Association between disability in activities of daily living and phase angle in hemodialysis patients.

BACKGROUND: Disability in activities of daily living (ADL) significantly increases the risk of mortality among patients undergoing hemodialysis. Malnutrition and decreased exercise capacity are closely correlated with ADL disability. Phase angle (PhA) has been proposed as a measure of nutritional status and exercise capacity. This study aims to investigate the prevalence of ADL disability in hemodialysis patients and its association with PhA. METHODS: A prospective, observational study was conducted, involving hemodialysis patients treated between November 2019 and January 2020 in an affiliated hospital of Chinese university. ADL was measured using both basic ADL (BADL) scales and instrumental ADL (IADL) scales. PhA measurements were obtained using a BIA device while the patients were in the supine position after dialysis. RESULTS: A total of 237 hemodialysis patients with a mean age of 60.01 ± 13.55 years were included in this study. The prevalence of disability in ADL was 43.5%. Multivariable analysis results showed a robust association between low PhA and disability in both BADL and IADL (for each unit decrease in PhA: odds ratio 4.83 [95% CI: 2.56-9.0], and 3.57 [95% CI: 2.14-5.95], respectively). The optimal cut-off values of PhA for disability in BADL and IADL were 4.8 and 5.4, with the area under the ROC curve (AUC) were 0.783 (0.727, 0.835) and 0.799 (0.743, 0.848), respectively. CONCLUSIONS: Low PhA is strongly associated with disability in ADL in hemodialysis patients. These findings suggest that PhA may serve as a potentially objective measure of ADL disability in hemodialysis patients.

Total cholesterol and mortality in peritoneal dialysis: a retrospective cohort study.

BACKGROUND: Total cholesterol is inversely associated with mortality in dialysis patients, which seems implausible in real-world clinical practice. May there be an optimal range of total cholesterol associated with a lower mortality risk? We aimed to evaluate the optimal range for peritoneal dialysis (PD) patients. METHODS: We conducted a retrospective real-world cohort study of 3565 incident PD patients from five PD centers between January 1, 2005, and May 31, 2020. Baseline variables were collected within one week before the start of PD. The associations between total cholesterol and mortality were examined using cause-specific hazard models. RESULTS: 820 (23.0%) patients died, including 415 cardiovascular deaths, during the follow-up period. Restricted spline plots showed a U-curved association of total cholesterol with mortality. Compared with the reference range (4.10-4.50 mmol/L), high levels of total cholesterol (> 4.50 mmol/L) were associated with increased risks of all-cause (hazard ratio [HR] 1.35, 95% confidence index [CI] 1.08-1.67) and cardiovascular mortality (HR 1.38, 95% CI 1.09-1.87). Similarly, compared with the reference range, low levels of total cholesterol (< 4.10mmol/L) were also associated with high risks of all-cause (HR 1.62, 95% CI 1.31-1.95) and cardiovascular mortality (HR 1.72, 95% CI 1.27-2.34). CONCLUSION: Total cholesterol levels at the start of PD between 4.10 and 4.50 mmol/L (158.5 to 174.0 mg/dL), an optimal range, were associated with lower risks of death than higher or lower levels, resulting in a U-shaped association.

