The risk factor for adverse pregnancy outcomes and its impact on clinical effect in IgA nephropathy: A retrospective observational study.

AIM: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Pregnant IgAN patients are more susceptible to adverse pregnancy outcomes (APO). However, the risk factor for APO and its effects on the long-term renal outcome of pregnant IgAN patients remained unclear. METHODS: We performed a retrospective observational study covering 2003-2019 that included 44 female IgAN patients with pregnancy history to investigate the risk factor for APO and its impact on clinical outcome in IgAN. Renal function outcome and proteinuria remission were evaluated in pregnant IgAN women with and without APO. RESULTS: In this retrospective and observational study, we found that patients with APO exhibited higher levels of serum creatinine and IgM, and lower haemoglobin levels while other clinical characteristics, pathological characteristics and therapy protocol had no significant difference. We found that anaemia and a higher level of serum IgM were independent risk factors for APO. IgAN pregnant women without APO experienced a higher proportion of proteinuria remission than those with APO, but there is no difference in the renal function outcome. CONCLUSION: Pregnant IgAN patients with higher risks, including lower haemoglobin levels and higher IgM levels deserve intensive monitoring, and aggressive therapy to reduce proteinuria should be carried out in pregnant IgAN patients with APO.

Knowledge, attitudes, and practices toward cardiovascular complications among end-stage renal disease patients undergoing maintenance hemodialysis.

BACKGROUND: This study aimed to investigate the knowledge, attitudes, and practices (KAP) toward cardiovascular complications among end-stage renal disease patients undergoing maintenance hemodialysis. METHODS: This web-based cross-sectional study was conducted at Guangdong Provincial People's Hospital between December 2022, and May 2023. RESULTS: A total of 545 valid questionnaires were collected, with an average age of 57.72 ± 13.47 years. The mean knowledge, attitudes and practices scores were 8.17 ± 2.9 (possible range: 0-24), 37.63 ± 3.80 (possible range: 10-50), 33.07 ± 6.10 (possible range: 10-50) respectively. Multivariate logistic regression analysis showed that patients from non-urban area had lower knowledge compared to those from urban area (odds ratio (OR) = 0.411, 95% CI: 0.262-0.644, P < 0.001). Furthermore, higher levels of education were associated with better knowledge, as indicated by OR for college and above (OR = 4.858, 95% CI: 2.483-9.504), high school/vocational school (OR = 3.457, 95% CI: 1.930-6.192), junior high school (OR = 3.300, 95% CI: 1.945-5.598), with primary school and below as reference group (all P < 0.001). Besides, better knowledge (OR = 1.220, 95% CI: 1.132-1.316, P < 0.001) and higher educational levels were independently associated with positive attitudes. Specifically, individuals with a college degree and above (OR = 2.986, 95% CI: 1.411-6.321, P = 0.004) and those with high school/vocational school education (OR = 2.418, 95% CI: 1.314-4.451, P = 0.005) have more positive attitude, with primary school and below as reference group. Next, better attitude (OR = 1.174, 95% CI: 1.107-1.246, P < 0.001) and higher education were independently associated with proactive practices. Those with college and above (OR = 2.870, 95% CI: 1.359-6.059, P = 0.006), and those with high school/vocational school education (OR = 1.886, 95% CI: 1.032-3.447, P = 0.039) had more proactive practices, with primary school and below as reference group. CONCLUSIONS: End-stage renal disease patients undergoing maintenance hemodialysis demonstrated insufficient knowledge, positive attitudes, and moderate practices regarding cardiovascular complications. Targeted interventions should prioritize improving knowledge and attitudes, particularly among patients with lower educational levels and income, to enhance the management of cardiovascular complications in end-stage renal disease.

