Long-term Dialysis Research Articles

Treatment decision-making and care among older adults with kidney failure: protocol for a multicentre, prospective observational cohort study with nested substudies and linked qualitative research (the Elderly Advanced CKD Programme)

IntroductionShared treatment decision-making and planning of care are fundamental in advanced chronic kidney disease (CKD) management. There are limited data on several key outcomes for the elderly population including survival,...

Inhibition of calpain9 attenuates peritoneal dialysis-related peritoneal fibrosis.

Aim: Peritoneal dialysis is a common renal replacement method for end-stage renal disease. Long-term peritoneal dialysis leads to peritoneal dialysis-related peritoneal fibrosis, which leads to a cessation of treatment. Calpain is a protein belonging to calcium-dependent endopeptidase family and plays an important role in extracellular matrix remodeling. Here, we evaluated the effect of calpain in peritoneal dialysis-related peritoneal fibrosis. Methods: We established two animal models of peritoneal fibrosis and inhibited the activity of Calpain, and then collected peritoneal tissue to evaluate the progress of fibrosis and the changes of Calpain and β-catenin. We obtained Rat peritoneal mesothelial cells and Human peritoneal mesothelial cell line and stimulated with TGF-β to produce extracellular matrix. Next we inhibited Calpain activity or reduced Calpain9 expression, and then assessed changes in extracellular matrix and β-catenin. Results: Inhibition of calpain activity attenuated chlorhexidine glucose and peritoneal dialysis-induced peritoneal thickening and β-catenin expression in mice. In addition, compared with the control group, when primary rat peritoneal mesothelial cells or human peritoneal mesothelial cells were treated with transforming growth factor beta, down-regulation of calpain activity inhibited the expression of Fibronectin and Collagen I, and increased the expression of E-cadherin. These changes could be adjusted after silencing calpain9. Finally, calpain9 deficiency was associated with down-regulation of Fibronectin and β-catenin in human peritoneal mesothelial cells. Conclusion: Our results suggest that calpain9 may be a key molecule in mediating peritoneal dialysis-related peritoneal fibrosis.

The rate of chronic kidney disease progression in advanced stages and the dynamics of the uremic syndrome parameters

Background. The current practice of patients with advanced CKD stages management is not optimal, as it leads to the risk of an emergency dialysis start with an unfavorable prognosis, does not utilize all the possibilities of nephroprotective therapy and does not provide optimal correction of the most important uremic syndromes before starting dialysis, which worsens the per spectives of long-term patient-oriented dialysis treatment. THE AIM. The obtained features of the standard practice will provide the possibility to assemble group carefully matched with intensive management group to compare outcomes in future prospective study and to assess the significance of the proposed program components of the intensive management of patients with advanced stages of chronic kidney disease in the "transition center". PATIENTS AND METHODS. A group with regular (at least 6 visits per year) follow-up of 540 patients with baseline CKD3B was retrospectively formed from the city nephrology center database (which included 7696 patients with CKD3 and higher) and was traced to the need for renal replacement therapy or to death. As part of the follow-up, patients underwent regular clinical and laboratory evaluation and received nephroprotective therapy, which were recorded in the database. RESULTS. The dynamics of an accelerating decrease in eGFR (according to CKD-EPICr) from median of -2.76 (-3.26÷-2.36) to -4.34 (-5.01÷-3.46) and further to -6.01 (-7.11÷-5.23) ml/min/1.73 m2/ year for the stages of CKD3B→CKD4→CKD5 in parallel with the dynamics of blood levels of hemoglobin (and iron), phosphate (and calcium), albumin, as well as proteinuria is described – factors that turned out to be significant in the multiple regression model with a dependent variable – the rate of eGFR reduction (the significance of the model F=2.864; p=0.015). CONCLUSION. The obtained detailed description of the progression of CKD in a typical regional population under standard management conditions will provide the possiblity to form a group from a cohort of regular monitoring in a nephrocenter, carefully compared with an intensive management group in the prototype of a transition center based on a large inpatient dialysis center to assess the significance of the components of the proposed control and interventions program.

Investigation of Renal Decline and New Onset Dialysis Following Endovascular Aneurysm Repair in the Vascular Quality Initiative.

