Inhibition of STAT3 by S3I-201 suppress peritoneal fibroblast phenotype conversion and alleviate peritoneal fibrosis.

Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis.

SARS-CoV-2 viral protein ORF3A injures renal tubules by interacting with TRIM59 to induce STAT3 activation.

Acute kidney injury occurs frequently in COVID-19 patients infected by the coronavirus SARS-CoV-2, and infection of kidney cells by this virus has been reported. However, little is known about the direct impact of the SARS-CoV-2 infection upon the renal tubular cells. We report that SARS-CoV-2 activated signal transducer and activator of transcription 3 (STAT3) signaling and caused cellular injury in the human renal tubular cell line. Mechanistically, the viral protein ORF3A of SARS-CoV-2 augmented both NF-κB and STAT3 signaling and increased the expression of kidney injury molecule 1. SARS-CoV-2 infection or expression of ORF3A alone elevated the protein level of tripartite motif-containing protein 59 (TRIM59), an E3 ubiquitin ligase, which interacts with both ORF3A and STAT3. The excessive TRIM59 in turn dissociated the phosphatase TCPTP from binding to STAT3 and hence inhibited the dephosphorylation of STAT3, leading to persistent STAT3 activation. Consistently, ORF3A induced renal injury in zebrafish and mice. In addition, expression of TRIM59 was elevated in the kidney autopsies of COVID-19 patients with acute kidney injury. Thus, the aberrant activation of STAT3 signaling by TRIM59 plays a significant role in the renal tubular cell injury caused by SARS-CoV-2, which suggests a potential targeted therapy for the renal complications of COVID-19.

Integrative ATAC-seq and RNA-seq analysis associated with diabetic nephropathy and identification of novel targets for treatment by dapagliflozin.

Dapagliflozin (DAPA) are clinically effective in improving diabetic nephropathy (DN). However, whether and how chromatin accessibility changed by DN responds to DAPA treatment is unclear. Therefore, we performed ATAC-seq, RNA-seq, and weighted gene correlation network analysis to identify the chromatin accessibility, the messenger RNA (mRNA) expression, and the correlation between clinical phenotypes and mRNA expression using kidney from three mouse groups: db/m mice (Controls), db/db mice (case group), and those treated with DAPA (treatment group). RNA-Seq and ATAC-seq conjoint analysis revealed many overlapping pathways and networks suggesting that the transcriptional changes of DN and DAPA intervention largely occured dependently on chromatin remodeling. Specifically, the results showed that some key signal transduction pathways, such as immune dysfunction, glucolipid metabolism, oxidative stress and xenobiotic and endobiotic metabolism, were repeatedly enriched in the analysis of the RNA-seq data alone, as well as combined analysis with ATAC-seq data. Furthermore, we identified some candidate genes (UDP glucuronosyltransferase 1 family, Dock2, Tbc1d10c, etc.) and transcriptional regulators (KLF6 and GFI1) that might be associated with DN and DAPA restoration. These reversed genes and regulators confirmed that pathways related to immune response and metabolism pathways were critically involved in DN progression.

The influencing factors of the erythropoietin resistance index and its association with all-cause mortality in maintenance hemodialysis patients.

Anemia is a common complication of chronic kidney disease with major option treatment of erythropoiesis-stimulating agents (ESAs). This study aimed to investigate the influencing factors of erythropoietin resistance index (ERI) and its association with mortality in maintenance hemodialysis (MHD) patients. Patients enrolled from China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5 were included. ERI was calculated as follows: ESA (IU/week)/weight (kg, post-dialysis)/hemoglobin level (g/dL). The Cox regression model was used to analyze the influencing factors on survival outcomes. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were performed. A total of 1270 MHD subjects (687 males and 583 females) were included, with an average age of 60 (49.0, 71.0) years. All subjects were divided into two groups by the median ERI of 14.03. Multivariate logistic regression showed that dialysis vintage (OR 0.957, 95% CI: 0.929-0.986), white blood cells (OR 0.900, 95% CI: 0.844-0.960), high flux dialyzer use (OR 0.866, 95% CI: 0.755-0.993), body mass index (OR 0.860, 95% CI: 0.828-0.892), males (OR 0.708, 95% CI: 0.625-0.801), and albumin (OR 0.512, 95% CI: 0.389-0.673) had a negative association with high ERI baseline (all p < 0.05). There were 176 (13.9%) deaths in total including 89 cardiac/vascular deaths during follow-up. Cox regression analysis showed that ERI was positively associated with all-cause mortality, especially in some subgroups. ERI was associated with increased all-cause mortality in MHD patients, indicating the possibility of death prediction by ERI. Patients with high ERI warrant more attention.