Factors associated with dysfunction of autogenous arteriovenous fistula in patients with secondary hyperparathyroidism after parathyroidectomy.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a prevalent chronic complication in patients undergoing hemodialysis. Parathyroidectomy (PTX) is crucial for reducing mortality and improving the prognosis in the treatment of refractory hyperparathyroidism. However, it is often associated with a number of postoperative complications such as postoperative hypotension, hyperkalemia, and hungry bone syndrome. A previous study demonstrated that low blood pressure influences the patency of autogenous arteriovenous fistulas (AVF). Few studies have examined AVF dysfunction following PTX. This study aimed to identify and describe the risk variables associated with AVF dysfunction after PTX. METHODS: Cases of AVF dysfunction after PTX between 2015 and 2021 were studied. Four controls were identified for each patient and were matched for sex and age. Biochemical parameters and blood pressure of the patients before and after PTX were recorded. Risk factors for AVF dysfunction after PTX were identified using conditional logistic regression analysis. RESULTS: Sixteen patients and 64 controls were included in this study. Baseline demographic and laboratory data were compared. Patients in the AVF dysfunction group had lower levels of postoperative calcium than the controls. After surgery, calcium levels decreased more in patients with AVF dysfunction than in the control group. The decrease in systolic blood pressure (ΔSBP) after PTX was greater in the AVF dysfunction group than that in the control group. For each 1 mmHg increment in ΔSBP, the risk of AVF dysfunction after surgery increased by 11.6% (OR = 1.116, 95% CI, 1.005-1.239, p = .040). The likelihood of developing AVF dysfunction after surgery was twelvefold higher in diabetic patients than in non-diabetic patients (OR = 12.506, 95% CI, 1.113-140.492, p = .041). Among patients with ΔSBP > 5.8 mmHg after PTX, the AVF failure rate was significantly greater in patients with diabetes than in those without diabetes. Patients with a history of AVF failure had a nine-fold higher risk of developing AVF dysfunction (OR = 9.143, 95% CI, 1.151-72.627, p = .036). Serum albumin, hemoglobin, ΔiPTH, and age were not independent predictors of AVF dysfunction. The cutoff value for SBP was 5.8 mmHg, as determined by the Youden index of the receiver operating characteristic curve. CONCLUSION: Decreased systolic blood pressure (ΔSBP) after PTX, diabetes, and AVF failure history were risk factors for AVF dysfunction following PTX in patients with SHPT. Diabetes patients with ΔSBP > 5.8 mmHg were more prone to AVF dysfunction after PTX.

Roxadustat Improves Erythropoietin Antibody-Mediated Pure Red Cell Aplasia in a Patient with Hemodialysis.

Anemia is a common complication of chronic kidney disease (CKD). Recombinant human erythropoietin (rHu-EPO) is used extensively in patients with CKD. However, anti-erythropoietin (anti-EPO) antibody has been reported during rHu-EPO treatment, which causes pure red cell aplasia (PRCA). We presented a case of 75-year-old man, who underwent hemodialysis for 2 years. He developed PRCA during rHu-EPO treatment. The rHu-EPO was immediately discontinued, and the patient was given roxadustat treatment. After 6 months of roxadustat treatment, the anti-EPO antibody was disappeared, and hemoglobin recovered normal range. The results suggest that roxadustat can be used to treat patients with anti-EPO antibody-mediated PRCA without immunosuppressive therapy.

Pharmacokinetics and Pharmacodynamics of Sacubitril/Valsartan in Maintenance Hemodialysis Patients with Heart Failure.

