Adult Chronic Disease Research Articles

Role of an Exclusion Diet (Reduced Disaccharides, Saturated Fats, Emulsifiers, Red and Ultraprocessed Meats) in Maintaining the Remission of Chronic Inflammatory Bowel Diseases in Adults.

Background and Objectives: Inflammatory bowel diseases are a main focus in current research, with diet being an emerging therapeutic line due to its links in both onset and progression. A Western-style diet high in processed foods, food additives, red meat, and animal fat has been linked to a higher risk of developing IBD. The aim of this study was to establish an association between an anti-inflammatory exclusion diet and maintenance of remission in IBD. Also, we assessed the efficacy and safety of this diet compared to a non-dietary group and the possible therapeutic effect of this diet in the maintenance of IBD remission. Materials and Methods: A total of 160 patients with IBD were screened for inclusion, but 21 did not met the inclusion criteria. Thus, 139 patients were assigned to either an exclusion diet or a regular diet according to their choice. Results: Clinical remission after six months was maintained in the exclusion diet arm (100%). In the control arm, four patients had clinically active disease (one patient with UC and three with CD), and 90 patients maintained the clinical remission state (95.7%) (p-value = 0.157). Regarding biochemical markers, ESR at baseline was higher in the exclusion diet arm: 29 (5-62) versus in the control arm 16 (4-48) (p-value = 0.019), but six months after, the groups were similar (p-value = 0.440). Conclusions: Patients who followed an exclusion diet maintained clinical remission more frequently. However, the threshold for statistical significance was not achieved. There was also a trend of improvement in inflammation tests in the intervention group.

Biological and Genetic Mechanisms of COPD, Its Diagnosis, Treatment, and Relationship with Lung Cancer.

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic adult diseases, with significant worldwide morbidity and mortality. Although long-term tobacco smoking is a critical risk factor for this global health problem, its molecular mechanisms remain unclear. Several phenomena are thought to be involved in the evolution of emphysema, including airway inflammation, proteinase/anti-proteinase imbalance, oxidative stress, and genetic/epigenetic modifications. Furthermore, COPD is one main risk for lung cancer (LC), the deadliest form of human tumor; formation and chronic inflammation accompanying COPD can be a potential driver of malignancy maturation (0.8-1.7% of COPD cases develop cancer/per year). Recently, the development of more research based on COPD and lung cancer molecular analysis has provided new light for understanding their pathogenesis, improving the diagnosis and treatments, and elucidating many connections between these diseases. Our review emphasizes the biological factors involved in COPD and lung cancer, the advances in their molecular mechanisms' research, and the state of the art of diagnosis and treatments. This work combines many biological and genetic elements into a single whole and strongly links COPD with lung tumor features.

Metabolic dysfunction-associated fatty liver disease can significantly increase the risk of chronic kidney disease in adults with type 2 diabetes

AimsThis study is to explore the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD) among populations with type 2 diabetes through longitudinal cohort study. Methods3,627 subjects who had received at least three health examinations between 2008 and 2015 were included. CKD was stated as subjects with an eGFR < 60 mL/min per 1·73 m2 or the occurrence of 2 or more proteinuria during their follow-up. ResultsAfter median of 10·0 years follow up, 837 (23·1%) developed CKD (244·7 per 10,000 person-years; 95 % CI, 228.4 − 261·8). MAFLD ([HR] 1·46; 95 % CI 1·26-1·70, P < 0.001) acts as an important risk factor of developing CKD. After adjusting for confounding factors, this association was consistent (HR 1·30; 95 % CI 1·11-1·53, P < 0.001). In stratified analysis, subjects aged < 60 years were likely to have greater risk of MAFLD-related CKD (HR 1·58 and 1·03; 95 % CI 1·28-1·95 and 0·79-1·33, P < 0.001 in both cases, respectively). ConclusionsThe risk of developing CKD in type 2 diabetes adults with MAFLD was higher, especially if they are below 60 years old. This study underscores the importance of early prevention strategies for MAFLD to reduce the occurrence of CKD in type 2 diabetes adults.

Breath Biopsy® to Identify Exhaled Volatile Organic Compounds Biomarkers for Liver Cirrhosis Detection.

