The non-linear associations between blood manganese level and sarcopenia in patients undergoing maintenance hemodialysis: A multicenter cross-sectional study.

BACKGROUND AND AIMS: Manganese (Mn), a vital element in energy metabolism, is predominantly stored in skeletal muscles and plays a crucial role in muscle function and strength. Patients on maintenance hemodialysis (MHD) often experience muscle wasting due to metabolic disruption and inflammation. This study aimed to explore the relationship between blood Mn levels and sarcopenia in a patient population. METHODS: In this multicenter cross-sectional study, conducted from March 2021 to March 2022, 386 patients on MHD from three medical centers were included. Blood Mn levels were measured using inductively coupled plasma mass spectrometry, and body composition was assessed post-dialysis using bioelectrical impedance analysis. Grip strength was measured using a digital dynamometer. The patients were categorized into groups with and without sarcopenia. Using a generalized additive model to fit a smooth curve, we employed a generalized linear model to identify the optimal inflection point and explore the threshold effect after discovering a segmented relationship. Subsequently, a binary logistic regression analysis was conducted to investigate the relationship between blood manganese levels and the risk of sarcopenia, with adjustments made for potential confounding factors. RESULTS: A negative correlation was observed between blood Mn levels and sarcopenia-related parameters (Appendicular Skeletal Muscle Mass Index and grip strength) in Spearman's correlation analysis (both P < 0.05). After adjusting for confounding factors, a nonlinear association was identified. When blood Mn was ≤ 10.6 µg/L, the increase in sarcopenia was not statistically significant (P > 0.05). Conversely, when blood Mn exceeded 10.6 µg/L, each 1 µg/L increase raised the risk of sarcopenia by 0.1 times. Considering confounders, multivariate binary logistic regression confirmed an independent association between elevated blood Mn levels and sarcopenia. CONCLUSION: This study revealed an independent association between elevated blood Mn levels (> 10.6 µg/L) and sarcopenia in patients undergoing MHD. These findings emphasize the importance of understanding the Mn metabolism in the context of muscle health in this patient population. Further research is warranted to explore the underlying mechanisms and potential interventions for mitigating sarcopenia in patients with elevated blood Mn levels undergoing MHD.

Associations between pinch strength, cardiovascular events and all-cause mortality in patients undergoing maintenance hemodialysis.

BACKGROUND AND AIMS: Patients undergoing maintenance hemodialysis (MHD) experience increased mortality and cardiovascular disease (CVD) risks; however, the potential connection between pinch strength (PS) and the prognosis of these patients remains unknown. Consequently, this study aimed to comprehensively assess the influence of PS and handgrip strength (HGS) on both survival and cardiovascular events (CVE) in patients undergoing MHD. METHODS: Data were gathered from patients undergoing MHD at the Hemodialysis Center of Guangzhou Red Cross Hospital in March 2021. We performed a retrospective follow-up spanning 24 months, with death serving as the primary endpoint for observation and CVE as the secondary endpoint. Multifactorial Cox regression analysis, Kaplan-Meier survival curves, trend tests, and restricted cubic spline were applied to explore the association. RESULTS: During a 24-month follow-up, data were collected from 140 patients undergoing MHD with an average age of 66.71 ± 12.61 years. Among them, 52 (37.14%) experienced mortality, whereas 36 (40.00%) had CVE without baseline CVD. Kaplan-Meier survival curves demonstrated better survival rates and reduced CVE risk for patients in the second, third, and fourth quartiles compared with those in the first quartile for PS. Adjusted analyses in different models revealed higher PS levels were independently associated with all-cause mortality (major model, model 4, HR, 0.78; 95% CI, 0.64-0.95) but not with CVE risk (unadjusted HR, 0.90; 95% CI, 0.77-1.05). Compared with lower quartile PS levels, higher PS levels significantly reduced all-cause mortality (HR, 0.31; 95% CI, 0.10-1.02), and this trend remained consistent (P for trend = 0.021). Finally, the restricted cubic spline method using different models showed a linear relationship between PS and all-cause mortality (P > 0.05), when PS exceeded 4.99 kg, the all-cause mortality of MHD patients significantly decreased. CONCLUSIONS: PS was independently associated with all-cause mortality but not with CVE in patients undergoing MHD.

Single-pool model urea clearance index is associated with sarcopenia and nutritional status in patients undergoing maintenance hemodialysis: a cross-sectional study.