Texture analysis of native T1 images as a novel method for non-invasive assessment of heart failure with preserved ejection fraction in end-stage renal disease patients.

OBJECTIVES: To explore the diagnostic potential of texture analysis applied to native T1 maps obtained from cardiac magnetic resonance (CMR) images for the assessment of heart failure with preserved ejection fraction (HFpEF) among patients with end-stage renal disease (ESRD). METHODS: This study, conducted from June 2018 to November 2020, included 119 patients (35 on hemodialysis, 55 on peritoneal dialysis, and 29 with kidney transplants) in Renji Hospital. Native T1 maps were assessed with texture analysis, using a freely available software package, in participants who underwent cardiac MRI at 3.0 T. Four texture features, selected by dimension reduction specific to the diagnosis of HFpEF, were analyzed. Multivariate logistic regression was performed to examine the independent association between the selected features and HFpEF in ESRD patients. RESULTS: Seventy-six of 119 patients were diagnosed with HFpEF. Demographic, laboratory, cardiac MRI, and echocardiogram characteristics were compared between HFpEF and non-HFpEF groups. The four texture features that were analyzed showed statistically significant differences between groups. In multivariate analysis, age, left atrial volume index (LAVI), and sum average 4 (SA4) turned out to be independent predictors for HFpEF in ESRD patients. Combining the texture feature, SA4, with typical predictive factors resulted in higher C-index (0.923 vs. 0.898, p = 0.045) and a sensitivity and specificity of 79.2% and 95.2%, respectively. CONCLUSIONS: Texture analysis of T1 maps adds diagnostic value to typical clinical parameters for the assessment of heart failure with preserved ejection fraction in patients with end-stage renal disease. KEY POINTS: • Non-invasive assessment of HFpEF can help predict prognosis in ESRD patients and help them take timely preventative measures. • Texture analysis of native T1 maps adds diagnostic value to the typical clinical parameters for the assessment of HFpEF in patients with ESRD.

Tubular basement membrane deposits after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Extraglomerular immune complex deposition is rare and only a few membranous nephropathy cases with tubular basement membrane deposits have been reported following allogeneic hematopoietic stem cell transplantation. CASE PRESENTATION: We reported a 56-year-old man with increased serum creatinine after allogeneic hematopoietic stem cell transplantation who underwent a renal biopsy. Tubular interstitial nephritis was identified on light microscope. The unique histologic features were diffuse tubular basement membrane immune complex deposition detected by both immunofluorescence and electron microscopy, while the glomerular involvement was inconspicuous. The differential diagnosis from other forms of tubular basement membrane deposition is discussed. CONCLUSION: Diffuse granular tubular basement membrane immune complex deposition with minimal glomerular involvement is also a manifestation of renal complication in hematopoietic stem cell transplantation recipient. However, the exact mechanism and target antigen remains unknown.

Hyperkalaemia prevalence and dialysis patterns in Chinese patients on haemodialysis: an interim analysis of a prospective cohort study (PRECEDE-K).

