Risk of bullous pemphigoid and pemphigus in patients on chronic dialysis: A nationwide population-based cohort study.

Bullous pemphigoid has a high incidence among dialysis patients. However, whether or not chronic dialysis is an independent risk factor of bullous pemphigoid remains unclear. We aimed to investigate the effect of chronic dialysis on the development of bullous pemphigoid and pemphigus. We performed a retrospective cohort study using records from Taiwan's National Health Insurance Research Database between 2008 and 2019. We identified a dialysis cohort that included patients on chronic hemodialysis and peritoneal dialysis, and the hazard ratios (HRs) for bullous pemphigoid and pemphigus were compared with those of a sex-, age-, and index-matched cohort, then the results were adjusted for various confounding factors. Among 93 538 patients on chronic dialysis and 93 538 patients in the control group, 287 and 139 developed incident bullous pemphigoid, and 45 and 35 developed incident pemphigus after a median follow-up of 3.7 and 5.6 years, respectively. The incidence rates of bullous pemphigoid in the dialysis patients and the control group were 74.2 and 25.2 per 100 000 person-years, respectively (difference between groups, P < 0.0001). The incidence rates of pemphigus in the dialysis patients and the control group were 11.6 and 6.3 per 100 000 person-years, respectively (difference between groups, P < 0.01). Cox proportional hazard adjustment showed the HR for bullous pemphigoid in dialysis patients was 2.12 (95% confidence interval [CI] 1.64-2.74, P < 0.0001) compared with the control group. Dialysis patients aged <75 years had an even higher risk of bullous pemphigoid development (5- to 8-fold) than the control group. The adjusted HR for pemphigus was not elevated in dialysis patients (adjusted HR 1.52, 95% CI 0.87-2.67, P = 0.14). Chronic dialysis is an independent risk factor for developing bullous pemphigoid, but not a risk factor for pemphigus. Physicians should be aware of the predisposition of chronic dialysis patients to bullous pemphigoid.

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND: Hemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain. METHODS: To compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and sex-matched hemodialysis patients with two homologous prime-boost vaccinations were recruited to detect anti-receptor-binding domain (RBD) IgG levels and seroconversion rates (SCRs) 14 days after a prime dose (PD14), before and 28 days after a boost dose (pre-BD0 and BD28). RESULTS: Both mRNA-1273 and ChAdOx1 vaccinations elicited immunogenicity in study subjects, and the former induced higher anti-RBD IgG levels than the latter. The SCRs of both groups increased over time and varied widely from 1.82% to 97.92%, and were significantly different at PD14 and pre-BD0 regardless of different thresholds. At BD28, the SCRs of the ChAdOx1 group and the mRNA-1273 group were comparable using a threshold ≥ 7.1 BAU/mL (93.96% vs. 97.92%) and a threshold ≥ 17 BAU/mL (92.73% vs. 97.92%), respectively, but they were significantly different using a threshold ≥ 20.2% of convalescent serum anti-RBD levels (52.73% vs. 95.83%). The seroconversion (≥20.2% of convalescent level) at BD28 was associated with mRNA-1273 vaccination after being adjusted for age, sex, body mass index, and the presence of solicited reactogenicity after a prime vaccination. CONCLUSION: Our prospective, observational cohort indicates that a full prime-boost mRNA-1273 vaccination is likely to provide higher immune protection in hemodialysis patients compared to ChAdOx1, and this population with a prime-boost ChAdOx1 vaccination should be prioritized for a third dose.

Luminal pressure gradient and risk of arteriovenous fistula nonmaturation.

