AST-120 improved uremic pruritus by lowering indoxyl sulfate and inflammatory cytokines in hemodialysis patients.

BACKGROUND AND HYPOTHESIS: Pruritus is a common and distressing symptom that affects patients with chronic kidney disease. The concentration of protein bounded uremic toxin was associated with the uremic pruritus. The aim is to assess the efficacy of AST-120 for uremic pruritus in hemodialysis patients. MATERIALS AND METHODS: The participants were enrolled and then divided into the AST-120 treatment group and control group with a ratio of 2:1. All participants underwent pre-observation screenings two weeks before the study with three visits. In the treatment phase (week 1 to week 4), the treatment group added 6g/day of AST-120 along with routine anti-pruritic treatment. Visual analog scale (VAS) and biochemical parameters were measured. RESULTS: The VAS score began to be lower in the AST-120 treatment group after the 5th visiting (p < 0.05). The reduction in indoxyl sulfate (IS) at 5th week along with TNF-alpha. The reduction ratio of indoxyl sulfate correlated with reduction of parathyroid hormone. CONCLUSION: This study has demonstrated that the four-week treatment of AST-120 decreased the severity of uremic pruritus in patients with ESRD. The concentration of IS and TNF-alpha decreased in the AST-120 treatment group. The reduction of iPTH correlated with the reduction of IS in the AST-120 treatment.

Dissecting the risk factors for hyperuricemia in vegetarians in Taiwan.

BACKGROUND: Vegetarian diets have been shown to lower the risks of hyperuricemia and gout. Little is known about the risk factors of hyperuricemia in vegetarians. METHODS: This community-based retrospective case-control study was conducted to establish prediction models for hyperuricemia. From September 5, 2005, to December 31, 2016, 7331 adult vegetarians were recruited at Taipei Tzu Chi Hospital. Hyperuricemia was defined as a serum uric acid concentration greater than 7 mg/dL. RESULTS: There were 593 (8.1%) vegetarians with hyperuricemia and 6738 (91.9%) without hyperuricemia. We stepwise built up three models for predicting hyperuricemia in vegetarians. The full model (model 3) has the highest area under the receiver operating characteristic curve (AUROC, 85.52%). Additionally, the AUROC of model 3 is 77.97% and 84.85% in vegetarians with or without prior gout history, respectively. Moreover, male gender, hyperlipidemia, body mass index, and serum albumin are independent risk factors for hyperuricemia in vegetarians. In contrast, estimated glomerular filtration rate and proteinuria are independently associated with lower risks of hyperuricemia in vegetarians. CONCLUSION: Our study revealed that risk factors for hyperuricemia, which includes clinical characteristics, account for more than 85% of discriminatory performance in Taiwanese vegetarians. This model may be helpful for monitoring and preventing hyperuricemia in the population.

Association of mono-2-ethylhexyl phthalate with adverse outcomes in chronic hemodialysis patients.

Phthalate exposure is widespread and has a global impact. Growing evidence shows that mono-2-ethylhexyl phthalate (MEHP) exposure has a negative impact on human health. However, whether MEHP exposure is associated with mortality and other adverse outcomes in hemodialysis patients remains unknown. This study prospectively enrolled 217 patients on maintenance hemodialysis from June 30, 2021, to August 16, 2022. Baseline serum MEHP, di-2-ethylhexyl phthalate (DEHP), and indoxyl sulfate (IS) concentrations were measured. Primary endpoints were all-cause mortality or composite adverse outcomes, including all-cause death plus hospitalization due to cardiovascular disease, heart failure, stroke, infection, or cancer. Serum MEHP concentrations were positively associated with DEHP but not indoxyl sulfate concentrations in hemodialysis patients. Additionally, serum MEHP concentrations were significantly and independently associated with all-cause mortality and composite adverse outcomes (adjusted hazard ratios [HRs], 1.04 and 1.03 per ng/mL, 95% confidence intervals [CIs], 1.01-1.07 and 1.00-1.05; p = 0.016 and 0.015, respectively). We found a cutoff value of MEHP for predicting both endpoints. Patients with serum MEHP concentrations of ≥ 41.8 ng/mL had much higher risks for all-cause mortality and composite adverse outcomes (adjusted HRs, 39.2 and 13; 95% CIs, 2.44-65.7 and 2.74-61.4; p = 0.011 and 0.001, respectively). MEHP exposure is significantly associated with higher risks for all-cause mortality and composite adverse outcomes. Hemodialysis patients with serum MEHP concentrations above 41.8 ng/mL had much poorer prognoses regarding both outcomes.