BACKGROUND: Hyperkalaemia is a known risk factor for cardiac arrhythmia and mortality in patients on haemodialysis. Despite standard adequate haemodialysis, hyperkalaemia is common in patients with end-stage renal disease (ESRD) at interdialytic intervals. Data on hyperkalaemia burden and its effects on dialysis patterns and serum potassium (sK) fluctuations in patients on haemodialysis in China remain limited. The prospective, observational cohort study (PRECEDE-K; NCT04799067) investigated the prevalence, recurrence, and treatment patterns of hyperkalaemia in Chinese patients with ESRD on haemodialysis. METHODS: Six hundred adult patients were consecutively enrolled from 15 secondary and tertiary hospitals in China. In this interim analysis, we report the baseline characteristics of the cohort, the prevalence of predialysis hyperkalaemia (sK > 5.0 mmol/L), and the trends in serum-dialysate potassium gradient and intradialytic sK shift at Visit 1 (following a long interdialytic interval [LIDI]). RESULTS: At baseline, most patients (85.6%) received three-times weekly dialysis; mean duration was 4.0 h. Mean urea reduction ratio was 68.0% and Kt/V was 1.45; 60.0% of patients had prior hyperkalaemia (previous 6 months). At Visit 1, mean predialysis sK was 4.83 mmol/L, and 39.6% of patients had hyperkalaemia. Most patients (97.7%) received a dialysate potassium concentration of 2.0 mmol/L. The serum-dialysate potassium gradient was greater than 3 mmol/L for over 40% of the cohort (1- < 2, 2- < 3, 3- < 4, and ≥ 4 mmol/L in 13.6%, 45.1%, 35.7%, and 5.2% of patients, respectively; mean: 2.8 mmol/L). The intradialytic sK reduction was 1- < 3 mmol/L for most patients (0- < 1, 1- < 2, 2- < 3, and ≥ 3 mmol/L in 24.2%, 62.2%, 12.8%, and 0.9% of patients, respectively; mean: 1.4 mmol/L). CONCLUSIONS: Hyperkalaemia after a LIDI was common in this real-world cohort of Chinese patients despite standard adequate haemodialysis, and led to large serum-dialysate potassium gradients and intradialytic sK shifts. Previous studies have shown hyperkalaemia and sK fluctuations are highly correlated with poor prognosis. Effective potassium-lowering treatments should be evaluated for the improvement of long-term prognosis through the control of hyperkalaemia and sK fluctuations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04799067.

Development and validation of the prediction model for mortality in patients with diabetic kidney disease in intensive care unit: a study based on medical information Mart for intensive care.

We aimed to explore factors associated with mortality of diabetic kidney disease (DKD), and to establish a prediction model for predicting the mortality of DKD. This was a cohort study. In total, 1,357 DKD patients were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, with 505 DKD patients being identified from the MIMIC-III as the testing set. The outcome of the study was 1-year mortality. COX proportional hazard models were applied to screen the predictive factors. The prediction model was conducted based on the predictive factors. A receiver operating characteristic (ROC) curve with the area under the curve (AUC) was calculated to evaluate the performance of the prediction model. The median follow-up time was 365.00 (54.50,365.00) days, and 586 patients (43.18%) died within 1 year. The predictive factors for 1-year mortality in DKD included age, weight, sepsis, heart rate, temperature, Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA), lymphocytes, red cell distribution width (RDW), serum albumin, and metformin. The AUC of the prediction model for predicting 1-year mortality in the training set was 0.771 [95% confidence interval (CI): 0.746-0.795] and the AUC of the prediction model in the testing set was 0.795 (95% CI: 0.756-0.834). This study establishes a prediction model for predicting mortality of DKD, providing a basis for clinical intervention and decision-making in time.

High facility-level serum potassium variability associated with mortality in hemodialysis patients: results from Chinese Dialysis Outcomes and Practice Patterns Study (DOPPS).

The role of facility-level serum potassium (sK+) variability (FL-SPV) in dialysis patients has not been extensively studied. This study aimed to evaluate the association between FL-SPV and clinical outcomes in hemodialysis patients using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5. FL-SPV was defined as the standard deviation (SD) of baseline sK+ of all patients in each dialysis center. The mean and SD values of FL-SPV of all participants were calculated, and patients were divided into the high FL-SPV (>the mean value) and low FL-SPV (≤the mean value) groups. Totally, 1339 patients were included, with a mean FL-SPV of 0.800 mmol/L. Twenty-three centers with 656 patients were in the low FL-SPV group, and 22 centers with 683 patients were in the high FL-SPV group. Multivariate logistic regression analysis showed that liver cirrhosis (OR = 4.682, 95% CI: 1.246-17.593), baseline sK+ (<3.5 vs. 3.5 ≤ sK+ < 5.5 mmol/L, OR = 2.394, 95% CI: 1.095-5.234; ≥5.5 vs. 3.5 ≤ sK+ < 5.5 mmol/L, OR = 1.451, 95% CI: 1.087-1.939), dialysis <3 times/week (OR = 1.472, 95% CI: 1.073-2.020), facility patients' number (OR = 1.088, 95% CI: 1.058-1.119), serum HCO3- level (OR = 0.952, 95% CI: 0.921-0.984), dialysis vintage (OR = 0.919, 95% CI: 0.888-0.950), other cardiovascular disease (OR = 0.508, 95% CI: 0.369-0.700), and using high-flux dialyzer (OR = 0.425, 95% CI: 0.250-0.724) were independently associated with high FL-SPV (all p < .05). After adjusting potential confounders, high FL-SPV was an independent risk factor for all-cause death (HR = 1.420, 95% CI: 1.044-1.933) and cardiovascular death (HR = 1.827, 95% CI: 1.188-2.810). Enhancing the management of sK+ of hemodialysis patients and reducing FL-SPV may improve patient survival.