The prevalence of chronic liver disease in adults exceeds 30% in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare burden. Breath is a rich sampling matrix that offers non-invasive solutions suitable for early-stage detection and disease monitoring. Having previously investigated targeted analysis of a single biomarker, here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical use. To identify candidate biomarkers we compared 46 breath samples from cirrhosis patients and 42 from controls. Collection and analysis used Breath Biopsy OMNI™, maximizing signal and contrast to background to provide high confidence biomarker detection based upon gas chromatography mass spectrometry (GC-MS). Blank samples were also analyzed to provide detailed information on background volatile organic compounds (VOCs) levels. A set of 29 breath VOCs differed significantly between cirrhosis and controls. A classification model based on these VOCs had an area under the curve (AUC) of 0.95±0.04 in cross-validated test sets. The seven best performing VOCs were sufficient to maximize classification performance. A subset of 11 VOCs was correlated with blood metrics of liver function (bilirubin, albumin, prothrombin time) and separated patients by cirrhosis severity using principal component analysis. A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and monitoring, showing correlation to disease severity and serum biomarkers at late stage.

The Effects of Isocaloric Intermittent Fasting vs Daily Caloric Restriction on Weight Loss and Metabolic Risk Factors for Noncommunicable Chronic Diseases: A Systematic Review of Randomized Controlled or Comparative Trials.

Intermittent fasting (IF) has gained favor as an alternative regimen to daily caloric restriction (DCR). Therefore, there is a need for systematic reviews of randomized controlled/comparison trials examining the effects of isocaloric IF vs DCR on metabolic risk factors for noncommunicable chronic diseases. To systematically investigate the effects of isocaloric IF vs DCR on metabolic risk factors for noncommunicable chronic diseases in adults with overweight and obesity. Five online databases (PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar) were searched for articles published from January 2000 through April 2022. The updated Cochrane Risk of Bias Assessment tool for randomized controlled/comparison trials was used to assess risk of bias in the included studies. This review includes randomized controlled/comparison trials with matched energy intakes (isocaloric) between IF and DCR among adults with overweight and obesity with ≥8-week durations, that assessed risk factors related to obesity and for diabetes, cardiovascular diseases, and cancers. Thirteen randomized controlled/comparison trials with matched energy intakes (isocaloric) between IF and DCR were identified. The effects of IF on weight loss and metabolic risk markers of diabetes, cardiovascular diseases, and cancers were varied but generally comparable with DCR. IF (4:3 and 5:2 diets) was superior to DCR for improving insulin sensitivity in two studies. Reductions in body fat were significantly greater with IF (5:2 diet and time-restricted eating) than DCR in two studies of isocaloric diets. With matched energy intakes, IF interventions produced similar beneficial effects for weight loss and chronic disease risk factors compared with DCR. Very limited evidence suggests that IF may be more effective vs DCR for fat loss and insulin sensitivity, but conclusions cannot be drawn based on the current evidence. Future clinical studies with larger populations and longer durations are needed for further elucidation of any potential effects of IF regimens for prevention of noncommunicable chronic diseases.

Chronic liver diseases in pediatrics and young adults: growing fast and furious?

Chronic liver diseases in pediatrics and young adults: growing fast and furious?

117 - Vitamin A Prevents Acute and Chronic Graft Versus Host Disease in Children and Young Adults: A Single-Center Randomized Double-Blinded Placebo-Controlled Clinical Trial

117 - Vitamin A Prevents Acute and Chronic Graft Versus Host Disease in Children and Young Adults: A Single-Center Randomized Double-Blinded Placebo-Controlled Clinical Trial

Skeletal muscle fiber force declines with chronic kidney disease in juvenile and adult mice.