The Qi-Bang-Yi-Shen formula ameliorates renal dysfunction and fibrosis in rats with diabetic kidney disease via regulating PI3K/AKT, ERK and PPARγ signaling pathways.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and a growing public health problem worldwide. Losartan potassium (Los), an angiotensin II receptor blocker, has been used to treat DKD clinically. Recently, multi-herbal formula has been shown to exhibit therapeutic activities in DKD in China. Thus, we aimed to explore the protective effects of combination of Los and Qi-Bang-Yi-Shen formula (QBF) on DKD rats. Streptozotocin (STZ) injection was used to establish a rat model of DKD. Next, the bloodurea nitrogen (BUN), creatinine (CRE) and uric acid (UA) levels were detected in serum samples from DKD rats. Hematoxylin and eosin (H&E), periodic Acid Schiff (PAS) and Masson staining were performed to observe glomerular injury and glomerular fibrosis in DKD rats. In this study, we found that QBF or Los treatment could decrease serum BUN, CRE, UA levels and reduce urine albumin-to-creatinine ratio (ACR) in DKD rats. Additionally, QBF or Los treatment obviously inhibited glomerular mesangial expansion and glomerular fibrosis, attenuated glomerular injury in kidney tissues of DKD rats. Moreover, QBF or Los treatment significantly reduced PI3K, AKT and ERK1/2 protein expressions, but increased PPARγ level in kidney tissues of DKD rats. As expected, combined treatment of QBF and Los could exert enhanced reno-protective effects compared with the single treatment. Collectively, combination of QBF and Los could ameliorate renal injury and fibrosis in DKD rats via regulating PI3K/AKT, ERK and PPARγ signaling pathways. These findings highlight the therapeutic potential of QBF to prevent DKD progression.

[Discussions Concerning the Generalist-Specialist Combination Management Model of Chronic Kidney Disease]. / æ ¢æ€§è‚¾è„ç— "å ¨-专"结合管理模式探讨.

In recent years, the effective management of patients with chronic kidney disease (CKD) is gaining growing attention. In 2014, our hospital established the CKD generalist-specialist combination management model, which incorporates a set of CKD management processes. The generalist component incorporates the following, general practitioners from 6 community health centers in the surrounding areas (with about 650 000 permanent residents in the region) joining hands, setting up a management team composed of doctors and nurses, and formulating management protocols for patient follow-up, patient record management, screening, risk assessment, examination and treatment, nutrition and exercise, and two-way referrals. The specialist component of the model incorporates the following, providing trainings for general practitioners in the in the community in the form of lectures on special topics and case discussion sessions, and organizing 7 national-level workshops for continuing medical education in the past decade, covering about 1 400 participants. In addition, regular meetings of the support groups of patients with renal diseases were organized to carry out information and education activities for patients. We have set up 4 community-based training centers and 6 specialized disease management centers, including one for diabetic nephropathy. We have retrospectively analyzed the risk factors of elderly CKD patients by establishing the elderly physical examination database (which has a current enrollment of 26 000 people), the elderly community CKD cross-sectional survey database, and the elderly CKD information management system. After 10 years of management practice, the level of institutionalization and standardization of CKD specialty management in our hospital has been improved. Moreover, we have expanded the management team and extended the management base from the hospital to community. We have improved the level of CKD management in community health centers and improved the specialty competence of the general practitioners in the communities. The generalist-specialist combination management model makes it possible for CKD patients to receive early screening and treatment, obtain effective and convenient follow-up and referral services, and improve their quality of life. Patients with complications such as diabetes, hypertension, and sarcopenia could access treatments with better precision. It is necessary to carry out the generalist-specialist integrated management of CKD, which is worthy of further development and improvement.

Variety-Specific Transcriptional and Alternative Splicing Regulations Modulate Salt Tolerance in Rice from Early Stage of Stress.

Salt stress poses physiological drought, ionic toxicity and oxidative stress to plants, which causes premature senescence and death of the leaves if the stress sustained. Salt tolerance varied between different rice varieties, but how different rice varieties respond at the early stage of salt stress has been seldom studied comprehensively. By employing third generation sequencing technology, we compared gene expressional changes in leaves of three rice varieties that varied in their level of tolerance after salt stress treatment for 6 h. Commonly up-regulated genes in all rice varieties were related to water shortage response and carbon and amino acids metabolism at the early stage of salt stress, while reactive oxygen species cleavage genes were induced more in salt-tolerant rice. Unexpectedly, genes involved in chloroplast development and photosynthesis were more significantly down-regulated in the two salt tolerant rice varieties 'C34' and 'Nona Bokra'. At the same time, genes coding ribosomal protein were suppressed to a more severe extent in the salt-sensitive rice variety 'IR29'. Interestingly, not only variety-specific gene transcriptional regulation, but also variety-specific mRNA alternative splicing, on both coding and long-noncoding genes, were found at the early stage of salt stress. In summary, differential regulation in gene expression at both transcriptional and post-transcriptional levels, determine and fine-tune the observed response in level of damage in leaves of specific rice genotypes at early stage of salt stress.