BACKGROUND: Heart failure (HF) is one of the main comorbidities in patients receiving maintenance hemodialysis (HD). Sacubitril/valsartan (SAC/VAL) is widely used in HF patients with reduced ejection fraction (HFrEF) or HF mid-range ejection fraction (HFmrEF). However, the pharmacokinetic (PK) and pharmacodynamic properties of SAC/VAL in HD patients with HF remain uncertain. OBJECTIVES: This study aimed to analyze the efficacy and PK properties of SAC/VAL in HD patients with HFrEF or HFmrEF. METHODS: HD patients with HFrEF or HFmrEF were treated with SAC/VAL 50 or 100 mg twice a day (BID) and the concentrations of valsartan and LBQ657 (active metabolite of SAC) were determined by high-performance liquid chromatography-tandem mass spectrometry during HD and on the days between HD sessions (interval days). N-terminal-pro B-type natriuretic peptide and high-sensitivity troponin T were measured, and left ventricular ejection fraction (LVEF) was evaluated by echocardiography. RESULTS: The mean maximum plasma concentrations (Cmax) of LBQ657 and VAL on the interval days were 15.46 ± 6.01 and 2.57 ± 1.23 mg/L, respectively. Compared with previous values in patients with severe renal impairment and healthy volunteers, these levels both remained within the safe concentration ranges during treatment with SAC/VAL 100 mg BID. Moreover, SAC/VAL significantly improved LVEF in HD patients with HFrEF or HFmrEF (p < 0.05). CONCLUSIONS: HD did not remove the SAC metabolite LBQ657 or VAL in patients with HF. However, SAC/VAL 100 mg BID was safe and effective in patients undergoing HD.

Receptor activator of NF-κB mediates podocyte injury in diabetic nephropathy.

Receptor activator of NF-κB (RANK) expression is increased in podocytes of patients with diabetic nephropathy. However, the relevance of RANK to diabetic nephropathy pathobiology remains unclear. Here, to evaluate the role of podocyte RANK in the development of diabetic nephropathy, we generated a mouse model of podocyte-specific RANK depletion (RANK-/-Cre T), and a model of podocyte-specific RANK overexpression (RANK TG), and induced diabetes in these mice with streptozotocin. We found that podocyte RANK depletion alleviated albuminuria, mesangial matrix expansion, and basement membrane thickening, while RANK overexpression aggravated these indices in streptozotocin-treated mice. Moreover, streptozotocin-triggered oxidative stress was increased in RANK overexpression but decreased in the RANK depleted mice. Particularly, the expression of NADPH oxidase 4, and its obligate partner, P22phox, were enhanced in RANK overexpression, but reduced in RANK depleted mice. In parallel, the transcription factor p65 was increased in the podocyte nuclei of RANK overexpressing mice but decreased in the RANK depleted mice. The relevant findings were largely replicated with high glucose-treated podocytes in vitro. Mechanistically, p65 could bind to the promoter regions of NADPH oxidase 4 and P22phox, and increased their respective gene promoter activity in podocytes, dependent on the levels of RANK. Taken together, these findings suggested that high glucose induced RANK in podocytes and caused the increase of NADPH oxidase 4 and P22phox via p65, possibly together with the cytokines TNF- α, MAC-2 and IL-1 ß, resulting in podocyte injury. Thus, we found that podocyte RANK was induced in the diabetic milieu and RANK mediated the development of diabetic nephropathy, likely by promoting glomerular oxidative stress and proinflammatory cytokine production.

Effect of Hemodialysis on Efficacy and Pharmacokinetics of Sofosbuvir Coformulated with Either Daclatasvir or Ledipasvir in Patients with End-Stage Renal Disease.

BACKGROUND/AIMS: Direct-acting antivirals (DAAs) play a key role in the eradication of hepatitis C virus (HCV) infection. However, limited data are available on DAA for treating HCV infection in hemodialysis (HD) patients. This study was to evaluate the pharmacokinetic characteristics and effectiveness of daclatasvir/sofosbuvir (DAC/SOF) and ledipasvir/SOF (LDV/SOF) in HD patients. METHODS: Seven patients were given SOF coadministered with DAC or LDV once daily for 12 weeks. The plasma concentrations of SOF007, DAC, and LDV were determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. RESULTS: A sustained virologic response in week 12 (SVR12) was achieved in 6 (100%) patients, except for 1 patient dying due to severe cerebral hemorrhage not related to antiviral therapy. The extraction ratio of SOF007 was 66.67%, and the estimated HD clearance of SOF007 was 5.65 L/h. CONCLUSION: The combination of SOF with either DAC or LDV is well tolerated and offers high SVR12 in HD patients.