Granulocyte Colony-Stimulating Factor Improves Endothelial Progenitor Cell-Mediated Neovascularization in Mice with Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) have a higher prevalence of peripheral arterial disease (PAD), and endothelial progenitor cells (EPCs) play a pivotal role. We examined the impact of granulocyte colony-stimulating factor (G-CSF) on EPC function in response to tissue ischemia. Eight-week-old male C57BL/6J male mice were divided into sham operation and subtotal nephrectomy (SNx) groups, received hindlimb ischemic operation after seven weeks, then randomly received G-CSF or PBS intervention for four weeks with weekly follow-ups. SNx mice had significantly reduced limb reperfusion, decreased plasma EPC mobilization, and impaired angiogenesis in ischemic hindlimbs compared to the control group. However, G-CSF increased IL-10 and reversed these adverse changes. Additionally, ischemia-associated protein expressions, including IL-10, phospho-STAT3, VEGF, and phospho-eNOS, were significantly downregulated in the ischemic hindlimbs of SNx mice versus control, but these trends were reversed by G-CSF. Furthermore, in cultured EPCs, G-CSF significantly attenuated the decrease in EPC function initiated by indoxyl sulfate through IL-10. Overall, we discovered that G-CSF can improve EPC angiogenic function through a hypoxia/IL-10 signaling cascade and impede neovascular growth in response to ischemia of SNx mice. Our results highlight G-CSF's potential to restore angiogenesis in CKD patients with PAD via EPC-based methods.

Using artificial intelligence algorithms to predict the overall survival of hemodialysis patients during the COVID-19 pandemic: A prospective cohort study.

BACKGROUND: Hemodialysis (HD) patients are a vulnerable population at high risk for severe complications from COVID-19. The impact of partial COVID-19 vaccination on the survival of HD patients remains uncertain. This prospective cohort study was designed to use artificial intelligence algorithms to predict the survival impact of partial COVID-19 vaccination in HD patients. METHODS: A cohort of 433 HD patients was used to develop machine-learning models based on a subset of clinical features assessed between July 1, 2021, and April 29, 2022. The patient cohort was randomly split into training (80%) and testing (20%) sets for model development and evaluation. Machine-learning models, including categorical boosting (CatBoost), light gradient boosting machines (LightGBM), RandomForest, and extreme gradient boosting models (XGBoost), were applied to evaluate their discriminative performance using the patient cohorts. RESULTS: Among these models, LightGBM achieved the highest F1 score of 0.95, followed by CatBoost, RandomForest, and XGBoost, with area under the receiver operating characteristic curve values of 0.94 on the testing dataset. The SHapley Additive explanation summary plot derived from the XGBoost model indicated that key features such as age, albumin, and vaccination details had a significant impact on survival. Furthermore, the fully vaccinated group exhibited higher levels of anti-spike (S) receptor-binding domain antibodies. CONCLUSION: This prospective cohort study involved using artificial intelligence algorithms to predict overall survival in HD patients during the COVID-19 pandemic. These predictive models assisted in identifying high-risk individuals and guiding vaccination strategies for HD patients, ultimately improving overall prognosis. Further research is warranted to validate and refine these predictive models in larger and more diverse populations of HD patients.

Leukocyte 8-hydroxy-2'-deoxyguanosine as an oxidative stress marker to predict cardiovascular events and death in chronic hemodialysis patients.