Efficacy and safety of tailin formulation combined with continuous low-dose antibiotic therapy in patients with recurrent urinary tract infection: A multicenter, randomized, controlled clinical trial.

Persistent inflammation associated with recurrent urinary tract infection (rUTI) is a crucial inducement of inflammation-driven renal fibrosis (IDRF). Although continuous low-dose antibiotic therapy (CLAT) is the common treatment for rUTI, its clinical efficacy remains unsatisfactory. Tailin formulation (TLF), a Chinese herbal formulation prescribed for treating rUTI, is effective in alleviating symptoms and reducing recurrence. This study was to evaluate the efficacy and safety of TLF combined with CLAT compared with CLAT used alone in patients with rUTI. In this multicenter, randomized, controlled clinical trial, patients were assigned (1:1) to receive either TLF + CLAT or CLAT for 12 weeks. The primary outcome was the effective rate at week 12 of the treatment. The secondary outcomes were the recurrent rate at week 4 and week 12 post treatment; the post-treatment changes in renal tubular injury markers (urinary N-acetyl-ß-d-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG)), profibrotic factors (urinary monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta1 (TGF-ß1)), and traditional Chinese medicine (TCM) symptoms, and vital signs indicators and serious adverse events (SAEs) were also monitored throughout the trial. A total of 195 patients were included in the final analysis. The TLF + CLAT group had a higher effective rate and a lower recurrence rate than the CLAT group (p < 0.01). Significant decrease of urinary NAG and ß2-MG was observed in the TLF + CLAT group vs. CLAT group (p < 0.01), and similar changes were observed in profibrotic factors (urinary MCP-1 and TGF-ß1) (p < 0.05), which indicated that TLF might have potential renal tubular protection and anti-fibrosis effects. Additionally, a positive correlation within a certain range was shown in the correlation analysis of medical history (months) of rUTI patients with urinary MCP-1 (r = 0.50, p < 0.05) and TGF-ß1 (r = 0.78, p < 0.01). A significant difference was also observed in TCM symptoms (p < 0.01). There were no obvious adverse reactions that occurred during this study. We conclude that TLF combined with CLAT was superior to CLAT used alone in reducing rUTI recurrence, alleviating the non-infection-related physical symptoms and protecting renal tubular and anti-fibrosis, which suggests this novel therapy might be an available treatment with great promise in treating rUTI.

Urine Albumin/Creatinine Ratio and Microvascular Disease in Elderly Hypertensive Patients without Comorbidities.

OBJECTIVES: A high urine albumin/creatinine ratio (UACR) is associated with microvascular disease in hypertensive patients. However, hypertensive patients frequently have other comorbidities. Thus, it is difficult to distinguish the role of UACR from that of comorbidities in microvascular disease. The aim of this study was to evaluate the association between UACR and microvascular disease in elderly hypertension patients without comorbidities. METHODS: A cross-sectional cohort study of 2252 essential hypertension patients aged 65-94 years without comorbidities between January 1, 2016, and December 31, 2017, was conducted. Microvascular disease was evaluated by hypertension retinopathy (HR). Multivariable adjusted odds of HR by UACR quartiles were determined using logistic regression. RESULTS: The HR prevalence was 22.1% (n = 472) among the cohort study and was significantly different among UACR quartiles (19.7%, 20.3%, 22.0%, and 26.4% in quartiles 1, 2, 3, and 4, respectively, P = 0.036). After adjustment for covariates, higher UACR (odds ratio (OR) = 1.42, 95% confidence interval (CI) 1.05-1.92, quartile 4 versus 1) were significantly associated with HR. Among male patients, higher UACR (OR = 1.65, 95% CI 1.07-2.55, quartile 4 versus 1) were significantly associated with HR after adjustment for covariates. Among female patients, however, 64% and 40% increased odds of HR were noted in the highest and lowest UACR (quartiles 4 and 1, respectively) compared to UACR quartile 2. CONCLUSIONS: Microvascular disease was associated with higher UACR in elderly male essential hypertension patients without comorbidities but was associated with lower and higher UACR in female patients without comorbidities.

