[Mechanism of Fushen Granules treat peritoneal dialysis-related peritonitis by regulating TLR4/NF-κB pathway:based on network pharmacology and animal experiments].

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1ß in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.

Mitochondrial targeted catalase improves muscle strength following arteriovenous fistula creation in mice with chronic kidney disease.

Hand dysfunction is a common observation after arteriovenous fistula (AVF) creation for hemodialysis access and has a variable clinical phenotype; however, the underlying mechanism responsible is unclear. Grip strength changes are a common metric used to assess AVF-associated hand disability but has previously been found to poorly correlate with the hemodynamic perturbations post-AVF placement implicating other tissue-level factors as drivers of hand outcomes. In this study, we sought to test if expression of a mitochondrial targeted catalase (mCAT) in skeletal muscle could reduce AVF-related limb dysfunction in mice with chronic kidney disease (CKD). Male and female C57BL/6J mice were fed an adenine-supplemented diet to induce CKD prior to placement of an AVF in the iliac vascular bundle. Adeno-associated virus was used to drive expression of either a green fluorescent protein (control) or mCAT using the muscle-specific human skeletal actin (HSA) gene promoter prior to AVF creation. As expected, the muscle-specific AAV-HSA-mCAT treatment did not impact blood urea nitrogen levels (P = 0.72), body weight (P = 0.84), or central hemodynamics including infrarenal aorta and inferior vena cava diameters (P > 0.18) or velocities (P > 0.38). Hindlimb perfusion recovery and muscle capillary densities were also unaffected by AAV-HSA-mCAT treatment. In contrast to muscle mass and myofiber size which were not different between groups, both absolute and specific muscle contractile forces measured via a nerve-mediated in-situ preparation were significantly greater in AAV-HSA-mCAT treated mice (P = 0.0012 and P = 0.0002). Morphological analysis of the post-synaptic neuromuscular junction uncovered greater acetylcholine receptor cluster areas (P = 0.0094) and lower fragmentation (P = 0.0010) in AAV-HSA-mCAT treated mice. Muscle mitochondrial oxidative phosphorylation was not different between groups, but AAV-HSA-mCAT treated mice had lower succinate-fueled mitochondrial hydrogen peroxide emission compared to AAV-HSA-GFP mice (P < 0.001). In summary, muscle-specific scavenging of mitochondrial hydrogen peroxide significantly improves neuromotor function in mice with CKD following AVF creation.

Health-related quality of life for pediatric patients with end-stage kidney disease: A systematic review and meta-analysis of the Pediatric Quality of Life Inventory (PedsQL).

INTRODUCTION: Health-related quality of life (HRQoL) studies demonstrate the impact of end-stage renal disease (ESRD) on the physical and psychosocial development of children. While several instruments are used to measure HRQoL, few have standardized domains specific to pediatric ESRD. This review examines current evidence on self and proxy-reported HRQoL among pediatric patients with ESRD, based on the Pediatric Quality of Life Inventory (PedsQL) questionnaires. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis on HRQoL using the PedsQL 4.0 Generic Core Scale (GCS) and the PedsQL 3.0 ESRD Module among 5- to 18-year-old patients. We queried PubMed, Embase, Web of Science, CINAHL, and Cochrane databases. Retrospective, case-controlled, and cross-sectional studies using PedsQL were included. FINDINGS: Of 435 identified studies, 14 met inclusion criteria administered in several countries. Meta-analysis demonstrated a significantly higher total HRQoL for healthy patients over those with ESRD (SMD:1.44 [95% CI: 0.78-2.09]) across all dimensional scores. In addition, kidney transplant patients reported a significantly higher HRQoL than those on dialysis (PedsQL GCS, SMD: 0.33 [95% CI: 0.14-0.53]) and (PedsQL ESRD, SMD: 0.65 [95% CI: 0.39-0.90]) concordant with parent-proxy reports. DISCUSSION: Patients with ESRD reported lower HRQoL in physical and psychosocial domains compared with healthy controls, while transplant and peritoneal dialysis patients reported better HRQoL than those on hemodialysis. This analysis demonstrates the need to identify dimensions of impaired functioning and produce congruent clinical interventions. Further research on the impact of individual comorbidities in HRQoL is necessary for developing comprehensive, integrated, and holistic treatment programs.