Treatment of Uremic Tumoral Calcinosis in Maintenance Hemodialysis Patients.

BACKGROUND/AIMS: Uremic tumoral calcinosis (UTC) is a rare disease with metastatic tissue calcification in maintenance hemodialysis (HD) patients. However, limited data are available on the treatment of UTC in HD patients. This article mainly discusses the diagnostic findings and efficacy of treatment on HD patients with UTC. METHODS: A retrospective analysis was conducted based on the data of 13 cases of UTC, including their clinical features, biochemical indicators, imaging findings, diagnosis, therapeutic methods, and follow-up results. Parathyroidectomy (PTX) or drug treatment was determined based on intact parathyroid hormone (iPTH) levels and clinical symptoms. RESULTS: All 13 patients were diagnosed as UTC definitely by imaging examination. The predominant areas involved were the buttocks (4 cases, 30.77%), shoulders (4 cases, 30.77%), and elbows (3 cases, 23.08%). Based on the levels of iPTH, cases were categorized into 2 different groups: PTX treatment group was associated with high levels of iPTH, while drug treatment group (lanthanum carbonate or sevelamer with sodium thiosulfate) was associated with lower iPTH levels. After PTX treatment, there was a significant decrease in serum iPTH, calcium (Ca), phosphate (P), and alkaline phosphatase levels (p < 0.05). In drug treatment group, the serum p levels were decreased significantly, along with a finding that hemoglobin levels were increased (p < 0.05). All the UTC had lessened or even disappeared after 4-6 months treatment. CONCLUSIONS: Although most UTC patients have an increased iPTH, a small number had lower iPTH levels. Based on iPTH levels and clinical symptoms, the patients were treated with PTX or drug therapy. With proper treatment, UTC disappeared without the need for surgery to remove calcinosis tissue.

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.

Soluble Urokinase Plasminogen Activator Receptor is Associated with Coronary Artery Calcification and Cardiovascular Disease in Patients Undergoing Hemodialysis.

BACKGROUND/AIMS: Cardiovascular disease (CVD) is an important cause of morbidity and mortality in hemodialysis patients. Vascular calcification is thought to play an important role in causing CVD. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker strongly predictive of cardiovascular outcomes in the pathogenesis of diabetic patients with renal disease treated with hemodialysis. We investigated the relationship between suPAR and coronary artery calcification (CAC) in patients undergoing maintenance hemodialysis. METHODS: A total of 99 adult hemodialysis patients were enrolled in this study. Plasma samples were analyzed for suPAR with an enzyme-linked immunosorbent assay and the CAC score was determined with multidetector computed tomography. The occurrence of cardiovascular events and all-cause mortality during follow-up were recorded from January 1, 2010 to June 1, 2016. RESULTS: In 99 patients treated with maintenance hemodialysis, 91 (91.9%) had varying degrees of CAC, and suPAR correlated positively with the CAC score in a Spearman analysis. In a mean follow-up period of 33 months, 36 patients (36.4%) experienced at least one cardiovascular event. When the quartiles of suPAR concentrations were used as the cutoff points for a subgroup analysis, the incidence of CVD and all-cause mortality was much higher in the higher quartiles of suPAR. In a univariate Cox regression analysis, high suPAR was a risk factor for CVD and all-cause mortality. CONCLUSION: suPAR is associated with the CAC score and is a risk factor for new-onset CVD in patients undergoing hemodialysis.

Urinary messenger RNA of the receptor activator of NF-kappaB could be used to differentiate between minimal change disease and membranous nephropathy.