BACKGROUND: The single-pool model urea clearance index (single-pool Kt/Vurea; spKt/V) is the most commonly used method for dialysis adequacy assessment. However, only a few studies have examined the relationship between spKt/V values and parameters related to sarcopenia and nutritional status. This study aimed to evaluate whether the spKt/V is an indicator of sarcopenia and nutritional status in patients undergoing maintenance hemodialysis (MHD). METHODS: A total of 142 patients were included in this single-center, cross-sectional study. Venous blood samples were collected shortly before the hemodialysis session. The adequacy of dialysis in patients receiving MHD was assessed using spKt/V. Sarcopenia was identified according to the Asian Working Group for Sarcopenia (2019) definition. Receiver operating characteristic curve and area under the curve were used to evaluate the predictive value of spKt/V in sarcopenia. Univariate and multivariate binary logistic regression analyses were used to determine the association between spKt/V and sarcopenia and nutritional status. RESULTS: The mean spKt/V level was 1.3 ± 0.2, the prevalence of sarcopenia was 15.5% in patients on MHD. The best cutoff value of spKt/V in sarcopenia was 1.45 for both sexes, 1.33 and 1.45 for men and women, respectively (P < 0.05). The multivariate binary logistic regression shown that the spKt/V was independently positively associated with sarcopenia (OR = 122.88, 95% CI = 0.64-0.87, P = 0.002). Grouping spKt/V by the best cutoff value, when spKt/V ≥ 1.45, the OR of sarcopenia was 11.75 (95% CI = 3.16-43.67, P < 0.001). Subgroup analyses showed that when spKt/V ≥ 1.33 in men and spKt/V ≥ 1.45 in woman, the OR of sarcopenia was 9.73 (95% CI = 2.25-42.11, P = 0.002) and 14.52 (95% CI = 1.06-199.67, P = 0.045), respectively. CONCLUSIONS: The present study showed that spKt/V was an important influencing factor of sarcopenia and malnutrition in Asian patients on MHD.

Lower serum insulin-like growth factor-1 levels are independently associated with anemia in patients undergoing maintenance hemodialysis.

The relationship between serum insulin-like growth factor-1 (IGF-1) levels and anemia in patients undergoing maintenance hemodialysis (MHD) remains unclear. This cross-sectional study included patients who underwent MHD treatment for >3 months at our dialysis center in March 2021. Demographic and clinical data were recorded. Blood samples were collected before the hemodialysis sessions, and general serum biochemical parameters, routine blood markers, and serum IGF-1 levels were measured. Patients were divided into a group without anemia (hemoglobin ≥110 g/L) and a group with anemia (hemoglobin <110 g/L), and multivariable linear and binary logistic regression analyses were performed to study the relationship between the levels of serum IGF-1 and anemia. A total of 165 patients (male/female = 99:66) with MHD were enrolled in the study, with a median age of 66.0 (58.0, 75.0) years and a median dialysis vintage of 27.0 (12.0, 55.0) months. The mean hemoglobin level was 96.38 ± 16.72 g/L, and 126 patients had anemia (76.4%). Compared to patients without anemia, patients with anemia had lower serum IGF-1 and triglyceride levels and higher intravenous iron supplementation on dialysis (all p < 0.05). After adjusting for confounding factors in different models, the nine-model multivariate binary logistic regression analyses also confirmed that lower serum IGF-1 levels and serum IGF-1 < 197.03 ng/ml were both independently associated with anemia in patients undergoing MHD. However, further multicenter studies with larger sample sizes are required to confirm these findings.

Association between sedentary behavior and depression in US adults with chronic kidney disease: NHANES 2007-2018.

BACKGROUND: Depression increases the risk of adverse clinical outcomes in patients with chronic kidney disease. Physical activity has been shown to improve depressive symptoms in this population, but the relationship of sedentary behavior with depression has not been studied. In this study, we examined the relationship between sedentary behavior and depression in patients with chronic kidney disease. METHODS: This cross-sectional study included 5,205 participants aged ≥ 18 years with chronic kidney disease participating in the 2007-2018 National Health and Nutrition Examination Survey. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Recreation activity, work activity, walking or cycling for transportation, and sedentary behavior were measured using the Global Physical Activity Questionnaire. A series of weighted logistic regression models were used to investigate the aforementioned relationship. RESULTS: The prevalence of depression among US adults with chronic kidney disease was 10.97% in our study. In addition, sedentary behavior was strongly associated with higher levels of depressive symptoms, as measured by the PHQ-9 (P < 0.001). In the fully adjusted model, we found that compared with participants who had shorter durations of sedentary behavior, participants who had the highest durations of sedentary behavior had 1.69 times (odd ratio 1.69, 95% confidence interval: 1.27, 2.24) greater risk of being clinically depressed. After adjusting for confounding factors, subgroup analyses showed that the association between sedentary behavior and depression still existed in all stratifications. CONCLUSION: We found an association between longer duration of sedentary behavior and more severe depression in US adults with chronic kidney disease; however, prospective studies with larger sample sizes are still needed to confirm the effects of sedentary behavior on depression in the chronic kidney disease population.