Juvenile and adult chronic kidney disease (CKD) patients frequently have compromised physical performance, which worsens with disease severity. Examining the underlying mechanisms behind this contractile dysfunction can be difficult to impossible in humans, especially in juveniles, but can be accomplished using animal models. We characterized CKD-induced changes in cellular (single fiber force) and molecular (myosin-actin interactions, myofilament properties) function in soleus and extensor digitorum longus muscles of 6-week-old (juvenile, control = 5, CKD = 6) and 16-week-old (adults, control = 10, CKD = 12) mice. CKD was induced by 0.2% adenine diet for 3 weeks (early-stage CKD) for juveniles and 8 weeks (late-stage CKD) for adults. Maximally activated (pCa 4.5, 25°C) specific tension (maximal isometric force divided by cross-sectional area) was reduced in all myosin heavy chain (MHC) I, IIA, and IIB fibers in juvenile (23-30%) and adult (36-51%) mice with CKD due, in a large part, to a reduction in strongly-bound myosin-actin cross-bridges. Additionally, myofilament stiffness was reduced in MHC IIA fibers from juveniles and adults as well as MHC IIB fibers from adults, potentially reducing force transmission. For adults, myosin-actin interactions were slower in MHC I and IIA fibers. In juveniles, myosin-actin interactions were slower only in MHC IIA fibers but faster in MHC IIB fibers. Fiber cross-sectional area with CKD was increased or unchanged in all fiber types, except for a decrease in MHC IIB fibers from adults. Overall, juvenile early-stage and adult late-stage CKD showed similar molecular mechanisms leading to reduced force production and cross-bridge kinetics, although alterations were generally larger in adult late-stage CKD. Thus, physical function in juvenile early-stage and adult late-stage CKD is being impaired on the molecular level due to intrinsic contractile deficits independent of skeletal muscle atrophy.

Iron supplementation improves skeletal muscle contractile properties in mice with chronic kidney disease.

Adult chronic kidney disease (CKD) patients commonly display decreased physical function, leading to increased mortality, which is exacerbated with iron deficiency and anemia. Interventions to mitigate CKD myopathy are scarce, potentially because the underlying contractile deficits have not been fully investigated. We examined single fiber force production, myosin-actin interactions and myofilament properties in soleus and extensor digitorum longus muscles of 16-week-old CKD mice without (CKD, N=12) and with iron supplementation (CKDFE, N=6, weekly injections of 0.2 mg/kg iron dextran) and controls (N=10). Late-stage CKD was induced by 0.2% adenine diet for 8 weeks. CKD with iron supplementation (CKDFE) improved anemia status compared to CKD, but not back to control levels. Maximally activated (pCa 4.5, 25°C) specific tension (maximal isometric force divided by cross-sectional area) was reduced 36-51% with CKD due, in a large part, to a reduction in strongly-bound myosin-actin cross-bridges in all myosin heavy chain (MHC) I, IIA, and IIB fibers. Iron supplementation improved specific tension and number of strongly-bound cross-bridges in MHC IIA and IIB fibers. Myosin-actin cross-bridge kinetics were slower with CKD in MHC I and IIA fibers, with iron supplementation restoring kinetics closer to control values in MHC IIA fibers. Higher hemoglobin levels were correlated to improvements in specific tension and strongly-bound cross-bridges in MHC IIA and IIB fibers, and with faster cross-bridge kinetics in MHC IIA fibers. However, CKD induced decreases in myofilament lattice stiffness for MHC IIA and IIB fibers were not improved with iron supplementation. Our findings show that iron supplementation improved various aspects of the cellular and molecular CKD-induced myopathy in fast-contracting fiber types. Thus, correction of iron imbalance and/or anemia may be an effective countermeasure to reduce contractile deficits and improve quality of life in late-stage CKD patients.

Machine Learning-based Classifiers for the Prediction of Low Birth Weight.

Low birth weight (LBW) is a global concern associated with fetal and neonatal mortality as well as adverse consequences such as intellectual disability, impaired cognitive development, and chronic diseases in adulthood. Numerous factors contribute to LBW and vary based on the region. The main objectives of this study were to compare four machine learning classifiers in the prediction of LBW and to determine the most important factors related to this phenomenon in Hamadan, Iran. We carried out a retrospective cross-sectional study on a dataset collected from Fatemieh Hospital in 2017 that included 741 mother-newborn pairs and 13 potential factors. Decision tree, random forest, artificial neural network, support vector machine, and logistic regression (LR) methods were used to predict LBW, with five evaluation criteria utilized to compare performance. Our findings revealed a 7% prevalence of LBW. The average accuracy of all models was 87% or higher. The LR method provided a sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and accuracy of 74%, 89%, 7.04%, 29%, and 88%, respectively. Using LR, gestational age, number of abortions, gravida, consanguinity, maternal age at delivery, and neonatal sex were determined to be the six most important variables associated with LBW. Our findings underscore the importance of facilitating timely diagnosis of causes of abortion, providing genetic counseling to consanguineous couples, and strengthening care before and during pregnancy (particularly for young mothers) to reduce LBW.