Modulation of transforming growth factor-ß-induced kidney fibrosis by leucine-rich ⍺-2 glycoprotein-1.

Kidney fibrosis is considered the final convergent pathway for progressive chronic kidney diseases, but there is still a paucity of success in clinical application for effective therapy. We recently demonstrated that the expression of secreted leucine-rich α-2 glycoprotein-1 (LRG1) is associated with worsened kidney outcomes in patients with type 2 diabetes and that LRG1 enhances endothelial transforming growth factor-ß signaling to promote diabetic kidney disease progression. While the increased expression of LRG1 was most prominent in the glomerular endothelial cells in diabetic kidneys, its increase was also observed in the tubulointerstitial compartment. Here, we explored the potential role of LRG1 in kidney epithelial cells and TGF-ß-mediated tubulointerstitial fibrosis independent of diabetes. LRG1 expression was induced by tumor necrosis factor-α in cultured kidney epithelial cells and potentiated TGF-ß/Smad3 signal transduction. Global Lrg1 loss in mice led to marked attenuation of tubulointerstitial fibrosis in models of unilateral ureteral obstruction and aristolochic acid fibrosis associated with concomitant decreases in Smad3 phosphorylation in tubule epithelial cells. In mice with kidney epithelial cell-specific LRG1 overexpression, while no significant phenotypes were observed at baseline, marked exacerbation of tubulointerstitial fibrosis was observed in the obstructed kidneys. This was associated with enhanced Smad3 phosphorylation in both kidney epithelial cells and α-smooth muscle actin-positive interstitial cells. Co-culture of kidney epithelial cells with primary kidney fibroblasts confirmed the potentiation of TGF-ß-mediated Smad3 activation in kidney fibroblasts through epithelial-derived LRG1. Thus, our results indicate that enhanced LRG1 expression-induced epithelial injury is an amplifier of TGF-ß signaling in autocrine and paracrine manners promoting tubulointerstitial fibrosis. Hence, therapeutic targeting of LRG1 may be an effective means to curtail kidney fibrosis progression in chronic kidney disease.

Magnetic Resonance Imaging Quantification of Accumulation of Epicardial Adipose Tissue Adds Independent Risks for Diastolic Dysfunction among Dialysis Patients.

BACKGROUND: Diastolic dysfunction (DD) frequently occurs in dialysis patients; however, the risk factors of DD remain to be further explored in such a population. Epicardial adipose tissue (EAT) volume has proven to be an independent clinical risk factor for multiple cardiac disorders. PURPOSE: To assess whether EAT volume is an independent risk factor for DD in dialysis patients. STUDY TYPE: Case-control study. POPULATION: A total of 113 patients (mean age: 54.5 ± 14.4 years; 41 women) who had underwent dialysis for at least 3 months due to uremia. FIELD STRENGTH: A 3 T, steady-state free precession (SSFP) sequence for cine imaging, modified Look-Locker imaging (MOLLI) for T1 mapping and gradient-recalled-echo for T2*. ASSESSMENT: All participants were performed cardiac magnetic resonance imaging (MRI) and echocardiogram. For MRI images analysis, borders of the EAT were manually delineated, as well as, pericardial adipose tissue (PeAT) and paracardial adipose tissue (PaAT), T1 mapping, T2* mapping, global longitudinal strain (GLS), and left atrial strain. For echocardiogram assessments, the thickness of PaAT, e' velocity, E velocity, E/e ratio, A velocity, and deceleration time were measured. STATISTICAL TESTS: Univariate and multivariate logistic regressions were performed to explore the independent risk factors for DD. P value less than 0.05 was considered as significant. RESULTS: Compared with the DD(-) group, the DD(+) group had significantly more epicardial tissue fat (18.5 ± 1.3 vs. 30.9 ± 2.3) In addition, EAT volumes increased significantly with the grades of DD (grade 1 vs. grade 2 and 3: 27.9 ± 15.9 vs. 35.4 ± 13.1). Moreover, EAT had significant correlations with T1 mapping, T2* mapping, GLS, left atrial strain, e' velocity, and E/e ratio. EAT accumulation added an independent risk for DD (Odds Ratio = 1.03) over conventional clinical risk factors including age, diabetes mellitus, and hemodialysis. DATA CONCLUSION: EAT was associated with diastolic function, and its accumulation may be an independent risk factor for DD among dialysis patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Blood flow rate: An independent risk factor of mortality in Chinese hemodialysis patients.