The purpose of this study is to identify variables significantly associated with renal function decline after elective endovascular infra-renal abdominal aortic aneurysm repair and to identify the rate and risks of subsequent progression to dialysis. Specifically, we investigate the long-term impact of supra-renal fixation, female gender, and physiologically stressful perioperative events on renal function following endovascular aneurysm repair (EVAR). Review of all EVAR cases in the Vascular Quality Initiative between 2003 and 2021 was conducted to investigate variable associations with three primary outcomes: postoperative acute renal insufficiency (ARI); greater than 30% decline in glomerular filtration rate (GFR) in patients beyond 1year of follow up; and new onset dialysis requirement at any point in follow up. Binary logistic regression analysis was performed for the events of acute renal insufficiency and new onset dialysis requirement. Cox proportional hazard regression was performed regarding long term GFR decline. Postoperative ARI occurred in 3.4% (1692/49772) of patients. Significant (P < .05) association with postoperative ARI was noted for: age (OR 1.014/year, 95% CI 1.008-1.021); female gender (OR 1.44, 95% CI 1.27-1.67); hypertension (OR 1.22, 95% CI 1.04-1.44); chronic obstructive pulmonary disease (OR 1.34, 95% CI 1.20-1.50); anemia (OR 4.24, 95% CI 3.71-4.84); reoperation at index admission (OR 7.86, 95% CI 6.47-9.54); baseline renal insufficiency (OR 2.29, 95% CI 2.03-2.56); larger aneurysm diameter; increased blood loss; and higher volumes of intra-operative crystalloid. Risk factors (P < .05) correlating with a decline of 30% in GFR at any time beyond 1year were: female gender (HR 1.43, 95% CI 1.24-1.65); body mass index (BMI) less than 20 (HR 1.34, 95% CI 1.03-1.74); hypertension (HR 1.38, 95% CI 1.15-1.64); diabetes (HR 1.34, 95% CI 1.17-1.53); COPD (HR 1.21, 95% CI 1.07-1.37); anemia (HR 1.92, 95% CI 1.52-2.42); baseline renal insufficiency (HR 1.31, 95% CI 1.15-1.49); absence of discharge ace-inhibitor (HR 1.27, 95% CI 1.13-1.42); long term re-intervention (HR 2.43, 95% CI 1.84-3.21) and larger AAA diameter. Patients who experienced long term GRF decline had a significantly higher long-term morality. New onset dialysis following EVAR occurred in .47% (234/49772) of those meeting inclusion criteria. Higher rate (P < .05) of new onset dialysis was associated with age (OR 1.03/year, 95% CI 1.02-1.05); diabetes (OR 1.376, 95% CI 1.005-1.885); baseline renal insufficiency (OR 6.32, 95% CI4.59-8.72); Reoperation at index admission (OR 2.41, 95% CI 1.03-5.67); postoperative ARI (OR 23.29, 95% CI 16.99-31.91); absence of beta blocker (OR 1.67, 95% CI 1.12-2.49); long term graft encroachment on renal arteries (OR 4.91, 95% CI 1.49-16.14). New onset dialysis following EVAR is a rare event. Perioperative variables influencing renal function following EVAR include blood loss, arterial injury, and reoperation. Supra-renal fixation is not associated with postoperative acute renal insufficiency or new onset dialysis in long term follow up. Renal protective measures are recommended for patients with baseline renal insufficiency undergoing EVAR as acute renal insufficiency following EVAR portends a 20-fold increased risk of new onset dialysis in long term follow up.

Association Between Nephrologist Ownership of Dialysis Facilities and Clinical Outcomes