Effectiveness of Narrowband Ultraviolet Light in Chronic Kidney Disease-Associated Pruritus.

INTRODUCTION:  Chronic kidney disease-associated pruritus (CKDaP) is a prevalent and challenging symptom in individuals suffering from advanced chronic kidney disease (CKD). Its underlying mechanism remains inadequately understood, leading to a limited array of unsatisfactory therapeutic interventions. Despite various attempts, identifying the most effective treatment remains inconclusive. Nevertheless, there is a growing interest in employing ultraviolet phototherapy, particularly for non-responsive patients, although its efficacy is not definitively established. To investigate the potential benefits of narrowband ultraviolet B (NB-UVB) phototherapy on individuals experiencing CKDaP, we report our experience with NB-UVB light in management of CKDaP in dialysis patients. MATERIALS AND METHODS: The study group consisted of patients with end-stage chronic kidney disease who underwent hemodialysis. These patients received dermatological consultations and follow-ups for itching. They were all unresponsive to the conventional treatment (emollients and antihistamines). Screening laboratory examinations, including complete blood count, liver function test, thyroid function, electrolytes, and others, were also arranged to exclude systemic etiologies. The main potential pruritogens were dosed: calcium, phosphate, and parathyroid hormone. Itch intensity was evaluated with a numerical rating scale (0-10), based on the worst level of itching in the past two weeks. They had sessions of NB-UVB light (311 nm, TL01) twice per week. After UVB exposure, patients were advised to use topical emollients. A questionnaire was employed to document the extent, intensity, frequency, and sleep disruption experienced to evaluate the efficiency of the treatment, using a scale from 0 to 10.  Results: In a group of 38 patients, the average age of the patients was 56 years (16-80); 63.2% were female and 36.8% were male. Median duration of pruritus was 4.7 years, and that of dialysis was 8.4 years. Pruritus was intermittent and diffuse in most cases, localized to the arteriovenous fistula site in two cases, and exacerbated by heat in all cases. Itch intensity was evaluated with a numerical rating scale (0-10) based on the worst level of itching in the past two weeks and showed a moderate average score (5/10). Xerosis was found in 63%, and scratch lesions such as excoriation in 34%. NB-UVB phototherapy was used twice per week on nonconsecutive days, with protection of the genital area and also the eyes using UVB-blocking goggles. The initial dose was 0.4 J/cm2 and further doses were introduced according to the erythema response until a maximum of 2 J/cm2. No sunburn, hyperpigmentation, or blistering was noted. Emollients were maintained in patients with xerosis. Average number of sessions was 13 (6-24) and reduction of itch intensity was observed starting from the sixth session. Total improvement was obtained at the end of treatment duration except for three patients who required additional sessions. One patient had recurrence one year later.  Conclusion: In conclusion, phototherapy represents a significant advancement in the treatment options for CKD-associated pruritus. Its positive impact on reducing itching and improving the quality of life for many patients is undeniable. However, to fully unlock its potential, ongoing research is needed to optimize dosing, understand relapse mechanisms, and identify the patients who will benefit most from this therapy.

Age-Related Changes in Clinical and Analytical Variables in Chronic Hemodialyzed Patients.

Worldwide, the number of elderly individuals receiving chronic hemodialysis is rising. The aim of our study was to evaluate several clinical and analytical biomarkers in chronically dialyzed patients and analyze how they change with age. A cross-sectional study was performed by evaluating 289 end-stage renal disease patients undergoing dialysis. We evaluated the hemogram, adipokines, the lipid profile, and several markers related to inflammation, endothelial function/fibrinolysis, nutrition, iron metabolism, and cardiac and renal fibrosis. Clinical data and dialysis efficacy parameters were obtained from all patients. The relationships between studied biomarkers and age were assessed by a statistical comparison between younger (adults with age < 65 years) and older (age ≥ 65 years) patients and by performing regression analysis. Participants presented a mean age of 68.7 years (±13.6), with 66.8% (n = 193) being classified as older. Compared to younger patients, older patients presented the following: (a) significantly lower values of diastolic blood pressure (DBP) and ultrafiltration volume; (b) lower levels of phosphorus, uric acid, creatinine, and albumin; and (c) higher circulating concentrations of tissue-type plasminogen activator (tPA), D-dimer, interleukin-6, leptin, N-terminal pro B-type natriuretic peptide, and tissue inhibitor of metalloproteinase-1. In the multiple linear regression analysis, DBP values, tPA, phosphorus, and D-dimer levels were independently associated with the age of patients (standardized betas: -0.407, 0.272, -0.230, and 0.197, respectively; p < 0.001 for all), demonstrating relevant changes in biomarkers with increasing age at cardiovascular and nutritional levels. These findings seem to result from crosstalk mechanisms between aging and chronic kidney disease.