Association between the Oxidative Balance Score and Incident Chronic Kidney Disease in Adults

Oxidative stress is a novel risk factor for chronic kidney disease (CKD). The oxidative balance score (OBS) was developed to represent the overall oxidative balance based on dietary and lifestyle pro-oxidant and antioxidant components. The aim of this study is to verify the relationship between the OBS and the incidence of CKD. Data from 5795 participants without CKD at the baseline survey of the Korean Genome and Epidemiology Study were analyzed. Participants were classified into sex-specific OBS tertiles. During the mean follow-up period of 13.6 years, 286 men and 382 women newly developed CKD. The Cox proportional hazard spline curve revealed an inverse dose-response association between the OBS and incident CKD in both men and women. Multiple Cox proportional hazard regression analysis revealed that the adjusted hazard ratios (95% confidence intervals) for sex-specific highest (T3) and middle (T2) OBS tertile groups were 0.80 (0.59-1.08) and 0.70 (0.51-0.95), respectively, in men and 0.76 (0.59-0.98) and 0.73 (0.55-0.96), respectively, in women, with the sex-specific lowest OBS tertile group (T1) as the reference. These results suggest that a healthy diet and lifestyle that increases the OBS may help prevent CKD in both men and women.

P698 Role of an exclusion diet (reduced disaccharides, saturated fats, emulsifiers, red and ultraprocessed meats) in maintaining the remission of chronic inflammatory bowel diseases in adults

Abstract Background Inflammatory bowel diseases (IBD) are a main focus in current research with diet being an emerging therapeutic line due to its links both in onset and progression. A Western-style diet high in processed foods, food additives, red meat, and animal fat has been linked to a higher risk of developing IBD. The aim of this study was to establish an association between an anti-inflammatory exclusion diet and maintenance of remission in IBD. Also, we assessed the efficacy and safety of this diet compared to a non-dietary group and the possible therapeutic effect of this diet in the maintenance of IBD remission. Methods One hundred seventeen adult IBD patients in remission (64 patients with Crohn’s disease- CD and 53 patients with ulcerative colitis- UC) were randomized at their own will to a 6-months exclusion diet (n=32) or a habitual diet (n=85). Dietary patterns, clinical activity of the disease and inflammatory markers were assessed at baseline and at the end of dietary intervention. Results The acceptance rate of the exclusion diet in our cohort was 27.35% (30% in UC and 20% in CD). The exclusion diet and control populations were similar, except for immunosuppressive treatment (only 30% of patients in the exclusion diet group had an immunomodullator compared to 70% in the control group (p-value &amp;lt;0.001)). The clinical remission after six months was maintained in the exclusion diet arm (100%). In the control arm, 3 patients had clinically active disease (1 patient with UC and 2 patients with CD) and 80 patients maintained the clinical remission state (96.4%) (p-value = 0.278). Figure 1 is depicting the remission rates in different patient groups. Regarding biochemical markers, erythrocyte sedimentation rate (ESR) at baseline was higher in the exclusion diet arm: 31 (5-62) than in the control arm 14.5 (4-48) (p-value=0.011), but six months after, the groups were similar (p-value = 0.440). Fecal calprotectin at baseline was higher than 300 micrograms/gram in 30% of cases in the exclusion diet arm and in 25.8% of cases in the control arm (p-value = 0.774). Six months after, 50% of cases had a higher fecal calprotectin (&amp;gt;300 micrograms/gram) in the intervention arm and only 20.5% in the control arm (p-value = 0.033). Figure 1. Maintenance of clinical remission 6 months after intervention Conclusion We found a better trend of sustained clinical remission in patients who follow an exclusion diet. However, the threshold for statistical significance was not achieved. The clinical study continues, these are preliminary data. There is also a trend of improvement in ESR in the intervention group, but the levels of fecal calprotectin did not improved.