Ownership of US dialysis facilities presents a financial conflict of interest for nephrologists, who may change their clinical practice to improve facility profitability. To investigate the association between nephrologist ownership of freestanding dialysis facilities and clinical outcomes. This cross-sectional study was conducted using US Renal Data System data linked to a data set of freestanding nonpediatric dialysis facility owners. Participants were a sample of all adults with fee-for-service Medicare receiving dialysis for end-stage kidney disease from January 2017 to November 2017 at included facilities. Data were analyzed from April 2020 through August 2022. Outcomes associated with nephrologist ownership were assessed using a difference-in-differences analysis comparing the difference in outcomes between patients treated by nephrologist owners and patients treated by nonowners within facilities owned by nephrologists after accounting for differences in patient outcomes between nephrologist owners and nonowners in other facilities. Outcomes plausibly associated with nephrologist ownership were evaluated: (1) treatment volumes (missed treatments and transplant waitlist status); (2) erythropoietin-stimulating agent (ESA) use and related outcomes (anemia, defined as hemoglobin level <10 g/dL, and blood transfusions), (3) quality metrics (mortality, hospitalizations, 30-day readmissions, hemodialysis adequacy, arteriovenous fistula use, and hemodialysis catheter use for ≥3 months), and (4) home dialysis use. A cohort of 251 651 patients (median [IQR] age, 66 [46-85] years; 112 054 [44.5%] women; 9765 Asian [3.9%], 86 837 Black [34.5%], and 148 617 White [59.1%]; 38 938 Hispanic [15.5%]) receiving dialysis for end-stage kidney disease were included. Patient treatment by nephrologist owners at their owned facilities was associated with a 2.4 percentage point (95% CI, 1.1-3.8 percentage points) higher probability of home dialysis, a 2.2 percentage point (95% CI, 3.6-0.7 percentage points) lower probability of receiving an ESA, and no significant difference in anemia or blood transfusions. Patient treatment by nephrologist owners at their owned facilities was not associated with differences in missed treatments, transplant waitlisting, mortality, hospitalizations, 30-day readmissions, hemodialysis adequacy, or fistula or long-term dialysis catheter use. This cross-sectional cohort study found that nephrologist ownership was associated with increased home dialysis use, decreased ESA use, and no change in anemia or blood transfusions.

LBODP041 Effects Of Sodium-glucose Co-transporter 2 Inhibitors (sglt-2 Inhibitors) On Adipokines And Inflammatory Biomarkers In Type2 Diabetic Patients

Abstract Background Type 2 diabetes mellitus is a chronic metabolic disease associated with high cardiovascular (CV) risk. SGLT-2 inhibitors reduce HbA1c and show favorable effects on body weight, blood pressure, lipid profile, arterial stiffness, and endothelial function. More importantly, SGLT-2 inhibitors have demonstrated impressive cardioprotective and renoprotective effects. The main mechanisms of cardioprotective effects have been attributed to improvement in cardiac cell metabolism, improvement in ventricular loading conditions, inhibition of the Na+/H+ exchanger in myocardial cells, alteration in adipokines and cytokines production. This exploratory research aimed to observe the effects of Canagliflozin, Dapagliflozin, and Empagliflozin on select inflammatory biomarkers, adiponectin, for instance. Methods Comparison of serum adiponectin between baseline with 16-week after SGLT-2 inhibitors therapy were assessed in type 2 diabetic participants. Changes of chosen metabolic and anthropometric variables were discussed. Results At 16-week after SGLT-2 inhibitors treatment, a striking increment in mean serum adiponectin by 1.25 mcg/mL (95% CI: 0. 02, 2.48) or 81% was revealed. Furthermore, they showed a reduction of mean BMI 1.12% (95% CI: -1.74%, -0.50%), systolic blood pressure 1 mmHg (95% CI: -1.85, -0.72), diastolic blood pressure 1 mmHg (95% CI: -1.65, -0.52), fasting plasma glucose 34 mg/dL (95% CI: -51.66, -17.10), and HbA1c 0.73% (95% CI: -1.25%, -0.21%). No between-group differences were expressed with the other biomarkers. Serious side effects such as ketoacidosis, hypoglycemic status, genitourinary tract infection, acute kidney injury, or long-term dialysis dependence were not appeared. Conclusions SGLT-2 inhibitors can improve changes in serum adiponectin which appreciatively benefit in cardiovascular outcomes among type 2 diabetes. Keywords: SGLT-2 inhibitors, adipokines, inflammatory biomarkers, type 2 diabetes mellitus, adiponectin, cardiovascular outcomes, cardioprotective, renoprotective Presentation: No date and time listed

Evaluating the results of MyTEMP, a cluster randomised trial of lower temperature haemodialysis: the end of a cool idea?

Globally, the burden of chronic kidney disease is growing at an alarming rate.1 If continued unchecked, almost 5 million people are predicted to require dialysis or a kidney transplant by 2030.2 Haemodialysis is the most common type of treatment for those with kidney failure, and its widespread use has extended the lives of millions of people since successful long-term dialysis was established in the 1960s. However, patients face high rates of cardiovascular disease, an average survival of less than 5 years, a significant symptom burden, and negative effects on quality of life.

Recent innovations in renal replacement technology and potential applications to transplantation and dialysis patients: a review of current methods.

