Abnormal sleep patterns are associated with depressive symptoms in Chinese community-dwelling older adults.

OBJECTIVE: Depression is an important public health issue among older adults, often associated with their sleep-related problems. We aimed to investigate the association between sleep-related problems and depressive symptoms among Chinese community-dwelling older adults. METHODS: This cross-sectional study utilized self-reported data from 2896 participants (aged ≥60 years) from Shanghai, China. Nocturnal sleep duration and difficulty initiating sleep (DIS) symptoms were obtained through face-to-face questionnaires. Nocturnal sleep duration was categorized as 'short' (<7 h), 'normal' (7-8 h), and 'long' (>8 h). Subsequently, the 3 groups were further divided into 6 groups based on the presence of DIS, and the combined sleep behaviors were termed 'sleep patterns'. Logistic regression was conducted to assess the association of sleep variables and sleep patterns with the risk of depressive symptoms. RESULTS: Compared to the reference group, 'short sleep duration' and DIS symptoms were associated with depressive symptoms (with odds ratios (OR) of 1.50 and 1.79, respectively, with 95% confidence intervals (CI) of 1.14-1.97 and 1.39-2.31). When compared to 'normal sleep duration without DIS', both 'short sleep duration with DIS' (OR = 2.60, 95% CI: 1.81-3.72) and 'normal sleep duration with DIS' (OR = 1.60, 95% CI: 1.03-2.49) were statistically associated with depressive symptoms in adjusted regression models. CONCLUSION: Short sleep duration and DIS symptoms were found to be associated with depressive symptoms. Combining DIS symptoms with sleep duration, DIS was identified as a risk factor for elevated depressive symptoms in individuals with short and normal sleep durations. In managing depressive symptoms, it is imperative to thoroughly evaluate insomnia and nighttime sleep, which can provide valuable insights for nursing and medical policy.

Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: A multicenter, double-blind, placebo-controlled, randomized trial.

BACKGROUND: Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy. OBJECTIVE: This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules. MAIN OUTCOME MEASURES: The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria. RESULTS: Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2 in the YQPY group and 5.78 mL/min per 1.73 m2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m2 (P < 0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively. CONCLUSION: The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051723. Please cite this article as: Wu JJ, Zhang TY, Qi YH, Zhu MY, Fang Y, Qi CJ, Cao LO, Lu JF, Lu BH, Tang LM, Shen JX, Mou S. Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: a multicenter, double-blind, placebo-controlled, randomized trial. J Integr Med. 2024; 22(3): 279-285.

PD-1/PD-L1 governed cross-talk of exhausted CD8+ T and memory B cells in systemic lupus erythematosus.

BACKGROUND: Indeterminate readout of the quantitative interferon-γ release test (QFT) for Mycobacterium tuberculosis screening is a specific laboratory finding for systemic lupus erythematosus (SLE), which may be due to T-cell exhaustion and abnormal programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) signalling. METHODS: We enrolled 104 patients with SLE and 225 with other rheumatic musculoskeletal diseases (RMDs) who presented to the outpatient clinic between 2020 and 2023. Twenty healthy donors served as the controls. The QFT was performed in all participants, and those with indeterminate results were compared among the groups. Immunophenotyping and functional assays were performed using blood mononuclear cells. Interferon (IFN)-γ was detected in vitro and ex vivo in patients with SLE with indeterminate or negative QFT results, before or after rituximab therapy. RESULTS: 104 patients with SLE had a significantly higher rate of indeterminate QFT results was significantly higher (17.31%) than that of 225 patients with RMD (3.56%). Patients with SLE with indeterminate QFT had more active disease (SLEDAI-2K, mean 10.94 vs 4.02, p<0.0001), including a higher incidence of active nephritis (55.56% vs 29.07%). Indeterminate QFT in SLE is mainly caused by an insufficient IFN-γ response in CD8+T cells with exhausted immunophenotypes. The abnormal interaction between exhausted PD-1 high CD8+ T cells and activated PD-L1 low memory B cells in SLE can be reversed with a PD-1 agonist or increased PD-L1 expression. Rituximab treatment indirectly reversed this IFN-γ response. CONCLUSION: The PD-1/PD-L1 signalling pathway, which governs the crosstalk between exhausted CD8+ T cells and activated memory B cells, is a mechanistic explanation for insufficient interferon-γ response in patients with SLE.