Podocyte damage and loss together have an important role in the pathogenesis and progression of glomerulonephritis. Glomerulonephritis patients and healthy controls were enrolled in this study. Biochemical, clinical and experimental procedures included measurement of total urinary protein, renal biopsy and gene expression analysis of the receptor activator of NF-kappaB (RANK). The urinary mRNA levels of RANK were significantly higher in the glomerulonephritis group compared to the controls. The urinary RANK level of glomerular subtypes was correlated significantly with proteinuria. The calculated area of RANK mRNA levels under the curve was 0.61 for minimal change disease (MCD), 0.97 for membranous nephropathy (MN), 0.65 for IgA nephropathy (IgAN), 0.70 for lupus nephritis (LN) and 0.70 for focal segmental glomerulosclerosis (FSGS). The urinary mRNA of RANK might be used to differentiate histologic subtypes of glomerulonephritis, particularly between MCD and MN.

N-acetylgalactosamine exposure of serum IgA1 was associated with glomerulosclerosis and tubular atrophy/interstitial fibrosis of IgA nephropathy patients.

AIM: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis with various histological and clinical phenotypes. N-acetylgalactosamine (GalNAc) exposure plays a pivotal role in the pathogenesis of IgAN. The aim of the current study is to investigate whether GalNAc exposure of serum IgA1 was associated with clinical and pathological manifestation of IgAN. METHODS: Sera from 199 patients with biopsy proved IgAN were collected. Clinical and pathological manifestations were collected. Biotinylated Helix aspersa were used in ELISA to examine GalNAc exposure on IgA1 molecules. Patients were divided into two groups according to the GalNAc exposure rate less or more than 0.4. RESULTS: Age, gender, and serum creatinine were comparable between the two groups. Univariate analysis showed that significantly higher urinary protein excretion rate but less severe glomerular sclerosis and tubularinterstitial fibrosis were observed in the lower GalNAc exposure group. Multivariate regression analysis demonstrated that adjusted by age and gender, the GalNAc exposure rate more than 0.4 was a risk factor of glomerular sclerosis and tubularinterstitial fibrosis, OR*(95% CI) were 2.76 (1.19-6.37) and 2.49 (1.18-5.25), respectively. CONCLUSION: Immunoglobulin A nephropathy patients with lower proteinuria had higher GalNAc exposure rates. The GalNAc exposure rate more than 0.4 was a risk factor of severe chronic renal tissue change.

Telitacicept Treatment Refractory Lupus Nephritis: A Case Report.

Introduction: Refractory lupus nephritis (LN) causes kidney disease progression and increases the risk of loss of renal function. Due to the high specificity and few side effects of biological agents, they are recommended for the treatment of systemic lupus erythematosus. There are few data on telitacicept for the treatment of refractory LN. Case Presentation: Here, we report the efficacy and safety of telitacicept in the treatment of refractory LN in a 25-year-old female patient. This patient with refractory lupus developed Pneumocystis jirovecii pneumonia while using multitargeted therapy, and the patient's urine protein was rapidly relieved after telitacicept combination with low-dose mycophenolate mofetil (MMF). Conclusion: This result suggests that telitacicept has a positive effect on refractory LN with no significant side effects. Further reports and a registry are necessary to confirm that telitacicept with low-dose MMF should be preferred in refractory LN.

LINC00355 Mediates CTNNBIP1 Promoter Methylation and Promotes Endoplasmic Reticulum Stress-Induced Podocyte Injury in Diabetic Nephropathy.