Longer serum phosphorus time in range associated with lower mortality risk among peritoneal dialysis patients: a multicenter retrospective cohort study.

BACKGROUND: Relationship between serum phosphorus time in range and mortality risk in peritoneal dialysis (PD) patients remains uncertain. We aimed to evaluate the association between serum phosphorus time in range and all-cause mortality in Chinese PD population. METHODS: This was a multicenter, retrospective, cohort study of 1,915 patients collected from January 2008 to October 2020 in 4 Chinese centers. Serum phosphorus time in range was estimated as the months during the first year that a patient's serum phosphorus level was within the target range (defined as 1.13-1.78 mmol/L). The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) mortality and PD withdrawal. Cox proportional hazards regression model with comprehensive adjustments was used to assess the association. RESULTS: The primary outcome occurred in 249 (13.0%) PD patients over a median follow-up of 28 months. Overall, the serum phosphorus time in range was negatively associated with all-cause mortality (per 3-month increments, adjusted HR [aHR], 0.83; 95%CI: 0.75-0.92), CV mortality (per 3-month increments, aHR, 0.87; 95%CI: 0.77-0.99), and PD withdrawal (per 3-month increments, aHR, 0.89; 95%CI: 0.83-0.95). Competing-risk model showed that the relationship of serum phosphorus time in range with all-cause mortality remained stable. None of the variables including demographics, history of diabetes and CV disease, as well as several PD-related and clinical indicators modified this association. CONCLUSIONS: PD patients with longer serum phosphorus time in range in the first year was negatively associated with all-cause mortality and CV mortality. Our findings highlight the importance of maintaining serum phosphorus levels within 1.13-1.78 mmol/L for PD patients.

Palliative Care for Adult Patients Undergoing Hemodialysis in Asia: Challenges and Opportunities.

This article underscores the importance of integrating comprehensive palliative care for noncancer patients who are undergoing hemodialysis, with an emphasis on the aging populations in Asian nations such as Taiwan, Japan, the Republic of Korea, and China. As the global demographic landscape shifts towards an aging society and healthcare continues to advance, a marked increase has been observed in patients undergoing hemodialysis who require palliative care. This necessitates an immediate paradigm shift to incorporate this care, addressing the intricate physical, psychosocial, and spiritual challenges faced by these individuals and their families. Numerous challenges impede the provision of effective palliative care, including difficulties in prognosis, delayed referrals, cultural misconceptions, lack of clinician confidence, and insufficient collaboration among healthcare professionals. The article proposes potential solutions, such as targeted training for clinicians, the use of telemedicine to facilitate shared decision-making, and the introduction of time-limited trials for dialysis to overcome these obstacles. The integration of palliative care into routine renal treatment and the promotion of transparent communication among healthcare professionals represent key strategies to enhance the quality of life and end-of-life care for people on hemodialysis. By embracing innovative strategies and fostering collaboration, healthcare providers can deliver more patient-centered, holistic care that meets the complex needs of seriously ill patients within an aging population undergoing hemodialysis.

Effects of upper limbs' neuromuscular electrical stimulation (NMES) superimposed to voluntary contraction added to a protocol of intradialytic leg cycle ergometer exercise, in muscle strength, functional capacity and quality of life of adult patients with CKD: a randomized clinical trial protocol.