While arteriovenous fistula (AVF) nonmaturation is a major issue of hemodialysis care, an effective treatment to improve AVF maturation remains lacking. AVF introduces pulsatile arterial blood flow into its venous limb and produces high luminal pressure gradient, which may have adverse effect on vascular remodeling. As such, the aim of the present study is to investigate effect of luminal pressure gradient on AVF nonmaturation. This single-center, prospective observational study includes patients receiving autologous AVF creation. Participants received early postoperative ultrasound 5-7 days after surgery to collect parameters including diameters, flow rates, and volume at inflow and outflow sites. Luminal pressure gradient was estimated by using modified Bernoulli equation. The outcome was spontaneous AVF maturation within 8 weeks after surgery without intervention. Thirty patients were included, of which the mean age was 66.9 years and 70% were male. At the end of study, 13 (43.3%) patients had spontaneous AVF maturation. All demographic and laboratory characteristics were similar between patients with mature and nonmature AVF. Regarding ultrasonographic parameters, nonmature AVF showed significantly higher inflow/outflow diameter ratio, inflow velocity, and luminal pressure gradient. While these 3 parameters were significantly correlated, multivariate logistic regression showed their significant association with AVF nonmaturation. Receiver operating characteristic curve exhibited their high predictive value for AVF nonmaturation. Our findings showed that higher inflow/outflow ratio, inflow velocity, and AVF luminal pressure gradient in early postoperative ultrasound predicted risk of AVF nonmaturation. Reducing inflow/outflow diameter ratio or inflow rate may be an approach to improve AVF maturation. The predictive value of this early assessment might have impact on the clinical practice of AVF care.

The Humoral Immune Response of the ChAdOx1 nCoV-19 Vaccine in Maintenance Dialysis Patients without Prior COVID-19 Infection.

BACKGROUND: Chronic kidney disease (CKD) patients tend to have a reduced immune response to infection and vaccination. The efficacy of current available COVID-19 vaccines in CKD patients has not been widely evaluated. METHODS: In the present study, three hundred and eight chronic dialysis patients received ChAdOx1 nCoV-19 (Oxford-AstraZeneca, AZ). Blood tests using an antibody against the receptor-binding domain (RBD) of the S1 subunit of the SARS-CoV-2 spike protein had performed at four designed time points before and after the first and second vaccine. RESULTS: The mean age of patients was 65.5 ± 12.38 years, and the male/female ratio was 61.4%:38.6% (189/119). Two weeks after the first vaccination, only 37.66% of patients had a positive antibody response (>50 AU/mL). However, 65.58% of the participants showed a delayed antibody response ten weeks after the first vaccine. Four weeks after the second vaccine, 94.16% of participants had positive antibody levels. Age was the most significant factor associated with antibody response. Flow cytometry analysis revealed that immune-naïve patients had significantly lower early active B cells and proliferative B cells than the age- and sex-matched immune responders. CONCLUSION: Despite a delayed response, 94.16% of chronic dialysis patients achieved a positive antibody response after two doses of the AZ vaccine. Age is the most significant factor associated with antibody response.

Oligosaccharides Ameliorate Acute Kidney Injury by Alleviating Cluster of Differentiation 44-Mediated Immune Responses in Renal Tubular Cells.

Acute kidney injury (AKI) is a sudden episode of kidney damage that commonly occurs in patients admitted to hospitals. To date, no ideal treatment has been developed to reduce AKI severity. Oligo-fucoidan (FC) interferes with renal tubular cell surface protein cluster of differentiation 44 (CD44) to prevent renal interstitial fibrosis; however, the influence of oligosaccharides on AKI remains unknown. In this study, FC, galacto-oligosaccharide (GOS), and fructo-oligosaccharide (FOS) were selected to investigate the influence of oligosaccharides on AKI. All three oligosaccharides have been proven to be partially absorbed by the intestine. We found that the oligosaccharides dose-dependently reduced CD44 antigenicity and suppressed the hypoxia-induced expression of CD44, phospho-JNK, MCP-1, IL-1ß, and TNF-α in NRK-52E renal tubular cells. Meanwhile, CD44 siRNA transfection and JNK inhibitor SP600125 reduced the hypoxia-induced expression of phospho-JNK and cytokines. The ligand of CD44, hyaluronan, counteracted the influence of oligosaccharides on CD44 and phospho-JNK. At 2 days post-surgery for ischemia-reperfusion injury, oligosaccharides reduced kidney inflammation, serum creatine, MCP-1, IL-1ß, and TNF-α in AKI mice. At 7 days post-surgery, kidney recovery was promoted. These results indicate that FC, GOS, and FOS inhibit the hypoxia-induced CD44/JNK cascade and cytokines in renal tubular cells, thereby ameliorating AKI and kidney inflammation in AKI mice. Therefore, oligosaccharide supplementation is a potential healthcare strategy for patients with AKI.