Aims: Endoplasmic reticulum stress (ER stress) plays an important role in podocyte injury in diabetic nephropathy. Wnt/ß-catenin signaling modulates ER stress, yet the epigenetic regulation of ß-catenin in ER stress and podocyte injury remains largely unknown. Herein, we tested the hypothesis that LINC00355 recruits EZH1 to the promoter region of CTNNBIP1 and trimethylates H3K4 to regulate ER-stress induced podocyte injury in DN. Results: LINC00355 is upregulated in podocytes and correlates with renal function decline in DN patients. LINC00355 localizes in the nucleus and exerts biological functions by directly binding EZH1, which epigenetically targets CTNNBIP1 through repressive trimethylation of H3K4 and activates Wnt/ß-catenin signaling and ER stress. Further, we provide mechanistic evidences that LINC00355 recruits EZH1 to the promoter region of CTNNBIP1 and regulates ER-stress induced podocyte injury in DN. Innovation and Conclusion: Our data reveal a major role of LINC00355/EZH1/CTNNBIP1 network in triggering podocyte injury, providing new evidences for understanding the role of ER stress in DN. Antioxid. Redox Signal. 39, 225-240.

Validation of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for diagnosis of suspected pulmonary infections in patients with systemic autoimmune rheumatic diseases receiving immunosuppressant therapy.

Background: The accuracy and sensitivity of conventional microbiological tests (CMTs) are insufficient to identify opportunistic pathogens in patients with systemic autoimmune rheumatic diseases (SARDs). The study aimed to assess the usefulness of metagenomic next-generation sequencing (mNGS) vs. CMTs for the diagnosis of pulmonary infections in patients with SARDs receiving immunosuppressant therapy. Methods: The medical records of 40 patients with pulmonary infections and SARDs treated with immunosuppressants or corticosteroids were reviewed retrospectively. Bronchoalveolar lavage fluid (BALF) samples were collected from all patients and examined by mNGS and CMTs. Diagnostic values of the CMTs and mNGS were compared with the clinical composite diagnosis as the reference standard. Results: Of the 40 patients included for analysis, 37 (92.5%) were diagnosed with pulmonary infections and 3 (7.5%) with non-infectious diseases, of which two were considered primary diseases and one an asthma attack. In total, 15 pathogens (7 bacteria, 5 fungi, and 3 viruses) were detected by CMTs as compared to 58 (36 bacteria, 12 fungi, and 10 viruses) by mNGS. Diagnostic accuracy of mNGS was superior to that of the CMTs for the detection of co-infections with bacteria and fungi (95 vs. 53%, respectively, p < 0.01), and for the detection of single infections with fungi (97.5 vs. 55%, respectively, p < 0.01). Of the 31 patients diagnosed with co-infections, 4 (12.9%) were positive for two pathogens and 27 (87.1%) for three or more. The detection rate of co-infection was significantly higher for mNGS than CMTs (95 vs. 16%, respectively, p < 0.01). Conclusion: The accuracy of mNGS was superior to that of the CMTs for the diagnosis of pulmonary infections in patients with SARDs treated with immunosuppressants. The rapid diagnosis by mNGS can ensure timely adjustment of treatment regimens to improve diagnosis and outcomes.

Impact of pulmonary hypertension on arteriovenous fistula failure of hemodialysis patients: A 10 years follow-up cohort study.

BACKGROUND: Pulmonary hypertension (PH) is common in patients with end-stage renal disease (ESRD). Arteriovenous fistulas (AVF) creation may involve in the pathogenesis of PH. The aim of this study was to explore the impact of PH after AVF creation on the AVF failure rate in maintenance hemodialysis (MHD) patients. METHODS: From January 1, 2009, to January 1, 2019, we retrospectively collected data of 578 MHD patients in Guangdong Provincial People's Hospital Blood Purification Center, China. Patients were followed-up until AVF failure or death or May 25, 2020. According to the systolic pulmonary artery pressure (SPAP) within 1 year after the establishment of AVF, the MHD patients were divided into three groups: SPAP ⩽ 35 mmHg, 35 < SPAP < 45 mmHg, SPAP ⩾ 45 mmHg. The primary outcome was AVF failure defined as AVF cannot complete hemodialysis. The secondary outcomes were all-cause mortality. RESULTS: A total of 578 patients were analyzed. The average age was 60.66 ± 15.34 years (58.1% men). Of these, 26.1% of patients were reported PH. The SPAP exhibited a left-skewed nonparametric distribution and the overall SPAP after the creation of AVF was 39.00 (29.00-52.00) mmHg. The median follow-up was 5.8 (5.5-6.3) years. Overall, 12.8% (74/578) patients were reported AVF failure events. There was no significant difference in AVF failure rate among three groups (p = 0.070). A total of 111 (19.2%) died during the follow-up period. Compared with the SPAP ⩽35 mmHg group, only the all-cause death rate significantly increased in MHD patients with PH (p < 0.001). CONCLUSIONS: The secondary pulmonary hypertension after AVF creation did not increase the risk of AVF failure in MHD patients, but significantly increased the risk of mortality for this portion of the patients. Future larger sample sizes, multi-center, and prospective trials are needed to make sure which type of access will benefit on their survival for MHD patients with SPAP ⩾35 mmHg.