OBJECTIVE: To investigate the effects of unilateral upper limbs' (ULM) neuromuscular electrical stimulation (NMES) superimposed on a voluntary contraction added to a protocol of intradialytic leg cycle ergometer exercise on muscle strength, functional capacity and quality of life of adult patients with chronic kidney disease (CKD). METHODS: This randomized controlled clinical trial will be carried out at a Brazilian University Hospital. The patients will be evaluated and randomly allocated to an intervention group (i.e., unilateral NMES on the upper limb without hemodialysis fistula for 20 min and leg cycle ergometer for 30 min) or a control group (i.e., unilateral NMES-Sham on the upper limb without hemodialysis fistula for 20 min and leg cycle ergometer for 30 min). The patients will be treated for 8 weeks, with three weekly treatment sessions totaling 24 sessions. MEASUREMENTS: ULM muscle strength, functional capacity, quality of life and also the feasibility, safety and patient adherence to the exercise protocol. All physical measurements will be collected by trained researchers before treatment (week 0) and at the end of treatment (week 9), always in the second hemodialysis session of the week. It will be used in an intention-to-treat analysis. RESULTS/CONCLUSIONS: The outcomes of this clinical trial protocol may help to know the possible benefits of unilateral ULM' NMES superimposed on a voluntary contraction added to a protocol of leg cycle ergometer for patients with CKD and to aid clinical decisions about future implementation or not of this technique (NMES) in intradialytic physical training programs.

Development and validation of a prediction model for all-cause mortality in maintenance dialysis patients: a multicenter retrospective cohort study.

BACKGROUND: The mortality risk varies considerably among individual dialysis patients. This study aimed to develop a user-friendly predictive model for predicting all-cause mortality among dialysis patients. METHODS: Retrospective data regarding dialysis patients were obtained from two hospitals. Patients in training cohort (N = 1421) were recruited from the Fifth Affiliated Hospital of Sun Yat-sen University, and patients in external validation cohort (N = 429) were recruited from the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine. The follow-up endpoint event was all-cause death. Variables were selected by LASSO-Cox regression, and the model was constructed by Cox regression, which was presented in the form of nomogram and web-based tool. The discrimination and accuracy of the prediction model were assessed using C-indexes and calibration curves, while the clinical value was assessed by decision curve analysis (DCA). RESULTS: The best predictors of 1-, 3-, and 5-year all-cause mortality contained nine independent factors, including age, body mass index (BMI), diabetes mellitus (DM), cardiovascular disease (CVD), cancer, urine volume, hemoglobin (HGB), albumin (ALB), and pleural effusion (PE). The 1-, 3-, and 5-year C-indexes in the training set (0.840, 0.866, and 0.846, respectively) and validation set (0.746, 0.783, and 0.741, respectively) were consistent with comparable performance. According to the calibration curve, the nomogram predicted survival accurately matched the actual survival rate. The DCA showed the nomogram got more clinical net benefit in both the training and validation sets. CONCLUSIONS: The effective and convenient nomogram may help clinicians quantify the risk of mortality in maintenance dialysis patients.

Hyperparathyroidism, Serum Phosphorus and Dietary Intake in Hemodialysis Patients: Is There a Novel Relationship?

The management of hyperparathyroidism (intact parathyroid hormone (iPTH) serum levels > 585 pg/mL), frequently focuses on the appropriate control of mineral and bone markers, with the decrease in serum and dietary phosphorus as two of the targets. We aimed to investigate the association between iPTH, serum phosphorus levels and dietary intake. This was a cross-sectional, multicenter, observational study with 561 patients on hemodialysis treatment. Clinical parameters, body composition and dietary intake were assessed. For the analysis, patients were divided into three groups: (a) iPTH < 130, (b) iPTH between 130 and 585 and (c) iPTH > 585 pg/mL. The association between PTH, serum phosphorus and dietary intake was analyzed using linear regression models. In the whole sample, 23.2% of patients presented an iPTH > 585 pg/mL. Patients with higher iPTH levels were those with longer HD vintage and lower ages, higher serum phosphorus, serum calcium, Ca/P product, albumin and caffeine intake, and a lower dietary intake of phosphorus, fiber, riboflavin and folate. Higher serum phosphorus predicted higher iPTH levels, even in the adjusted model. However, lower dietary phosphorus and fiber intake were predictors of higher iPTH levels, including in the adjusted model. Our results bring new data to the relationship between dietary intake and iPTH values. Despite higher serum phosphorus being observed in patients with HPTH, an opposite association was noted regarding dietary phosphate and fiber.

Enhancing Bromelain Recovery from Pineapple By-Products: A Sustainable Approach for Value Addition and Waste Reduction.