Association Between Advanced Glycation End Products and Sarcopenia: The Mediating Role of Osteoporosis.

CONTEXT: Advanced glycation end products (AGEs) are a group of molecules formed through nonenzymatic reactions. These compounds are associated with several age-related diseases, including sarcopenia and osteoporosis. OBJECTIVE: This work aimed to investigate the relationships between AGEs, osteoporosis, and sarcopenia in community-dwelling older adults. METHODS: This cross-sectional study included 1991 older adults aged 72.37 ± 5.90 years from China. AGE levels were measured by the AGE Reader device. Bone mineral density was assessed using dual-energy X-ray absorptiometry, and osteoporosis was diagnosed based on a T score of less than -2.5. Sarcopenia was defined as loss of muscle mass plus loss of muscle strength and/or reduced physical performance. Presarcopenia was defined as low muscle mass with normal muscle strength and normal physical performance. RESULTS: The prevalence of sarcopenia was 18.5%, and that of osteoporosis was 40.5%. Compared to the lowest AGE quartile, the highest AGE quartile showed a significant association with sarcopenia (odds ratio [OR] 2.42; 95% CI, 1.60-3.66) (P for trend <.001), but not with presarcopenia. Per-SD increase in AGE was associated with higher odds of sarcopenia (OR 1.44; 95% CI, 1.26-1.66). Additionally, in the mediation analysis, when AGEs were treated as a continuous variable (the mediation effect is denoted by Za*Zb = 18.81; 95% CI, 8.07-32.32]-the 95% CI does not contain zero, representing a significant mediating effect) or a categorical variable (the mediating effect is expressed as Zmediation = 3.01 > 1.96, which represents a significant mediating effect), osteoporosis played a partial mediating role in the association between AGEs and sarcopenia. CONCLUSION: Elevated AGEs are associated with sarcopenia but not with presarcopenia. This association was partially mediated by osteoporosis.

Corrigendum: The neutrophil-to-lymphocyte ratio is associated with mild cognitive impairment in community-dwelling older women aged over 70 years: a population-based cross-sectional study.

[This corrects the article DOI: 10.3389/fnagi.2023.1261026.].

The neutrophil-to-lymphocyte ratio is associated with mild cognitive impairment in community-dwelling older women aged over 70 years: a population-based cross-sectional study.

Background: The neutrophil-to-lymphocyte ratio (NLR) is a marker of inflammation that can be obtained quickly, conveniently, and cheaply from blood samples. However, there is no research to explore the effects of sex and age on the relationship between the NLR and mild cognitive impairment (MCI) in community-dwelling older adults. Methods: A total of 3,126 individuals aged over 60 years in Shanghai were recruited for face-to-face interviews, and blood samples were collected. MCI was assessed by the Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale, and neutrophil count and lymphocyte counts were measured in fasting blood samples. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Results: In females, the NLR in the MCI group was significantly higher than that in the cognitively normal group (2.13 ± 0.94 vs. 1.85 ± 0.83, p < 0.001) but not in men. Logistic regression showed that a higher NLR was an independent risk factor for MCI in women [odds ratio (OR) = 1.33; 95% confidence interval (CI) = 1.14-1.55]. In addition, the elevated NLR quartile was associated with an increased risk of MCI, especially in women older than 70 years (p value for trend = 0.012). Conclusion: Compared with males, female MCI patients had a significantly higher NLR than cognitively normal controls. In addition, elevated NLR was found to be significantly associated with MCI risk in women older than 70 years. Therefore, elderly Chinese women with a higher NLR value may be the target population for effective prevention of MCI.