BACKGROUND: Studies suggested the association between blood flow rate (BFR) and mortality might be beyond dialysis adequacy. This study aimed to explore if BFR is an independent predictor of clinical outcomes in Chinese hemodialysis (HD) patients. METHODS: This study included data from patients in China Dialysis Outcomes and Practice Patterns Study (DOPPS) Phase 5. Patients with a record of BFR were included, and demographic data, comorbidities, hospitalization, and death records were collected. Associations between BFR and all-cause mortality and hospitalization were analyzed using Cox regression models. RESULTS: One thousand four hundred twelve (98.9%) patients were included. Most patients were with BFR < 300 ml/min. After full adjustment, each 10-ml/min increase of BFR was associated with a 6.4% decrease in all-cause mortality risk (HR: 0.936, 95% CI: 0.880-0.996) but not first hospitalization (HR: 0.987, 95% CI: 0.949-1.027). The impact of BFR on mortality may be more prominent in patients who were male gender, nondiabetic, albumin < 4.0 g/dl, and hemoglobin ≥ 9.0 g/dl. CONCLUSION: Increased BFR is independently associated with a lower risk of all-cause mortality within the range of BFR 200-300 ml/min. And this effect is more pronounced in patients who were male gender, nondiabetic, albumin < 4.0 g/dl, and hemoglobin ≥ 9.0 g/dl.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Thrombocytopenia predicts mortality in Chinese hemodialysis patients- an analysis of the China DOPPS.

BACKGROUND: Hemodialysis (HD) patients have a higher mortality rate compared with general population. Our previous study revealed that platelet counts might be a potential risk factor. The role of platelets in HD patients has rarely been studied. The aim of this study is to examine if there is an association of thrombocytopenia (TP) with elevated risk of all-cause mortality and cardiovascular (CV) death in Chinese HD patients. METHODS: Data from a prospective cohort study, China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5, were analyzed. Demographic data, comorbidities, platelet counts and other lab data, and death records which extracted from the medical record were analyzed. TP was defined as the platelet count below the lower normal limit (< 100*109/L). Associations between platelet counts and all-cause and CV mortality were evaluated using Cox regression models. Stepwise multivariate logistic regression was used to identify the independent associated factors, and subgroup analyses were also carried out. RESULTS: Of 1369 patients, 11.2% (154) had TP at enrollment. The all-cause mortality rates were 26.0% vs. 13.3% (p < 0.001) in patients with and without TP. TP was associated with higher all-cause mortality after adjusted for covariates (HR:1.73,95%CI:1.11,2.71), but was not associated with CV death after fully adjusted (HR:1.71,95%CI:0.88,3.33). Multivariate logistic regression showed that urine output < 200 ml/day, cerebrovascular disease, hepatitis (B or C), and white blood cells were independent impact factors (P < 0.05). Subgroup analysis found that the effect of TP on all-cause mortality was more prominent in patients with diabetes or hypertension, who on dialysis thrice a week, with lower ALB (< 4 g/dl) or higher hemoglobin, and patients without congestive heart failure, cerebrovascular disease, or hepatitis (P < 0.05). CONCLUSION: In Chinese HD patients, TP is associated with higher risk of all-cause mortality, but not cardiovascular mortality. Platelet counts may be a useful prognostic marker for clinical outcomes among HD patients, though additional study is needed.

The initial attempt at home hemodialysis in mainland China.

