Identification of discriminative neuroimaging markers for patients on hemodialysis with insomnia: a fractional amplitude of low frequency fluctuation-based machine learning analysis.

BACKGROUND AND OBJECTIVE: Insomnia is one of the common problems encountered in the hemodialysis (HD) population, but the mechanisms remain unclear. we aimed to (1) detect the spontaneous brain activity pattern in HD patients with insomnia (HDWI) by using fractional fractional amplitude of low frequency fluctuation (fALFF) method and (2) further identify brain regions showing altered fALFF as neural markers to discriminate HDWI patients from those on hemodialysis but without insomnia (HDWoI) and healthy controls (HCs). METHOD: We compared fALFF differences among HDWI subjects (28), HDWoI subjects (28) and HCs (28), and extracted altered fALFF features for the subsequent discriminative analysis. Then, we constructed a support vector machine (SVM) classifier to identify distinct neuroimaging markers for HDWI. RESULTS: Compared with HCs, both HDWI and HDWoI patients exhibited significantly decreased fALFF in the bilateral calcarine (CAL), right middle occipital gyrus (MOG), left precentral gyrus (PreCG), bilateral postcentral gyrus (PoCG) and bilateral temporal middle gyrus (TMG), whereas increased fALFF in the bilateral cerebellum and right insula. Conversely, increased fALFF in the bilateral CAL/right MOG and decreased fALFF in the right cerebellum was observed in HDWI patients when compared with HDWoI patients. Moreover, the SVM classification achieved a good performance [accuracy = 82.14%, area under the curve (AUC) = 0.8202], and the consensus brain regions with the highest contributions to classification were located in the right MOG and right cerebellum. CONCLUSION: Our result highlights that HDWI patients had abnormal neural activities in the right MOG and right cerebellum, which might be potential neural markers for distinguishing HDWI patients from non-insomniacs, providing further support for the pathological mechanism of HDWI.

Nomogram for the prediction of crescent formation in IgA nephropathy patients: a retrospective study.

BACKGROUND: The 2017 Oxford classification of immunoglobulin A nephropathy (IgAN) recently reported that crescents could predict a worse renal outcome. Early prediction of crescent formation can help physicians determine the appropriate intervention, and thus, improve the outcomes. Therefore, we aimed to establish a nomogram model for the prediction of crescent formation in IgA nephropathy patients. METHODS: We retrospectively analyzed 200 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator(LASSO) regression and multivariate logistic regression was applied to screen for influencing factors of crescent formation in IgAN patients. The performance of the proposed nomogram was evaluated based on Harrell's concordance index (C-index), calibration plot, and decision curve analysis. RESULTS: Multivariate logistic analysis showed that urinary protein ≥ 1 g (OR = 3.129, 95%CI = 1.454-6.732), urinary red blood cell (URBC) counts ≥ 30/ul (OR = 3.190, 95%CI = 1.590-6.402), mALBU ≥ 1500 mg/L(OR = 2.330, 95%CI = 1.008-5.386), eGFR < 60ml/min/1.73m2(OR = 2.295, 95%CI = 1.016-5.187), Serum IgA/C3 ratio ≥ 2.59 (OR = 2.505, 95%CI = 1.241-5.057), were independent risk factors for crescent formation. Incorporating these factors, our model achieved well-fitted calibration curves and a good C-index of 0.776 (95%CI [0.711-0.840]) in predicting crescent formation. CONCLUSIONS: Our nomogram showed good calibration and was effective in predicting crescent formation risk in IgAN patients.

Comparison between outcomes of IgA nephropathy with nephrotic-range proteinuria and nephrotic syndrome: do podocytes play a role?