BACKGROUND: Hemodialysis patients have a markedly increased risk of cardiovascular (CV) morbidity and mortality. Oxidative stress plays a pathogenic role in the progression of atherosclerosis and CV disease among chronic hemodialysis patients. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) content in leukocyte deoxyribonucleic acid (DNA) has been shown as a sensitive and well-known biomarker of oxidant-induced DNA damage in chronic hemodialysis patients. METHODS: We conducted a retrospective cohort study to investigate the association of leukocyte 8-OHdG and CV events and deaths in patients of chronic hemodialysis. In this study, 217 chronic hemodialysis patients were recruited from 2016 to 2021. The 8-OHdG content of leukocyte DNA was measured by a high-performance liquid chromatography electrochemical detection method. Study outcomes were CV events as well as CV and all-cause deaths. The patients were followed until May 2021. RESULTS: The median follow-up period was 34.8 months. At the end of May 2021, 57 first CV events and 89 all-CV events occurred. Among the first and all CV events, 17 (29.8%) and 32 (36.0%) were fatal, respectively. Multivariate Cox regression analysis showed per 1/10 5 dG increment in leukocyte 8-OHdG values increased risk of CV events (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.10-1.41; p < 0.001), CV death (aHR, 1.27; 95% CI, 1.03-1.72; p = 0.034), and all-cause death (aHR, 1.11; 95% CI, 1.01-1.30; p = 0.038). CONCLUSION: This is the first study to demonstrate that oxidative stress assessed by 8-OHdG levels of leukocyte DNA predicted CV events as well as CV and all-cause deaths among chronic hemodialysis patients.

Theranostic Role of Iron Oxide Nanoparticle for Treating Renal Anemia: Evidence of Efficacy and Significance by MRI, Histology and Biomarkers.

(1) Background: Increasing attention has been given to applying nanosized iron oxide nanoparticles (IOPs) to treat iron deficiency anemia (IDA). Chronic kidney disease (CKD) patients who suffer from IDA often need long-term iron supplements. We aim to evaluate the safety and therapeutic effect of MPB-1523, a novel IOPs, in anemic CKD mice and to monitor iron storage by magnetic resonance (MR) imaging. (2) Methods: MPB-1523 was intraperitoneally delivered to the CKD and sham mice, and blood were collected for hematocrit, iron storage, cytokine assays, and MR imaging throughout the study. (3) Results: The hematocrit levels of CKD and sham mice dropped initially but increased gradually to reach a steady value 60 days after IOP injection. The body iron storage indicator, ferritin gradually rose and total iron-binding capacity stabilized 30 days after IOP injection. No significant inflammation or oxidative stress were observed in both groups. By T2-weighted MR imaging, the liver signal intensity gradually increased in both groups but was more pronounced in the CKD group, indicating aggressive utilization of MPB-1523. MR imaging, histology and electron microscopy showed MPB-1523 is liver-specific. (4) Conclusions: MPB-1523 can serve as a long-term iron supplement and is monitored by MR imaging. Our results have strong translatability to the clinic.

Risks of Topical Carbonic Anhydrase Inhibitors in Glaucoma Patients With Chronic Kidney Disease: A Nationwide Population-Based Study.

PURPOSE: To investigate the risks of metabolic acidosis and renal outcomes after topical carbonic anhydrase inhibitor (CAI) use in patients with both primary open-angle glaucoma (POAG) and advanced chronic kidney disease (CKD). DESIGN: Nationwide, population-based cohort study. METHODS: This study was conducted with population data from Taiwan's National Health Insurance (NHI) Research Database between January 2000 and June 2009. Patients with advanced CKD who were diagnosed with glaucoma (International Classification of Diseases, Ninth Revision [ICD-9] code 365) and had been receiving eye drops for glaucoma (including carbonic anhydrase inhibitors selected by NHI drug code) were enrolled. Using Kaplan-Meier methods, we compared the cumulative incidence of mortality, long-term dialysis, and cumulative incidence of metabolic acidosis over time between CAI users and CAI non-users. Primary outcomes comprised mortality, renal outcome (progression to hemodialysis), and metabolic acidosis. RESULTS: In this cohort, topical CAI users had a higher incidence of long-term dialysis than non-users (incidence = 1,216.85 vs 764.17 events per 100 patient-years; adjusted hazard ratio = 1.17, 95% CI = 1.01-1.37). Hospital admissions due to metabolic acidosis were higher in CAI users compared with non-users (incidence = 21.54 vs 11.87 events per 100 patient-years; adjusted hazard ratio = 1.89, 95% CI = 1.07-3.36). CONCLUSIONS: Topical CAIs may be associated with higher risks of long-term dialysis and metabolic acidosis in patients with POAG and pre-dialysis advanced CKD. Therefore, topical CAIs should be used with caution in advanced CKD patients.