Association Between Sarcopenia and Its Components and Dependency in Activities of Daily Living in Patients on Hemodialysis.

OBJECTIVES: To investigate the association of sarcopenia and its components (muscle mass, muscle strength, and physical performance) with dependency in activities of daily living (ADLs) in maintaining patients on hemodialysis. DESIGN AND METHODS: This is a cross-sectional study. Sarcopenia was identified according to the Asian Working Group for Sarcopenia 2019 criteria. Basic ADLs (BADLs) and instrumental ADLs (IADLs) were assessed. Logistic regression was used to estimate the association of sarcopenia and its components with dependency. Area under the receiver-operating characteristic curve of gait speed corresponding with dependency was calculated. RESULTS: A total of 238 patients on hemodialysis were included. The proportion of enrolled male candidates was 67.6%, and the average age was 60.9 years. In all, 49.2% (n = 117) and 30.7% (n = 73) of patients on dialysis were diagnosed with sarcopenia and severe sarcopenia, respectively. Dependency in BADLs was 21.0% (n = 50), and dependency in IADLs was 41.2% (n = 98). Severe sarcopenia was significantly associated with dependency in BADLs and IADLs after adjustment of clinical covariables (odds ratio [OR], 4.68 [95% confidence interval (CI): 2.11-10.40]; OR, 3.24 [95% CI: 1.61-6.53], respectively), whereas those effects for sarcopenia were not significant. With all three sarcopenia components in the analysis model, high gait speed remained strongly associated with low function dependency in BADLs and IADLs (per 0.1 m/s increase of gait speed: OR, 0.52 [95% CI: 0.41-0.66]; and 0.46 [95% CI: 0.35-0.59], respectively). Area under the receiver-operating characteristic curve of gait speed corresponding with dependency in BADLs and IADLs was 0.827 (0.759, 0.896) and 0.878 (0.832, 0.925), respectively. CONCLUSIONS: Severe sarcopenia was closely related to dependency in ADL in patients on hemodialysis. Gait speed was the most important factor affecting dependency in sarcopenia and had good diagnostic accuracy for screening dependency in ADL.

Asymptomatic hyperuricemia and incident congestive heart failure in elderly patients without comorbidities.

BACKGROUND AND AIMS: Although hyperuricemia is associated with congestive heart failure (CHF), hyperuricemic patients frequently have other comorbidities. Thus, it is difficult to distinguish the role of hyperuricemia from that of other comorbid conditions in CHF. The aim of this study was to evaluate the association between hyperuricemia and CHF in elderly patients without comorbidities. METHODS AND RESULTS: Subjects aged ≥65 years were analyzed at enrollment (2009-2012) and during the 4-year follow-up period at the Kangjian Community Health Center of Shanghai. Subjects were excluded if they had hypertension, diabetes mellitus, preexisting cardiovascular disease, hyperlipidemia, overweight or obesity, a history of gout or hyperuricemia and were taking medication for their condition, or chronic kidney disease. The primary outcome of this study was to investigate the impact of asymptomatic hyperuricemia on incident CHF. We used Cox regression to estimate the hazard ratio (HR) for incident CHF events between hyperuricemic (defined as an SUA level >7 mg/dL in men and ≥6 mg/dL in women) and normouricemic subjects. A total of 2749 subjects (70.9 ± 6.0 years) were followed for 47.4 ± 3.6 months. Asymptomatic hyperuricemia was associated with an increased cumulative incidence of incident CHF events (6.5% versus 3.1%, odds ratio [OR] = 2.15, 95% confidence index [CI]: 1.39-3.33, p = 0.001). After adjusting for confounding factors, including baseline eGFR, hyperuricemia independently predicted the risk of incident CHF events (HR = 2.34, 95% CI: 1.50-3.63, p < 0.001). CONCLUSION: Asymptomatic hyperuricemia was a valuable biomarker for predicting the development of incident CHF in elderly patients without comorbidities.