BACKGROUND: Nephrotic syndrome (NS) and nephrotic-range proteinuria (NRP) are uncommon in IgA nephropathy (IgAN), and their clinicopathology and prognosis have not been discussed. Podocytes may play an important role in both clinical phenotypes. METHODS: We investigated 119 biopsy-proven IgAN patients with proteinuria over 2 g/d. The patients were divided into three groups according to proteinuria level: the overt proteinuria (OP) group, NS group, and NRP group. In addition, according to the severity of foot process effacement (FPE), the patients were divided into three groups: the segmental FPE (SFPE) group, moderate FPE (MFPE) group, and diffuse FPE (DFPE) group. The outcome was survival from a combined event defined by a doubling of the baseline serum creatinine and a 50% reduction in eGFR or ESRD. RESULTS: Compared with the NRP group, patients in the NS group had more severe microscopic hematuria, presented with more severe endocapillary hypercellularity and had a higher percentage of DFPE. The Kaplan-Meier curve showed that MFPE patients had a better outcome in the NRP group <50% of tubular atrophy/interstitial fibrosis. In the multivariate model, the NRP group (HR = 17.098, 95% CI = 3.835-76.224) was associated with an increased risk of the combined event, while MFPE (HR = 0.260, 95% CI = 0.078-0.864; p = 0.028) was associated with a reduced risk of the combined event. After the addition of renin-angiotensin system inhibitors (RASi), the incidence of the combined event in the MFPE group (HR = 0.179, 95% CI = 0.047-0.689; p = 0.012) was further reduced. CONCLUSIONS: NS presented more active lesions and more severe FPE in IgAN. NRP was an independent risk factor for progression to the renal endpoint, while MFPE indicated a better prognosis in NRP without obvious chronic renal lesions, which may benefit from RASi.

Volume of Crescents Affects Prognosis of IgA Nephropathy in Patients without Obvious Chronic Renal Pathology.

INTRODUCTION: A working group on the Oxford classification of IgA nephropathy (IgAN) recently reported that crescents detected in the kidney tissue predicted a worse renal outcome. However, the effect of C1 lesion (crescents in <1/4th of all glomeruli) and their volume on the prognosis of IgAN is still unclear. We explored the association of C1 lesion with the renal prognosis in IgAN patients without obvious chronic renal lesions (glomerulosclerosis <25%, T score <2). METHODS: We investigated 305 biopsy-proven IgAN patients without obvious chronic renal lesions. Clinicopathologic features and treatment modalities were recorded. The patients were divided into several groups according to the presence or absence of a global crescent: no crescent (NC) group, only segmental crescent (SC) group, and global crescent (GC) group. The outcome was the survival from a combined event defined by a ≥15% decline in the estimated glomerular filtration rate (eGFR) after 1 year or ≥30% decline in the eGFR after 2 years. RESULTS: Among all patients, 75.7% were in the NC group, 14.8% were in the SC group, and 9.5% were in the GC group. Compared with the NC group, patients in the SC group and the GC group had more urine protein, lower eGFR, and presented with more severe pathological change. During a median follow-up of 34.8 (26.16-57.95) months, the combined event occurred in 34 individuals (11.1%). In a multivariate model, the GC group (HR = 2.756, 95% CI = 1.068-7.109) was associated with an increased risk of the combined event. CONCLUSIONS: In IgAN patients without obvious chronic renal lesions, the GC group had more severe clinical and pathological manifestations than in the NC group. GC is an independent risk factor for the progression of IgAN renal function.

Serum and Tissue Levels of Advanced Glycation End Products and Risk of Mortality in Patients on Maintenance Hemodialysis.

BACKGROUND: The relation of tissue and circulating advanced glycation end products (AGEs) with mortality in hemodialysis (HD) patients remains inconclusive. We aimed to investigate the association of serum AGEs (CML) and tissue AGEs estimated by skin autofluorescence (SAF) with all-cause and cardiovascular disease (CVD) mortality, and examine the possible modifiers for the association in HD patients with by far the largest sample size in any similar studies. METHODS: A total of 1,634 HD patients were included from the China Cooperative Study on Dialysis (CCSD), a multicenter prospective cohort study. The primary and secondary outcomes were all-cause mortality and CVD mortality, respectively. RESULTS: The median follow-up duration was 5.2 years. Overall, there was a positive relation of baseline SAF levels with the risk of all-cause mortality (per 1 AU increment, adjusted hazard ratio (HR), 1.30; 95% confidence interval (CI): 1.12, 1.50) and CVD mortality (per 1 AU increment, adjusted HR, 1.36; 95% CI: 1.14, 1.62). Moreover, a stronger positive association between baseline SAF (per 1 AU increment) and all-cause mortality was found in participants with shorter dialysis vintage, or lower C-reactive protein levels (Both p interactions <0.05). Nevertheless, there was no significant association between serum CML and the risk of mortality. CONCLUSIONS: In patients undergoing long-term HD, baseline SAF, but not serum CML, was significantly associated with the risk of all-cause and CVD death.

Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: a prospective randomized study of three anticoagulation strategies.

BACKGROUND: Recommended regular saline flushing presents clinical ineffectiveness for hemodialysis (HD) patients at high risk of bleeding with heparin contraindication. Regional citrate anticoagulation (RCA) has previously been used with a Ca2+ containing dialysate with prefiltered citrate in one arm (RCA-one). However, anticoagulation is not always achievable and up to 40% results in serious clotting in the venous expansion chamber. In this study, we have transferred one-quarter of the TSC from the prefiltered to the post filter based on RCA-one, which we have called RCA-two. The objective of this study was to compare the efficacy and safety of RCA-two with either saline flushing or RCA-one in HD patients with a high bleeding risk. METHOD: In this investigator-initiated, multicenter, controlled, prospective, randomized clinical trial, 52 HD patients (77 sessions) were randomized to the RCA-2 and RCA-one group in part one of the trial, and 45 patients (64 sessions) were randomized to the RCA-2 and saline group in part two of the trial. Serious clotting events, adverse events and blood analyses were recorded. RESULTS: Serious clotting events in the RCA-two group were significantly lower compared with the RCA-one and saline group (7.89% vs. 30.77%, P = 0.011; 3.03% vs. 54.84%, P < 0.001, respectively). The median circuit survival time was 240 min (IQR 240 to 240) in the RCA-two group, was significantly longer than 230 min (IQR 155 to 240, P < 0.001) in the RCA-one group and 210 min (IQR 135 to 240, P = 0.003) in the saline group. The majority of the AEs were hypotension, hypoglycemia and chest tightness, most of which were mild in intensity. Eight patients (20.51%) in the RCA-one group, 4 patients (12.90%) in the saline group and 10 patients (26.31%) in the RCA-two group, P > 0.05. CONCLUSIONS: Our data demonstrated that the modified anticoagulation protocol was more effective and feasible during hemodialysis therapy for patients at high risk of bleeding. TRIAL REGISTRATION: GDREC, GDREC2017250H. Registered February 2, 2018; retrospectively registered.

Rationale and design of the Helping Ease Renal failure with Bupi Yishen compared with the Angiotensin II Antagonist Losartan (HERBAAL) trial: a randomized controlled trial in non-diabetes stage 4 chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. Currently, as for advanced CKD populations, medication options limited in angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), which were partially effective. A Chinese herbal compound, Bupi Yishen formula, has showed renal protective potential in experiments and retrospective studies. This study will evaluate the efficacy and safety of Bupi Yishen formula (BYF) in patients with CKD stage 4. DESIGN: In this double blind, double dummy, randomized controlled trial (RCT), there will be 554 non-diabetes stage 4 CKD patients from 16 hospitals included and randomized into two groups: Chinese medicine (CM) group or losartan group. All patients will receive basic conventional therapy. Patients in CM group will be treated with BYF daily while patients in control group will receive losartan 100 mg daily for one year. The primary outcome is the change in estimated glomerular filtration rate (eGFR) over 12 months. Secondary outcomes include the incidence of endpoint events, liver and kidney function, urinary protein creatinine ratio, cardiovascular function and quality of life. DISCUSSION: This study will be the first multi-center, double blind RCT to assess whether BYF, compared with losartan, will have beneficial effects on eGFR for non-diabetes stage 4 CKD patients. The results will help to provide evidence-based recommendations for clinicians. TRIAL REGISTRATION: Chinese Clinical Trial Registry Number: ChiCTR-TRC-10001518 .

Development and Validation of Prediction Models for All-Cause Mortality and Cardiovascular Mortality in Patients on Hemodialysis: A Retrospective Cohort Study in China.