Folic Acid Ameliorates Renal Injury in Experimental Obstructive Nephropathy: Role of Glycine N-Methyltransferase.

Folic acid exerts both anti-inflammatory and antifibrotic effects. Glycine N-methyltransferase (GNMT), the major folic acid-binding protein in the liver, is a crucial enzyme that regulates the cellular methylation process by maintaining S-adenosylmethionine levels. However, as yet neither the therapeutic effects of folic acid in renal fibrosis nor whether GNMT is involved in these folic acid-associated mechanisms has been investigated. First, the expression of GNMT was examined in human kidneys with or without obstructive nephropathy. Later, wild-type and GNMT knockout (GNMT-/-) mice were subjected to unilateral ureteral obstruction (UUO) and then treated with either folic acid or vehicle for 14 days. Renal tubular injury, inflammation, fibrosis, and autophagy were evaluated by histological analysis and Western blotting. We observed increased expression of GNMT in humans with obstructive nephropathy. Furthermore, UUO significantly increased the expression of GNMT in mice; in addition, it caused renal injury as well as the development of both hydronephrosis and tubular injury. These were all alleviated by folic acid treatment. In contrast, GNMT-/- mice exhibited exacerbated UUO-induced renal injury, but the protective effect of folic acid was not observed in GNMT-/- mice. We propose a novel role for folic acid in the treatment of renal fibrosis, which indicates that GNMT may be a therapeutic target.

Vegan Diet Is Associated with a Lower Risk of Chronic Kidney Disease in Patients with Hyperuricemia.

Hyperuricemia is a well-known risk factor for chronic kidney disease (CKD). Little is known about whether a vegetarian diet is associated with a lower risk of CKD in patients with hyperuricemia. From 5 September 2005, to 31 December 2016, we retrospectively included clinically stable patients with hyperuricemia who received health check-ups at Taipei Tzu Chi Hospital. All participants completed a dietary habits questionnaire to determine whether they were omnivorous, lacto-ovo vegetarian, or vegan. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the presence of proteinuria. A total of 3618 patients with hyperuricemia were recruited for this cross-sectional study, consisting of 225 vegans, 509 lacto-ovo vegetarians, and 2884 omnivores. After adjusting for age and sex, vegans had a significantly lower odds ratio (OR) of CKD than omnivores (OR, 0.62; p = 0.006). The OR of CKD remained significantly lower in vegans after adjusting for additional confounders (OR, 0.69; p = 0.04). Additionally, age (per year OR, 1.06; p < 0.001), diabetes mellitus (OR, 2.12; p < 0.001), hypertension (OR, 1.73; p < 0.001), obesity (OR, 1.24; p = 0.02), smoking (OR, 2.05; p < 0.001), and very high uric acid levels (OR, 2.08; p < 0.001) were independent risk factors for CKD in patients with hyperuricemia. Moreover, structural equation modeling revealed that a vegan diet was associated with a lower OR of CKD (OR, 0.69; p < 0.05). A vegan diet is associated with a 31% lower risk of CKD in patients with hyperuricemia. A vegan diet may be beneficial in reducing the occurrence of CKD in patients with hyperuricemia.

Di-(2-ethylhexyl) Phthalate Limits the Lipid-Lowering Effects of Simvastatin by Promoting Protein Degradation of Low-Density Lipoprotein Receptor: Role of PPARγ-PCSK9 and LXRα-IDOL Signaling Pathways.