Diosgenin prevents periodontitis by inhibiting inflammation and promoting osteogenic differentiation.

Diosgenin, an essential dietary steroidal sapogenin, possess multiple pharmacological activities. This study aimed to assess the effects of diosgenin on periodontitis and elucidate the mechanisms. Lipopolysaccharide (LPS)-stimulated human periodontal ligament stem cells (hPDLCs) and a Porphyromonas gingivalis (P.g) plus ligation-induced animal model were used for in vitro and in vivo studies, respectively. Inflammatory responses, nuclear factor κ-B (NF-κB) signaling and osteogenesis-related markers were measured both in LPS-stimulated hPDLSCs and in gingival tissue of periodontitis rats. Treatment with diosgenin significantly inhibited the production of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, and interleukin (IL)-6 and the activation of NF-κB pathway in LPS-stimulated hPDLSCs. Further, treatment with diosgenin enhanced the expression of osteoblast-related genes and increased the osteogenic differentiation capacity. Further, activation NF-κB pathway largely abolished the protective effects of diosgenin. Consistent with the in vitro studies, in vivo studies showed that administering diosgenin to periodontitis rats significantly lowered the levels of the TNF-α, IL-1ß, and IL-6 and the inflammatory transcription factor NF-κB in gingival tissue. In addition, osteoblast-related genes were promoted. Diosgenin attenuates periodontitis by adjusting NF-κB signaling to inhibit inflammatory effects and promoting osteogenesis, suggesting diosgenin might be developed as a therapeutic strategy for treating periodontitis in the future.

Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China.

Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a Bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL), and disability in 1082 severely and critically ill patients with COVID-19 between 8 December 2022 and 9 February 2023 in Shanghai, China. The final 60-day follow-up was completed on 10 April 2023. Results: Among 1082 patients (mean age, 78.0 years, 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24-0.79]), and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, baricitinib and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR > 0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]) and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Paxlovid, Azvudine, and therapeutic anticoagulation showed a significant reduction in disability (p < 0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in a resource-limited scenario. Treatment with an IL-6 receptor antagonist, baricitinib, and a-thymosin also had high probabilities of benefit in improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine, and therapeutic anticoagulation could significantly reduce disability at day 60.

Low thyroid function is associated with an increased risk of advanced fibrosis in patients with metabolic dysfunction-associated fatty liver disease.

AIMS: Observational studies showed that low thyroid function may perturb liver function. We aimed to evaluate the association of low thyroid function with both metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced hepatic fibrosis. METHODS: Participants who underwent abdominal ultrasonography and thyroid function test in a Chinese hospital from 2015 to 2021were enrolled. Fibrosis-4 index (FIB-4) > 2.67 and/or non-alcoholic fatty liver disease fibrosis score (NFS) > 0.676 were used to define advanced fibrosis. Descriptive analyses were performed to characterize the epidemiology of MAFLD according to levels of thyroid-stimulating hormone (TSH). The logistic regression model was applied to estimate the association of low thyroid function with MAFLD and advanced fibrosis. RESULTS: A total of 19,946 participants (52.78% males, mean age: 47.31 years, 27.55% MAFLD) were included, among which 14,789 were strict-normal thyroid function, 4,328 were low-normal thyroid function, 829 were subclinical hypothyroidism. TSH levels were significantly higher in MAFLD patients with a FIB-4 > 2.67 and /or NFS > 0.676 than their counterparts. The logistic regression model adjusted for age and sex showed that low-normal thyroid function increased the risk of MAFLD (odds ratio [OR] = 1.09; 95% confidence interval [CI] 1.01-1.18). Multivariable regression model adjusted for age, sex, body mass index, type 2 diabetes, and hypertension showed low-normal thyroid function increased the risk of advanced fibrosis in patients with MAFLD (FIB-4 > 2.67: OR = 1.41, 95% CI 1.02-1.93; NFS > 0.676: OR = 1.72, 95% CI 1.08-2.72). CONCLUSION: Elevated TSH concentrations are associated with advanced hepatic fibrosis, even in the euthyroid state.