Purpose: This study aimed to develop two predictive nomograms for the assessment of long-term survival status in hemodialysis (HD) patients by examining the prognostic factors for all-cause mortality and cardiovascular (CVD) event mortality. Patients and methods: A total of 551 HD patients with an average age of over 60 were included in this study. The patients' medical records were collected from our hospital and randomly allocated to two cohorts: the training cohort (n=385) and the validation cohort (n=166). We employed multivariate Cox assessments and fine-gray proportional hazards models to explore the predictive factors for both all-cause mortality and cardiovascular event mortality risk in HD patients. Two nomograms were established based on predictive factors to forecast patients' likelihood of survival for 3, 5, and 8 years. The performance of both models was evaluated using the area under the curve (AUC), calibration plots, and decision curve analysis. Results: The nomogram for all-cause mortality prediction included seven factors: age ≥ 60, sex (male), history of diabetes and coronary artery disease, diastolic blood pressure, total triglycerides (TG), and total cholesterol (TC). The nomogram for cardiovascular event mortality prediction included three factors: history of diabetes and coronary artery disease, and total cholesterol (TC). Both models demonstrated good discrimination, with AUC values of 0.716, 0.722 and 0.725 for all-cause mortality at 3, 5, and 8 years, respectively, and 0.702, 0.695, and 0.677 for cardiovascular event mortality, respectively. The calibration plots indicated a good agreement between the predictions and the decision curve analysis demonstrated a favorable clinical utility of the nomograms. Conclusion: Our nomograms were well-calibrated and exhibited significant estimation efficiency, providing a valuable predictive tool to forecast prognosis in HD patients.

China collaborative study on dialysis: a multi-centers cohort study on cardiovascular diseases in patients on maintenance dialysis.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of death in patients on chronic dialysis. The question whether dialysis modality impacts cardiovascular risk remains to be addressed. China Collaborative Study on Dialysis, a multi-centers cohort study, was performed to evaluate cardiovascular morbidity during maintenance hemodialysis (HD) and peritoneal dialysis (PD). METHOD: The cohort consisted of chronic dialysis patients from the database of 9 of the largest dialysis facilities around China. The inclusion period was between January 1, 2005, and December 1, 2010. Cardiovascular morbidity was defined as the presence of clinically diagnosed ischemic heart disease, heart failure, peripheral vascular disease, and/or stroke. The patients who had cardiovascular morbidity before initiation of dialysis were excluded. Data collection was based on review of medical record. RESULT: A total of 2,388 adult patients (1,775 on HD and 613 on PD) were enrolled. Cardiovascular morbidity affected 57% patients and was comparable between HD and PD patients. However, clinically diagnosed ischemic heart disease and stroke was more prevalent in PD than HD patients. When the patients were stratified by age or dialysis vintage, the cardiovascular morbidity was significantly higher in PD than HD among those aged 50 years or older, or those receiving dialysis over 36 months. Multivariate analysis revealed that the risk factors for cardiovascular morbidity had different pattern in PD and HD patients. Hyperglycemia was the strongest risk factor for cardiovascular morbidity in PD, but not in HD patients. Hypertriglyceridemia and hypoalbuminemia were independently associated with CVD only in PD patients. CONCLUSIONS: Cardiovascular morbidity during chronic dialysis was more prevalent in PD than HD patients among those with old age and long-term dialysis. Metabolic disturbance-related risk factors were independently associated with CVD only in PD patients. Better understanding the impact of dialysis modality on CVD would be an important step for prevention and treatment.

[Effects of Chinese herbal enema therapy combined basic treatment on BUN, SCr, UA, and IS in chronic renal failure patients].

OBJECTIVE: To assess the clearance role and safety of Chinese herbal enema therapy (CHET) in clearing enterogenic uremic toxins in chronic renal failure (CRF) patients, thus providing evidence for further optimizing the comprehensive treatment. METHODS: Using nonrandomized concurrent control trial, 96 CRF inpatients of Department of Nephropathy, Guangdong Provincial Hospital of Traditional Chinese Medicine, from March 2010 to December 2010 were assigned to the treatment group and the control group according to their willingness. All patients were treated with basic treatment referring to clinical plans in the non-dialysis phase, while those in the treatment group were additionally treated with CHET, once daily, 2 weeks as one therapeutic course. The symptoms, serum enterogenic uremic toxin levels [including indoxyl sulfate (IS), blood urea nitrogen (BUN), and uric acid (UA)], and serum creatinine (SCr) were observed in the two groups between and after treatment. The adverse reactions were also monitored during the treatment period. The clinical efficacy and safety were also assessed. RESULTS: Totally 84 patients completed this clinical observation, 48 in the treatment group and 36 in the control group. The levels of SCr, BUN, and IS were obviously lower in the treatment group after treatment, showing statistical difference when compared with before treatment (P<0.01). There was no statistical difference in each index in the control group between before and after treatment (P>0.05). The post-treatment the IS level was lower in the treatment group than in the control group with statistical difference (P<0.05). Symptoms like fatigue, soreness of waist and knees, constipation and edema were partially relieved in both groups (P<0.05, P<0.01). The ratios of anorexia and nausea in patients of the treatment group was lowered after treatment (P<0.05). Besides, patients in the treatment group could defecate for more than once daily during the enema treatment period, dominated as rotten and soft feces. No severe adverse event occurred during the treatment period. CONCLUSION: CHET combined basic treatment could lower the serum levels of enterogenic uremic toxins (IS and BUN) of CRF patients in a short period.