Dialysis prevents death from uremia in patients with end-stage renal disease (ESRD). Nevertheless, during hemodialysis, circulating levels of di-(2-ethylhexyl) phthalate (DEHP) are increased due to phthalates leaching from medical tubes. Statins are an effective therapy for reducing the risks associated with cardiovascular diseases in patients with chronic kidney disease; however, the mechanism by which statins fail to reduce cardiovascular events in hemodialysis ESRD patients remains unclear. In this study, we investigated whether DEHP and its metabolites interfere with the lipid-lowering effect of statins in hepatocytes. In Huh7 cells, treatment with DEHP and its metabolites abolished the simvastatin-conferred lipid-lowering effect. Mechanistically, DEHP down-regulated the expression of low-density lipoprotein receptor (LDLR) and led to a decrease in LDL binding, which was mediated by the activation of the PPARγ-PCSK9 and LXRα-IDOL signaling pathways. Additionally, the NOX-ROS-TRPA1 pathway is involved in the DEHP-mediated inhibition of LDLR expression and LDL binding activity. Blockage of this pathway abrogated the DEHP-mediated inhibition in the LDLR expression and LDL binding of simvastatin. Collectively, DEHP induces the activation of the NOX-ROS-TRPA1 pathway, which in turn activates PPARγ-PCSK9- and LXRα-IDOL-dependent signaling, and, ultimately, diminishes the statin-mediated lipid-lowering effect in hepatocytes.

Omega-3 fatty acids for uremic pruritus: A meta-analysis of randomized controlled trials.

Uremic pruritus (UP) is common in the late stages of chronic kidney disease. Currently, there is a lack of effective treatment for UP. Limited evidence exists on the therapeutic effect of omega-3 fatty acid (O3FA). The aim of this study was to evaluate the efficacy of O3FA supplements in UP patients. We evaluated the efficacy of O3FA supplements in patients with UP through a systematic review and a meta-analysis of randomized control trials retrieved from PubMed, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov databases. The included studies were summarized and assessed for the risk of bias, and pruritus assessment results were analyzed. To compared with a controlled group, five articles including 164 participants published between 2012 and 2019 using different pruritus scales reported that patients taking O3FA supplement exhibited no significant decrease in the pruritus score (standardized mean difference [SMD] =1.34, 95% confidence interval [CI] = -2.70-0.01, P = 0.05), but three articles using same pruritus scale significant decrease Duo pruritus score (SMD = -0.85, 95% CI = -1.39 to -0.30, P < 0.05). O3FA supplement could be an appealing complementary therapy for UP patients. More rigorously designed studies are needed before recommending the O3FA supplement.

Indoxyl Sulfate Alters the Humoral Response of the ChAdOx1 COVID-19 Vaccine in Hemodialysis Patients.

Background and aims: Vaccination for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is strongly recommended. The efficacy of SARS-CoV-2 vaccine for patients with end-stage renal disease is low. Indoxyl sulfate (IS) is a representative protein bound uremic toxin arousing immune dysfunction in CKD patients. It is unknown whether IS impairs the efficacy of vaccines for SARS-CoV-2. Materials and Methods: From 1 June 2021, to 31 December 2021, hemodialysis patients (n = 358) and a control group (n = 59) were eligible to receive the first dose of the ChAdOx1 COVID-19 vaccine. Titer measurements indicative of the humoral response (anti-S1 IgG and surrogate virus neutralization test (sVNT) results) and indoxyl sulfate concentration measurement were performed 4 weeks after ChAdOx1 vaccine injection. Results: The serum concentrations of anti-S1 IgG were 272 ± 1726 AU/mL and 2111 ± 4424 AU/mL in hemodialysis patients and control group (p < 0.05), respectively. The sVNT values were 26.8 ± 21.1% and 54.0 ± 20.2% in the hemodialysis and control groups (p < 0.05), respectively. There was a decreasing trend for the anti-S1 IgG titer from the lowest to highest quartile of IS (p < 0.001). The patients with higher concentrations of IS had lower sVNT (p for trend < 0.001). Conclusion: Hemodialysis patients had weaker humoral immunity after the first dose of the ChAdOx1 vaccine. Higher concentration of IS altered the development of anti-S1 antibodies and sVNT-measured neutralization.

Vegetarian Diet Was Associated With a Lower Risk of Chronic Kidney Disease in Diabetic Patients.