Circulating Nitric Oxide and Metabolic Syndrome in Arab Children and Adolescents: A Case–Control Study

Metabolic syndrome (MetS) represents a cluster of known cardiometabolic risk factors, which elevates the risk of type 2 diabetes mellitus (T2DM), atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) in adults and, only recently, even in children and adolescents. Circulating nitric oxide (NOx) has been observed to influence MetS risk factors in adults, but this has been scarcely investigated in children. The aim of the present study was to determine whether circulating NOx levels correlate with known components of MetS in Arab children and adolescents. Anthropometrics, serum NOx, lipid profile and fasting glucose levels were measured in 740 Saudi Arabs aged 10-17 years (68.8% girls). The presence of MetS was screened using the criteria of de Ferranti et al. Results: Overall, serum NOx levels were significantly higher in MetS participants compared to non-MetS (25.7 µmol/L (10.1-46.7) versus 11.9 µmol/L (5.5-22.9), p < 0.001) even after adjustments for age, BMI and sex. With the exception of elevated blood pressure, higher circulating NOx significantly increased the odds for MetS and its components. Lastly, receiver operating characteristics (ROC) showed that NOx, as a diagnostic marker for MetS, had good sensitivity and was higher in boys than girls (all MetS participants: area under the curve (AUC) = 0.68, p < 0.001), (girls with MetS: AUC = 0.62, p = 0.002), (boys with MetS: AUC = 0.83, p < 0.001)). MetS and most of its components were significantly associated with circulating NOx levels in Arab adolescents and may be a promising diagnostic biomarker for MetS.

Association Between CKD and Major Hemorrhage in Older Persons: Data From the Aspirin in Reducing Events in the Elderly Randomized Trial

Data on the association between chronic kidney disease (CKD) and major hemorrhage in older adults are lacking. We used data from a double-blind randomized controlled trial of aspirin in persons aged≥ 70 years with prospective capture of bleeding events, including hemorrhagic stroke and clinically significant bleeding. CKD was defined as an estimated glomerular filtration rate (eGFR)< 60 ml/min per 1.73 m2 and/or urinary albumin-to-creatinine ratio (UACR)≥ 3 mg/mmol (26.6 mg/g). We compared bleeding rates in those with and without CKD, undertook multivariable analyses, and explored effect modification with aspirin. Of 19,114 participants, 17,976 (94.0%) had CKD status recorded, of whom 4952 (27.5%) had CKD. Participants with CKD had an increased rate of major bleeding events compared with those without CKD (10.4/1000 vs. 6.3/1000 person-years [py], respectively) and increased bleeding risk (risk ratio [RR] 1.60; 95% confidence interval [CI]: 1.40, 1.90 for eGFR< 60 ml/min per 1.73 m2) and RR (2.10; 95% CI: 1.70, 2.50) for albuminuria. In adjusted analyses, CKD was associated with a 35% increased risk of bleeding (hazard ratio [HR] 1.37; 95% CI: 1.15, 1.62; P< 0.001). Other risk factors were older age, hypertension, smoking, and aspirin use. There was no differential effect of aspirin on bleeding by CKD status (test of interaction P= 0.65). CKD is independently associated with an increased risk of major hemorrhage in older adults. Increased awareness of modifiable risk factors such as discontinuation of unnecessary aspirin, blood pressure control, and smoking cessation in this group is warranted.

Association between sleep duration and quality with rapid kidney function decline and development of chronic kidney diseases in adults with normal kidney function: The China health and retirement longitudinal study.

Research have shown that sleep is associated with renal function. However, the potential effects of sleep duration or quality on kidney function in middle-aged and older Chinese adults with normal kidney function has rarely been studied. Our study aimed to investigate the association of sleep and kidney function in middle-aged and older Chinese adults. Four thousand and eighty six participants with an eGFR ≥60 ml/min/1.73 m2 at baseline were enrolled between 2011 and 2015 from the China Health and Retirement Longitudinal Study. Survey questionnaire data were collected from conducted interviews in the 2011. The eGFR was estimated from serum creatinine and/or cystatin C using the Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI). The primary outcome was defined as rapid kidney function decline. Secondary outcome was defined as rapid kidney function decline with clinical eGFR of <60 ml/min/1.73 m2 at the exit visit. The associations between sleep duration, sleep quality and renal function decline or chronic kidney disease (CKD) were assessed based with logistic regression model. Our results showed that 244 (6.0%) participants developed rapid decline in kidney function, while 102 (2.5%) developed CKD. In addition, participants who had 3-7 days of poor sleep quality per week had higher risks of CKD development (OR 1.86, 95% CI 1.24-2.80). However, compared with those who had 6-8 h of night-time sleep, no significantly higher risks of rapid decline in kidney function was found among those who had <6 h or >8 h of night time sleep after adjustments for demographic, clinical, or psychosocial covariates. Furthermore, daytime nap did not present significant risk in both rapid eGFR decline or CKD development. In conclusion, sleep quality was significantly associated with the development of CKD in middle-aged and older Chinese adults with normal kidney function.