The current standard of care for patients with end-stage renal disease (ERSD) is a kidney transplant or dialysis when a donor organ isnot available. The growing gap between patients who require a kidney transplant and the availability of donor organs as well as thenegative effects of long-term dialysis, such as infection, limited mobility, and risk of cancer development, drive the impetus to developalternative renal replacement technology. The goal of this review is to assess the potential of two of the most recent innovations inkidney transplant technology-the implantable bioartificial kidney (BAK) and kidney regeneration technology-in addressing the aforementionedproblems related to kidney replacement for patients with ERSD. Both innovations are fully implantable, autologous, personalizedwith patient cells, and can replace all aspects of kidney function. Not only do these new innovations have the potential toimprove the possibility of transplantation for more patients, they also have potential to improve the outcome of transplantation or dialysis-related renal cancer diagnosis. A major limitation of the current technology is that both implantable BAK and kidney regenerationtechnology are still in preclinical stages, and thus their potential effects cannot be comprehensively generalized to human patients.

Cost-Utility of Immunosuppressive Therapy Post-Renal Transplantation in Saudi Arabia: The Saudi Ministry of Health Perspective

ObjectivesChronic kidney disease is ranked fourth among the top 10 causes of death in Saudi Arabia. Renal transplantation has been recognized as the treatment of choice compared with long-term dialysis to maintain graft survival and prolong a patient’s healthy living. Immunosuppressants (ISs) must be administered lifelong. The choice between IS therapies can be challenging because of the similarity in efficacy with some differences in adverse events profile. The objective of this study was to assess the cost-effectiveness of different IS regimens in Saudi Arabia. MethodsA 25-year Markov model was developed based on a previously published study from the Saudi Ministry of Health payer perspective. Efficacy parameters were driven from the literature, whereas cost data were estimated from the Ministry of Health database. A Monte Carlo simulation was conducted to test the base-case model results’ robustness. ResultsAll comparators resulted in 6.2 quality-adjusted life-years (QALYs) except for Advagraf® treatment (5.5 QALYs). Generic tacrolimus plus mycophenolate mofetil (MMF) will cost 70 701.45 US dollars ($) (Saudi riyal 265 130.44) per patient to gain 6.2 QALYs over 25 years’ time horizon. In the improved adherence scenario, Envarsus® plus generic MMF generated 9.6 QALYs with a cost of $59 849 per patient. Monte Carlo simulation results have shown that generic tacrolimus is still the cheapest treatment option compared with other treatment arms. ConclusionsThe current analysis suggested that all IS options are not cost-effective strategies relative to the willingness-to-pay threshold of $20 000. Nevertheless, Envarsus plus generic MMF regimen could become the most cost-effective regimen at different willingness-to-pay thresholds.

Survival Benefit of First Single-Organ Deceased Donor Kidney Transplantation Compared With Long-term Dialysis Across Ages in Transplant-Eligible Patients With Kidney Failure

Kidney transplant is considered beneficial in terms of survival compared with continued dialysis for patients with kidney failure. However, randomized clinical trials are infeasible, and available evidence from cohort studies is at high risk of bias. To compare restricted mean survival times (RMSTs) between patients who underwent transplant and patients continuing dialysis across transplant candidate ages and depending on waiting time, applying target trial emulation methods. In this retrospective cohort study, patients aged 18 years or older appearing on the wait list for their first single-organ deceased donor kidney transplant between January 1, 2000, and December 31, 2018, in Austria were evaluated. Available data were obtained from the Austrian Dialysis and Transplant Registry and Eurotransplant and included repeated updates on wait-listing status and relevant covariates. Data were analyzed between August 1, 2019, and December 23, 2021. A target trial was emulated in which patients were randomized to either receive the transplant immediately (treatment group) or to continue dialysis and never receive a transplant (control group) at each time an organ became available. The primary outcome was time from transplant allocation to death. Effect sizes in terms of RMSTs were obtained using a sequential Cox approach. Among the 4445 included patients (2974 men [66.9%]; mean [SD] age, 52.2 [13.2] years), transplant was associated with increased survival time across all considered ages compared with continuing dialysis and remaining on the wait list within a 10-year follow-up. The estimated RMST differences were 0.57 years (95% CI, -0.14 to 1.84 years) at age 20 years, 3.01 years (95% CI, 2.50 to 3.54 years) at age 60 years, and 2.48 years (95% CI, 1.88 to 3.04 years) at age 70 years. The survival benefit for patients who underwent transplant across ages was independent of waiting time. The findings of this study suggest that kidney transplant prolongs the survival time of persons with kidney failure across all candidate ages and waiting times.