Introduction: Diabetes mellitus (DM) is a pathological hyperglycemic state related to the dysregulation of insulin. Chronic kidney disease (CKD) is a common chronic complication in diabetic patients. A vegetarian diet could be one of the preventive strategies for the occurrence of CKD in patients with diabetes mellitus. However, it is still unknown whether a vegetarian diet lowers the occurrence of CKD in DM patients. Research Design and Methods: This retrospective study was conducted at Taipei Tzu Chi Hospital from 5 September 2005 to 31 December 2016. Subjects with an HbA1c level > 6.5% or previous history of diabetes mellitus elder than 40 years were grouped based on self-reported dietary habits (vegetarians, lacto-ovo vegetarians and omnivores) in the structured questionnaire. Structural equation modeling (SEM) was applied to estimate the direct and indirect effects of variables on the occurrence of chronic kidney disease. Results: Among these 2,797 subjects, the participants were grouped into dietary habits as vegans (n = 207), lacto-ovo vegetarians (n = 941) and omnivores (n = 1,649). The incidence of overall CKD was higher in the omnivore group [36.6% vs 30.4% (vegans) and 28.5% (lacto-ovo vegetarian), p < 0.001]. In the SEM model, after adjusting for age and sex, the lacto-ovo vegetarian [OR: 0.68, 95% confidence interval (CI): 0.57-0.82] and vegan groups (OR 0.68, 95% CI: 0.49-0.94) were both associated with a lower risk of CKD occurrence than the omnivore group. The vegan diet and lacto-ovo diet lowered the risk related to a high BMI (OR: 0.45, p < 0.001, OR: 0.58, p < 0.001) and hyperuricemia (OR: 0.53, p < 0.001; OR: 0.55, p < 0.001) for the occurrence of CKD. Conclusion: Vegetarian dietary habits were associated with a lower occurrence of CKD in DM patients.

Association of anemia and iron parameters with mortality among prevalent peritoneal dialysis patients in Taiwan: the AIM-PD study.

In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10-11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.

Clinical Efficacy and Safety of Sodium Thiosulfate in the Treatment of Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials.

Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the efficacy of intravenous sodium thiosulfate in patients with uremic pruritus. A systematic search of electronic databases up to June 2021 was conducted for randomized controlled trials that evaluated the clinical effects of sodium thiosulfate in the management of patients with uremic pruritus. Two reviewers selected eligible articles and evaluated the risk of bias; the results of pruritus assessment and uremic pruritus-related laboratory parameters in selected studies were analyzed. There are four trials published between 2018 and 2021, which include 222 participants. The sodium thiosulfate group displayed significant decrease in the pruritus score (standardized mean difference = -3.52, 95% confidence interval = -5.63 to -1.41, p = 0.001), without a significant increase in the adverse effects (risk ratio = 2.44, 95% confidence interval = 0.37 to 15.99, p = 0.35) compared to the control group. Administration of sodium thiosulfate is found to be a safe and efficacious complementary therapy in improving uremic pruritus in patients with chronic kidney disease.

Western and complementary alternative medicine treatment of uremic pruritus: A literature review.

Uremic pruritus (UP), also called chronic kidney disease-associated pruritus (CKD-aP), is a bothersome symptom that causes sleep disturbance, anxiety, depression, and reduced quality of life. Pruritus often occurs in patients with end-stage renal disease. There is still no definite treatment for UP due to its unclear pathogenesis. We searched electronic databases (PubMed and Google Scholar) and gathered the latest clinical trials and pilot studies of Western and complementary alternative medicine (CAM) therapies for UP in English. These UP studies were separated into three main groups: systemic, topical, and others and CAM. Gabapentin, nalfurafine, acupuncture, and Chinese herbal bath therapy (CHBT) show antipruritic effects, with higher evidence grades in the meta-analysis. Emollients with additive compounds are more effective for reducing itch than emollients without additives. Supplements for deficient elements, such as zinc, omega-3, and omega-6, also show benefits for pruritus improvement. CAM therapies such as acupuncture, herbs, and herbal baths or creams all have good results for UP treatment. We summarize the treatments and suggest a treatment algorithm for UP according to severity. Some UP therapies are already supported by large-scale clinical evidence, and some new treatments can provide patients with new hope and treatment options. However, these new methods still need large population studies and further exploration.