The association between thyroid hormones and MAFLD is mediated by obesity and metabolic disorders and varies among MAFLD subtypes.

BACKGROUND: Thyroid hormone (TH) disorders increased the risk of metabolic dysfunction-associated fatty liver disease (MAFLD). AIM: To assess whether the association between TH and MAFLD is mediated via metabolic dysfunctions and varies among MAFLD subtypes (diabetes-MAFLD, overweight/obesity-MAFLD, metabolic disorders-MAFLD). METHODS: A total of 18,427 participants (661 diabetes-MAFLD, 3,600 overweight/obesity-MAFLD, 691 metabolic disorder-MAFLD cases, 13,475 non-MAFLD controls) from a Chinese hospital were enrolled. Hepatic ultrasound measurements and thyroid function were assessed. RESULTS: Overweight/obesity mediated the associations of MAFLD with triiodothyronine (T3), free triiodothyronine (FT3), free thyroxine (FT4), and the mediator accounted for 46.43%, 39.69%, and 42.68%, respectively. Metabolic disorder mediated the association of MAFLD with T3, FT3, FT4, thyroid stimulating hormone (TSH), and the mediator accounted for 36.57%, 23.19%, 34,65%, and 60.92%, respectively. Diabetes did not complementary mediate any association between TH and MAFLD. Elevated T3, FT3, TSH and decreased FT4 increased the risk of overweight/obesity-MAFLD, and the odds ratios were 1.59, 1.72, 1.18, and 0.60, respectively (Q4 vs.Q1, false discovery rate (FDR)<0.05). Elevated T3, FT3, and decreased FT4 increased the risk of metabolic disorder-MAFLD, and the odds ratios were 1.45, 1.33, and 0.52, respectively (Q4 vs.Q1, FDR<0.05). No significant association between TH and diabetes-MAFLD was detected. CONCLUSION: The association between TH and MAFLD is mediated by overweight/obesity and metabolic disorders and varies among MAFLD subtypes.

Adherence to a healthy lifestyle and its association with cognitive impairment in community-dwelling older adults in Shanghai.

Introduction: There is a growing body of recent literature linking the association of specific or multiple lifestyles with cognitive impairment, but most of these studies have been conducted in Western populations, and it is necessary to study multiple lifestyles and cognitive abilities in different populations, with the primary population of this study being a select group of community-dwelling older adults in Shanghai, China. Methods: The sample included 2,390 community-dwelling Chinese participants. Their cognitive function was assessed using the Mini-Mental State Examination (MMSE). We defined a healthy lifestyle score on the basis of being non-smoking, performing ≥210 min/wk moderate/vigorous-intensity physical activity, having light to moderate alcohol consumption, eating vegetables and fruits daily, having a body mass index (BMI) of 18.5-23.9 kg/m2, and having a waist-to-hip ratio (WHR) <0.90 for men and <0.85 for women, for an overall score ranging from 0 to 6. Results: Compared with participants with ≤2 healthy lifestyle factors, the adjusted odds ratio (OR) and 95% confidence interval (CI) for participants with 4, 5, and 6 healthy lifestyle factors were 0.53 (95% CI, 0.29-0.98), 0.40 (95% CI, 0.21-0.75), and 0.36 (95% CI, 0.16-0.79), respectively. Only WHR (OR = 0.54, 95% CI = 0.37-0.78) and physical activity (OR = 0.69, 95% CI = 0.51-0.92) were associated with cognitive impairment. A healthy lifestyle correlated with overall cognition (ß = 0.066, orientation (ß = 0.049), language ability (ß = 0.060), delayed recall (ß = 0.045) and executive function (ß = 0.044) (P all < 0.05). Conclusion: The study provides evidence on an inverse association between healthy lifestyles and cognitive impairment. We investigated whether healthy lifestyle was related to specific cognitive functions to provide a theoretical basis for accurate clinical prescription.