Deformation analysis in advanced chronic kidney disease: an important prognostic indicator

Abstract Background Chronic kidney disease (CKD) is associated with a higher incidence of cardiovascular manifestations, particularly in patients with advanced renal impairment on long-term dialysis. Cardiac deformation analysis, assessed by speckle tracking echocardiography has been shown to be a significant prognostic index in various specific populations. Objective To assess the prognostic value of deformation analysis measurements including both systolic parameters as left ventricular (LV) global longitudinal strain, and diastolic indices as left atrial (LA) strain, in patients with end-stage renal disease. Methods We enrolled 67 patients (mean age 62.3±11.8, 65.7% men) with end-stage renal disease. Patients with a confirmed diagnosis of pre/existing cardiac conditions, such as obstructive coronary artery disease, heart failure, severe arrhythmias or severe valvular disease were excluded from the study. A comprehensive transthoracic echocardiography study was performed at baseline. All images were stored digitally and subsequent analysis was performed offline. LV global longitudinal strain (GLS) and LA strain were calculated semi-automatically using dedicated software. The primary endpoints of the study were major adverse cardiovascular events such as all-cause mortality, cardiovascular mortality, myocardial infarction, and hospitalizations for cardiac adverse events. The median follow-up was five years. Results The study population had normal or mildly impaired systolic function with a mean LV ejection fraction (EF) of 49.17% (±10.41) while 70% of patients had reduced LV GLS, mean 14.35% (±4.49). Regarding LA parameters, 50% of our cohort had impaired LA strain: mean LA reservoir, LA conduit, and LA contractile reserve were 24.11% (±12.61), 10.56% (±5.88), and 13.60% (±9.15) respectively. The 5-year cumulative event-free survival was 58.2% (±6.7), while 30% of major events occurred in the first 2 years after baseline. Age had a moderate correlation with poor prognosis (p=0.013). Of the echocardiographic parameters LV EF, LV GLS, the conduit phase of LA strain, LA volume and various doppler parameters related to diastolic function, such as mitral E/A ratio and late mitral diastolic velocity A, were found to have a significant negative association with total prognosis (p=0.003, p=0.02, p=0.048, p=0.045, p=0.008, and p=0.017 respectively). Logistic regression analysis showed that of the different echocardiographic parameters LV EF, LV GLS, and the conduit phase of LA strain were significantly associated with the overall prognosis (p=0.009, p=0.007, p=0.05). The conduit element of LA strain was the strongest predictor among them (OR=0.77 p=0.04). Conclusion Left ventricular systolic and diastolic dysfunction is a significant prognostic indicator in patients with end stage renal disease. Assessing cardiac mechanics with speckle tracking echocardiography could provide valuable information in this specific population. Funding Acknowledgement Type of funding sources: None.

Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis

Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β2-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigate the effects of human sera on β2m amyloid fibril formation, revealing that sera markedly inhibit amyloid fibril formation. Results from over 100 sera indicate that, although the inhibitory effects of sera deteriorate in long-term dialysis patients, they are ameliorated by maintenance dialysis treatments in the short term. Serum albumin prevents amyloid fibril formation based on macromolecular crowding effects, and decreased serum albumin concentration in dialysis patients is a tertiary risk factor for the onset of DRA. We construct a theoretical model assuming cumulative effects of the three risk factors, suggesting the importance of monitoring temporary and accumulated risks to prevent the development of amyloidosis, which occurs based on supersaturation-limited amyloid fibril formation in a crowded milieu.

Survival and renal outcomes of direct heart transplant from veno-arterial extracorporeal membrane oxygenation support

