CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing hemodialysis.

BACKGROUND: T cell dysfunction observed in patients undergoing hemodialysis (HD) has been linked to an extremely high morbidity of cardiovascular events (CVEs) and infections. The cell-surface 5'-nucleotidase CD73 sets the balance between pro-inflammatory nucleotides and anti-inflammatory adenosine. METHODS: A total of 395 patients who had been receiving HD for at least six months were evaluated for proportions of CD73+ cells in both the CD4+ T cell and CD8+ T cell compartment and followed for one year to document CVEs and infections. Differences in the proportions of CD73-expressingT cells between healthy controls and patients undergoing HD were compared. The relationship between CD73+ T cells and clinical outcomes was analyzed using the Kaplan-Meier curve and Cox regression. RESULTS: HD was significantly related to a lower fraction of CD4+CD73+ T cells. In patients on HD, lower proportions of CD4+ CD73+T cells and CD8+ CD73+T cells were both associated with systemic inflammation and T cell terminal differentiation. More importantly, a lower CD4+CD73+T cell ratio independently predicted CVEs and infection in these patients. CONCLUSION: We identified CD73 as a T cell dysfunction marker predicting cardiovascular and infection events in patients undergoing HD, which provides a potential target in future studies of uremia-related immune dysfunction.

Immunological features of ESRD patients undergoing hemodialysis of various ages.

AIMS: To investigate the immunological characteristics of hemodialysis (HD) patients with end-stage renal disease (ESRD) of various ages, and the impact of age-related immune alterations on these patients, with a focus on peripheral T cells. METHODS: From September 2016 to September 2019, HD patients were enrolled and followed prospectively for 3 years. Patients were divided into three groups based on their ages: < 45, 45 to 64, and ≥ 65. The distribution of T cell subsets in different age groups was investigated and compared. The effects of altered T cell subsets on overall survival were also investigated. RESULTS: A total of 371 HD patients were enrolled. The reduced number of naive CD8+ T cells (P < 0.001) and increased number of EMRA CD8+ T cells (P = 0.024) were independently associated with the advanced age among all T cell subsets studied. Patient survival may be affected by numerical changes in naive CD8+ T cells. However, when HD patients were < 45 or ≥ 65 years, the reduction had no significant impact on survival. Only in HD patients aged 45 to 64 years, the number of naïve CD8+ T cells found to be insufficient but not deficient, identified as an independent predictor of poor survival. CONCLUSIONS: The most significant age-related immune change in HD patients was a decrease in peripheral naive CD8+ T cells, which was an independent predictor of 3-year overall survival in HD patients aged 45 ~ 64 years.

Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease.

BACKGROUND: The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking. RESULTS: Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression. CONCLUSION: This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.

A NOVEL RAT MODEL OF CONTRAST-INDUCED ACUTE KIDNEY INJURY BASED ON RENAL CONGESTION AND THE RENO-PROTECTION OF MITOCHONDRIAL FISSION INHIBITION.

ABSTRACT: Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication in patients receiving intravenous iodinated contrast medium (CM). Clinically, congestive heart failure is the most critical risk factor for CI-AKI and always leads to renal congestion for increased central venous pressure and fluid overload. Here, we aimed to investigate a novel CI-AKI rat model based on renal congestion. After the exploratory testing phase, we successfully constructed a CI-AKI rat model by inducing renal congestion by clamping the unilateral renal vein, removing the contralateral kidney, and a single tail vein injection of iohexol. This novel CI-AKI rat model showed elevated serum creatinine, urea nitrogen, and released tubular injury biomarkers (KIM-1 and NGAL), reduced glomerular filtration rate, and typical pathologic features of CM-induced tubular injury with extensive foamy degeneration, tubular edema, and necrosis. Electron microscopy and confocal laser scanning revealed excessive mitochondrial fission and increased translocation of Drp1 from the cytoplasm to the mitochondrial surface in tubular epithelial cells. As a Drp1 inhibitor, Mdivi-1 attenuated excessive mitochondrial fission and exerted reno-protection against CM injury. Simultaneously, Mdivi-1 alleviated oxidative stress, apoptosis, and inflammatory responses induced by CM toxicity. We concluded that renal congestion exacerbated CM toxicity and presented a novel CI-AKI rat model. Excessive mitochondrial fission plays a crucial role in CM reno-toxicity and is a promising target for preventing and treating CI-AKI.