Xuesaitong Protects Podocytes from Apoptosis in Diabetic Rats through Modulating PTEN-PDK1-Akt-mTOR Pathway.

Diabetic kidney disease (DKD) is a major cause of end-stage renal disease (ESRD), and therapeutic strategies for delaying its progression are limited. Loss of podocytes by apoptosis characterizes the early stages of DKD. To identify novel therapeutic options, we investigated the effects of Xuesaitong (XST), consisting of total saponins from Panax notoginseng, on podocyte apoptosis in streptozotocin- (STZ-) induced diabetic rats. XST (5 mg/kg·d) or Losartan (10 mg/kg·d) was given to diabetic rats for 12 weeks. Albuminuria, renal function markers, and renal histopathology morphological changes were examined. Podocyte apoptosis was determined by triple immunofluorescence labelling including a TUNEL assay, WT1, and DAPI. Renal expression of Nox4, miRNA-214, PTEN, PDK1, phosphorylated Akt, mTOR, and mTORC1 was detected. In diabetic rats, severe hyperglycaemia and albuminuria developed, and apoptotic podocytes were markedly increased in diabetic kidneys. However, XST attenuated albuminuria, mesangial expansion, podocyte apoptosis, and morphological changes of podocytes in diabetic rats. Decreased expression of PTEN, as well as increased expression of Nox4, miRNA-214, PDK1, phosphorylated Akt, mTOR, and mTORC1, was detected. These abnormalities were partially restored by XST treatment. Thus, XST ameliorated podocyte apoptosis partly through modulating the PTEN-PDK1-Akt-mTOR pathway. These novel findings might point the way to a natural therapeutic strategy for treating DKD.

Astragalus membranaceus and Panax notoginseng, the Novel Renoprotective Compound, Synergistically Protect against Podocyte Injury in Streptozotocin-Induced Diabetic Rats.

This study was aimed at investigating the synergistical protective effects of Astragalus membranaceus (AG) and Panax notoginseng (NG) on podocyte injury in diabetic rats. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at 55 mg/kg. Diabetic rats were then orally administrated with losartan, AG, NG, and AG plus NG (2 : 1) for 12 weeks. Albuminuria, biochemical markers, renal histopathology, and podocyte number per glomerulus were measured. Podocyte apoptosis was determined by triple immunofluorescence labeling including TUNEL assay, WT1, and DAPI. Renal expression of nephrin, α-dystroglycan, Bax, Bcl-xl, and Nox4 was evaluated by immunohistochemistry, western blot, and RT-PCR. AG plus NG ameliorated albuminuria, renal histopathology, and podocyte foot process effacement to a greater degree than did AG or NG alone. The number of podocytes per glomerulus, as well as renal expression of nephrin, α-dystroglycan, and Bcl-xl, was decreased, while podocyte apoptosis, as well as renal expression of Bax and Nox4, was increased in diabetic rats. All of these abnormalities were partially restored by AG plus NG to a greater degree than did AG or NG alone. In conclusion, AG and NG synergistically ameliorated diabetic podocyte injury partly through upregulation of nephrin, α-dystroglycan, and Bcl-xl, as well as downregulation of Bax and Nox4. These findings might provide a novel treatment combination for DN.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min-1•1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min-1•1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min-1•1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Is the mean platelet volume a predictive marker of a high in-hospital mortality of acute cardiorenal syndrome patients receiving continuous renal replacement therapy?