Gene polymorphisms of VEGF and KDR are associated with initial fast peritoneal solute transfer rate in peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is an effective and successful renal replacement therapy. The baseline peritoneal solute transfer rate (PSTR) is related to local membrane inflammation and may be partially genetically determined. Herein, we focused on vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain containing receptor (KDR). METHODS: This study recruited 200 PD patients from Renji Hospital in Shanghai, China. We analysed the association between the polymorphisms of VEGF and KDR and the 4-hour dialysate-to-plasma ratio for creatinine (4 h D/P Cr), which was measured between one and three months after initiating PD. RESULTS: The CC genotype in VEGF rs3025039 and the AA genotype in KDR rs2071559 were both positively associated with a fast baseline PSTR (VEGF rs3025039 CC vs. TT + TC: 0.65 ± 0.12 vs. 0.61 ± 0.11; P = 0.029; KDR rs2071559 AA vs. GA + GG: 0.65 ± 0.12 vs. 0.62 ± 0.12; P = 0.039). CONCLUSION: Baseline PSTR was partly determined by VEGF and KDR gene polymorphisms.

C4d as a Screening Tool and an Independent Predictor of Clinical Outcomes in Lupus Nephritis and IgA Nephropathy.

BACKGROUND: As an indispensable marker of complement cascades activation, C4d was confirmed of its crucial role in the pathogenesis of both lupus nephritis (LN) and IgA nephropathy (IgAN). While the studies directly comparing the diagnostic value, and outcomes predicting function of C4d between LN and IgAN are still absent. METHODS: A cohort of 120 LN patients, 120 IgAN patients who were diagnosed by renal biopsy between January 2015 and December 2017 and 24 healthy age matched controls were prospectively analyzed. The patients were followed till December 2020. The outcomes were adverse disease treatment response (disease relapse) and kidney disease progression event (decline of estimated glomerular filtration rate by more than 20% or end-stage kidney disease). The renal C4d deposition proportion and pattern were compared between IgAN and LN patients. In addition, the relationship between renal C4d deposition and disease subtypes, disease relapse as well as disease progression for LN and IgAN patients were also analyzed. RESULTS: The LN, IgAN patients and healthy controls were well matched in ages. The follow-up period was 38.5 (30.3-60.8) months for LN patients and 45.0 (30.5-57.0) months for IgAN patients. 78 patients (65.0%) with LN had renal C4d deposition, compared with only 39 IgAN patients (32.5%) with C4d deposition in renal tissues (P < 0.001). The LN patients shared different renal C4d distribution patterns with IgAN patients. Compared with IgAN patients, the C4d deposition in LN patients was significantly more in renal glomerulus (P < 0.001) and less in renal tubules (P = 0.003). For disease subtypes, renal C4d deposition was especially strong in class V membranous LN and IgAN with tubulointerstitial fibrosis (T1/T2) lesions. Renal C4d deposition was independently correlated with the disease relapse of LN patients (HR = 1.007, P = 0.040), and acted as an independent predictor of disease progression during the follow-up period for IgAN patients (HR = 1.821, P = 0.040). CONCLUSIONS: Renal C4d distribution proportion and pattern differed between LN and IgAN patients. The presence of C4d in renal tissue acted as an independent predictor of relapse for LN patients and disease progression for IgAN patients.

Improvement of polydopamine-loaded salidroside on osseointegration of titanium implants.