Effects of p-cresol, a uremic toxin, on cancer cells.

Background: Though p-cresol exists at a low concentration in the blood, it accumulates in various organs of uremic patients. Previous research has shown that the p-cresol promoted bladder cancer cell invasion and migration. This study aims to see if p-cresol had similar effects on kidney cancer cells and liver cancer cells. Methods: For 48 hours, 786-O human renal cancer cells and HepG2 human liver cancer cells were treated with p-cresol at concentrations of 0, 10, 20, 40, and 70 µM. The effects of p-cresol on cell viability, apoptosis, migration, and invasion were then analyzed using the CCK-8, TUNEL, and Transwell migration/invasion assays, respectively. Results: P-cresol at 0 to 70 µM for 48 hours had no significant toxic effects on 786-O cells or HepG2 cells. We chose 40 µM p-cresol for 48 hours for the following experiment. The viability and proliferation of 786-O cells and HepG2 cells were unaffected after 48 hours of treatment, with 40 µM p-cresol. However, 40 µM p-cresol for 48 hours promoted HepG2 cell migration and invasion but did not have the same effect on the 786-O cell line. Conclusions: P-cresol may be responsible for HepG2 cells' malignant biological behavior. Because the liver is the primary site of p-cresol metabolism, it is important to study the responses of cancer cells in the liver to p-cresol.

Predictive role of cardiac valvular calcification in all-cause mortality of Chinese initial haemodialysis patients: a follow-up study of 4 years.

BACKGROUND: Cardiac valvular calcification (CVC) is prevalent in haemodialysis (HD) patients. Its association with mortality in Chinese incident haemodialysis (IHD) patients remains unknown. METHODS: A total of 224 IHD patients who had just begun HD therapy at Zhongshan Hospital, Fudan University, were enrolled and divided into two groups according to the detection of cardiac valvular calcification (CVC) by echocardiography. The patients were followed for a median of 4 years for all-cause mortality and cardiovascular mortality. RESULTS: During follow-up, 56 (25.0%) patients died, including 29 (51.8%) of cardiovascular disease. The adjusted HR related to all-cause mortality was 2.14 (95% CI, 1.05-4.39) for patients with cardiac valvular calcification. However, CVC was not an independent risk factor for cardiovascular mortality in patients who had just begun HD therapy. CONCLUSION: CVC at baseline is an independent risk factor for all-cause mortality in HD patients and makes an independent contribution to the prediction of all-cause mortality. These findings support the use of echocardiography at the beginning of HD.

Altered gut microbiota and gut-derived p-cresyl sulfate serum levels in peritoneal dialysis patients.

Peritoneal dialysis (PD) is a renal replacement therapy for end-stage renal disease. Gut microbiota-derived uremic solutes, indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine-N-oxide (TMAO) accumulate in PD patients. The objective was to explore the gut microbiota and their influence on uremic toxins in PD patients and healthy controls (HC). Fecal samples were collected from PD patients (n = 105) and HC (n = 102). 16S rRNA gene regions were sequenced for gut microbiota analysis. IS, PCS, and TMAO levels were measured using HPLC-MS. PD patients exhibited lower alpha diversity and altered gut microbiota composition compared to HC. At the genus level, PD patients showed increased abundance of opportunistic pathogenic bacteria, and decreased abundance of beneficial bacteria. Three Operational Taxonomic Units discriminated PD patients from HC. Phenylalanine metabolism increased in PD, whereas tryptophan metabolism was unaltered. Low serum PCS did not necessarily mean healthier due to the loss of alpha diversity, increased Proteobacteria and opportunistic pathogenic bacteria. High serum PCS was mainly caused by elevated p-cresol-producing bacteria, enriched amino acid related enzymes, and enhanced sulfur metabolism, rather than declined residual renal function. In patients with different urine volumes, the gut microbiota alpha diversity and composition were unaltered, but serum IS and TMAO were significantly elevated in anuric patients. In conclusion, the gut microbiota abundance, composition, and function were altered in PD patients, which increased the PCS levels. We provided a better understanding of the microbiota-metabolite-kidney axis in PD patients. Targeting certain bacteria could decrease the PCS levels, whereas preserving the residual renal function could reduce the IS and TMAO levels.

Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury.

Acute kidney injury (AKI) is associated with high risk of mortality, post-disease renal fibrosis, kidney dysfunction and renal failure. Renal macrophages play a key role in the pathogenesis (M1 subpopulation), healing and remodeling (M2 subpopulation) in AKI and, thus, have been a promising target for clinical treatment of AKI. Here, in a mouse renal ischemia/reperfusion injury (IRI) model for AKI, we showed that renal macrophages could be further classified into Clec7a+ M1 macrophages, Clec7a- M1 macrophages, Clec7a+ M2 macrophages and Clec7a- M2 macrophages, representing distinct macrophage populations with different functionality. Interestingly, Clec7a+ M1 macrophages exhibited potent pro-inflammatory and phagocytic effects compared to Clec7a- M1 macrophages, while Clec7a- M2 macrophages exhibited better proliferating and migrating potential, which is critical for their role in tissue repairing after injury. These data from mice were further strengthened by bioinformatics analyses using published database. In vivo, combined expression of Clec7a in M1 macrophages and depletion of Clec7a in M2 macrophages significantly improved the renal function after IRI-AKI. Together, our data suggest that Clec7a is crucial for the fine regulation of macrophage phenotype during AKI and could be a novel target for boosting clinical therapy.

The Proportion of Memory CD8+ T Cell Predicts Infection Event in Patients with Peritoneal Dialysis.

INTRODUCTION: The immune senescence marked by the inflation of memory T cell is established in end-stage renal disease (ESRD) patients with peritoneal dialysis (PD). These patients suffer high incidence of infectious disease, which has been relevant to immune dysfunction. However the association of immune senescence with infection in PD patients is not clear. This prospective study aimed to investigate the relationship between proportion of T cell subsets and infection event in patients on PD. METHODS: We enrolled patients on PD >6 months from January 1, 2016 to December 30, 2016 and followed them until April 30, 2020. Baseline T cell subsets from blood were collected at the time of recruitment. The primary end point was infection event including peritonitis, exit site infection, pneumonia, urinary tract infection, and other infection. RESULTS: There were 94 patients (46 male) with a mean age of 56.1 ± 14.9 years old enrolled during the follow-up period, and 26 patients suffered infection events. A higher proportion of effector memory (EM) CD8+ T cells was found in patients with infection than in those without infection. There was no difference in the distribution of EM CD8+ T cells between PD-related and non-dialysis infection. Increased level of EM CD8+ T cells was risk factor for first infection event in PD patients. CONCLUSION: High level of EM CD8+ T cells could be a significant predictor of infection event in patients on PD.

p-Cresyl Sulfate Predicts Ischemic Stroke among Patients on Hemodialysis: A Prospective Cohort Study.