Inhibition of ß-catenin signaling attenuates arteriovenous fistula thickening in mice by suppressing myofibroblasts.

BACKGROUND: Arteriovenous fistula (AVF) is the most important vascular access for hemodialysis; however, preventive treatment to maintain the patency of AVFs has not been developed. In endothelium, ß-catenin functions in both the intercellular adherens complex and signaling pathways that induce the transition of endothelial cells to myofibroblasts in response to mechanical stimuli. We hypothesize that mechanical disturbances in the AVF activate ß-catenin signaling leading to the transition of endothelial cells to myofibroblasts, which cause AVF thickening. The present study aimed to test this hypothesis. METHODS: Chronic kidney disease in mice was induced by a 0.2% adenine diet. AVFs were created by aortocaval puncture. Human umbilical vein endothelial cells (HUVECs) were used in the cell experiments. A pressure-culture system was used to simulate mechanical disturbances of the AVF. RESULTS: Co-expression of CD31 and smooth muscle alpha-actin (αSMA), loss of cell-cell adhesions, and the expression of the myofibroblast marker, integrin subunit ß6 (ITGB6), indicated transition to myofibroblasts in mouse AVF. Nuclear translocation of ß-catenin, decreased axin2, and increased c-myc expression were also observed in the AVF, indicating activated ß-catenin signaling. To confirm that ß-catenin signaling contributes to AVF lesions, ß-catenin signaling was inhibited with pyrvinium pamoate; ß-catenin inhibition significantly attenuated AVF thickening and decreased myofibroblasts. In HUVECs, barometric pressure-induced nuclear localization of ß-catenin and increased expression of the myofibroblast markers, αSMA and ITGB6. These changes were attenuated via pretreatment with ß-catenin inhibition. CONCLUSIONS: The results of this study indicate that mechanical disturbance in AVF activates ß-catenin signaling to induce the transition of endothelial cells to myofibroblasts. This signaling cascade can be targeted to maintain AVF patency.

Tuberculosis treatment delay and nosocomial exposure remain important risks for patients undergoing regular hemodialysis.

BACKGROUND AND OBJECTIVE: Studies have reported an increased tuberculosis (TB) incidence among patients with end-stage renal disease (ESRD). This nationwide nested Case-control study investigated the risk of active TB due to nosocomial exposure and its correlation with the delay in TB treatment in hemodialysis patients. METHODS: Adult (aged ≥20 years) patients with incident ESRD over 2000-2010 were identified from Taiwan National Health Insurance Research Database; 2331 patients with incident active TB (Case) were matched with 11,655 patients without TB (control) by age, sex, year of ESRD onset, Charlson comorbidity index, chronic obstructive pulmonary disease, and diabetes mellitus, at a 1:5 case-to-control ratio. RESULTS: Compared with the control group, the Case group had greater nosocomial exposure to index patients with pulmonary TB (2.36 vs. 0.11 month of exposure, p < 0.001). Nosocomial exposure increased active TB risk (adjusted odds ratio [OR; 95% confidence interval, CI]: 1.60 [1.55-1.66] per month of exposure), particularly when the exposure time was either within 6 months before the index case was diagnosed or 6-15 months before the ESRD patient became an incident active TB case. For patients with active TB, cough-related medication prescriptions (proxy for cough symptoms) exponentially increased over 6 months before TB treatment. CONCLUSION: Nosocomial exposure attributed to delay in the diagnosis of index pulmonary TB is important in TB transmission among patients undergoing regular hemodialysis. Additional studies investigating how TB can be diagnosed and treated early are warranted. SUMMARY AT A GLANCE: Our study revealed that nosocomial exposure, attributed to delay in pulmonary TB diagnosis, is important in TB transmission among patients undergoing regular hemodialysis. Strategies to diagnose and treat TB early are crucial to infection control, and they warrant further investigations.

Hemodialysis acutely altered interferon-gamma release assay test result and immune cell profile.

Patients receiving hemodialysis (HD) are at risk of TB development. IGRA-positive patients showed significant decrease in quantitative IGRA result with alterations in CD3+CD4+CD45RO+, NK cell, and monocyte subsets immediately upon HD procedure. Our result suggested that the timing of IGRA testing is crucial in end-stage renal disease population.