Pineapple by-products are good sources of bromelain, a complex enzyme with commercial applications. This study evaluated the feasibility of producing bromelain powders from pineapple waste using an organic solvent-free approach. Pineapple by-products (from var. MD2), including cores, peels, crowns, stems, and basal stems, were homogenized with deionized water, and the pH of the mixture was adjusted to 4.5 and 9 (isoelectric points of fruit bromelain and stem bromelain), clarified, ultra-filtered, and freeze-dried to produce bromelain powders. The enzymatic activity of the bromelain powders was measured using the gelatin and casein digestion methods. The bromelain powders from the crowns did not show significant enzymatic activity (p < 0.05). Meanwhile, bromelain powders produced from the cores and peels had an enzymatic activity of 694 gelatin digesting units (GDU)/g and 124 casein digesting units (CDU)/mg, and 1179 GDU/g and 217 CDU/mg, respectively. Bromelain powders from the basal stems showed the highest enzymatic activity (2909 GDU/g and 717 CDU/mg). Increasing the pH of the liquid mixture before the purification and freeze drying significantly (p < 0.05) reduced the enzymatic activity of the bromelain powders. Using a practical and organic solvent-free approach, this study demonstrates the feasibility of producing bromelain powders with high enzymatic activity from pineapple waste.

Dialysis for older adults: why should the targets be different?

The number of patients aged > 75-years treated by dialysis continues to increase, particularly in developed countries. Haemodialysis is a well-established treatment with national and international clinical guidelines designed to provide patients with optimal treatment. However, these were developed when the dialysis population was younger, and less co-morbid. This change in patient demographics questions whether these guideline targets still apply to older patients. More patients now start dialysis with residual kidney function and could benefit from a less frequent dialysis schedule. Older patients have a lower thirst drive, so lower interdialytic gains, reduced appetite, muscle mass and physical activity would potentially allow starting dialysis with less frequent sessions a practical option. Similarly, patients with residual kidney function and lower metabolic activity may not need to meet current dialyser Kt/Vurea clearance targets to remain healthy. Instead, some elderly patients may be at risk of malnutrition and might need liberalisation of the low salt, potassium and phosphate dietary restrictions, or even additional supplements to ensure adequate protein intake. Although a fistula is the preferred vascular access, a forearm fistula may not be an option due to vascular disease, while a brachial fistula can potentially compromise cardiovascular reserve, so a dialysis catheter becomes the de facto access, especially in patients with limited life expectancy. Thus, clinical guideline targets designed for a younger less co-morbid dialysis population may not be equally applicable to the older patient initiating dialysis, and so a more individualised approach to dialysis prescription and vascular access is required.

A novel scenario in the therapeutic management of anemia of chronic kidney disease: placement and use of roxadustat.

Anemia is a frequent and early chronic kidney disease (CKD) complication. Its management is currently based on oral or intravenous iron supplements, erythropoiesis-stimulating agents, and red blood cell transfusions, when the benefits of transfusion outweigh the risks. Anemia in CKD patients is underdiagnosed and undertreated. Current standard of care is associated with challenges and therefore new treatment approaches have been sought. Hypoxia-inducible factor-prolyl-hydroxylase enzyme inhibitors are a new class of orally administered drugs used to treat anemia associated with CKD. Small-molecule hypoxia-inducible factor-prolyl-hydroxylase inhibitors have a novel mechanism of action that activates the hypoxia-inducible factor (oxygen-sensing) pathway resulting in a coordinated erythropoietic response, leading to increased endogenous erythropoietin production, improved iron absorption and transport, and reduced hepcidin. Roxadustat is the first hypoxia-inducible factor-prolyl-hydroxylase inhibitor approved by the European Medicines Agency (EMA) and reimbursed in Italy by the Italian Medicines Agency (AIFA) for the treatment of adult patients with symptomatic CKD-related anemia. This authorization was based on the outcome of a globally-conducted phase 3 clinical trial program comprising eight pivotal multicenter randomized studies. In the absence of up-to-date guidelines, we performed a critical appraisal of the placement and use of roxadustat in this therapeutic context.

Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations.