METHOD: Patients on hemodialysis over 6 months were enrolled in this prospective cohort study and were divided into 2 groups based on plasma p-cresyl sulfate level. The primary end point was the first episode of ischemic stroke during follow-up. The association between p-cresyl sulfate and ischemic stroke incidence was analyzed by Kaplan-Meier method and Cox proportional hazard model. RESULTS: 220 patients were enrolled in this study. 44 patients experienced episodes of first ischemic stroke during follow-up for 87.8 (47.6-119.5) months. Kaplan-Meier analysis demonstrated that the incidence of ischemic stroke in the high p-cresyl sulfate group was significantly higher than that in the low p-cresyl sulfate group (Log-Rank P = 0.007). Cox regression analysis as well proved that p-cresyl sulfate level was significantly associated with the first incidence of ischemic stroke (HR (hazard ratio) 2.332, 95% CI (95% confidence interval) 1.236-4.399, P = 0.009). After being adjusted for other confounding risk factors, the results persisted significant (model 11: HR 2.061, 95% CI 1.030-4.125, P = 0.041). CONCLUSION: Plasma p-cresyl sulfate predicts the first incidence of ischemic stroke in hemodialysis patients.

Rationale and validation of predicting high sodium intake by spot urinary chloride in patients with chronic kidney disease.

OBJECTIVE: To analyze the rationale and evaluate the validity of spot urinary chloride or derived formulas to predict high sodium intake in patients with chronic kidney disease (CKD). METHODS: We collected consecutive CKD patients at stages 1-4 who were admitted to our Nephrology department in a single center from January 01, 2014, to December 31, 2017, and tested spot and 24-hour urinary analysis on the same day. The feasibility of urinary chloride to predict urinary sodium was firstly analyzed by calculating their correlations. The validity of predicting excessive sodium intake by spot urinary sodium and chloride, two derived formulas based on spot urinary sodium or chloride, and our previous "CKDSALT" equation were accessed. We finally conducted Receiver operating characteristic (ROC) curves to compare their performance in detecting high sodium intake. RESULTS: All 5204 patients were eventually analyzed. In the derivation cohort (n = 2447), a strong positive linear correlation existed between urinary sodium and chloride in both spot urine (R2 = 0.804) and 24-hour urine samples (R2 = 0.905), and two predictive equations based on spot urinary sodium or chloride were derived. In the validation cohort (n = 2757), spot urinary sodium and chloride only showed "fair" performance. However, both urinary sodium and chloride equations had a "good" performance in ICC, Pearson's correlation, Bland-Altman plots, and ROC curves, while and CKDSALT equation showed the best performance. CONCLUSIONS: Spot urinary chloride is a feasible method to predict and monitor high sodium intake in CKD patients, while a novel derived formula could elevate its diagnostic accuracy.

METTL14 aggravates podocyte injury and glomerulopathy progression through N6-methyladenosine-dependent downregulating of Sirt1.

Podocytes are known to play a determining role in the progression of proteinuric kidney disease. N6-methyladenosine (m6A), as the most abundant chemical modification in eukaryotic mRNA, has been reported to participate in various pathological processes. However, its role in podocyte injury remains unclear. In this study, we observed the elevated m6A RNA levels and the most upregulated METTL14 expression in kidneys of mice with adriamycin (ADR) and diabetic nephropathy. METTL14 was also evidently increased in renal biopsy samples from patients with focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy and in cultured human podocytes with ADR or advanced glycation end product (AGE) treatment in vitro. Functionally, we generated mice with podocyte-specific METTL14 deletion, and identified METTL14 knockout in podocytes improved glomerular function and alleviated podocyte injury, characterized by activation of autophagy and inhibition of apoptosis and inflammation, in mice with ADR nephropathy. Similar to the results in vivo, knockdown of METTL14 facilitated autophagy and alleviated apoptosis and inflammation in podocytes under ADR or AGE condition in vitro. Mechanically, we identified METTL14 knockdown upregulated the level of Sirt1, a well-known protective deacetylase in proteinuric kidney diseases, in podocytes with ADR or AGE treatment. The results of MeRIP-qPCR and dual-luciferase reporter assay indicated METTL14 promoted Sirt1 mRNA m6A modification and degradation in injured podocytes. Our findings suggest METTL14-dependent RNA m6A modification contributes to podocyte injury through posttranscriptional regulation of Sirt1 mRNA, which provide a potential approach for the diagnosis and treatment of podocytopathies.