BACKGROUND: Microarc oxidation (MAO) on the surface of medical pure titanium can improve its histocompatibility, and loading drugs on the surface can resist excessive intimal hyperplasia. METHODS: In this study, salidroside (SAL) was loaded on the surface of porous titanium (Ti) with polydopamine (PDA) carrier. The effects of SAL on the osteogenesis and angiogenesis of Ti implants were studied by phalloidin staining, alizarin red staining, ALP staining, wound-healing assay, cell transwell assay, matrigel tube formation, and osteogenic and angiogenic genes and proteins expression detected by PCR and western blot in vitro. The bone defect model experiments in rats was established in vivo including X-ray, micro CT, hematoxylin and eosin staining (HE), immunohistochemistry (IHC), Goldner's trichrome analysis, Safranin O-fast green staining and determination of contents of TNF-α and IL-6 in serum. RESULTS: EDS and EDS mapping showed that SAL could be loaded on the surface of the MAO coating by PDA. A drug release experiment showed that SAL loaded on the Ti coating could release slowly and stably without sudden release risk. In vitro cell experiments showed that the SAL coating could promote the proliferation, morphology, calcification and alkaline phosphate activity of MC3T3-E1 cells. At the same time, it promoted the migration and tube formation of HUVEC cells. The SAL coating promoted osteogenesis and angiogenesis by promoting the expression of genes and proteins related to. In vivo experiments, HE and IHC showed that SAL significantly promoted the expression of COL-1 and CD31. Goldner's trichrome and Safranin O-fast green staining showed that SAL coating could increase the new bone tissue around the implantation site. The SAL coating had anti-inflammatory activity by reducing the levels of TNF-α and IL-6 in vivo. CONCLUSION: Therefore, SAL could improve osteogenesis and angiogenesis in conjunction with the Ti-PDA coating.

Elevated levels of serum sclerostin are linked to adverse cardiovascular outcomes in peritoneal dialysis patients.

PURPOSE: To investigate the correlation between elevated serum sclerostin levels and chronic kidney disease outcomes for patients receiving peritoneal dialysis (PD). METHODS: We performed a prospective observational study in stable PD patients. Serum sclerostin levels were determined via enzyme immunoassay, and median levels of sclerostin were used to divide patients into high and low sclerostin groups. New-onset cardiovascular events (CVEs) and cardiovascular mortality were evaluated during a 6-year follow-up period. RESULTS: Ninety-eight patients [mean age 52.5 ± 10.9 years, 49% males, 21.4% diabetic, median dialysis vintage 40.7 (range 17.9-72.2) months] were recruited. Compared with those in the low sclerostin group, patients in the high sclerostin group demonstrated higher levels of total-cholesterol, NT-proBNP, and osteoprotegerin (all P < 0.05). During the 6-year study period, 25 CVEs and 17 cardiovascular deaths occurred in the high sclerostin group, whereas 11 CVEs and four cardiovascular deaths occurred in the low sclerostin group. A Cox regression analysis determined that high sclerostin levels significantly increased the risk for CVEs (HR 2.475, 95% CI 1.116-5.489, P = 0.026) and cardiovascular death (HR 3.484, 95% CI1.134-10.706, P = 0.029), after multiple adjustments were made. CONCLUSIONS: Our data suggest that high sclerostin levels may predict the onset of CVEs and cardiovascular mortality among PD patients.

The role of hemoglobin variability as a prognostic indicator in peritoneal dialysis patients: a retrospective descriptive study.

PURPOSE: To investigate the effect of hemoglobin fluctuations on cardiovascular prognosis of patients on peritoneal dialysis (PD). METHODS: Retrospective descriptive study, with sample composed of 333 patients treated with PD at the Renal Unit. Two indicators were adopted to indicate hemoglobin fluctuations of PD patients: absolute value of hemoglobin variability (HV) and HV trend. Moreover, the new cardiovascular events and recurrent rate of cardiovascular events within 3 months after PD were recorded and were compared in groups of PD patients classified by hemoglobin fluctuation indicators. RESULTS: Patients whose HV value is less than 10 g/l have an increased risk of new cardiovascular events than patients with HV value > 10 g/l (27.2 vs. 12.2%, p < 0.05) during 3 months after PD. Patients who kept high hemoglobin values (≥ 110 g/l) 3 months after PD are prone to develop recurrent cardiovascular events than patients with relatively low hemoglobin values (< 110 g/l; p < 0.05). CONCLUSIONS: Hemoglobin fluctuations were associated with the cardiovascular prognosis in patients on PD. A limitation of our study is its retrospective design. However, the results in this research indicated anemia in PD patients without cardiovascular events history should be timely treated. Instead, hemoglobin should be kept within a relatively low level in patients with history of cardiovascular events. Additional clinical researches are needed to verify and improve our findings.