Risk factors for infection-related hospitalization in end-stage renal disease patients during peri-dialysis period.

Infection-related hospitalization during the peri-dialysis period (PDP) in patients with end-stage renal disease (ESRD) has received less attention. Considering the limited data, we explored the risk factors in this population. Retrospective analysis using the data system to examine factors for infection in ESRD during PDP between January 2012 and December 2017. Patients were divided into infected group and non-infected group according to the history of infection. Binary Logistic Regression Model was used to search for risk factors. A total of 478 patients were hospitalized during their PDP. One hundred and ninety patients developed infection (39.75%). Thirty-six patients (18.95%) had two or more infection events, all due to recurrent respiratory infections. The respiratory system was the main site of infection (63.68%), followed by the urinary system and digestive system. Compared with the non-infected group, the infected group had more patients with hypoproteinemia and coronary heart disease. The following factors: C-reactive protein >15 mg/L, procalcitonin >1 ng/L, neutrophil percentage >75%, age >52.5 years, platelet >300 × 109 /L, neutrophil to lymphocyte ratio, and concomitant coronary heart disease were associated with the occurrence of infection in ESRD patients during PDP. Patients with ESRD have a high incidence of infection during the PDP, with respiratory infection most commonly seen. This research identified several factors associated with risk for infection, which should guide the design of infection prevention strategies.

Diet-Related Inflammation is Associated with Malnutrition-Inflammation Markers in Maintenance Hemodialysis Patients: Results of a Cross-Sectional Study in China Using Dietary Inflammatory Index.

Purpose: This cross-sectional study aimed to explore the association between the inflammation potential of the diet and malnutrition-inflammation status in Chinese maintenance hemodialysis (MHD) patients. Methods: Dietary Inflammatory Index (DII) was computed based on a semi-quantitative food frequency questionnaire. Malnutrition-inflammation status was assessed by six indexes, including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), hemoglobin (HB), albumin (ALB) and malnutrition-inflammation score (MIS). Multivariable linear regression and logistic regression were employed adjusting for covariables including age, gender, body mass index and dialysis vintage. Results: A total of 161 Chinese MHD patients with an average age of 60.0 ± 13.6 years were enrolled. The median (IQR) DII score among participants was 0.60 (-0.80, 2.32), revealing a generally pro-inflammatory diet. DII was positively associated with MIS score (ß= 0.61, 95% CI: 0.51, 0.69, p < 0.0001) and CRP (ß = 0.54, 95% CI: 0.46, 0.63, p < 0.0001). A negative relationship between DII and NLR (ß = -0.37, 95% CI: -0.61, -0.13, p = 0.008) was found in the most anti-inflammatory diet. Multivariable logistic regression showed that each unit increase in DII was linked with 3.06 (95% CI: 1.39, 6.69, p = 0.005) times increased odds of MIS. Conclusion: Diet with a higher DII score may act as a potential trigger contributing to the development of malnutrition-inflammation status. Further studies for verification and for developing strategies to decrease the dietary inflammation burden are warranted.

Rhubarb Enema Increasing Short-Chain Fatty Acids that Improves the Intestinal Barrier Disruption in CKD May Be Related to the Regulation of Gut Dysbiosis.