Higher Levels of Blood Selenium are Associated with Higher Levels of Serum Lipid Profile in US Adults with CKD: Results from NHANES 2013-2018.

The association between selenium (Se) and lipid profile has been controversial in different populations, and the aim of the study was to investigate the relationship between Se and lipid profile in patients with chronic kidney disease (CKD). A total of 861 US adult patients with CKD (male: female = 404:457) from the National Health and Nutrition Examination Survey database were enrolled in this cross-sectional study. We used smoothing spline plots and multivariate binary logistic regression analyses to elucidate the relationships between blood Se and lipid profile. Multivariate adjusted smoothing spline plots showed that higher levels of blood Se were associated with higher levels of serum remnant cholesterol (RC), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels. Threshold and saturation effects were also observed between serum RC, TC, TG, LDL-C, and blood Se. In multivariate binary logistic regression analyses, the fully adjusted model showed that as blood Se increases by every 1 µg/L, the OR of high RC, high TG and high LDL-C in patients was 1.012 (95% CI: 1.001, 1.023 P = 0.046), 1.011 (95% CI: 1.001, 1.021 P = 0.043) and 1.009 (95% CI: 1.003, 1.016 P = 0.012), respectively. Furthermore, stratified analyses showed that the associations between blood Se and high RC/high TG were significantly stronger in patients aged < 65 years. Higher levels of blood Se were associated with increased serum lipid profile levels and increased risk of high RC, high TC, high LDL-C, and low HDL-C dyslipidemia in adult patients with CKD in the US. However, the real associations between blood Se and lipid profiles in this population should be verified in future prospective and randomized trials.

Associations between insulin-like growth factor-1 standard deviation score and overall nutritional parameters in patients with maintenance hemodialysis: a cross-sectional study.

BACKGROUND: This study investigated the association between insulin-like growth factor-1 and nutritional status indicators in patients undergoing maintenance hemodialysis (MHD). METHODS: Patients undergoing MHD for > 3 months were included in this single-center cross-sectional study in March 2021. Clinical, demographic, and body mass data and blood samples were collected before the hemodialysis sessions. Serum insulin-like growth factor-1 (IGF-1) levels were measured using a radioimmunoassay, and serum IGF-1 standard deviation score (SDS) was calculated for MHD patients according to age and sex. The nutritional status of patients was assessed using serum albumin, serum prealbumin, handgrip strength, pinching strength, upper arm muscle circumference, lean body mass, phase angle, seven-point subjective global assessment (SGA) score, and geriatric nutritional risk index (GNRI). The patients were divided into groups according to tertiles of serum IGF-1 SDS levels. Spearman correlation analyses and univariate and multivariate binary logistic regression analyses were used to determine the association between serum IGF-1 SDS and nutritional status parameters. RESULTS: A total of 155 MHD patients (male: female = 90:65) were enrolled in the study, with a median dialysis vintage of 28.0 (11.0, 55.0) months, and an average age of 66 (65.5 ± 13.0) years. The median of IGF-1 SDS was - 0.1 (- 0.6 to 0.6). Compared to patients with higher IGF-1 SDSs, patients with lower IGF-1 SDSs had lower levels of serum ceruloplasmin (341.0 [287.5, 416.0] vs 395.0 [327.0, 451.0] vs 409.0 [349.5, 507.5], p = 0.002), serum albumin (34.7 ± 3.0 vs 37.0 ± 3.1 vs 37.8 ± 2.6, p < 0.001), serum prealbumin (270.3 [233.7, 327.8] vs 326.0 [279.3, 355.6] vs 363.0 [324.2, 398.2], p < 0.001), handgrip strength (13.8 [10.0, 20.7] vs 17.7 [10.7, 22.5] vs 23.3 [16.6, 27.8], p < 0.001), pinch strength (4.6 [3.9, 6.0] vs 4.9 (3.9, 6.9) vs 6.5 [4.7, 8.7], p = 0.002), phase angle (3.3 [3.0, 3.8] vs 3.9 [3.4, 4.7] vs 4.3 [3.6, 5.2, p < 0.001), modified Creatinine Index (83.1 ± 19.7 vs 93.1 ± 23.4 vs 113.9 ± 24.3, p < 0.001), intracellular water (14.5 ± 4.4 vs 16.1 ± 4.9 vs 16.9 ± 4.4, p = 0.031), higher extracellular water (26.9 ± 5.8 vs 25.7 ± 5.5 vs 25.1 ± 3.1, p = 0.042), and higher malnutrition risk as defined by GNRI (49.0% vs 15.7% vs 11.5%, p < 0.001) and SGA (53.9% vs 23.5% vs 7.7%, p < 0.001). CONCLUSIONS: Lower IGF-1 SDSs are independently associated with higher malnutrition risk in patients with MHD.