Pharmacological inhibition of heparin-binding EGF-like growth factor promotes peritoneal angiogenesis in a peritoneal dialysis rat model.

BACKGROUND: Molecular mechanisms of peritoneal dialysis (PD) ultrafiltration failure, peritoneal neo-angiogenesis, and fibrosis remain to be determined. We aimed to determine the role of heparin-binding EGF-like growth factor (HB-EGF) inhibition on angiogenesis of peritoneal membrane in a PD rat model. METHODS: 32 male Wistar rats were assigned into (1) control group; (2) uremic non-PD group: subtotal nephrectomy-induced uremic rats without PD; (3) uremic rats subjected to PD: uremic rats that were dialyzed with Dianeal® for 4 weeks; (4) CRM 197 group: dialyzed uremic rats were supplemented with CRM197, a specific HB-EGF inhibitor. Peritoneal transport function was examined by peritoneal equilibration test. Expression of HB-EGF and EGFR in peritoneal samples were examined by real-time PCR, immunohistochemical staining, and western blot. RESULTS: Progressive angiogenesis and fibrosis were observed in uremic PD rats, and there were associated with decreased net ultrafiltration (nUF), increased permeability of peritoneal membrane, and reduced expression of HB-EGF and EGFR protein and mRNA in uremic PD rats compared to uremic non-PD or control groups (both p < 0.05). CRM197 significantly induced peritoneal membrane permeability, decreased nUF, increased higher vessel density, and reduced pericyte count compared to that of uremic PD rats. The levels of HB-EGF and EGFR expression negatively correlated with vessel density in peritoneal membrane (both p < 0.001). CONCLUSION: PD therapy was associated with peritoneal angiogenesis, functional deterioration, and downregulation of HB-EGF/EGFR. Pharmacological inhibition of HB-EGF promoted PD-induced peritoneal angiogenesis and fibrosis and ultrafiltration decline, suggesting that HB-EGF downregulation contributes to peritoneal functional deterioration in the uremic PD rat model.

Comparison of combined leflunomide and low-dose corticosteroid therapy with full-dose corticosteroid monotherapy for progressive IgA nephropathy.

IgA nephropathy is the most common primary glomerulonephritis and one of the leading causes of end-stage renal disease. We performed a randomized, controlled, prospective, open-label trial to determine whether leflunomide combined with low-dose corticosteroid is safe and effective for the treatment of progressive IgA nephropathy, as compared to full-dose corticosteroid monotherapy. Biopsy-proved primary IgA nephropathy patients with an estimated glomerular filtration rate ≥ 30 ml/min/1.73m2 and proteinuria ≥1.0 g/24h were randomly assigned to receive leflunomide+low-dose corticosteroid (leflunomide group; n = 40) or full-dose corticosteroid (corticosteroids group; n = 45). The primary outcome was renal survival; secondary outcomes were proteinuria and adverse events. After 12 months of treatment and an average follow-up of 88 months, 11.1% vs. 7.5% of patients reached end-stage renal disease and 20% versus 10% of patients had a ≥ 50% increase in serum creatinine in the corticosteroids and leflunomide groups, respectively. Kaplan-Meier analysis did not reveal a between-group difference in these outcomes. Decreases in 24-hour proteinuria were similar in the two groups during the treatment period, but a more marked reduction was observed during follow-up in the leflunomide group. Although the incidence of adverse events was similar in the two groups, serious adverse events were observed only in the corticosteroid group. Thus, leflunomide combined with low-dose corticosteroid is at least as effective as corticosteroid alone for the treatment of progressive IgA nephropathy, and showed a greater reduction of proteinuria during long-term follow-up and fewer severe adverse events.