Gender and Age Differences of Genitourinary Cancers Among Chronic Dialysis Patients in Taiwan.

BACKGROUND: To investigate the age and gender differences among chronic dialysis patients who developed genitourinary cancers in Taiwan. PATIENTS AND METHODS: Incident hemodialysis patients aged 20 years or older were selected for retrospective cohort study from the National Health Insurance Research Database between 2002 and 2015, and the Taiwan Cancer Registry Database between 2007 and 2015. A two-step approach was employed to find the respective matched controls of non-dialysis patients. Finally, 65,450 dialysis patients and 261,800 non-dialysis patients were matched for further analysis. New diagnosis of genitourinary cancers during follow-up was the primary outcome of interest. RESULTS: Dialysis was significantly associated with increased risk of all types of genitourinary cancers (P < .001), substantially within the first two years after dialysis initiation. Cox proportional hazard analysis showed a significantly increased hazard ratio (HR 6.58, 95% CI 6.05-7.16) among dialysis patients after multivariate adjustment, and the highest risk was bladder cancer (HR 7.85, 95% CI 6.97-8.84). Subgroup analysis showed younger dialysis patients (20-49 years old) had the highest risk of genitourinary cancer, especially females, in this subgroup with the highest risk of bladder cancer (HR 58.08, 95% CI 13.88-243.06). CONCLUSION: The risks of all site-specific genitourinary cancers were increased in chronic dialysis patients, especially in younger females. Developing different screening strategies for these high-risk patients is necessary. MICRO ABSTRACT: This study compared the effect of sex, age and dialysis duration on the susceptibility to develop genitourinary cancers in dialysis patients through the national health database linkage in Taiwan. We matched 65,450 dialysis patients and 261,800 non-dialysis patients for further analysis. Younger and female dialysis patients were at higher risk of kidney and bladder cancers.

Renal protective effect of sacubitril/valsartan in patients with heart failure.

Sacubitril/valsartan is a combined neprilysin inhibitor/angiotensin II receptor blocker designed for treatment of heart failure (HF). Nonetheless, its renal protective effect remained an issue of debate. This retrospective cohort study investigated the renal protective effect of sacubitril/valsartan in HF patients. HF patients on sacubitril/valsartan or valsartan for > 30 days were matched for gender, age, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF) to be enrolled into analysis. The follow-up period was 18 months. The outcomes included end eGFR, renal function decline defined as 20% reduction of eGFR, mortality, and HF-related hospitalization. Each group had 137 patients after matching. The mean age was 72.7 years and 65.7% were male. Mean eGFR was 70.9 mL/min/1.73 m2 and LVEF was 54.0% at baseline. Overall, the eGFR of sacubitril/valsartan groups was significantly higher than valsartan group at the end (P < 0.01). Subgroup analysis showed that the difference in eGFR was significant in subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2. Multivariate Cox regression model showed that sacubitril/valsartan group had significantly reduced risk for renal function decline (hazard ratio: 0.5, 95% confidence interval: 0.3-0.9). Kaplan-Meier curve showed no difference in the risk for cardiovascular mortality, all-cause mortality or HF-related hospitalization. We showed renal protective effect of neprilysin inhibition in HF patients and specified that subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2 were sensitive to this effect, suggesting an optimal subgroup of this treatment.

Parathyroid Hormone Induces Transition of Myofibroblasts in Arteriovenous Fistula and Increases Maturation Failure.