BACKGROUND: Observational studies have shown home hemodialysis (HHD) to be associated with better survival than facility hemodialysis (HD) and peritoneal dialysis (PD). Patients on HHD have reported higher quality of life and independence. HHD is considered to be an economical way to manage end-stage kidney disease (ESKD). The coronavirus disease 2019 pandemic has had a significant impact on patients with ESKD. Patients on HHD may have an advantage over in-center HD patients because of a lower risk of exposure to infection. PARTICIPANTS AND METHODS: We enrolled HD patients from our dialysis center. We first established the HHD training center. The training center was approved by the Chinese government. Doctors, nurses and engineers train and assess patients separately. There are three forms of patient monitoring: home visits, internet remote monitoring, and outpatient services. Demographic and medical data included age, sex, blood pressure, and dialysis-related data. Laboratory tests were conducted in our central testing laboratory, including hemoglobin (Hgb), serum creatinine (Cr), urea nitrogen (BUN), uric acid (UA), albumin (Alb), calcium (Ca), phosphorus (P), parathyroid hormone (PTH), and brain natriuretic peptide (BNP) levels. RESULTS: Six patients who underwent regular dialysis in the HD center of our hospital were selected for HHD training. We enrolled 6 patients, including 4 males and 2 females. The mean age of the patients was 47.5 (34.7-55.7) years, and the mean dialysis age was 33.5 (11.2-41.5) months. After an average of 16.0 (11.2-25.5) months of training, Alb, P and BNP levels were improved compared with the baseline values. After training, three patients returned home to begin independent HD. During the follow-up, there were no serious adverse events leading to hospitalization or death, but there were several adverse events. They were solved quickly by extra home visits of the technicians or online by remote monitoring. During the follow-up time, the laboratory indicators of all the patients, including Hgb, Alb, Ca, P, PTH, BNP, and ß2-MG levels, remained stable before and after HHD treatment. CONCLUSION: HHD is feasible and safe for ESKD in China, but larger-scale and longer-term studies are needed for further confirmation.

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.

A novel contrast-induced acute kidney injury mouse model based on low-osmolar contrast medium.

The contrast-induced acute kidney injury (CI-AKI) has been becoming the third common cause of hospital-acquired acute kidney injury. An ideal animal model is essential for understanding the pathophysiology of CI-AKI. Previous CI-AKI studies were mostly performed on rats with high-osmolar contrast medium (HOCM), which is unsuitable for transgenic researches. This study provides a novel, efficient and reproducible CI-AKI model which was developed in mouse by administrating a low-osmolar contrast medium (LOCM). First of all, we applied the frequently used pretreatments (uninephrectomy and water deprivation), which combined with HOCM on rats could induce CI-AKI, on mice with LOCM. Secondly, we attempted to find a novel pretreatment suitable for mouse and LOCM by combining two classic pretreatments(uninephrectomy, water deprivation and furosemide administration). Finally, we evaluate the kidney damage of the novel model. We found that this mouse model possessed a significant reduction in renal function, severe renal tissue damage, and increased renal tubular cells apoptosis, indicating that LOCM is a feasible inducer for CI-AKI mice model. Taken together, we found that uninephrectomy (UPHT) combined with 24 h water deprivation and furosemide administration 20 min before LOCM (iohexol, 10 ml/kg) application is a feasible pretreatment to establish a novel CI-AKI mouse model.

Texture Analysis of Native T1 Images as a Novel Method for Noninvasive Assessment of Uremic Cardiomyopathy.