Patients with end-stage kidney disease (ESKD) have a high symptom-burden and high rates of morbidity and mortality. Despite this, evidence has shown that this patient group does not have timely discussions to plan for deterioration and death, and at the end of life there are unmet palliative care needs. Advance care planning is a process that can help patients share their personal values and preferences for their future care and prepare for declining health. Earlier, more integrated and holistic advance care planning has the potential to improve access to care services, communication, and preparedness for future decision-making and changing circumstances. However, there are many barriers to successful implementation of advance care planning in this population. In this narrative review we discuss the current evidence for advance care planning in patients on dialysis, the data around the barriers to advance care planning implementation, and interventions that have been trialled. The review explores whether the concepts and approaches to advance care planning in this population need to be updated to encompass current and future care. It suggests that a shift from a problem-orientated approach to a goal-orientated approach may lead to better engagement, with more patient-centred and satisfying outcomes.

Magnesium and Vascular Calcification in Chronic Kidney Disease: Current Insights.

Magnesium (Mg) plays crucial roles in multiple essential biological processes. As the kidneys are the primary organ responsible for maintaining the blood concentration of Mg, people with chronic kidney disease (CKD) may develop disturbances in Mg. While both hyper- and hypomagnesemia may lead to adverse effects, the consequences associated with hypomagnesemia are often more severe and lasting. Importantly, observational studies have shown that CKD patients with hypomagnesemia have greater vascular calcification. Vascular calcification is accelerated and contributes to a high mortality rate in the CKD population. Both in vitro and animal studies have demonstrated that Mg protects against vascular calcification via several potential mechanisms, such as inhibiting the formation of both hydroxyapatite and pathogenic calciprotein particles as well as limiting osteogenic differentiation, a process in which vascular smooth muscle cells in the media layer of the arteries transform into bone-like cells. These preclinical findings have led to several important clinical trials that have investigated the effects of Mg supplementation on vascular calcification in people with CKD. Interestingly, two major clinical studies produced contradictory findings, resulting in a state of equipoise. This narrative review provides an overview of our current knowledge in the renal handling of Mg in health and CKD and the underlying mechanisms by which Mg may protect against vascular calcification. Lastly, we evaluate the strength of evidence from clinical studies on the efficacy of Mg supplementation and discuss future research directions.

Can curcumin supplementation break the vicious cycle of inflammation, oxidative stress, and uremia in patients undergoing peritoneal dialysis?

BACKGROUND & AIMS: Turmeric (a source of curcumin) is an excellent food to modulate oxidative stress, inflammation, and gut dysbiosis in patients with chronic kidney disease (CKD). However, no studies report the benefits of curcumin in patients undergoing peritoneal dialysis (PD). This study aims to evaluate the effects of curcuminoid supplementation on oxidative stress, inflammatory markers, and uremic toxins originating from gut microbiota in patients with CKD undergoing PD. METHODS: This longitudinal, randomized, single-blind, placebo-controlled trial evaluated 48 patients who were randomized into two groups: Curcumin (three capsules of 500 mg of Curcuma longa extract, with 98.42 % total curcuminoids) or placebo (three capsules of 500 mg of starch) for twelve weeks. In the peripheral blood mononuclear cells (PBMCs), the transcriptional expression levels of Nrf2, HOX-1 and NF-κB were evaluated by quantitative real-time PCR. Oxidative stress was evaluated by malondialdehyde (MDA) and total Thiol (T-SH). TNF-α and IL-6 plasma levels were measured by ELISA. P-cresyl sulphate plasma level, a uremic toxin, was evaluated by high-performance liquid chromatography (HPLC) with fluorescent detection. RESULTS: Twenty-four patients finished the study: 10 in the curcumin group (57.5 ± 11.6 years) and 14 in the placebo group (56.5 ± 10.0 years). The plasma levels of MDA were reduced after 12 weeks in the curcumin group (p = 0.01), while the placebo group remained unchanged. However, regarding the difference between the groups at the endpoint, no change was observed in MDA. Still, there was a trend to reduce the p-CS plasma levels in the curcumin group compared to the placebo group (p = 0.07). Likewise, the concentrations of protein thiols, mRNA expression of Nrf2, HOX-1, NF-κB, and cytokines plasma levels did not show significant changes. CONCLUSION: Curcuminoid supplementation for twelve weeks attenuates lipid peroxidation and might reduce uremic toxin in patients with CKD undergoing PD. This study was registered on Clinicaltrials.gov as NCT04413266.