The incidence of CKD seriously endangers people's health. Researchers have proposed that improving the intestinal barrier damage in CKD may be an effective target for delaying the progression of CKD. Rhubarb can effectively improve the intestinal barrier and renal fibrosis, which may be related to the regulation of gut dysbiosis, but the mechanism needs to be further studied. Short-chain fatty acids (SCFAs) are important metabolites of the gut microbiota and play an important role in maintaining the intestinal barrier. The purpose of this study was to investigate whether rhubarb enema regulates the production of short-chain fatty acid-related gut microbiota and improves the intestinal barrier damage of CKD. 5/6 nephrectomy rats were used as the animal model, sevelamer was used as the positive control group, and the sham operation rats were used as the control group. After 4 weeks of enema treatment, the general clinical indicators, short-chain fatty acid levels, renal pathology, intestinal tissue pathology, intestinal tight junction protein, and changes in gut microbiota were detected. The results showed that rhubarb enema can increase the level of short-chain fatty acids in the 5/6 nephrectomy model rats, improve the intestinal barrier damage, inhibit the decrease of intestinal tight junction proteins, reduce inflammation levels, improve kidney pathology, reduce blood creatinine levels, and regulate the intestinal tract, the abundance, and composition of the flora. Further correlation analysis showed that rhubarb enema increased the level of short-chain fatty acids in 5/6 nephrectomy model rats, which may be related to the 7 strains that may regulate the production of short-chain fatty acids. This study indicated that rhubarb enema can improve the intestinal barrier damage of 5/6 nephrectomy model rats and improve CKD, which may be related to the regulation of short-chain fatty acid-producing gut microbiota.

Propensity-matched comparison of mortality between peritoneal dialysis and hemodialysis in patients with type 2 diabetes.

BACKGROUND: The optimal choice of dialysis modality for diabetic patients remains controversial. This study aimed to compare mortality between peritoneal dialysis (PD) and hemodialysis (HD) in end-stage renal disease (ESRD) patients with type 2 diabetes (T2D). METHODS: Our observational, longitudinal cohort consisted of all incident ESRD patients with T2D who received either PD or HD in our center from January 2012 to December 2017 and were followed until December 2019. Propensity scores were used to select a 1:1 matched cohort. Mortality was compared between dialysis modalities using Kaplan-Meier survival analysis, and risk factors for mortality were estimated using multivariate Cox regression analyses. RESULTS: The median follow-up times were 35.5 months in the PD group (n = 134) and 41.6 months in the HD group (n = 134, p = 0.0381). The 1-, 2-, 3-, 5-, and 7-year patient survival rates were 98%, 91%, 77%, 61%, and 35% for diabetic PD patients and 96%, 88%, 81%, 60%, and 57% for diabetic HD patients. Kaplan-Meier survival analysis showed that overall mortality did not significantly differ between modalities (log-rank = 0.9473, p = 0.6575). Using a multivariate Cox regression model, advanced age and increased cholesterol at the initiation of PD treatment were independent risk factors associated with mortality, whereas under HD therapy, the risk factors associated with mortality were lower BMI and higher HbA1c. CONCLUSIONS: These results suggest that in patients with T2D, mortality is comparable between PD and HD irrespective of whether there are the first 2 years or over the 2-year period, and that different mortality predictor patterns exist between patients treated with PD versus HD.

The role of urine IgG in the progression of IgA nephropathy with a high proportion of global glomerulosclerosis.

BACKGROUND: IgA nephropathy (IgAN), the most common glomerulonephritis in the world, is an important cause of end-stage renal disease (ESRD). It is necessary to explore new prognostic markers for predicting the activity and progress of IgAN. There are few studies on new prognostic markers in IgAN patients with high proportion of glomerulosclerosis. This study aims to explore the value of urine IgG in predicting the prognosis of IgAN patients. METHODS: The primary end point of this retrospective study was a composite event with a reduction in estimated glomerular filtration rate (eGFR) of ≥ 50% or ESRD or death. This study assessed the association between urinary IgG and clinicopathological parameters, as well as the prognosis of a high proportion of patients with global glomerulosclerotic IgAN. RESULTS: This study included 105 IgAN patients with high proportion of global glomerulosclerotic. The level of urinary protein IgG was significantly correlated with clinical prognostic factors. The level of urinary protein IgG was positively correlated with urinary protein excretion (rs = 0.834, P < 0.001), CRP (rs = 0.375, P < 0.001), and C4 (rs = 0.228, P = 0.019), and negatively correlated with eGFR (rs = - 0.307, P = 0.001). In addition, the level of urinary IgG increased with the increase of tubulointerstitial injury rate, which was positively correlated with endothelial cell proliferation and crescent (all P < 0.05). Prognostic analysis using the Cox proportional hazard regression model and Kaplan-Meier survival curve further determined that urine IgG is an independent risk factor for the prognosis of IgAN with high proportion of global glomerulosclerosis. CONCLUSIONS: This study determined that urine IgG can be used as a useful predictor of the prognosis of IgAN patients with high proportion global glomerulosclerosis. The mechanism of urine IgG trends in IgAN with high proportion of glomerulosclerosis needs further study.