A high mean platelet volume (MPV) level has been demonstrated to predict poor clinical outcomes in patients with cardiovascular disease. However, the relationship between MPV and mortality in patients with acute cardiorenal syndrome (ACRS) is unknown. Therefore, we investigated the predictive value of MPV for in-hospital mortality of patients with ACRS who received continuous renal replacement therapy (CRRT) in this study.We retrospectively analyzed the demographics, etiology, severity of illness, prognosis, and risk factors of ACRS patients who underwent CRRT in our hospital from January 2009 to December 2014. Patients were classified into 2 groups based on the prognosis and timing of CRRT. The receiver operating characteristic curve was used to examine the performance of MPV in predicting in-hospital mortality. Baseline characteristics, clinical, and hematological parameters at CRRT initiation were compared between the 2 groups. Factors influencing in-hospital mortality were analyzed by univariate logistic regression analysis.The median age of patients was 74 years. Acute myocardial infarction was the most common cause of ACRS, followed by acute decompensated heart failure. The in-hospital mortality was 51.4%. Age, number of organ failure, APACHE II score, and MPV in the nonsurvivors were significantly higher than those in the survivors (P < .05). However, the cardiac function and mean arterial pressure were significantly lower in the nonsurvivors (P < .05). The prognosis of the early intervention group was better than the late-intervention group, but no significant difference was found (P > .05). The area under the curve (AUC) for in hospital mortality based on MPV was 0.735. Univariate analysis showed that age, cardiac function NYHA class, number of organ failure, APACHE II score, MAP, MPV, and use of vasopressors were associated with the prognosis of patients (P < .05).These findings suggest that the prognosis of patients with ACRS who received CRRT was poor, and MPV might be useful as a marker for predicting the in-hospital mortality of these patients.

Tanshinone IIA Attenuates Contrast-Induced Nephropathy via Nrf2 Activation in Rats.

BACKGROUND/AIMS: Tanshinone IIA is a chemical compound extracted from Salvia miltiorrhiza Bunge, a perennial plant also known as red sage used in traditional Chinese medicine. Tanshinone IIA has been shown to protect against various organ injuries. In this study, we hypothesized that Tanshinone IIA could play an anti-oxidative role in contrast-induced nephropathy (CIN) through enhancing Nrf2/ARE activation. METHODS: To test whether Tanshinone IIA can attenuate CIN, oxidative stress, and apoptosis, we utilized two models: an in vivo Sprague-Dawley rat model of ioversol-induced CIN and an in vitro cell model of oxidative stress in which HK2 cells, a human renal tubular cell line, are treated with hydrogen peroxide (H2O2). Rats were randomly assigned to 4 groups (n = 6 per group): control group, ioversol group (ioversol-induced CIN), vehicle group (ioversol-induced CIN rats pretreated with vehicle), and Tanshinone IIA group (ioversol-induced CIN rats pretreated with 25mg/kg Tanshinone IIA). Renal functions, renal injuries and apoptosis were evaluated by using serum creatinine, histological scoring, and TUNEL staning respectively. Malondialdehyde, 8-hydroxy-2' -deoxyguanosine, and intracellular reactive oxygen species were used for oxidative stress assessment. Levels of Nrf2 and heme oxygenase-1 (HO-1) were measured in vivo and in vitro. RESULTS: Tanshinone IIA attenuated renal tubular necrosis, apoptosis and oxidative stress in rats and oxidative stress in HK2 cells. Furthermore, Tanshinone IIA activated Nrf2, and up-regulated HO-1 expression in vivo and in vitro, resulting in a reduction in oxidative stress. CONCLUSION: Tanshinone IIA may protect against CIN through enhancing Nrf2/ARE activation.

