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.

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.

Exercise Alleviates Osteoporosis in Rats with Mild Chronic Kidney Disease by Decreasing Sclerostin Production.

Chronic kidney disease-mineral bone disorder (CKD-MBD), comprising mineral, hormonal, and bone metabolic imbalance, is a major CKD-related issue; it causes osteoporosis prevalence in CKD patients. Osteocyte-derived sclerostin inhibits the osteogenic Wnt/ß-catenin signaling pathway; its levels rise when kidney function declines. Exercise modulates the physiological functions of osteocytes, potentially altering sclerostin production. It may aid bone and mineral electrolyte homeostasis in CKD. Mild CKD was induced in rats by partial nephrectomy. They were divided into: sham (no CKD), CKD, and CKD + exercise (8 weeks of treadmill running) groups. Micro-CT scanning demonstrated that the CKD + exercise-group rats had a higher bone mineral density (BMD) of the spine and femoral metaphysis and higher femoral trabecular bone volume than the CKD-group rats. Bone formation rates were not significantly different. The CKD + exercise-group rats had lower serum sclerostin (157.1 ± 21.1 vs 309 ± 38.1 pg/mL, p < 0.05) and CTX-1 (bone resorption marker) levels. Immunohistochemistry revealed higher tibial ß-catenin concentrations in the CKD + exercise-group rats. Serum FGF-23, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, and phosphate levels showed no significant differences between these groups. Thus, exercise improves BMD and bone microstructure in mild CKD by inhibiting sclerostin production, but does not alter serum minerals.

Risk of Non-melanoma Skin Cancer in Patients with Chronic Kidney Disease and its Relationship to Uraemic Pruritus.

This study investigated the risk of non-melanoma skin cancer (NMSC) in pre-dialysis patients with chronic kidney disease (CKD) and explored associated risk factors. A population-based cohort of 1,515,858 Taiwanese CKD patients was included. The standardized incidence ratio (SIR) for incident NMSC was determined. Compared with the general population, a 1.14-fold risk of NMSC was found in the CKD cohort. NMSC risk was significant in patients with pre-dialysis stage 5 CKD and anaemia (1.48-fold), and in those with uraemic pruritus after long-term antihistamine treatment (1.38-fold). A higher SIR for NMSC was found in younger patients with CKD (age < 70 years, 1.34-fold; age 20-39 years, 1.63-fold), stage 5 CKD with anaemia (age < 70 years, 2.09-fold), and uraemic pruritus (age <70 years, 2.22-fold). Pre-dialysis patients with CKD are at higher risk of NMSC, especially those with advanced-stage CKD, and those with uraemic pruritus.

Effect of pulmonary tuberculosis on clinical outcomes of long-term dialysis patients: Pre- and post-DOTS implementation in Taiwan.

BACKGROUND AND OBJECTIVE: The link between tuberculosis (TB) and dialysis is known; however, the impact of TB on the clinical outcomes remains to be elucidated. This study aims to determine the clinical consequences of pulmonary TB among patients under long-term dialysis. METHODS: A retrospective propensity-scores matched (1:4) cohort study was conducted by retrieving patient data for pulmonary TB after long-term dialysis commencement from the Taiwan National Health Insurance Research Database between 1999 and 2013. Patients with TB (n = 1993) or without TB (n = 7972) were compared for 3-year morbidity and mortality. The effect of Directly Observed Treatment, Short-Course (DOTS) implementation was also evaluated. Cox proportional hazards models were used to determine adjusted hazard ratios (HRs). RESULTS: TB patients had a significantly higher risk of mortality than non-TB patients even after multivariate adjustment (HR: 1.48; 95% CI: 1.36-1.60; P < 0.001). DOTS implementation reduced the risk of some morbidities such as pneumonia, hospitalization and intensive care unit stay >7 days, but not inotropic agent usage, ventilator therapy >21 days and mortality in TB patients. In pulmonary TB patients with treatment duration ≥180 days, DOTS implementation also lowered the risk of TB relapse (HR: 0.33; 95% CI: 0.19-0.55; P < 0.001), irrespective of treatment duration (180-224 or ≥225 days). CONCLUSION: Pulmonary TB increases the risk of morbidity and mortality in dialysis patients; DOTS implementation reduces some morbidities and TB relapse. Continuing DOTS implementation should be encouraged to improve clinical outcomes in dialysis patients.

Effects of tattoo ink's absorption spectra and particle size on cosmetic tattoo treatment efficacy using Q-switched Nd:YAG laser.

The mechanisms responsible for variable responses of cosmetic tattoos to Q-switched laser removal treatment remain unclear. We sought to investigate the properties of tattoo inks that may affect the efficacy of laser-assisted tattoo removal. The absorption of white, brown, and black inks before and after Q-switched neodymium-doped yttrium aluminum garnet laser irradiation were analyzed by a reflectance measurement system. Rats were tattooed using the three inks and treated with the same laser for two sessions. Skin biopsies were taken from the treated and untreated sites. Black ink showed strong absorption, reduced after laser irradiation, over the entire spectrum. White ink had low absorption over the visible light spectrum, and brown ink had strong absorption at 400-550 nm wavelengths. White and brown inks turned dark after laser exposure, and the absorption of laser-darkened inks were intermediate between their original color and black ink. White, brown, and black tattoos in rat skin achieved poor, fair to good, and excellent responses to laser treatment, respectively. Transmission electron microscopy showed that white tattoo particles were the largest, brown were intermediate, and black were the smallest before laser. After laser treatment, white and brown tattoo particles were mixtures of large and small particles, while black particles showed overall reduction in number and size. Black tattoo ink's excellent response to Q-switched lasers was associated with its strong absorption and small particle size. White tattoo ink's poor response was associated with its poor absorption, even after laser darkening, and large particle size.