Effects of oral non-protein calorie supplements on nutritional status among maintenance hemodialysis patients with protein-energy wasting: a multi-center randomized controlled trial.

Protein-energy wasting (PEW) is prevalent in maintenance hemodialysis (MHD) patients, and is one of the major risk factors for poor outcomes and death. This study aimed to investigate the effects of non-protein calorie supplements on the nutritional status of MHD patients with PEW. MHD patients with PEW were enrolled in this multi-center, open-label, randomized controlled trial. Then, they were randomly assigned to the intervention group to receive the non-protein calorie supplements containing 280 kcal of energy every day for 6 months or the control group to complete all aspects of the study without receiving supplements. Patients in both groups received dietary counselling from dietitians. Data on nutritional assessments, anthropometric measurements, blood analysis and dietary recall were collected at the baseline and at six months from both groups. Statistical analyses were performed using analysis of covariance (ANCOVA) adjusted for sex and baseline values. Ninety-two MHD patients completed the study. A significant increase in the subjective global assessment (SGA) score was found in the intervention group compared with the control group (4.88 ± 1.41 vs. 4.40 ± 1.16, p = 0.044). The ratio of PEW patients (diagnosed with SGA ≤5) in the intervention group (61.2%) was also significantly lower than that in the control group (83.7%) (p < 0.001). Moreover, significant improvements in body mass index (20.81 ± 2.46 kg m-2vs. 19.51 ± 2.60 kg m-2, p < 0.001), nutrition risk screening 2002 (2.45 ± 1.40 vs. 3.12 ± 1.37, p = 0.038), mid-upper arm circumference (23.30 ± 2.78 cm vs. 21.75 ± 2.87 cm, p = 0.001), and mid-arm muscle circumference (20.51 ± 2.32 cm vs. 19.06 ± 2.92 cm, p = 0.005) were observed in the intervention group compared with the control group. Patients in the intervention group took in more dietary energy than the control group (26.96 ± 4.75 kcal per kg body weight per day vs. 24.33 ± 2.68 kcal per kg body weight per day, p < 0.001). In conclusion, non-protein calorie supplements may improve the nutritional status of MHD patients with PEW.

Correlation between intestinal flora disruption and protein-energy wasting in patients with end-stage renal disease.