CONTEXT: Arteriovenous fistula (AVF) maturation failure remains a clinical dilemma, and its pathobiology is largely unclear. Secondary hyperparathyroidism is a complication of chronic renal failure that is associated with cardiovascular disease. While parathyroid hormone (PTH) has a prosclerotic effect on vascular smooth muscle cells (VSMCs), its role in AVF maturation failure remained unknown. OBJECTIVE: This work aimed to investigate the association between plasma PTH and AVF maturation. METHODS: Patients receiving AVF creation were enrolled retrospectively. A mouse model of secondary hyperparathyroidism and aortocaval AVF was used to investigate the effect of PTH on an AVF lesion. A cell model of VSMCs treated with PTH in a pressurized culture system was used to disclose the signaling pathway underlying the effect of PTH on an AVF lesion. RESULTS: In patients receiving AVF creation, higher PTH was associated with an increased risk for maturation failure. In a mouse model, vascular wall thickness and myofibroblasts of AVF significantly increased with higher PTH. When the same mice were treated with cinacalcet, AVF lesions were attenuated by suppression of PTH. A cell model showed that PTH increased the marker of myofibroblasts, integrin ß6 subunit (ITGB6), via the phosphorylated protein kinase B pathway. Finally, in the same model of mice AVF, higher PTH also increased the expression of ITGB6 in the smooth muscle layer of AVF, suggesting the transition to myofibroblast. CONCLUSION: Overall, our results suggest that higher PTH increased the risk of AVF maturation failure through increasing the transition of VSMCs to myofibroblasts. Lowering PTH may be a strategy to enhance AVF maturation.

Combined protective effects of oligo-fucoidan, fucoxanthin, and L-carnitine on the kidneys of chronic kidney disease mice.

Chronic kidney disease (CKD) is a common global progressive disease, but there are no ideal drugs for the treatment. Fucoidan and fucoxanthin, and L-carnitine are one of the very few natural products that have a therapeutic effect on CKD in animal experiments. However, the combined effects of these compounds on CKD are unknown. We established a mouse CKD model by right nephrectomy with transient ischemic injury to the left kidney. Oligo-fucoidan and fucoidan were extracted from Laminaria japonica. We fed CKD mice with the two compounds and L-carnitine to evaluate the combined effects on CKD. Oligo-fucoidan and fucoidan inhibited renal fibrosis and reduced serum creatine in CKD mice to a greater extent than any single compound. L-carnitine had no measurable effect on renal fibrosis but promoted the protective effect of the mixture of oligo-fucoidan and fucoidan on renal function in CKD mice. In the two-month safety test, the combined mixture further improved renal function and did not elevate serum aspartate aminotransferase and alanine aminotransferase levels in CKD mice. Furthermore, the weights of CKD mice treated with the combination increased to the normal level. We also found that all oligo-fucoidan, fucoxanthin, and L-carnitine inhibit H2O2-induced apoptosis and activated Akt in rat renal tubular cells. Our results confirm that oligo-fucoidan, fucoxanthin, and L-carnitine have a combined protective effect on the kidneys. The combined mixture may be beneficial for CKD patients.

Effects of cardiovascular medications on primary patency of hemodialysis arteriovenous fistula.

While the patency of vascular access is essential for hemodialysis patients, optimal pharmaceutical treatment to maintain arteriovenous fistula (AVF) patency remains lacking. As cardiovascular diseases are highly prevalent in patients with end-stage renal disease, various cardiovascular medications have also been used to maintain AVF patency. However, previous studies revealed inconsistent therapeutic effects and a comprehensive evaluation of this issue is needed. The present retrospective, longitudinal cohort study included patients receiving successful AVF creation. The evaluated cardiovascular medications included antiplatelet agents, antihypertensive agents, nitrates and nitrites, statins, dipyridamole, and pentoxifylline. The outcome was AVF primary patency. All laboratory data and medication profiles were recorded at baseline and followed at 3-month interval, until the end of the 2-year study period. Cox proportional regression model with time-dependent covariates was used to evaluate the risk for AVF patency loss. A total of 349 patients were included in the present study, in which 57% were men and the mean age was 65 ± 14 years. Among the included patients, 40% used antiplatelet agents, 27% used dipyridamole and 36% used statins at baseline. Of all the evaluated cardiovascular medications, only dipyridamole showed significant association with a higher risk for loss of AVF patency. To evaluate the effect of combination of antiplatelet agents and dipyridamole, the patients were classified into four groups, I: combine use of antiplatelet agents and dipyridamole, II: antiplatelet only, III: dipyridamole only; IV: none of both were used. Of the four groups, group IV exhibited highest AVF patency (52.4%), which was followed by group III (42.7%), group II (40%), and group I (28.6%), respectively. Compared with group IV, only group I showed a significantly higher risk for AVF patency loss. None of the cardiovascular medications evaluated in the present study showed a beneficial effect on AVF patency. Furthermore, dipyridamole showed an association with a higher risk of AVF patency loss. We do not suggest a beneficial effect of dipyridamole on maintaining AVF patency, particularly in combination with antiplatelet agents.