Prevalence of COVID-19 Vaccine Hesitancy and Its Associated Factors among Chronic Disease Patients in a Resource Limited Setting in Ethiopia: A Cross-Sectional Study

Background. The COVID-19 pandemic disproportionately affects patients with chronic diseases. Thus, chronic disease patients are among the first high-risk population groups to get vaccinated. This might be challenged by vaccine hesitancy as it is one of the top ten global health issues for 2019. Furthermore, vaccination myths and conspiracy theories have been proliferating, and the developing world can readily embrace them, which might cause vaccine hesitancy. However, there is a paucity of evidence regarding chronic illness patient’s willingness to be vaccinated. As a result, the aim of this study is to determine the magnitude of vaccine hesitancy and associated factors among chronic disease patients in Ethiopia. Method. An institutional-based cross-sectional study was conducted among adult ambulatory chronic disease patients who were selected using stratified sampling technique from June 1 to August 1, 2021. Data were collected through a face-to-face interviewer-administered questionnaire. Vaccine hesitancy was measured based on a questionnaire which was adapted from the reviewed literature. Bivariable and multivariable logistic regression was used to identify factors, and variables with p &lt; 0.05 were considered statistically significant. Result. A total of 422 respondents participated in the survey; the response rate was 99.7%. The mean age of the participants was 45 years ± 16.95 and 228 (54%) of them were male. Almost half of the respondents (49.5%) were hesitant toward the COVID-19 vaccine. Participants who were male (AOR = 1.56, 95% CI: 1.03, 2.35), having good knowledge about the COVID-19 vaccine (AOR = 1.60 95% CI: 1.06, 2.41) and having a comorbidity (AOR = 3.36, 95% CI: 1.73, 6.56), were factors associated with the acceptance of the COVID-19 vaccine. Conclusion. The level of COVID-19 vaccine hesitancy was high. The COVID-19 vaccine’s acceptability was influenced by being a man, having knowledge about the vaccine and having comorbidities. Furthermore, the most prevalent reason for refusing to take the vaccination is a fear that it may not be safe. As a result, public awareness campaigns should concentrate on delivering more information about the COVID-19 vaccine’s safety and efficacy. Furthermore, it is critical to disseminate accurate information, particularly among women, and to educate people about the vaccine.

Effect of air pollution on adult chronic diseases: Evidence from a quasi-natural experiment in China.

We utilize a quasi-experiment derived from China's Huai River policy to investigate the effect of air pollution on adult chronic diseases. The policy led to higher pollution exposure in cities north of the river boundary because they received centralized coal-based heating supply from the government during winter, whereas cities in the south did not. By applying a geographic regression discontinuity design based on distance from the Huai River, we determine that a 10 μg/m3 increase in fine particulate matter (PM2.5) raises chronic diseases rates by 3.2% in adults, particularly cardiorespiratory system diseases. Furthermore, the same effects are observed on multiple chronic disease rates, but the rates are reduced to 1.3%. The effect of pollution exposure varies depending on age, gender, and urban/rural status. Our findings imply that reducing 10 μg/m3 of the average nationwide level of PM2.5 concentration will save 27.46 billion CNY (4.16 billion USD) in chronic disease costs.

Association of subclinical thyroid dysfunction with chronic kidney disease in adults: A systematic review and meta-analysis

Association of subclinical thyroid dysfunction with chronic kidney disease in adults: A systematic review and meta-analysis

High dietary and lifestyle inflammatory scores are associated with increased risk of chronic kidney disease in Iranian adults