Abstract Backgrounds Patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support are given the highest priority for cardiac transplantation (OHT) in the new UNOS heart allocation policy adopted in October 2018. Although patients may receive an organ quicker there may not be enough time to recover end-organ function. To date, little is known about survival and renal outcomes of direct OHT in patients that have been supported with VA-ECMO as a bridge to transplant due to limited experience in most transplant centers. Purpose The aim of this study was to investigate survival and renal outcomes of direct OHT in patients supported with VA-ECMO prior to transplant. Methods From January 2010 to February 2022, 23 patients who received single organ OHT alone directly from VA-ECMO support were retrospectively analyzed (16 patients after the new allocation policy). Kaplan-Meier analysis was used to estimate event-free survival. Results The median age of recipients was 48 years. The median length of pre-transplant VA-ECMO support was 5 days. Additional pre-transplant support with intra-aortic balloon pump or Impella was utilized in 15 patients (65.2%) and 2 patients (9%) respectively. There was a trend toward improvement of serum creatinine after initiation of VA-ECMO support (Pre-ECMO: 1.66±1.22 mg/dl vs. Pre-OHT: 1.20±0.74 mg/dl, P=0.084). Four patients required preoperative renal replacement therapy (RRT); three were on RRT at the time of OHT. The median ischemic time of donor hearts was 168 minutes. VA-ECMO support was continued in 10 patients (43.5%) after OHT. Hospital mortality was 8.7% (2 patients). Post-transplant RRT was required in 9 patients (39.1%), and, of these, 5 patients were transitioned to permanent dialysis. Among the 14 patients who did not require post-transplant RRT, none required RRT during the follow-up period (median, 21.5 months). Kaplan-Meier survival analysis showed that estimated survival at 1 year and 3 years were 86.1%, and 77.5%, respectively (Figure 1A). The freedom from dialysis rate was 82.4% at 1 year, and 74.9% at 3 years (Figure 2A). Both survival (100% vs. 66.7%, P=0.008, Fig.1B) and dialysis free rate (100% vs. 55.6%, P=0.002, Figure 2B) at one-year were significantly worse in patients who required postoperative RRT. Conclusions To our knowledge this is the largest single center study of OHT in patients that were supported with VA-ECMO. VA-ECMO as a bridge to end-organ recovery and OHT resulted in excellent outcomes. Patients who required post-transplant RRT more likely to require long-term dialysis, while those that did not receive RRT showed favorable outcomes. Overall survival in this patient population is comparable to patients that were not on VA-ECMO prior to transplant. Funding Acknowledgement Type of funding sources: None.

HOW LOW CAN YOU GO: RECOVERY AFTER A SERUM PH OF 6.62 DUE TO ETHYLENE GLYCOL POISONING

HOW LOW CAN YOU GO: RECOVERY AFTER A SERUM PH OF 6.62 DUE TO ETHYLENE GLYCOL POISONING

Dialysis Decision Making, Dialysis Experiences, and Illness Perceptions: A Qualitative Study of Pakistani Patients Receiving Maintenance Hemodialysis

The incidence and prevalence of patients with kidney failure requiring dialysis are increasing in Pakistan. However, in-depth perspectives on kidney care from Pakistani people requiring maintenance dialysis are lacking. Qualitative interview study. Between September 2020 and January 2021, we interviewed 20 adults receiving maintenance hemodialysis in 2 outpatient dialysis units in Pakistan. We asked open-ended questions to explore their experiences with various aspects of kidney care. We recorded, transcribed, and then, using a phenomenological approach, thematically analyzed interviews. We observed the following 6 main themes: (1) Patients perceived various supernatural phenomena as causes of their illness and chose traditional medicine for chronic kidney disease (CKD) treatment. (2) Patients expressed dissatisfaction with their physicians' communication. They felt poorly informed and resented their decision to initiate dialysis. (3) Family members tried to dissuade patients away from dialysis but also provided support once dialysis was initiated. (4) Patients and families found it challenging to afford dialysis and transplantation and also to arrange for transportation. (5) Women found it challenging to fulfill their obligations as wives and mothers while receiving maintenance dialysis. (6) Patients seemed reluctant to discuss end-of-life care. We collected data from only 2 hospitals in neighboring cities. Additionally, patients on peritoneal dialysis were not included. Our findings shed light on patients' perspectives on kidney care in Pakistan and call for financially feasible solutions to raise kidney disease awareness and improve patients' experiences with dialysis. Physician training in communication and shared dialysis decision making along with the development of culturally adapted decision aids are needed to improve CKD knowledge and shared decision making. Although financial challenges preclude many from receiving long-term dialysis, cost-effective strategies to improve the availability of other options (eg, supportive kidney care, peritoneal dialysis, and transplantation) are still warranted.