Integrin ß3 overexpression contributes to podocyte injury through inhibiting RhoA/YAP signaling pathway.

Axis formed by integrin ß3 (ITGß3)-Ras homolog gene family, member A (RhoA), and Yes-associated protein (YAP) plays an important role in atherosclerosis. In addition, ITGß3 overexpression was noted in high-glucose (HG) exposure podocytes. However, the ITGß3-RhoA-YAP axis on HG-induced podocyte injury remains unclear. This study aimed to investigate whether ITGß3 regulates podocyte injury by regulating the RhoA-YAP axis. The function and potential mechanism of ITGß3 were observed through in vitro wound-healing assays, flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot assay. Results showed that HG treatment increased the ability of wound closure and apoptosis; however, in spite of HG treatment, ITGß3 inhibition mitigated the ability of wound closure and apoptosis in podocytes. By contrast, overexpression of ITGß3 increased the wound closure and apoptosis abilities of podocytes. Under HG treatment, ITGß3 knockdown is associated with upregulation of RhoA, total YAP1, and nucleus YAP1, whereas ITGß3 overexpression has opposite effect. In addition, RhoA overexpression in podocytes reverses the effect of ITGß3 overexpression on the wound closure and apoptosis abilities of podocytes, rescue the expression of YAP in ITGß3 overexpression podocytes. Taken together, ITGß3 overexpression promotes podocytes injury by inhibiting RhoA-YAP axis. This will provide a new clue for preventing podocyte from damage.

Predictors associated with early and late restenosis of arteriovenous fistulas and grafts after percutaneous transluminal angiography.

BACKGROUND: The objective of this study was to assess postintervention patency and analyze the predictive factors associated with early and late restenosis after intervention in hemodialysis arteriovenous fistulas (AVF) and arteriovenous grafts (AVG). METHODS: This study retrospectively analyzed 284 hemodialysis patients who underwent percutaneous transluminal angioplasty (PTA) due to AVF and AVG stenosis. A total of 350 PTA procedures were performed. Clinical, anatomical, biochemical, and technical variables were analyzed. Using univariate and multivariate analyses, we assessed the postintervention patency of PTA by follow-up, and identified the predictive factors taking into account competing risks. RESULTS: Postintervention patency rates at 3, 6, 12, and 24 months were 86.5%, 66.4%, 42.6%, and 29.8%, respectively, with a median patency duration of 11±0.71 months. Kaplan-Meier analysis showed that the patency rate of the AVF group (n=271) was dramatically higher than the AVG group (n=79) at 3, 6, and 12 months after PTA, respectively (88.9% vs. 78.5%, 69.0% vs. 57.4%, 48.8% vs. 20.0%, P<0.01). Cox survival analysis revealed that the factors associated with postintervention patency of AVF included age of fistulas, serum albumin (ALB) levels, location of stenoses, lesion length longer than 2 cm, multiple stenoses, and maximal pressure of dilatation lower than 16 atm. In addition, factors related to postintervention patency of AVG included the presence of diabetes and hypertension, and serum ALB. CONCLUSIONS: This study demonstrated that the risk factors associated with postintervention patency of AVF included age of fistulas, lower levels of serum ALB, location of stenoses, lesion length longer than 2 cm, multiple stenoses, and maximal pressure of dilatation lower than 16 atm. In addition, risk factors related to postintervention patency of AVG included the presence of diabetes and lower levels of serum ALB, while the presence of hypertension was found to be a protective factor for reducing patency loss of AVG. Among all these factors, serum ALB and multiple stenoses tended to predict early restenosis, while pressure of dilatation tended to predict late restenosis.