BACKGROUND: Different dialysis treatments may affect the composition and structure of the intestinal flora of dialysis-treated chronic kidney disease (CKD) patients. This study aimed to analyze the correlations between the different flora and the nutritional indexes and further explore the potential metabolic pathways in patients with CKD in end-stage renal disease (ESRD). METHODS: Altogether, 102 patients with ESRD were recruited and categorized into the hemodialysis (HD) group (N = 49) and the peritoneal dialysis (PD) group (N = 53). Their biochemical indexes, anthropometric indicators, and inflammatory markers were determined. The total genomic DNA was extracted for 16S ribosomal DNA sequencing. Furthermore, bioinformatics analysis was employed for functional analysis. RESULTS: Anthropometric indicators, including handgrip strength, mid-upper arm circumference, mid-upper arm muscle circumference, and body mass index, in the HD and PD groups showed a positive correlation with butyric acid-producing bacteria (Rosella and Phascolarctobacterium) and a negative correlation with conditional pathogens (Escherichia spp.). Meanwhile, the inflammatory markers, including high-sensitivity C-reactive protein and interleukin-6, were significantly higher in the PD-protein-energy wasting (PEW) group than in the PD-non-protein-energy wasting (NPEW) group; although they showed an increasing trend in the HD-PEW group, no significant difference was noted. Rosella was considerably scarce in the HD-PEW group than in the HD-NPEW group, whereas Escherichia was substantially more abundant in the PD-PEW group than in the PD-NPEW group. Compared with the HD group, the essential amino acid synthesis pathway, amino acid metabolism-related enzyme pathways, and aminoacyl-transfer RNA biosynthesis pathways were weakened in the PD group. Most carbohydrate metabolic pathways were weakened, although the tricarboxylic acid cycle was slightly enhanced. Concurrently, the fatty acid metabolism was enhanced, whereas fatty acid synthesis was weakened; the metabolic pathways of B vitamins were also weakened. These potential metabolic pathways of the various compounds released by intestinal flora showed a significant correlation with blood biochemical indexes, anthropometric indicators, and inflammatory markers. CONCLUSION: In patients with ESRD, different dialysis treatments affected the abundance of butyric acid-producing bacteria (Rosella and Phascolarctobacterium) and conditional pathogens (Escherichia spp.). Butyric acid-producing bacteria showed a positive correlation with PEW and showed a negative correlation with Escherichia. Improving the intestinal diversity and increasing the amount of butyric acid-producing bacteria, such as Blautella, Faecococcus, and Phascolarctobacterium, are potential therapeutic approaches to enhance protein-energy consumption in patients with ESRD.

Prevalence and associated factors of frailty among Southern Chinese Han patients on haemodialysis: a multicentre, observational cross-sectional study.

OBJECTIVES: Frailty has been extensively studied in the general population. However, there is little information on frailty among patients undergoing haemodialysis (HD) in China. This study analysed the prevalence and associated factors of frailty among Southern Chinese Han patients on HD. DESIGN: Observational cross-sectional study. SETTING: Three HD centres in Southern China. PARTICIPANTS: Three hundred patients who underwent regular HD between June 2019 and October 2019. MAIN OUTCOMES AND MEASURES: Frailty was assessed using the Tilburg indicator of frailty (TFI) questionnaire, and the psychological status of the respondents was evaluated by the Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS). RESULTS: Seventy-five per cent of participants were in the frailty group, and the TFI score of HD patients was 6.89±2.87, with 8.15±2.06 in the frailty group and 2.87±1.31 in the non-frailty group. Frailty patients had higher SDS and SAS scores, and were more likely to suffer depression and anxiety than non-frailty patients. Multivariate logistic regression analysis excluding depression and anxiety showed that age, Charlson Comorbidity Index (excluding end-stage renal disease), a nuclear family (compared with living alone), and albumin were independently associated with frailty (all p<0.05). In the model including depression and anxiety, age, diabetes mellitus, living as a couple (compared with living alone), a nuclear family (compared with living alone), an extended family (compared with living alone), low phosphorus, depression and anxiety were associated with frailty by multivariate logistic regression analysis (all p<0.05). CONCLUSIONS: Approximately three-quarters of patients with HD in Southern China are frail, often accompanied with depression and anxiety. Age, diabetes mellitus, family structure, phosphorus, depression and anxiety were associated with frailty.

Association between the blood manganese (Mn) and hemoglobin in patients undergoing maintenance hemodialysis.

BACKGROUND AND AIMS: Manganese (Mn) and iron metabolism are closely related. Iron metabolism disorders often lead to anemia in patients undergoing maintenance hemodialysis (MHD). Here, we aimed to investigate the relationship between blood Mn and hemoglobin (Hb) in patients undergoing MHD. METHODS: Patients undergoing MHD in September 2019 were included in a cross-sectional study. Clinical and demographic data and blood samples were collected before hemodialysis sessions, and blood levels of Mn were measured by inductively coupled plasma mass spectrometry. Both multivariable linear and binary logistic regression analyses were performed to study the relationship between the blood Mn and Hb. RESULTS: A total of 144 patients undergoing MHD were enrolled in the study. The patients had a mean age of 64.33 ± 13.39 years, median vintage of 33.50 (16.25-57.50) months. Among them, 66 were females (45.8%). The median blood Mn level was 13.55 µg/L (IQR:9.92-17.48). Ninety-nine patients were anemic (68.8%). The mean Hb level was 99.83 ± 19.68 g/L. The patient group with high blood Mn had a high proportion of females, and these patients had high levels of RBC, hemoglobin, Hct, UIBC, serum TCHOL, and serum LDL, yet short dialysis vintage, low prevalence of anemia, low levels of serum ferritin, serum iron, and TSAT. Following adjustment for confounding factors, we found that low blood Mn level was independently associated with lower Hb level and anemia in patients undergoing MHD by multivariate linear and multivariate binary logistic regression, respectively, in different models. CONCLUSION: Whilst our study showed that high levels of blood Mn were independently associated with high hemoglobin in patients undergoing MHD, further multicenter studies with large sample sizes are still required.