Three Versus 4 Daily Exchanges and Residual Kidney Function Decline in Incident CAPD Patients: A Randomized Controlled Trial.

BACKGROUND: Incident patients treated with continuous ambulatory peritoneal dialysis (CAPD) are often prescribed either 3 or 4 exchanges per day. However, the effects on residual kidney function and clinical outcomes of 3 versus 4 exchanges are not known. STUDY DESIGN: Prospective, randomized, controlled, open-label study. SETTING & PARTICIPANTS: Incident CAPD patients aged 18 to 80 years with glomerular filtration rates (GFRs; mean of renal urea and creatinine clearance from a 24-hour urine collection) ≥ 2mL/min and urine volume ≥ 500mL/d. Exclusion criteria included refusal for informed consent, history of maintenance hemodialysis therapy or transplantation, or limited life expectancy. INTERVENTION: 24-month intervention with 3- or 4-exchange CAPD using glucose-based peritoneal dialysis fluids. OUTCOMES: Primary outcomes were GFR, urine volume, and anuria-free survival. Secondary outcomes included peritonitis, patient survival, and technique survival. RESULTS: The study recruited 139 patients, 70 in the 3-exchange group and 69 in the 4-exchange group. Baseline body mass indexes were 21.4±3.0 and 21.9±3.2kg/m2 for the 3- and 4-exchange groups, respectively (P=0.4). After 24 months, for 3 versus 4 exchanges, GFR (1.6±2.0 vs 1.7±1.9mL/min; P=0.8), urine volume (505±522 vs 474±442mL/d; P=0.8), and anuria-free survival (log-rank test statistic = 0.055; P=0.8) did not differ between groups, but Kt/V (1.95±0.39 vs 2.19±0.48; P=0.03) and ultrafiltration (404±499 vs 742±512mL/d; P=0.004) were lower in the 3-exchange group. The 3-exchange group had nominally longer peritonitis-free survival time (log-rank test statistic = 3.811; P=0.05), and nominally fewer patients had peritonitis in this group, though this was not statistically significant (13% vs 26%; P=0.06). Patient survival (log-rank test statistic = 0.978; P=0.3) and technique survival (log-rank test statistic = 0.347; P=0.6) were similar between groups. LIMITATIONS: Single-center design; no formal sample-size calculations. CONCLUSIONS: In this small trial, CAPD regimens with 3 and 4 exchanges had similar effects on residual GFR, urine volume, and time to anuria. Incremental peritoneal dialysis starts appear safe when patients are monitored.

Possible role of IL-6 and TIE2 gene polymorphisms in predicting the initial high transport status in patients with peritoneal dialysis: an observational study.

OBJECTIVES: The aim of this study was to investigate the effect of interleukin (IL)-6 and TIE2 gene polymorphisms on baseline peritoneal transport property. DESIGN: An observational study. SETTING: Renji Hospital in Shanghai, China. PARTICIPANTS: This study included 220 patients with continuous ambulatory peritoneal dialysis (PD). OUTCOME MEASURES: Patients were divided into 2 groups based on the results of an initial peritoneal equilibration test performed within 3 months of starting PD therapy: group 1 consisted of low/low average transporters (n=123), and group 2 consisted of high/high average transporters (n=97). We genotyped TIE2 and IL-6 polymorphisms and analysed their effects on baseline transport status. RESULTS: The genotype AT in IL-6 Rs13306435 and the genotype CC in TIE2 Rs639225 were both negatively associated with a higher initial peritoneal transport status (IL-6 Rs13306435: OR=0.408, 95% CI 0.227 to 0.736; TIE2 Rs639225: OR=0.188, 95% CI 0.044 to 0.806). CONCLUSIONS: IL-6 and TIE2 polymorphisms are associated with baseline peritoneal transport property.