Effectiveness of mindfulness-based interventions delivered via technology versus therapist among patients on peritoneal dialysis at an outpatient clinic in Singapore.

AIMS: This study aimed to (i) evaluate the effectiveness of mindfulness-based interventions in improving self-efficacy, reducing stress and anxiety among peritoneal dialysis patients, and (ii) compare the most effective method of mindfulness based interventions. METHODS: This randomized three-arm controlled trial recruited first-time peritoneal dialysis patients from the peritoneal dialysis outpatient clinic in Singapore. Patients were randomly allocated to either video-assisted mindfulness training, therapist-assisted mindfulness training or treatment-as-usual. All groups received 4.5 days of structured peritoneal dialysis training at the peritoneal dialysis centre, while video-assisted mindfulness training and therapist-assisted mindfulness training groups were taught additional mindfulness-based techniques. The perceived stress scale, self-efficacy, and anxiety (State and Trait Anxiety Inventory) were measured at baseline, 4- and 12 weeks post-randomization, using reliable and valid instruments. RESULTS: Thirty-nine patients were recruited (13 in each group). All the therapies showed a significant time trend in anxiety. Only therapist- and video-assisted mindfulness training showed a significant trend in perceived stress scale scores but not treatment-as-usual. All Intervention X Time interactions were not significant. Patients in therapist- and video-assisted mindfulness training groups had reduced perceived stress scale scores compared to treatment-as-usual at week 12. CONCLUSION: This study demonstrated the potential of mindfulness-based interventions in reducing stress among first-time PD patients.

Italian healthcare resource consumption for patients on hemodialysis treated for chronic kidney disease-associated pruritus (CKD-aP).

Background: Chronic kidney disease-associated pruritus (CKD-aP) affects patients on hemodialysis. This study identified hemodialysis patients presumably affected or not affected by CKD-aP and integrated healthcare costs, from the perspective of the Italian administrative healthcare data. Methods: Through cross-linkage of Italian administrative healthcare data collected between 2015 and 2017 (accrual period) in the database of Fondazione ReS (Ricerca e Salute), patients undergoing in-hospital/outpatient hemodialysis were selected. Cohorts with and without CKD-aP were created based on the presence/absence of CKD-aP-related treatment (according to common clinical practice and guidelines) supplies and assessed in terms of CKD-aP-related treatments and mean healthcare costs per capita paid by the Italian National Health Service (INHS). Results: Of 1,239 people on hemodialysis for ≥2 years, CKD-aP affected 218 patients. Patients with CKD-aP were older and with more comorbidities. During the follow-up year, on average, the INHS spent €37,065 per case, €31,286 per control and € 35,988 per non-CKD-aP subject. High-efficiency dialytic therapies performed to people on hemodialysis with CKD-aP largely weighed on the overall mean annual cost. Conclusions: This real-world study identified patients on chronic hemodialysis potentially treated for CKD-aP. Interestingly, high-efficiency dialysis seems the most frequent and expensive choice for the treatment of CKD-aP. The discovery of appropriate and effective treatments for this condition might offer cost offsets.

Advanced Image-Guided Percutaneous Technique Versus Advanced Laparoscopic Surgical Technique for Peritoneal Dialysis Catheter Placement.