Survival analysis in the incident dialysis patients by different modalities.

BACKGROUND: To analysis survival in onset uremic patients who initiating HD or PD dialysis in our dialysis center. METHODS: Between Jan. 2015 and June. 2018, patients with onset uremia and initiating planned-start dialysis were retrospectively enrolled in this study and followed up to January, 2019. The relationships between the types of dialysis modality and patient prognosis were assessed. RESULTS: A total of 460 patients were included in the final analysis. Of which, 213 patient (46.30%) undergoing PD and 247 patients (53.70%) undergoing HD with arteriovenous fistula. The average follow-up time was 27.9 months. Eighty-seven (18.91%) patients died during the study period. The all-cause mortality was 127 per 1000 person-year. It was 102 per 1000 person-year in the HD group and 171 per 1000 person-year in the PD group (p < 0.01). However, dialysis modality was not an independent predictor for survival. During the first year after dialysis initiation, patient survival was comparable between the PD and HD groups (log-rank p = 0.14). As the dialysis age increased over 1 year, HD patients seemed to have a better survival as compared to that of PD patient (log-rank p < 0.05), especially those older than 65 years and without DN. CONCLUSIONS: Though dialysis modality was not an independent factor for overall survival, HD therapy seemed to be more suitable for patients without DN.

Epidemiology of Takayasu arteritis in Shanghai: A hospital-based study and systematic review.

BACKGROUND: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. METHODS: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. RESULTS: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. CONCLUSIONS: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

Orosomucoid can predict baseline peritoneal transport characteristics in peritoneal dialysis patients and reduce peritoneal proteins loss.

Peritoneal dialysis (PD) is a replacement therapy for end-stage renal disease patients. In the first 4-8 weeks of PD, the patients were given an empirical dialysis prescription due to unknown peritoneal transport characteristics. Proteomic analysis could be used to identify serum biomarkers. In a discovery set, patients were divided into three groups according to the peritoneal equilibration test (PET) results: high (H), high average (HA), low average and low (LA&L) groups. A total of 1051 identified proteins were screened by Nano HPLC-MS/MS. The top two proteins among different peritoneal transport characteristics were Orosomucoid 2 (ORM2) and C-reactive protein (CRP). In a validation set, CRP was significantly elevated in H group than LA&L group, consistent with proteomic analysis. Serum ORM2 was enhanced in LA&L group compared with H and HA group. The expression of ORM2 in peritoneum was also enriched in LA&L group. At last, supplying exogenous ORM could reduce peritoneal proteins loss, without causing a pro-inflammatory response in mice. ORM2 and CRP could be used as biomarkers to predict the baseline peritoneal transport characteristics, and guide the early PD treatment. ORM may serve as a novel therapeutic target for decreasing peritoneal proteins loss in PD patients. SIGNIFICANCE: Peritoneal dialysis (PD) is associated with the functional alterations of the peritoneum. PD patients were often given an empirical dialysis prescription due to the unknown peritoneal transport characteristics in the first 4-8 weeks since PD started. Therefore, it is urgently needed to find biomarkers to predict the baseline peritoneal transport characteristics. In this study, we employed a proteomic analysis to identify serum biomarkers in a training set and verified the screened biomarkers in a validation set. We also found that Orosomucoid (ORM) has the potential to decrease peritoneal proteins loss in PD therapy.

Decreased Peripheral Naïve T Cell Number and Its Role in Predicting Cardiovascular and Infection Events in Hemodialysis Patients.