BACKGROUND: Noncontrast cardiac T1 times are increased in dialysis patients which might indicate fibrotic alterations in uremic cardiomyopathy. PURPOSE: To explore the application of the texture analysis (TA) of T1 images in the assessment of myocardial alterations in dialysis patients. STUDY TYPE: Case-control study. POPULATION: A total of 117 subjects, including 22 on hemodialysis, 44 on peritoneal dialysis, and 51 healthy controls. FIELD STRENGTH: A 3 T, steady-state free precession (SSFP) sequence, modified Look-Locker imaging (MOLLI). ASSESSMENT: Two independent, blinded researchers manually delineated endocardial and epicardial borders of the left ventricle (LV) on midventricular T1 maps for TA. STATISTICAL TESTS: Texture feature selection was performed, incorporating reproducibility verification, machine learning, and collinearity analysis. Multivariate linear regressions were performed to examine the independent associations between the selected texture features and left ventricular function in dialysis patients. Texture features' performance in discrimination was evaluated by sensitivity and specificity. Reproducibility was estimated by the intraclass correlation coefficient (ICC). RESULTS: Dialysis patients had greater T1 values than normal (P < 0.05). Five texture features were filtered out through feature selection, and four showed a statistically significant difference between dialysis patients and healthy controls. Among the four features, vertical run-length nonuniformity (VRLN) had the most remarkable difference among the control and dialysis groups (144 ± 40 vs. 257 ± 74, P < 0.05), which overlap was much smaller than Global T1 times (1268 ± 38 vs. 1308 ± 46 msec, P < 0.05). The VRLN values were notably elevated (cutoff = 170) in dialysis patients, with a specificity of 97% and a sensitivity of 88%, compared with T1 times (specificity = 76%, sensitivity = 60%). In dialysis patients, VRLN was significantly and independently associated with left ventricular ejection fraction (P < 0.05), global longitudinal strain (P < 0.05), radial strain (P < 0.05), and circumferential strain (P < 0.05); however, T1 was not. DATA CONCLUSION: The texture features obtained by TA of T1 images and VRLN may be a better parameter for assessing myocardial alterations than T1 times. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

αKlotho protein has therapeutic activity in contrast-induced acute kidney injury by limiting NLRP3 inflammasome-mediated pyroptosis and promoting autophagy.

Contrast-induced acute kidney injury (CI-AKI) is a main cause of hospital-acquired renal failure. Nevertheless, limited measures have been shown to be effective for the treatment of CI-AKI. Here, we demonstrated that αKlotho, which is highly expressed in kidney, has therapeutic activity in CI-AKI. Our data showed that αKlotho expression levels were decreased both in the kidney and serum of CI-AKI mice. Administration of αKlotho protein protected the kidney and HK-2 cells against contrast-induced injury. Mechanistically, αKlotho reduced contrast-induced renal tubular cells pyroptosis by limiting NLRP3 inflammasome activation. Meanwhile, αKlotho up-regulated autophagy via inhibiting the AKT/mTOR pathway and decreased mitochondrial ROS level. Inhibition of autophagy blunted the suppression effect of αKlotho on NLRP3 inflammasome activation and cell pyroptosis in contrast-treated HK-2 cells. Taken together, our data suggest that αKlotho protein protects against CI-AKI through inhibiting NLRP3 inflammasome-mediated pyroptosis, which is likely by promoting autophagy. αKlotho may be a promising therapeutic strategy for CI-AKI.

Understand the difference between clinical measured ultrafiltrationand real ultrafiltration in peritoneal dialysis.

BACKGROUND: It has been noticed for years that ultrafiltration (UF) is important for survival in peritoneal dialysis. On the other hand, precise and convenient UF measurement suitable for patient daily practice is not as straight forward as it is to measure UF in the lab. Both overfill and flush before fill used to be source of measurement error for clinical practice. However, controversy finding around UF in peritoneal dialysis still exists in some situation. The current study was to understand the difference between clinical measured UF and real UF. The effect of evaporation and specific gravity in clinical UF measurement were tested in the study. METHODS: Four different brands of dialysate were purchased from the market. The freshest dialysate available in the market were intentionally picked. The bags were all 2 L, 2.5% dextrose and traditional lactate buffered PD solution. They were stored in four different conditions with controlled temperature and humidity. The bags were weighted at baseline, 6 months and 12 months of storage. Specific gravity was measured in mixed 24 h drainage dialysate from 261 CAPD patients when they come for their routine solute clearance test. RESULTS: There was significant difference in dialysate bag weight at baseline between brands. The weight declined significantly after 12 month's storage. The weight loss was greater in higher temperature and lower humidity. The dialysate in non-PVC package lose less weight than PVC package. The specific gravity of dialysate drainage was significantly higher than pure water and it was related to dialysate protein concentration. CONCLUSION: Storage condition and duration, as well as the type of dialysate package have significant impact in dialysate bag weight before use. Evaporation is likely to be the reason behind. The fact that specific gravity of dialysate drainage is higher than 1 g/ml overestimates UF in manual exchanges, which contributes to systemic measurement error of ultrafiltration in CAPD. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03864120 (March 8, 2019) (Understand the Difference Between Clinical Measured Ultrafiltration and Real Ultrafiltration).