Revision of Aneurysmal Arteriovenous Access with Immediate Use Graft Is Safe and Avoids Prolonged Use of Tunneled Hemodialysis Catheters

Aneurysmal arteriovenous fistulas (AVF) can pose a difficult treatment dilemma for the vascular surgeons. Prolonged tunneled dialysis catheters (TDCs) in patients requiring long-term dialysis are associated with significantly increased mortality compared to AVF. We aimed to elucidate the outcomes of aneurysmal arteriovenous (AV) access revision with aneurysm resection and Artegraft® (LeMaitre, New Brunswick, NJ) Collage Vascular Graft placement to avoid prolonged use of TDCs. We reviewed all patients with aneurysmal AV access in whom the access was revised with aneurysm resection and jump graft placement at a single institution from 2018 to 2021. Outcomes were time to cannulation, reintervention rates, time to reintervention, and patency (primary, primary assisted, and secondary). Patency rates were estimated with Kaplan-Meier Survival analysis. A total of 51 revised aneurysmal AV accesses in 51 patients were studied, of which 23.5% (n=12) had perioperative TDC placement. Three patients were done for emergent bleeding. The cohort was 62.8% male (n=32) with a median age of 58years (interquartile range: 49-67). Most patients had brachiocephalic AVF (n=37 [72.6%]). The median follow-up time was 280days. The median time to cannulation was 2days. Time to cannulation was significantly longer in patients with perioperative TDC as compared with those without TDC (24days vs. 2days, P<0.001). Reintervention was required in 41.2% of patients (n=21), at median time of 47days. At 30, 90, 180, and 365days, primary patency rates were 84.3%, 78.3%, 66.6%, and 54.9%; primary assisted patency rates were 94.1%, 88.1%, 79.4%, and 79.4%; and secondary patency rates were 100%, 97.8%, 91.6%, and 91.6%, respectively. The revision of aneurysmal AV access (urgent or elective) with Artegraft as jump graft is safe, with acceptable short- and mid-term patency results. This allows dialysis patients to continue to have a functional access, decreasing the need for a tunneled catheter and reducing the associated risk of sepsis and increased mortality. This should be considered for all patients with aneurysmal, dysfunctional fistulas to maintain AV access and avoid TDC placement.

Immunogenicity and safety of SARS-CoV-2 vaccine in hemodialysis patients: A systematic review and meta-analysis.

Rationale and objectiveCOVID-19 vaccination is the most effective way to prevent COVID-19. For chronic kidney disease patients on long-term dialysis, there is a lack of evidence on the pros and cons of COVID-19 vaccination. This study was conducted to investigate the immunogenicity and safety of COVID-19 vaccines in patients on dialysis.MethodsPubMed, MEDLINE, EMBASE, and the Cochrane Library were systemically searched for cohort, randomized controlled trials (RCTs), and cross-sectional studies. Data on immunogenicity rate, antibody titer, survival rate, new infection rate, adverse events, type of vaccine, and patient characteristics such as age, sex, dialysis vintage, immunosuppression rate, and prevalence of diabetes were extracted and analyzed using REVMAN 5.4 and Stata software. A random effects meta-analysis was used to perform the study.ResultsWe screened 191 records and included 38 studies regarding 5,628 participants. The overall immunogenicity of dialysis patients was 87% (95% CI, 84-89%). The vaccine response rate was 85.1 in hemodialysis patients (HDPs) (1,201 of 1,412) and 97.4% in healthy controls (862 of 885). The serological positivity rate was 82.9% (777 of 937) in infection-naive individuals and 98.4% (570 of 579) in patients with previous infection. The Standard Mean Difference (SMD) of antibody titers in dialysis patients with or without previous COVID-19 infection was 1.14 (95% CI, 0.68–1.61). Subgroup analysis showed that the immunosuppression rate was an influential factor affecting the immunogenicity rate (P < 0.0001). Nine studies reported safety indices, among which four local adverse events and seven system adverse events were documented.ConclusionsVaccination helped dialysis patients achieve effective humoral immunity, with an overall immune efficiency of 87.5%. Dialysis patients may experience various adverse events after vaccination; however, the incidence of malignant events is very low, and no reports of death or acute renal failure after vaccination are available, indicating that vaccine regimens may be necessary.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42022342565, identifier: CRD42022342565.

Endoglin aggravates peritoneal fibrosis by regulating the activation of TGF-β/ALK/Smads signaling.