Patients with end-stage renal disease (ESRD) are at high risk of morbidity and mortality from cardiovascular and infectious diseases, which have been found to be associated with a disturbed immune response. Accelerated T-cell senescence is prevalent in these patients and considered a significant factor contributing to increased risk of various morbidities. Nevertheless, few studies have explicated the relevance of T-cell senescence to these fatal morbidities in ESRD patients. In this study, we designed a longitudinal prospective study to evaluate the influence of T-cell senescence on cardiovascular events (CVEs) and infections in hemodialysis (HD) patients. Clinical outcomes of 404 patients who had been on HD treatment for at least 6 months were evaluated with respect to T-cell senescence determined using flow cytometry. We found that T-cell senescence was associated with systemic inflammation. High-sensitivity C-reactive protein was positively associated with decreased naïve T cell levels. Elevated tumor necrosis factor-α and interleukin 6 levels were significantly associated with lower central memory T cell and higher T effector memory CD45RA cell levels. Decreased CD4+ naïve T cell count was independently associated with CVEs, whereas decreased CD8+ naïve T cell count was independently associated with infection episodes in HD patients. In conclusion, HD patients exhibited accelerated T-cell senescence, which was positively related to inflammation. A reduction of naïve T cell could be a strong predictor of CVEs and infection episodes in HD patients.

Prostaglandin E2 induced cardiac hypertrophy through EP2 receptor-dependent activation of ß-catenin in 5/6 nephrectomy rats.

AIMS: Prostaglandin E2 (PGE2) is involved in the development of cardiac hypertrophy. However, whether PGE2 regulates the chronic kidney disease-associated cardiac hypertrophy and the tentative mechanism remains to be elucidated. METHODS AND RESULTS: We explored the effect of PGE2 receptor inhibitors on cardiac hypertrophy in vitro and in a 5/6 nephrectomy (5/6NT) rat model using quantitative reverse transcription polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and immunofluorescence staining assays. The result showed that EP2 and EP4 receptors were both up-regulated in the PGE2-treated cardiomyocyte cells. PGE2 treatment enhanced active ß-catenin (non-phosphorylated) signalling through mediating EP2 and EP4 receptors. Interestingly, inhibition of EP2 receptor suppressed PGE2-induced cardiomyocyte hypertrophy and cardiac fibrosis-related proteins in vitro. In the 5/6NT rat model, the increased secretion PGE2 was identified in the 5/6NT rat model for 2 weeks (P = 0.0251). EP2 receptor inhibitor administration significantly improved the cardiac function and fibrosis in 5/6NT rats. CONCLUSIONS: Our study demonstrated that inhibition of EP2 receptor could improve PGE2-induced cardiac hypertrophy in 5/6NT rats. The exploration of these mechanisms may contribute to the optimization of therapy in chronic kidney disease accompanied cardiac hypertrophy in clinic.

Association of N-Terminal Pro-brain Natriuretic Peptide With Volume Status and Cardiac Function in Hemodialysis Patients.

Introduction: N-terminal-pro-brain natriuretic peptide (NT-pro BNP) is secreted by cardiomyocytes in cases of cardiac structure disorder and volume overload. However, the relationship between NT-pro BNP level and body fluid status in dialysis patients with reduced cardiac ejection function (EF) is uncertain. Therefore, we aimed to investigate this relationship. Methods: We enrolled patients who had been receiving hemodialysis for >3 months. Blood sample, transthoracic echocardiographic, and bioimpedance spectroscopy measurements were performed during a midweek non-dialysis day. The predictive value of NT-pro BNP in hemodialysis patients with volume overload was analyzed. Results: A total of 129 hemodialysis patients (74 men and 55 women; mean age: 59.4 ± 13.0 years) were recruited. The average hemodialysis duration was 55.5 (23.9-93.4) months, the NT-pro BNP level was 4992 (2,033-15,807) pg/mL, and the value of overhydration was 2.68 ± 0.19 (-1.9 to 12.2) L. The NT-pro BNP level was independently correlated with overhydration in both the LVEF ≥ 60% (ß = 0.236, P = 0.044) and LVEF <60% (ß = 0.516, P = 0.032) groups, even after adjustments for potentially confounding variables. In receiver operating characteristic curves of NT-pro BNP for predicting volume overload, the area under the curve was 0.783 [95% CI (0.688-0.879), P < 0.001) and 0.788 [95% CI (0.586-0.989), P < 0.001] in the LVEF ≥ 60% and LVEF < 60% groups, respectively. Conclusions: NT-pro BNP is a predictive factor for volume overload in hemodialysis patients with or without EF declines.