The Therapeutic Strategies for Uremic Toxins Control in Chronic Kidney Disease.

Uremic toxins (UTs) are mainly produced by protein metabolized by the intestinal microbiota and converted in the liver or by mitochondria or other enzymes. The accumulation of UTs can damage the intestinal barrier integrity and cause vascular damage and progressive kidney damage. Together, these factors lead to metabolic imbalances, which in turn increase oxidative stress and inflammation and then produce uremia that affects many organs and causes diseases including renal fibrosis, vascular disease, and renal osteodystrophy. This article is based on the theory of the intestinal-renal axis, from bench to bedside, and it discusses nonextracorporeal therapies for UTs, which are classified into three categories: medication, diet and supplement therapy, and complementary and alternative medicine (CAM) and other therapies. The effects of medications such as AST-120 and meclofenamate are described. Diet and supplement therapies include plant-based diet, very low-protein diet, probiotics, prebiotics, synbiotics, and nutraceuticals. The research status of Chinese herbal medicine is discussed for CAM and other therapies. This review can provide some treatment recommendations for the reduction of UTs in patients with chronic kidney disease.

The Efficacy of COVID-19 Vaccines in Chronic Kidney Disease and Kidney Transplantation Patients: A Narrative Review.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has posed a huge threat to global health because of its rapid spread and various mutant variants. Critical illness occurs in the elderly and vulnerable individuals, such as those with chronic kidney disease. The severity of SARS-CoV-2 infection is associated with the severity of chronic kidney disease (CKD)and even kidney transplantation (KT) because of the chronic use of immunosuppressive agents. To develop adaptive immunity against SARS-CoV-2, vaccination against the spike protein is important. Current phase III trials of vaccines against SARS-CoV-2 have not focused on a specific group of individuals, such as patients with CKD or those undergoing dialysis or kidney transplantation. Chronic use of immunosuppressive agents might disturb the immune response to the SARS-CoV-2 spike protein. On the basis of limited evidence, the immune compromised status of CKD patients might decrease neutralizing antibody development after a single dose of a specific vaccine. Boosting dosage more than the protocol might increase the titer of the neutralizing antibody in CKD patients. Further evidence is needed to understand the factors disturbing the immunogenicity of the SARS-CoV-2 vaccine, and CKD patients should receive the recommended dose of the SARS-CoV-2 vaccine due to their relatively immune compromised status.

Di-(2-ethylhexyl) phthalate limits the pleiotropic effects of statins in chronic kidney disease patients undergoing dialysis and endothelial cells.

The level of di-(2-ethylhexyl) phthalate (DEHP) is elevated in chronic kidney disease patients undergoing dialysis. However, statins are unable to reduce the cardiovascular events in chronic dialysis patients. In this study, we investigated the effects of DEHP on statin-conferred pleiotropic effects and the underlying molecular mechanism in peritoneal dialysis (PD) patients and endothelial cells (ECs). In PD patients with serum DEHP level ≥0.0687 µg/mL, statin treatment was not associated with lower risk of cardiovascular disease. In ECs, exposure to DEHP abrogated the simvastatin-induced NO bioavailability and EC-related functions. Additionally, DEHP abolished the anti-inflammatory effect of simvastatin on the tumor necrosis factor α-induced upregulation of adhesion molecules and monocyte adhesion to ECs. Mechanistically, DEHP blunted the activation of transient receptor potential vanilloid type 1 (TRPV1), which is required for NO production by simvastatin in ECs. Notably, DEHP increased the activity and expression of protein phosphatase 2B (PP2B), a negative regulator of TRPV1 activity. The effect of DEHP on PP2B activation was mediated by the activation of the NADPH oxidase/reactive oxygen species (NOX-ROS) pathway. Inhibition of PP2B activity by pharmacological antagonists prevented the inhibitory effects of DEHP on simvastatin-induced Ca2+ influx, NO bioavailability, and EC migration, proliferation, tube formation, and anti-inflammatory action. Collectively, DEHP activates the NOX-ROS-PP2B pathway, which in turns inhibits TRPV1/Ca2+-dependent signaling and abrogates the statin-conferred pleiotropic protection in ECs.