Thromboxane A2 is involved in the development of hypertension in chronic kidney disease rats.

Hypertension is one of the most common complications of chronic kidney disease (CKD). Some research has indicated that changes in large artery function especially caused by thromboxane A2 (TXA2) may be a novel factor acting to induce hypertension in CKD. We studied the 5/6 nephrectomy rat model and measured serum levels of creatinine (Cr), calcium (Ca), phosphorus (P), TXA2-stable metabolites (thromboxane B2, TXB2), and caudal artery pressure after nephrectomy. The tension variations in thoracic aortas were measured after stimulating by vasoconstrictor/vasodilator using the cumulative concentration administration method and then tested the expression of TXA2 receptors in the thoracic aortas through western blots. The CKD rats developed uremia, electrolyte imbalances，and hypertension. They also exhibited a significant increase in TXB2 concentration. The aortic rings of CKD rats showed an increased contraction response to U46619 (a TXA2 analogue) and the expression of TXA2 receptors also enhanced. In the meanwhile, the diastolic function decreased in the CKD group. Our results demonstrate that the impairment of artery contractile function caused by the increase of TXA2 receptors on the wall of aortic rings may be involved in hypertension in CKD rats.

Diabetic Kidney Disease Benefits from Intensive Low-Protein Diet: Updated Systematic Review and Meta-analysis.

A dietary protein intake (DPI) of between 0.6 and 0.8 g protein per kilogram body weight per day (g/kg/day) is frequently recommended for adults with moderate-to-advanced chronic kidney disease (CKD). However, evidence on whether patients with diabetic kidney disease (DKD) actually benefit from a DPI of ≤ 0.8 g/kg/day and from a low-protein diet (LPD) at CKD stages 1-3 has not been consistent. We systematically searched MEDLINE, EMBASE, Cochrane Library, Web of Knowledge, as well as the bibliographies of articles identified in the search, for eligible randomized controlled trials that had investigated the effects of LPD (prescribed DPI < 0.8 g/kg/day) versus control diet on the progression of DKD. Nine trials that included 506 participants and follow-up periods varying from 4.5 to 60 months were included in the subsequent systematic review and meta-analysis. The data showed that patients with DKD who consumed < 0.8 g protein/kg/day had a significantly reduced decline in glomerular filtration rate (GFR) (mean difference [MD] 22.31 mL/min/1.73 m2, 95% confidence interval [CI] 17.19, 27.42; P < 0.01) and a significant decrease in proteinuria (standard mean difference [SMD] - 2.26 units, 95% CI - 2.99, - 1.52; P < 0.001) versus those on the control diet. The benefits of LPD to patients with DKD at CKD stages 1-3 were a markedly decreased proteinuria (SMD - 0.96 units, 95% CI - 1.81, - 0.11; P = 0.03) and slight but significant decreases in glycated hemoglobin (- 0.42%) and cholesterol levels (- 0.22 mmol/L). Our meta-analysis indicated that a DPI of < 0.8 g/kg/day was strongly associated with a slow decline in GFR and decreased proteinuria in the patients with DKD. Patients with CKD stages CKD 1-3 benefited from LPD in terms of a marked decrease of proteinuria and slight but significant improvements in lipid and glucose control.