Paradoxical Association Between Intradialytic Blood Pressure Change and Long-Term Mortality with Different Levels of Interdialytic Weight Gain.

BACKGROUND: A greater interdialytic weight gain (IDWG) implies a greater ultrafiltration rate, which might lead to hemodynamic instability and intradialytic blood pressure (BP) change in hemodialysis patients. However, current studies have not explicated the impact of IDWG on the association between intradialytic BP changes and prognosis, especially in patients without cardiac dysfunction and diabetes. In this study, we aimed to explore the relationship between absolute intradialytic BP changes and mortality with different IDWG levels. METHODS: A total of 204 hemodialysis patients (without cardiac dysfunction and diabetes) were included in this prospective observation study, with a mean follow-up of 55.32±20.99 months. Initially, we collected IDWG, IDWG% (percentages according to dry weight), and pre-/post-BPs of 36 consecutive dialysis sessions during three months enrollment. And the average value of them was defined as baseline value. Patients were divided into 3 cohorts according to IDWG% tertiles (<3.3%, 3.3%-4.6%, ≥4.6%). Comparisons between different tertiles were analyzed. RESULTS: Compared to the low IDWG% group (tertile 1, T1), patients of high IDWG% group (tertile 3, T3) were younger, had higher ultrafiltration rate, less residual kidney function, lower BMI and dry weight, longer dialysis vintage and higher N terminal pro B type natriuretic peptide levels (P<0.05). Correlations were found between IDWG% and intradialytic BP changes. Kaplan-Meier analysis and multivariate Cox regression model adjusted for demographic data, dialysis information and predialysis BPs indicated that greater absolute intradialytic BP changes were associated with worse prognosis in T1 group (P<0.05). While in T3 group, less absolute intradialytic BP changes were associated with higher mortality (P<0.05). CONCLUSION: There is a paradoxical association between absolute intradialytic BP changes and long-term mortality with different IDWG levels. Both BP stability and volume balance are crucial to patients' prognosis.

Pro-inflammatory cytokines as potential predictors for intradialytic hypotension.

BACKGROUND: Intradialytic hypotension (IDH) is a common complication in maintaining hemodialysis (MHD) patients. Immune activation might be part of the mechanisms. However, the association between pro-inflammatory cytokines and blood pressure (BP) has not been deeply explored. So we aim to evaluate the potential role of pro-inflammatory cytokines in IDH. METHODS: MHD patients starting hemodialysis before January 2016 were enrolled in our retrospective study. Patients' characteristics, laboratory results, and intradialytic BP were collected. IDH was defined as nadir systolic BP ≤ 90 mmHg during hemodialysis. The definition of IDH group was that those who suffered from more than one hypotensive event during one month after the enrollment (10% of dialysis treatments). Spearman correlation analysis and logistic regression were employed to explore the relationship between pro-inflammatory cytokines and IDH. RESULTS: Among 390 patients, 72 were identified with IDH (18.5%). High levels of serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were observed in the IDH group (p < 0.001). Both TNF-α and IL-1ß positively correlated with predialysis BP (p < 0.01). Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracy of serum IL-1ß and TNF-α for IDH. The area under the curve of IL-1ß was 0.772 (95% CI: 0.708-0.836, p < 0.01), and that of TNF-α was 0.701 (95% CI: 0.620-0.781, p < 0.01). After adjusting for patients' characteristics, biochemical parameters, comorbid conditions, predialysis BP, and medications, elevated TNF-α and IL-1ß were still risk factors for IDH. CONCLUSION: Pro-inflammatory cytokines (TNF-α and IL-1ß) could be potential predictors for IDH.