High Blood Cu/Zn Ratio is Associated with Nutritional Risk in Patients Undergoing Maintenance Hemodialysis.

Patients undergoing maintenance hemodialysis (MHD) are at risk of an imbalance of copper and zinc homeostasis. We hypothesized that there is an association between the blood copper-zinc (Cu/Zn) ratio and nutritional status in these patients. For this cross-sectional study, blood samples were collected from patients undergoing MHD at Guangzhou Red Cross Hospital in September 2019. Zinc and copper levels were measured using inductively coupled plasma mass spectrometry. The seven-point subjective global assessment (SGA), nutritional risk screening 2002 (NRS2002), and geriatric nutritional risk index (GNRI) were used to evaluate the overall nutritional status. We enrolled 144 MHD patients (men:women = 78:66), with an average age of 64.33 ± 13.39 years and a median dialysis vintage of 33.50 (16.25-57.50) months. Patients with a higher blood Cu/Zn ratio had lower levels of hemoglobin, blood zinc, serum prealbumin, albumin, and creatinine as well as low SGA and GNRI scores, but higher modified Charlson comorbidity index score, serum C-reactive protein level, interleukin-6 level, blood copper level, and NRS2002 score (all p < 0.05). After adjustment for confounding factors in multivariable models, a high blood Cu/Zn ratio was independently associated with nutritional risk defined by all nutritional parameters (SGA, NRS2002, and GNRI). Prospective studies with larger sample sizes are warranted to confirm these results.

Association Between the Blood Copper-Zinc (Cu/Zn) Ratio and Anemia in Patients Undergoing Maintenance Hemodialysis.

Copper (Cu) and zinc (Zn) imbalances are common in dialysis patients. This study aimed to investigate the relationship between the blood Cu/Zn ratio and anemia in patients undergoing maintenance hemodialysis (MHD) treatment. This cross-sectional study included patients undergoing MHD at our center in September 2019. Clinical and demographic data and blood samples were collected before the hemodialysis sessions, and the blood levels of Zn and Cu were measured by inductively coupled plasma mass spectrometry. Multivariable linear and binary logistic regression analyses were performed to study the relationship between blood Cu/Zn ratio and anemia. A total of 144 MHD patients were enrolled in this study. The patients had a mean age of 64.33 ± 13.39 years, a median dialysis vintage of 33.50 (16.25-57.50) months, with 66 being females (45.8%). The median blood Cu/Zn ratio was 15.55 (interquartile range: 12.47-20.31). Anemia was present in 99 patients (68.8%). Groups with higher hemoglobin levels had decreased blood Cu/Zn ratios (p < 0.05). After adjustments for confounding factors, higher blood Cu/Zn ratios were independently associated with lower hemoglobin levels and anemia in MHD patients based on multivariate linear and multivariate binary logistic regression, respectively, in different models. Our study found that the blood Cu/Zn ratio is independently associated with anemia in MHD patients, but prospective multicenter studies with larger sample sizes are still needed to determine the appropriate cutoff values for blood zinc, blood copper, and blood Cu/Zn levels in this patient population.

Circular RNA expression profile in transgenic diabetic mouse kidneys.

BACKGROUND: Diabetic nephropathy is one of the most important complications in patients with diabetes. The etiology and pathogenesis of diabetic nephropathy remain unclear. Several studies have indicated that circular RNAs (circRNAs) play crucial regulatory roles in numerous human diseases and normal physiology; however, to date, no study has focused on the comprehensive expression profile of circRNAs in the kidneys of diabetic mice. Therefore, we aimed to identify differentially expressed circRNAs in diabetic mouse kidneys to explore the possible roles of dysregulated circRNAs in diabetic nephropathy development. RESULTS: Diabetic BKS-Leprem2Cd479/Nju (BKS-DB/Nju) mice and their nondiabetic wild-type littermates of C57BL/KsJ wild-type (WT) mice were used as experimental animals. Among all circRNAs identified by high-throughput RNA sequencing, four circRNAs were upregulated and ten were downregulated in diabetic mouse kidneys compared to those in nondiabetic mouse kidneys. After verification using quantitative reverse transcriptase polymerase chain reaction assays, we found that circR_1084, circR_182, circR_4, circR_50, circR_596, circR_897, and circR_203 were downregulated, whereas circR_627, circR_628, circR_735, and circR_801 were upregulated in the renal tissues of 8- and 16-week-old BKS-DB/Nju mice compared to those in WT mice. CONCLUSION: We studied the circRNA expression profile in the kidneys of diabetic mice. Differentially expressed circRNAs may be useful as candidate biomarkers for diabetic nephropathy. Collectively, our results provide a novel theoretical basis for further investigation of the regulatory roles of circRNA in the etiology and pathogenesis of diabetic nephropathy.