Author Correction: Simvastatin reduces the carcinogenic effect of 3-methylcholanthrene in renal epithelial cells through histone deacetylase 1 inhibition and RhoA reactivation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The influence of atrial fibrillation on the mortality of incident ESRD patients undergoing maintenance hemodialysis.

BACKGROUND: Atrial fibrillation (AF) is highly prevalent, occurring in 1%-2% of the adult population, increasing the risk of stroke, and resulting in considerable healthcare costs. While stroke is a major complication of AF, end-stage renal disease (ESRD) patients also have a high risk of stroke, suggesting that AF is a possible risk factor for mortality of ESRD patients. However, whether the existence of AF at the initiation of hemodialysis predicts higher mortality risk of incident ESRD patients remains to be defined. METHODS: This retrospective cohort study was performed at Wanfang Hospital from January 2004 to May 2018. The end points were mortality of patients or the end of the study. Incident ESRD patients who were on maintenance hemodialysis for more than 3 months were eligible for inclusion. Cox proportional regression and Kaplan-Meier survival curves were used to determine the association between predictors and mortality. The association between AF and echocardiographic parameters, causes of death were also investigated. RESULTS: Of the 393 incident ESRD patients at initiation of hemodialysis, 57 (14.5%) had AF and the median age was 71 years. Patients with AF were significantly older; showed significantly higher C-reactive protein levels, more heart failure, chronic obstructive pulmonary disease and mortality. Multivariate Cox regression showed that AF had a hazard ratio of 4.1 (95% confidence interval: 2.4-7.0) for mortality. Age-specific analysis showed that AF was significantly associated with mortality in all age groups. Echocardiography measurements including ejection fraction and left ventricular hypertrophy (LVH) were similar in AF and non-AF patients. Cause-specific analysis showed that AF significantly associated with overall cardiovascular death and death due to acute myocardial infarction/coronary artery disease and sepsis. CONCLUSIONS: AF at the initiation of hemodialysis predicts higher mortality risk of incident ESRD patients regardless of age. The systolic function and degree of LVH were similar in AF and non-AF patients. The association between AF and sepsis-related death suggested the role of systemic inflammation on the pathogenesis of AF.

Increased Risk of Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients and Patients on Chronic Dialysis: A Cancer Registry-based Study in Taiwan.

This study investigated the predominant skin cancer subtype among organ transplant recipients, patients on chronic dialysis, and patients with chronic kidney disease in Asian subjects. Among 23,644 patients with skin cancer, identified from Taiwan Cancer Registry Database, 53 were organ transplant recipients, 255 were on chronic dialysis, 1,792 had chronic kidney disease, and 21,544 were in the control group. The proportions of squamous cell carcinoma were 52.8%, 47.8%, 40.1%, and 33.5%, respectively. Compared with the control group, organ transplant recipients (1.99-fold) and patients on chronic dialysis (1.25-fold) were at higher risk of developing squamous cell carcinoma than other skin cancers after adjustment for potential confounders. Subgroups or covariates associated with increased squamous cell carcinoma compared with other skin cancer risk included patients with chronic kidney disease aged < 70 years (vs. control group; 1.3-fold), old age (vs. young age; 2.8-fold), male sex (vs. female sex; 1.1-fold), and south Taiwan residency (vs. north Taiwan residency; 1.1-fold). Organ transplant recipients and patients on chronic dialysis had immune dysregulation, resulting in a higher risk of squamous cell carcinomas.

Study protocol for a prospective observational study to investigate the role of luminal pressure on arteriovenous fistula maturation.