BackgroundSystemic inflammation can be the initiator in developing chronic diseases that may be affected by the lifestyle and diet of individuals. In the current study, we aimed to assess the association of the inflammatory potential of diet and lifestyle, determined by the food-based index of dietary inflammatory potential (FBDI), dietary inflammation score (DIS), and lifestyle inflammation score (LIS), with risk of chronic kidney disease(CKD) in Iranian adults.MethodsA total of 6044 CKD-free individuals aged ≥ 18 years, were recruited from among participants of the Tehran Lipid and Glucose Study(surveys 3 and 4) and followed a mean of 6.03 years(follow-up rate:94.95%). Data on dietary intakes were determined using a food frequency questionnaire. The inflammatory potential of diet and lifestyle were determined based on three indices, including FBDI, DIS, and LIS. Using the National Kidney Foundation guidelines, we defined CKD as eGFR < 60 mL/min/1.73 m2.ResultsMean ± SD age of the study population(54.3% women) was 37.8 ± 12.8 years. We identified 1216(20.1%) new cases of CKD during the 6.03 years of follow-up (46,889.8 person-years). In the multivariable-adjusted model, the risk of CKD incident is increased across quartiles of FBDI (HR = 1.21;95%CI:1.03–1.42, Ptrend:0.014) and LIS (HR = 1.28;95%CI:1.07–1.55,Ptrend:0.006). However, no significant relationship was observed between the higher DIS score and CKD risk.ConclusionOur findings showed that a higher inflammatory potential of diet and lifestyle, characterized by a higher score of FBDI and LIS, was related to increased incidence of CKD, while no significant relationship was reported between the DIS score and CKD incident.

Identification of Novel Genetic Risk Factors for Focal Segmental Glomerulosclerosis in Children: Results From the Chronic Kidney Disease in Children (CKiD) Cohort

Focal segmental glomerulosclerosis (FSGS) is a major cause of pediatric nephrotic syndrome, and African Americans exhibit an increased risk for developing FSGS compared with other populations. Predisposing genetic factors have previously been described in adults. Here we performed genomic screening of primary FSGS in a pediatric African American population. Prospective cohort with case-control genetic association study design. 140 African American children with chronic kidney disease from the Chronic Kidney Disease in Children (CKiD) cohort, including 32 cases with FSGS. Over 680,000 common single-nucleotide polymorphisms (SNPs) were tested for association. We also ran a pathway enrichment analysis and a human leucocyte antigen (HLA)-focused association study. Primary biopsy-proven pediatric FSGS. Multivariate logistic regression models. The genome-wide association study revealed 169 SNPs from 14 independent loci significantly associated with FSGS (false discovery rate [FDR]<5%). We observed notable signals for genetic variants within the APOL1 (P=8.6×10-7; OR, 25.8 [95% CI, 7.1-94.0]), ALMS1 (P=1.3×10-7; 13.0% in FSGS cases vs 0% in controls), and FGFR4 (P=4.3×10-6; OR, 24.8 [95% CI, 6.3-97.7]) genes, all of which had previously been associated with adult FSGS, kidney function, or chronic kidney disease. We also highlighted novel, functionally relevant genes, including GRB2 (which encodes a slit diaphragm protein promoting podocyte structure through actin polymerization) and ITGB1 (which is linked to renal injuries). Our results suggest a major role for immune responses and antigen presentation in pediatric FSGS through (1) associations with SNPs in PTPRJ (or CD148, P=3.5×10-7), which plays a role in T-cell receptor signaling, (2) HLA-DRB1∗11:01 association (P=6.1×10-3; OR, 4.5 [95% CI, 1.5-13.0]), and (3) signaling pathway enrichment (P=1.3×10-6). Sample size and no independent replication cohort with genomic data readily available. Our genetic study has identified functionally relevant risk factors and the importance of immune regulation for pediatric primary FSGS, which contributes to a better description of its molecular pathophysiological mechanisms. We assessed the genetic risk factors for primary focal segmental glomerulosclerosis (FSGS) by simultaneously testing over 680,000 genetic markers spread across the genome in 140 children, including 32 with FSGS lesions. Fourteen independent genetic regions were significantly associated with pediatric FSGS, including APOL1 and ALMS1-NAT8, which were previously found to be associated with FSGS and chronic kidney diseases in adults. Novel genes with relevant biological functions were also highlighted, such as GRB2 and FGFR4, which play a role in the kidney filtration barrier and in kidney cell differentiation, respectively. Finally, we revealed the importance of immune regulation in pediatric FSGS through associations involving cell surface proteins presenting antigens to the immune system and interacting with T-cell receptors.