Background: Peritoneal fibrosis (PF) is an intractable complication in patients on long-term peritoneal dialysis (PD). Transforming growth factor-β (TGF-β) is a key pro-fibrogenic factor involved in PD-associated PF, and endoglin, as a coreceptor for TGF-β, plays a role in balancing the TGF-β signaling pathway. Here, we investigated whether endoglin could be a potential therapeutic target for PF. Methods: In vivo, we established PF model in SD rats by daily intraperitoneal injection of peritoneal dialysis fluids (PDF) containing 4.25% glucose for 6 weeks and downregulated endoglin expression by tail vein injection of AAV9-ENG on day 14 to assess the effect of endoglin on peritoneal morphology and markers related to fibrosis, angiogenesis, and epithelial-mesenchymal transition (EMT). In vitro, we treated human peritoneal mesothelial cells (HPMCs) transfected with ENG siRNA in high glucose medium to explore the potential mechanism of endoglin in PF. Results: Compared to control group, continuous exposure to biologically incompatible PDF induced exacerbated PF, accompanied by a significant increase in endoglin expression. Conversely, knockdown of endoglin ameliorated peritoneal injury characterized by increased peritoneal thickening and collagen deposition, angiogenesis, as well as EMT. Consistently, HPMCs cultured in high glucose medium underwent the EMT process and exhibited over-expression of fibronectin, collagen type I, vascular endothelial growth factor (VEGF), whereas these aforementioned alterations were alleviated after ENG siRNA transfection. In addition, we also found that ENG siRNA inhibited TGF-β-induced phosphorylation of Smad2/3 and Smad1/5/9 in HPMCs treated with high glucose (HG). Conclusion: Our findings confirmed for the first time that endoglin exacerbated PF by regulating the activation of TGF-β/ALK/Smads signaling, which will provide a novel potential therapeutic target in PF.

Insignificant Difference in Biocompatibility of Regenerated Silk Fibroin Prepared with Ternary Reagent Compared with Regenerated Silk Fibroin Prepared with Lithium Bromide.

Bombyx mori silk fibroin (SF) is widely used in the field of biomaterials due to its excellent biocompatibility and mechanical properties. However, SF cannot be used directly in many applications and needs to be dissolved first. Lithium bromide (LiBr) is a traditional solvent which is usually used to dissolve SF. However, LiBr has several limitations, e.g., it is expensive, it is toxic to organisms, and it is environmentally unfriendly. Herein, we investigate the possibility of developing a ternary reagent system that is inexpensive, non-toxic to organisms, and environmentally friendly as an alternative for silk fibroin solubilization. The results confirm that regenerated silk fibroin (RSF) prepared using a ternary reagent has the same morphology and amino acid composition as that prepared using LiBr, but the RSF prepared using a ternary reagent still had a small amount of calcium residue even after long-term dialysis. Further research found that the residual calcium does not cause significant differences in the structure and biological performance of the RSF, such as its cytotoxicity, blood compatibility, and antibacterial properties. Therefore, we believe that ternary reagents are an ideal alternative solvent for dissolving SF.

Using publicly available data to describe multiple environmental pressures and explore the link with end-stage renal disease.

End-stage renal disease (ESRD) is the final stage of chronic kidney disease, where renal function is highly impaired leading to the need of a long-term dialysis or a kidney transplant. Etiology of ESRD remains partly unknown and in particular the role of the environment. The objective of this work is to identify new etiological hypothesis related to the environment. The main argument supporting its influence is the spatial and temporal heterogeneity observed in ESRD incidence at various geographical scales. Since 2005, in Northern France, newly detected ESRD cases are recorded in a health register called Nephronor. On this basis, standardized incidence ratios were calculated at the municipal level after being adjusted for age, sex, social deprivation and distance to dialysis centers. Using an isotonic spatial scan statistic, six significant spatial clusters were detected : three of high incidence and four of low incidence. In parallel, a complete environmental database was built using publicly available data. After an exhaustive inventory of existing data, the most appropriate databases were selected and a long data management process was achieved. Finally, more than one hundred variables were included and allocated in one of the six following dimensions : Contamination levels (air, water, soils), Emission levels, Source locations, Land use, Agricultural practices and Climate. Therefore, physical environment was described as completely as possible and for each dimension, a composite indicator was built at the municipal level. Each of these composite indicators were used to test etiological hypothesis, by comparing high-incidence with low-incidence ESRD spatial clusters. With this territorial approach, the ambition is not to demonstrate causal effects but rather to identify hypothesis that could be tested at the individual level in future epidemiological studies. KEYWORDS : spatial composite indices, multiple environmental pressures, publicly available data, spatial heterogeneity of incidence, end-stage renal disease.