Combination of Mean Platelet Volume/Platelet Count Ratio and the APACHE II Score Better Predicts the Short-Term Outcome in Patients with Acute Kidney Injury Receiving Continuous Renal Replacement Therapy.

BACKGROUND/AIMS: Both the Acute physiology and Chronic Health Evaluation (APACHE II) score and mean platelet volume/platelet count Ratio (MPR) can independently predict adverse outcomes in critically ill patients. This study was aimed to investigate whether the combination of them could have a better performance in predicting prognosis of patients with acute kidney injury (AKI) who received continuous renal replacement therapy (CRRT). METHODS: Two hundred twenty-three patients with AKI who underwent CRRT between January 2009 and December 2014 in a Chinese university hospital were enrolled. They were divided into survivals group and non-survivals group based on the situation at discharge. Receiver Operating Characteristic (ROC) curve was used for MPR and APACHE II score, and to determine the optimal cut-off value of MPR for in-hospital mortality. Factors associated with mortality were identified by univariate and multivariate logistic regression analysis. RESULTS: The mean age of the patients was 61.4 years, and the overall in-hospital mortality was 48.4%. Acute cardiorenal syndrome (ACRS) was the most common cause of AKI. The optimal cut-off value of MPR for mortality was 0.099 with an area under the ROC curve (AUC) of 0.636. The AUC increased to 0.851 with the addition of the APACHE II score. The mortality of patients with of MPR > 0.099 was 56.4%, which was significantly higher than that of the control group with of ≤ 0.099 (39.6%, P= 0.012). Logistic regression analysis showed that average number of organ failure (OR = 2.372), APACHE II score (OR = 1.187), age (OR = 1.028) and vasopressors administration (OR = 38.130) were significantly associated with poor prognosis. CONCLUSION: Severity of illness was significantly associated with prognosis of patients with AKI. The combination of MPR and APACHE II score may be helpful in predicting the short-term outcome of AKI.

Asymptomatic hyperuricemia and coronary artery disease in elderly patients without comorbidities.

Because many subjects with hyperuricemia have comorbidities, it can be difficult to differentiate the role of hyperuricemia from that of other comorbidities of coronary artery disease (CAD). Subjects aged ≥ 65 years were enrolled in the study and were available at enrollment and at 5-year follow-up. Subjects were excluded if they were overweight or obese, hypertensive, diabetic, hyperlipidemic, had a pre-existing cardiovascular disease, a history of gout or hyperuricemia on medications, or chronic kidney disease as estimated by a glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2. We used Poisson regression to estimate the hazard ratio (HR) for incident CAD events between hyperuricemic (> 7 mg/dL in men and ≥ 6 mg/dL in women) and normouricemic subjects. A total of 2,142 subjects without comorbidities (mean age of 70.7 ± 5.9 years, 1,194 men) were followed for 57.4 ± 8.9 months. Hyperuricemia was associated with an increased cumulative incidence of incident CAD events (15.0% versus 8.8%, P < 0.001). After adjusting for confounding factors, hyperuricemia independently predicted the risk of incident CAD events (HR=1.71, 95% CI 1.26-2.34). In conclusion, asymptomatic hyperuricemia is a valuable biomarker for predicting the development of incident CAD events.

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. METHODS: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

Increased Serum Uric Acid Level Is a Risk Factor for Left Ventricular Hypertrophy but Not Independent of eGFR in Patients with Type 2 Diabetic Kidney Disease.