Rationale & Objective: Timely placement of a functional peritoneal dialysis (PD) catheter is crucial to long-term PD success. Advanced image-guided percutaneous and advanced laparoscopic techniques both represent best practice catheter placement options. Advanced image-guided percutaneous is a minimally invasive procedure that does not require general anesthesia. Study Design: Retrospective cohort study comparing time from referral to procedure, complication rate, and 1-year catheter survival between placement techniques. Setting & Participants: Patients who had advanced laparoscopic or advanced image-guided percutaneous PD catheter placement from January 1, 2011 to December 31, 2013 in an integrated Northern California health care delivery system. Exposure: PD catheter placement using advanced laparoscopic or advanced image-guided percutaneous techniques. Outcomes: One-year PD catheter survival; major, minor, and infectious complications; time from referral to PD catheter placement; and procedure time. Analytical Approach: Wilcoxon rank sum tests to compare referral and procedure times; χ2/Fisher exact tests to compare complications; and modified least-squares regression to compare adjusted 1-year catheter survival between PD placement techniques. Results: We identified 191 and 238 PD catheters placed through advanced image-guided percutaneous and advanced laparoscopic techniques, respectively. Adjusted 1-year PD catheter survival was 80% (95% CI, 74%-87%) using advanced image-guided percutaneous technique vs 91% (87%-96%) using advanced laparoscopic technique (P = 0.01). Major complications were <1% in both groups. Minor and infectious complications were 45.6% and 38.7% in advanced image-guided percutaneous and advanced laparoscopic techniques, respectively (P = 0.01). Median days from referral to procedure were 12 and 33 for patients undergoing advanced image-guided percutaneous and advanced laparoscopic techniques, respectively (P < 0.001). Median procedure time was 30 and 44.5 minutes for patients undergoing advanced image-guided percutaneous and advanced laparoscopic techniques, respectively (P < 0.001). Limitations: Retrospective study with practice preference influenced by timing, local expertise, and resources. Conclusions: Both advanced image-guided percutaneous and advanced laparoscopic techniques reported rare major complications and demonstrated excellent (advanced laparoscopic) and acceptable (advanced image-guided percutaneous) 1-year PD catheter survival. For patients referred for PD catheter placement at centers where advanced laparoscopic resources or expertise remain limited, the advanced image-guided percutaneous technique can provide a complementary and timely option to support the utilization of PD. Plain-Language Summary: Peritoneal dialysis is a preferred dialysis modality for many patients. However, the lack of available skilled surgeons can limit the placement of the peritoneal dialysis catheter in a timely manner. In the past decade, interventional radiology has developed expertise in placing peritoneal dialysis catheters. Using data from an integrated health care system, we compared the outcome of peritoneal dialysis catheters placed using laparoscopic surgery and interventional radiology techniques. Our results showed excellent 1-year patency of peritoneal dialysis catheters placed using laparoscopic surgery, whereas interventional radiology placement of catheters had lower but acceptable 1-year patency survival, based on best practice guideline criteria. Hence, interventional radiology placement of peritoneal dialysis catheters may be a viable alternative when laparoscopic surgery is not available or feasible.

Investigation of the effect of Jacobson's relaxation technique on the fatigue of family caregivers of hemodialysis patients: a single-blinded randomized controlled trial.

BACKGROUND: Caring for hemodialysis patients could be a heavy burden on family caregivers, causing them to become fatigued and decrease their quality of life. This study aimed to investigate whether Jacobson's relaxation can help alleviate the fatigue of family caregivers of hemodialysis patients. METHODS: This randomized controlled trial was conducted in 2021. Sixty-six family caregivers of hemodialysis patients were recruited by convenience sampling from a referral hospital in Tehran, Iran, and assigned randomly by coin toss to two groups of experimental (n = 32) and control (n = 34). Caregivers in the experimental group performed Jacobson's relaxation three times a week, each time for 30-45 min, for 30 days. The score and severity of fatigue before, 2 weeks after, and 1 month after the intervention were measured with the Fatigue Severity Scale. Data analysis was performed in the statistics software SPSS using descriptive statistics (frequency, percentage, mean, and standard deviation) and analytic statistics (Independent Samples t-test, Mann-Whitney U test, Chi-Square test, Fisher's exact test, and RM-ANOVA test). The significance level was less than 0.05. RESULTS: The fatigue scores of the experimental and control groups were not significantly different before the intervention (4.42 ± 0.42 vs. 4.38 ± 0.42, P = 0.696). However, the experimental group had significantly lower fatigue scores than the control group 2 weeks after the intervention (4.11 ± 0.63 vs. 4.39 ± 0.42, P = 0.036) and 1 month after the intervention (3.5 ± 0.71 vs. 4.4 ± 0.44, P = 0.001). The results also showed a significant drop in the fatigue score of the experimental group after the intervention (P < 0.0001), but no such change in the control group (P = 0.662). CONCLUSION: Jacobson's relaxation technique was effective in alleviating the fatigue of family caregivers of hemodialysis patients. Nurses are therefore recommended to promote the technique as a safe and easy method of fatigue management for family caregivers.