Associations Between Blood Trace Element Levels and Nutritional Status in Maintenance Hemodialysis.

OBJECTIVE(S): We aimed to investigate the associations between blood trace element levels and nutritional status in patients undergoing maintenance hemodialysis (MHD). METHODS: This cross-sectional study included patients undergoing MHD who were treated at our center in September 2019. Clinical and demographic data and blood samples were collected before hemodialysis sessions, and the levels of manganese, lead, selenium, zinc, and copper were measured by inductively coupled plasma mass spectrometry. The Simplified Nutritional Appetite Questionnaire scale was used to assess patient appetite. Skinfold thickness, bicep circumference, upper arm muscle circumference, 7-point Subjective Global Assessment, Nutritional Risk Screening 2002 (NRS 2002), and Geriatric Nutritional Risk Index (GNRI) were used to assess patient nutritional status. Univariate and multivariate logistic regression analyses were performed to study the relationship between trace elements and nutritional indicators. RESULTS: In total, 118 patients (64 males and 54 females) were included, with a median dialysis vintage of 34.0 months (16.0-54.5 months) and an average age of 63.20 ± 14.26 years. Malnourished patients, as defined by the GNRI, Subjective Global Assessment, and NRS 2002, accounted for 28.0%, 49.2%, and 26.3% of enrolled patients, respectively. The multivariate binary logistic regression showed that higher blood copper levels were independently associated with nutritional risk defined as GNRI ≤91.2 (odds ratio [OR] = 1.003, 95% confidence interval [CI] = 1.000-1.006; P = .020), whereas lower blood zinc levels (OR = 0.634, 95% CI = 0.439-0.916; P = .015), blood zinc < 4.220 mg/L (OR = 3.723, 95% CI = 1.274-10.879; P = .016), lower blood selenium levels (OR = 0.959, 95% CI = 0.929-0.990; P = .010), and blood selenium < 85 µg/L (OR = 5.568, 95% CI = 1.039-29.840; P = .045) were independently associated with a nutritional risk defined as NRS 2002 ≥ 3. CONCLUSION(S): Higher levels of blood copper and lower levels of blood zinc and selenium were independently associated with higher nutritional risk in MHD patients.

Levels of trace blood elements associated with severe sleep disturbance in maintenance hemodialysis patients.

PURPOSE: Sleep disturbance is frequently observed in patients on maintenance hemodialysis (MHD), and this population usually presents imbalances in trace elements. We investigated the association between blood trace element levels and sleep quality in patients on MHD. METHODS: This cross-sectional and single-center study was performed in September 2019. Patients regularly undergoing hemodialysis for > 3 months at our center were recruited, and demographic, clinical, and laboratory parameters were recorded. The Pittsburgh Sleep Quality Index (PSQI) was applied to define sleep disturbance. Blood trace element (zinc, manganese, copper, selenium, and lead) levels were measured using an inductively coupled plasma mass spectrometer. RESULTS: In total, 121 patients on MHD (male/female = 68:53) were enrolled in the study (mean age 63.7 ± 13.9 years, median dialysis vintage 38.0 [20.0, 60.0] months). According to PSQI, 56 (46%) patients experienced severe sleep disturbance. These patients were characterized by older age, higher serum parathyroid hormone levels, and lower blood selenium levels (all P < 0.05). No significant differences in blood zinc, manganese, copper, and lead levels were observed between groups. Univariate binary logistic regression showed that lower blood selenium levels were associated with severe sleep disturbance (odds ratio = 0.976, 95% confidence interval: 0.954-0.999, P = 0.038). Multivariate analyses also confirmed the results after adjusting for confounding factors. CONCLUSION: Our study indicated an association between lower blood selenium levels and the occurrence of severe sleep disturbances in patients on MHD. However, a prospective study with a larger sample size and assessing the importance of selenium supplementation are needed to confirm the results.