High-volume plasma exchange in a patient with acute liver failure due to non-exertional heat stroke in a sauna.

Heat stroke is a life-threatening condition characterized by an increased core body temperature (over 40°C) and a systemic inflammatory response, which may lead to a syndrome of multiple organ dysfunction. Heat stroke may be due to either strenuous exercise or non-exercise-induced exposure to a high environmental temperature. Current management of heat stroke is mostly supportive, with an emphasis on cooling the core body temperature and preventing the development of multiple organ dysfunction. Prognosis of heat stroke depends on the severity of organ involvement. Here, we report a rare case of non-exercise-induced heat stroke in a 73-year-old male patient who was suffering from acute liver failure after prolonged exposure in a hot sauna room. We successfully managed this patient by administering high-volume plasma exchange, and the patient recovered completely after treatment.

Treatment of cosmetic tattoos with nonablative fractional laser in an animal model: a novel method with histopathologic evidence.

BACKGROUND AND OBJECTIVE: Cosmetic tattoos are difficult to treat using Q-switched lasers. We introduce a novel method for the treatment of cosmetic tattoos using a nonablative fractional laser and investigate the underlying pathophysiological mechanisms in an animal model. STUDY DESIGN/MATERIALS AND METHODS: Ten rats were tattooed on their backs with white and flesh-colored pigments. One-half of each tattoo was treated with a 1,550-nm, erbium:glass fractional laser system with energy settings of 17 mJ and 169 MTZ/cm(2) × 2 passes for five sessions at 1-month intervals. The untreated half of each tattoo served as the control. An independent physician reviewed the photographs and scored the clinical response. Serial skin samples were obtained at baseline and at various times after laser treatment. These tissue sections were stained with hematoxylin and eosin, and immunostained for types I, III, and IV collagen; laminin; fibronectin; and α-smooth muscle actin. RESULTS: White tattoos showed excellent responses in two rats and good responses in eight rats, whereas flesh-colored tattoos showed excellent responses in four rats and good responses in six rats (P = 0.001 in both cases compared with baseline). Both tattoos exhibited a similar clearance rate (P > 0.05) and histological reactions. Microscopic epidermal necrotic debris (MEND) containing tattoo pigments and collagen fibrils appeared on day 1, increased on day 2, and was exfoliated after 5 days. The dermal-epidermal junction lost integrity 30 minutes after treatment, but recovered completely on day 3. The expression of fibronectin and collagen-III, which play key roles in wound healing, increased around the microscopic treatment zone on days 1-5 and 4-7, respectively. A few myofibroblasts appeared on days 4-7. CONCLUSION: Nonablative fractional lasers (NAFLs) successfully remove cosmetic tattoos by transepidermal elimination of tattoo pigments through the disrupted dermal-epidermal junction. This action is facilitated by the wound healing process.

Treatment of cosmetic tattoos using carbon dioxide ablative fractional resurfacing in an animal model: a novel method confirmed histopathologically.

BACKGROUND: Treating cosmetic tattoos using quality-switched lasers is difficult. OBJECTIVE: We used carbon dioxide ablative fractional resurfacing (CO2 AFR) to remove cosmetic tattoos and examined the pathophysiologic mechanisms involved in this technique in an animal model. METHODS AND MATERIALS: Twelve rats were tattooed on their backs with white and flesh-colored pigments. Half of each tattoo was treated with CO2 AFR (5 sessions at 1-month intervals), and the other half was the untreated control. An independent observer reviewed photographic documentation of clinical response. Serial skin samples obtained at baseline and at various times after laser treatment were evaluated using histologic and immunohistochemical methods. RESULTS: Four rats had excellent responses to laser treatment and eight had good responses. White and flesh-colored tattoos had similar clearance rates and tissue reactions. Histologic analysis showed immediate ablation of tattoo pigments in the microscopic ablation zones. Tattoo pigments in the microscopic coagulation zones migrated to the epidermis and became part of the microscopic exudative necrotic debris appearing on day 2 that was exfoliated after 5 days. Increased fibronectin expression around the microscopic treatment zones during the extrusion of tattoo pigments indicated that wound healing facilitates this action. CONCLUSION: CO2 AFR successfully removes cosmetic tattoos.

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.

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.

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.

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.

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.

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.

Nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus bacteraemia.

AIM: Vancomycin and teicoplanin are the two most used glycopeptides for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin is suspected to have more nephrotoxicity but this has not been clearly established. The aim of this study was to assess its nephrotoxicity by a consensus definition of acute kidney injury (AKI): the risk (R), injury (I), failure (F), loss and end-stage renal disease (RIFLE) classification. METHODS: Patients with MRSA bacteraemia who were prescribed either vancomycin or teicoplanin between 2003 and 2008 were classified. Patients who developed AKI were classified by RIFLE criteria. Variables such as comorbidities, laboratory data and medical cost information were also obtained from the database. Outcomes determined were: (i) the rate of nephrotoxicity and mortality; and (ii) the association of nephrotoxicity with the length of hospital stay and costs. RESULTS: The study included 190 patients (vancomycin 33, teicoplanin 157). Fifteen patients on vancomycin and 27 patients on teicoplanin developed AKI (P = 0.0004). In the vancomycin group, four, eight and three patients were classified to RIFLE criteria R, I and F, respectively. In the teicoplanin group, 17, nine and one patient were classified to RIFLE criteria R, I and F, respectively. Kaplan-Meier analysis showed significant difference in time to nephrotoxicity for the vancomycin group compared to the teicoplanin group. No significant differences were found between the groups in terms of total mortality, length of hospital stay and costs. CONCLUSION: The study data suggest that vancomycin is associated with a higher likelihood of nephrotoxicity using the RIFLE classification.

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.

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.