Auricular Acupressure for Hemodialysis Patients with Insomnia: A Multicenter Double-Blind Randomized Sham-Controlled Trial.

Background and objectives: The effect of auricular acupressure (AA) for maintenance hemodialysis (MHD) patients with insomnia has been controversial. This study assessed the efficacy and safety of AA for MHD patients with chronic insomnia. Design, setting, participants, and measurements: This was a multicenter, double-blind (participant and assessor), randomized sham-controlled trial. A total of 133 subjects were randomized to receive AA on active points (AA group, n = 64) or on sham auricular acupressure (SAA) points (SAA group, n = 69) for 8 weeks and followed up for 12 weeks. AA was provided by assigned qualified nurses who were not involved in assessment. The primary outcome was the clinical response rate, which was defined as the percentage of participants who reached a reduction of Pittsburgh Sleep Quality Index (PSQI) global score ≥3 in each group. Secondary outcomes included changes in PSQI scores over time, PSQI scores and hypnotics use at each visit, and changes in the weekly dose of hypnotics for drug-dependent subjects. Results: At week 8, the AA group yielded a higher clinical response rate than the SAA group (AA: 55% vs. SAA: 36%, odds ratio: 1.5, 95% confidence interval: 1.0-2.2, p = 0.033). Both groups showed a reduction in PSQI global scores during treatment and follow-up, compared with the baseline, respectively. A significant change of PSQI global score was observed over time (F = 28.387, p < 0.001). PSQI global score of the AA group was relatively lower than that of the SAA group at each visit (p < 0.05 at week 16 and 20). For those depending on hypnotics, AA reduced their consumption of hypnotics. The intervention was safe, and its adherence was satisfactory. Conclusion: AA could serve as a complementary or alternative therapy for MHD patients with insomnia by improving their sleep quality and reducing their use of hypnotics. Clinical trial registration: Clinicaltrials.gov, Identifier: NCT03015766.

Rhubarb Enema Decreases Circulating Trimethylamine N-Oxide Level and Improves Renal Fibrosis Accompanied With Gut Microbiota Change in Chronic Kidney Disease Rats.

Objectives: Trimethylamine N-oxide (TMAO), a metabolic product of gut flora, is increased in chronic kidney disease (CKD) subjects and is recognized as one type of uremic toxins which is associated with poor cardiovascular outcomes and kidney function loss. Previous studies have suggested that rhubarb enema could reduce circulating uremic toxins such as urea, creatinine, and indoxyl sulfate and also regulate the intestinal microbiota. However, whether rhubarb enema retards kidney dysfunction by reducing circulating TMAO and its underlying mechanism, are still unclear. The present study aims to investigate the impact of rhubarb enema on TMAO and its precursors, as well as on the intestinal microbiota in 5/6 nephrectomized (5/6Nx) CKD rats. Design: Rats in the treatment groups were given rhubarb enema after modeling. At the end of the study, blood, feces, and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses. Results: Rhubarb enema reduced serum TMAO and trimethylamine (TMA) levels, inhibited the expression of inflammatory markers (interleukin-6, tumor necrosis factor α and Interferon-γ) and alleviated tubular atrophy, monocyte infiltration and interstitial fibrosis in 5/6Nx CKD rats. Moreover, rhubarb enema significantly increased the abundance of some symbiotic bacteria and probiotics, while reduced the abundance of some potential pathogens at the genus level. In addition, Spearman's correlation analysis revealed that lachnospiraceae and romboutsia were positively correlated with TMAO. Conclusion: Rhubarb enema decreases circulating TMAO level and improves renal fibrosis in 5/6Nx CKD rats, which may be related to the regulation of intestinal microbial community.

Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

BACKGROUND: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD. METHODS: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up. RESULTS: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching. CONCLUSIONS: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.

Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial.

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: -2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: -4.03,-0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.