INTRODUCTION: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis due to its higher patency and lower infection rate. However, its suboptimal maturation rate is a major weakness. Although substantial risk factors for AVF maturation failure have been disclosed, modifiable risk factors remain unknown. During the AVF maturation process, an elevated luminal pressure is required for outward remodeling; however, excessively high luminal pressure may also be detrimental to AVF maturation, which remains to be defined. We hypothesized that higher AVF luminal pressure is harmful to its maturation, and investigate its potential as a modifiable factor to improve AVF maturation. METHODS AND ANALYSIS: This prospective study includes patients undergoing surgical creation for a native AVF. The exclusion criteria were as follows: age <20 years, inability to sign an informed consent, and failure to create a native AVF due to technical difficulties. Demographic and laboratory profiles will be collected before AVF surgery. Vascular sonography will be performed within 1 week of AVF creation to measure the diameters, flow rates, and flow volumes of AVF and its branched veins. The pressure gradient within AVF will be estimated from the blood flow rates using the modified Bernoulli equation. The primary outcome is spontaneous AVF maturation defined as provision of sufficient blood flow for hemodialysis within 2 months of its creation without any interventional procedures. The secondary outcome is assisted AVF maturation, which is defined as AVF maturation within 2 months from its creation aided by any interventional procedure before the successful use of AVF. DISCUSSION: While contemporary theory for AVF maturation failure focuses on disturbed wall shear stress, complicate assumptions and measurement preclude its clinical applicability. AVF luminal pressure, which may be manipulated pharmaceutically and surgically, may be a target to improve the outcome of AVF maturation. TRIAL REGISTRATION: This study has been registered at the protocol registration and results system. The Protocol ID: NCT04017806.

Point of Care eGFR and the Prediction of Outcomes in Pneumonia.

Pneumonia is a leading cause of mortality. Severity-assessment scores in pneumonia guide treatment crucially, but the ones currently in existence are limited in their use. Community-based studies demonstrated the association between pre-existing low estimated glomerular filtration rate (eGFR) and outcomes in pneumonia. However, whether a single emergency department-eGFR measurement could predict outcomes in pneumonia remains unclear. This retrospective cohort study included 1554 patients hospitalized with pneumonia. The predictor was the first eGFR measurement. Outcomes included mortality, intensive care unit (ICU) admission, durations of hospital and ICU stay, and ventilator use. Receiver operating characteristic curves was used to determine optimal cutoff values to predict mortality. Of 1554 patients, 263 had chronic kidney disease, demonstrated higher C-reactive protein and SMART-COP scores, and had more multilobar pneumonia, acute kidney injury, ICU admission, and mortality. Patients with higher pneumonia severity scores tended to have lower eGFR. For predicting in-hospital mortality, the optimal eGFR cutoff value was 56 mL/min/1.73 m2. eGFR < 56 mL/min/1.73 m2 had an odds ratio of 2.5 (95% confidence interval, 1.6-4.0) for mortality by multivariate logistic regression. In Conclusion, eGFR < 56 mL/min/1.73 m2 is an independent predictor of mortality, indicating that even mild renal impairment affects the outcome of pneumonia adversely.

Microbial etiology of pneumonia in patients with decreased renal function.

BACKGROUND: Patients with renal impairment have altered immunity, which might cause vulnerability to specific pathogens and worsen pneumonia-related outcomes. Nonetheless, the microbiological features of pneumonia in patients with decreased renal function remain unknown. METHODS: Therefore, we conducted a retrospective cohort study enrolling adult patients hospitalized with pneumonia to assess this knowledge gap. The baseline estimated glomerular filtration rate (eGFR) and first sputum microbiology during hospitalization were used for statistical analyses. RESULTS: Overall, 1554 patients hospitalized with pneumonia (mean age, 76.1 ± 16.7) were included, and 162 patients had died at the end of hospitalization. The cutoff eGFR value predicting mortality was <55 mL/min/1.73 m2, which defined decreased renal function in this study. Patients with decreased renal function demonstrated a significantly higher risk of fungi and Staphylococcus aureus (S. aureus) infection. On the other hand, this group of patients showed significantly higher neutrophil-to-lymphocyte ratio (NLR), which associated with higher mortality. Additionally, patients with S. aureus had a significantly lower eGFR, lymphocyte count and a higher NLR. CONCLUSIONS: These findings suggested the altered immunity and vulnerability to S. aureus infection in patients with decreased renal function, which may be the underlying cause of worse outcomes of pneumonia in this group of patients.