Lower Levels of Blood Zinc Associated with Intradialytic Hypertension in Maintenance Hemodialysis Patients.

Intradialytic hypertension (iHTN) has been related with an increased risk of mortality, with imbalances in trace elements being frequent in maintenance hemodialysis (MHD) patients. The aim of this study was to analyze the relationships between the levels of blood trace elements and iHTN in MHD patients. A total of 144 MHD patients were enrolled in September, 2019 (66 females; 5616 hemodialysis treatments), with a mean age of 64.33 ± 13.39 years and median vintage of 33.50 (16.25-57.50) months. Patients exhibited an average peridialytic systolic blood pressure (SBP) change of - 4.18 ± 20.22 mm Hg in the next 3 months. Thirty-four (23.6%) patients had persistent iHTN (piHTN). These patients were characterized by older age, higher rate of hypozincemia, and modified Charlson comorbidity score, whereas lower blood zinc and hemoglobin, at the time of their recruitment. No significant difference in the levels of other blood trace elements was observed between groups. A general linear mixed (GLM) model showed that with every mg/L point lower mean blood zinc at baseline, the peridialytic SBP change was increased by 4.524 mm Hg (P < 0.001). Binary logistic model in modulate of the GLM model revealed that the lower level of blood zinc was associated with piHTN (OR = 0.433, 95 % CI 0.295 to 0.637, P < 0.001). Multivariate analysis confirmed both above results. Our study indicated that lower blood zinc was independently associated with piHTN in patients undergoing MHD, but prospective studies with larger population are still needed.

Graph embeddings on gene ontology annotations for protein-protein interaction prediction.

BACKGROUND: Protein-protein interaction (PPI) prediction is an important task towards the understanding of many bioinformatics functions and applications, such as predicting protein functions, gene-disease associations and disease-drug associations. However, many previous PPI prediction researches do not consider missing and spurious interactions inherent in PPI networks. To address these two issues, we define two corresponding tasks, namely missing PPI prediction and spurious PPI prediction, and propose a method that employs graph embeddings that learn vector representations from constructed Gene Ontology Annotation (GOA) graphs and then use embedded vectors to achieve the two tasks. Our method leverages on information from both term-term relations among GO terms and term-protein annotations between GO terms and proteins, and preserves properties of both local and global structural information of the GO annotation graph. RESULTS: We compare our method with those methods that are based on information content (IC) and one method that is based on word embeddings, with experiments on three PPI datasets from STRING database. Experimental results demonstrate that our method is more effective than those compared methods. CONCLUSION: Our experimental results demonstrate the effectiveness of using graph embeddings to learn vector representations from undirected GOA graphs for our defined missing and spurious PPI tasks.

Auxiliary genetic analysis in a Chinese adolescent NPH family by single nucleotide polymorphism screening.

Hereditary nephropathy is a progressive fatal renal disease caused by genetic changes. In this study, genetic screening was used to reveal mutations in a family in Southern China, in which there are two patients with confirmed hereditary nephropathy, who are alive at the time of publication. Imaging tests, including color Doppler ultrasonography and magnetic resonance imaging (MRI), as well as pathological examinations, including hematoxylin­eosin staining, electron microscopy and immunohistochemistry were performed. Target sequencing of nephrosis 2 (NPHS2), wilms tumor 1 (WT1), phospholipase C ε 1 (PLCE1), actinin α 4 (ACTN4), angiotensin I converting enzyme (ACE), uromodulin (UMOD) and nephrocystin 1 (NPHP1) was also carried out. This study indicated that heterozygous genetic variants of NPHS2, WT1, ACTN4, PLCE1 and UMOD found in the patients were gene polymorphisms. A renal biopsy showed sclerosing glomerulonephritis, dilated tubules and lymphocyte/monocyte infiltration in the interstitium of the index patients. Genetic analysis showed vertical transmission of the disease­causing mutations, including a homozygous deletion in NPHP1 and a nonsense mutation in ACE found via PCR­based single nucleotide polymorphism screening. Further network analysis identified direct and indirect co­location genes between NPHP1 and ACE. To conclude, familial adolescent nephronophthisis was diagnosed in two index patients in this study. It is recommended that comprehensive gene mutation screening is used in the diagnosis of complex hereditary diseases.