BACKGROUND: Although the relation between serum uric acid (SUA) and left ventricular hypertrophy (LVH) has been studied for decades, however, their association remains debatable. METHODS: This is a retrospective study in which a total of 435 hospitalized Chinese patients with type 2 DKD were enrolled. The subjects were stratified into quartiles according to SUA level. LVH was assessed by two-dimensional guided M-mode echocardiography. RESULTS: There was a significant increase in the prevalence of LVH in patients with type 2 DKD across SUA quartiles (28.9, 26.5, 36.1, and 49.5%; p < 0.001). The Spearman analysis indicated that SUA was positively correlated to LVMI and negatively correlated to eGFR. The logistic regression analysis revealed that the odd ratio for LVH in the highest SUA quartile was 2.439 (95% CI 1.265-4.699; p = 0.008; model 1) or 2.576 (95% CI 1.150-5.768; p = 0.021; model 2) compared with that in the lowest SUA quartile. However, there was no significant increased risk of LVH in the subjects with the highest SUA quartile after adjusting the eGFR (OR = 1.750; 95% CI 0.685-4.470; p = 0.242; model 3). CONCLUSIONS: In selected population, such as type 2 DKD, the elevated SUA level is positively linked with the increased risk of LVH, but this relationship is not independent of eGFR.

Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy.

We previously reported a critical role of reticulon (RTN) 1A in mediating endoplasmic reticulum (ER) stress in kidney tubular cells and the expression of RTN1A correlates with the renal function and the severity of kidney injury in patients with diabetic nephropathy (DN). Here, we determined the roles of RTN1A and ER stress in podocyte injury and DN. We used db/db mice with early unilateral nephrectomy (Unx) as a murine model of progressive DN and treated mice with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress. We found increased expression of RTN1A and ER stress markers in the kidney of db/db-Unx mice. Treatment of TUDCA not only attenuated proteinuria and kidney histological changes, but also ameliorated podocyte and glomeruli injury in diabetic mice, which were associated with reduction of RTN1A and ER stress marker expression in the podocytes of TUDCA-treated mice. In vitro, we showed RTN1A mediates albumin-induced ER stress and apoptosis in human podocytes. A positive feedback loop between RTN1A and CHOP was found leading to an enhanced ER stress in podocytes. Our data suggest that ER stress plays a major role in podocyte injury in DN and RTN1A might be a key regulator of ER stress in podocytes.

Notoginsenoside R1 ameliorates podocyte adhesion under diabetic condition through α3ß1 integrin upregulation in vitro and in vivo.

BACKGROUND: Decreased expression of α3ß1 integrin may contribute to reduction in podocyte adhesion to glomerular basement membrane (GBM), which represents a novel early mechanism leading to diabetic kidney disease (DKD). Here, we examined the protective effects of Notoginsenoside R1 (NR1) on podocyte adhesion and α3ß1 integrin expression under diabetic condition in vitro and in vivo. METHODS: Conditionally immortalized mouse podocytes were exposed to high glucose (HG) with 10 and 100µg /ml of NR1 for 24 h. Podocyte adhesion, albuminuria, oxidative markers, renal histopathology, podocyte number per glomerular volume, integrin-linked kinase (ILK) activity and α3ß1 integrin expression were measured in vitro and in vivo. RESULTS: HG decreased podocyte adhesive capacity and α3ß1 integrin expression, the main podocyte anchoring dimer to the GBM. However, NR1 ameliorated impaired podocyte adhesive capacity and partially restored α3ß1 integrin protein and mRNA expression. These in vitro observations were confirmed in vivo. In streptozotocin(STZ)-induced diabetic rats, treatment with NR1 (5 and 10 mg· kg(-1)· d(-1)) for 12 weeks partially restored the number of podocytes per glomerular volume and glomerular α3ß1 integrin expression, as well as ameliorated albuminuria, histopathology and oxidative stress. NR1 also inhibited glomerular ILK activity in diabetic rats. CONCLUSION: NR1, a novel antioxidant, ameliorated glucose-induced impaired podocyte adhesive capacity and subsequent podocyte depopulation partly through α3ß1 integrin upregulation. These findings might provide a potential new therapeutic option for the treatment of DKD.