervised exercise days at months 2 and 4 were 237.5 (6.5, 444.4) for controls and 250.9 (7.7, 529.8) for the exercise group (P = 0.74). No difference was observed in the change in counts/min between the exercise and control groups over 3 time points (β [fold change], 0.96, 95% confidence interval [CI], 0.91, 1.02).ConclusionEngaging in a supervised exercise program does not increase overall weekly physical activity in individuals with stage 3 to 4 CKD.

THE ASSOCIATION OF HEMOGLOBIN LEVELS WITH QUALITY OF LIFE AND PHYSICAL ACTIVITY IN HEMODIALYSIS PATIENT IN WANGAYA REGIONAL GENERAL HOSPITAL, DENPASAR

Objective: Anemia in chronic kidney disease (CKD) contributes in decreasing quality life, but specific hemoglobin associated with quality of life is still in debate. Anemia was thought to be one of contributing factors of low physical activity in CKD, but this finding is inconsistent across studies. This research study aims to investigate the association of hemoglobin levels with quality of life and physical activity in hemodialysis patients in our settings.&#x0D; Methods: This study was conducted between March 30, 2020, and April 30, 2020, in hemodialysis unit, Wangaya Regional General Hospital, Bali. The study included 50 subjects on regular hemodialysis. Subject-reported quality of life was evaluated by interview, based on Kidney Disease Quality of Life (KDQOL)-36TM questionnaire. Self-reported physical activity level was assessed by International Physical Activity Questionnaires (IPAQ).&#x0D; Results: Quality of life in burden of kidney disease categories is different significantly between hemoglobin levels group (*p=0.034). There is significant difference between hemoglobin levels &lt; 8 g/dL with 8.1–12 g/dL (**p=0.01) and hemoglobin levels &lt; 8 g/dL with &gt; 12 g/dL (*p=0.034). For self-reported physical activity, hemoglobin level was not associated with physical activity in Fisher’s exact test analysis (p=1.000).&#x0D; Conclusion: We found that hemoglobin levels &gt; 8 g/dL were associated with higher quality of life in hemodialysis patient. Hemoglobin levels were not associated with physical activity. Recommended hemoglobin levels to support the best quality of life and physical activity without increasing mortality rate are still in need to be further evaluated.

Physical activity in chronic kidney disease and the EXerCise Introduction To Enhance trial.

It is well known from observational studies that sedentary lifestyle and reduced physical activity are common in dialysis and chronic kidney disease (CKD) patients and associate with an increased risk of morbidity and mortality in this patient population. Epidemiological studies indicate that CKD patients undergo physical activity ~9 days/month and 43.9% of dialysis patients report not exercising at all. On the basis of awareness about the strong link between sedentary lifestyle and adverse clinical outcomes, the National Kidney Foundation and Kidney Disease: Improving Global Outcomes have provided specific recommendations for physical activity in patients with kidney disease. Given the fact that CKD is a public health problem and it is still debated which type of exercise should be prescribed in these patients, this review focuses on the most robust evidence accumulated so far on the beneficial effect of various types of physical exercise on clinical outcomes in CKD and dialysis patients. This review does not treat this very important topic in another CKD category of patients, such as kidney-transplanted patients, for whom a special issue should be dedicated.

Multiple consequences of HIF activation in CKD

Tubulointerstitial hypoxia negatively influences the balance between injury and repair, and serves as a final common pathway in chronic kidney disease (CKD). Studies on erythropoietin (EPO) transcription led to the identification of hypoxia inducible factors (HIFs) and their key regulators, prolyl hydroxylases (PHDs). Based on these, several small molecule PHD inhibitors are developed for the treatment of anemia in CKD, which are currently in phase II/III clinical trials. In addition to treating anemia, application of PHD inhibitors may have several potential implications; there is a promising view that activation of the HIF signaling might protect the ischemic kidney from injury. This is extensively tested in multiple acute kidney injury models, whereas knowledge is limited in the context of CKD. Some studies demonstrate the protective effects of ameliorating inflammation and reducing oxidative stress, whereas negative consequences of sustained HIF activation, such as renal fibrosis and aggravation of polycystic kidney disease, are also reported. Recent human clinical studies reported amelioration in glucose and lipid metabolism, which may be beneficial for the treatment of metabolic kidney disorders. Renal consequences of PHD inhibitors are likely determined by multiple systemic effects of sustained HIF activation and may thus differ depending on the clinical context and the pathological stages.

Molecular mechanisms of the nephroprotective action of polyphenols in experimental chronic kidney disease. Association with hydrogen sulfide system

Annotation. The results of a study of the effects of genistein, resveratrol and quercetin on the main markers of oxidative stress, thiol disulfide equilibrium and the state of the nitric oxide system in rat kidneys after modelling chronic kidney disease (CKD) (5/6 of a single kidney nephrectomy) is shown. Blood and single rat kidney homogenate were used for biochemical studies. Statistical processing of the obtained results was performed in the program “STATISTICA 6.1”. The results are presented as M±m. The significance of the difference between the scores was evaluated using the Student's t-test or the Mann-Whitney U-test. A nonparametric Spearman correlation coefficient was used to determine the correlation between two independent indicators. It was shown that the studied substances, especially quercetin, caused antioxidant activity in CKD, which was manifested by a significant decrease of MDA, CGP and NADPH oxidase activity (by 21.0–40.4%), as well as an increase in SOD activity (by 29.7–38.7%) in kidney compared with untreated animals. Reliable strong correlation (r=ǀ0.65–0.74ǀ) between the H2S content and oxidative stress markers was established. The use of polyphenols in CKD reduced the thiol-disulfide imbalance in rat kidneys: the activity of thioredoxin reductase significantly increased, the content of reduced thiol groups of proteins (by 16.0–66.4%) and the level of disulfides decreased (by 21.1–25.3%), in comparison with untreated animals. Stabilization of the thiol disulfide equilibrium is one of the mechanisms of the effect of polyphenols on the H2S system in the kidneys, since significant and strong correlation relationships were recorded between these indicators and the H2S content (r=ǀ0.63–0.75ǀ). The administration of resveratrol, and especially genistein, was accompanied by an increase in the activity of the eNOS (by 36.3–44.7%) and a decrease in the activity of iNOS (by 15.4–20.9%), in comparison with untreated animals. The NO system in the kidneys is an important molecular target for influence of genistein and resveratrol on the production of H2S during CKD is realized, since reliable strong correlation were recorded between the H2S content and the activity of NO synthase isoforms (r=ǀ0.70–0.75ǀ).