Dialysis Study Research Articles

#2814 WHAT ABOUT THE IMPACT ON INFORMAL CAREGIVERS? EFFECTS OF DIALYSIS PATIENTS' HEALTH-RELATED QUALITY OF LIFE AND SYMPTOM BURDEN ON CAREGIVERS

Abstract Background and Aims Starting dialysis has a major impact on patients’ lives. Dialysis patients experience impairments in health-related quality of life (HRQoL) and high symptom burden. Informal caregivers are crucial for dialysis patients’ well-being, as patients often rely on their support and care. However, informal caregivers who provide long-lasting, intensive care may also experience a significant burden. This, in turn, may lead to impaired HRQoL of both the informal caregiver and the patient. To date, little research has been done among informal caregivers of dialysis patients, even though they may experience negative effects of the impaired functioning of the patient. Therefore, the aim of this study was to assess the impact of dialysis patients’ HRQoL and symptom burden on HRQoL of their informal caregivers. We hypothesize that impaired HRQoL and high symptom burden of dialysis patients have a significant impact on informal caregivers’ mental HRQoL, but little to no impact on their physical HRQoL. Method We conducted a cross-sectional study with 193 dyads of adult dialysis patients and their informal caregivers. Data at dialysis initiation were obtained from the ongoing multicenter, observational cohort study on informal caregivers of dialysis patients, which is an extension of the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). The 12-item Short Form Health Survey (SF-12), which provides mental component summary (MCS) and physical component summary (PCS) scores (range 0-100), was used to measure HRQoL in both informal caregivers and dialysis patients. The number of symptoms (range 0-30) and symptom burden (range 0-150) were measured with the Dialysis Symptom Index (DSI). Data were analyzed using linear regression and adjusted for possible confounders. Results Mean age of informal caregivers was 60 ± 15 years, 72.0% were female, and 77.2% were spouses of the dialysis patient. Mean age of patients was 65 ± 14 years, 32.1% were female, and 62.7% were on in-centre hemodialysis. Mean MCS and PCS scores of informal caregivers were 47.8 ± 9.7 and 48.7 ± 9.8, respectively. Mean MCS and PCS scores of patients were 47.9 ± 9.0 and 35.7 ± 10.3, respectively, and mean symptom number and burden were 11.3 ± 5.9 and 31.5 ± 17.6, respectively. After adjustment for confounders, significant effects of patients’ (1) MCS score (β = 0.305; p = 0.003), (2) symptom number (β = -0.434; p = 0.002), and (3) symptom burden (β = -0.151; p < 0.001) were found on caregivers’ MCS score. No significant effects on caregivers’ PCS score were found. Conclusion Lower mental HRQoL, higher symptom number, and higher symptom burden of dialysis patients are associated with lower mental HRQoL of their informal caregivers. These findings underline the importance of maintaining patients’ HRQoL and reducing symptom burden, as these also affect informal caregivers. In addition, given that improving patients’ HRQoL and reducing symptom burden are not always within reach, these findings emphasize the importance of supporting informal caregivers of dialysis patients.

#3968 DIFFERENCES IN MENTAL HEALTH STATUS DURING COVID-19 PANDEMIC BETWEEN IN-CENTER HEMODIALYSIS AND PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Results from previous studies suggest that mental health of dialysis patients was unaffected during the first wave of the COVID-19 pandemic. However, the location of dialysis treatment might have had a different impact on patients during the ongoing COVID-19 pandemic, especially at time of restrictions. Studies comparing the mental health of ICHD and PD patients during the pandemic are scarce. Therefore, we aimed to assess whether dialysis modality differently affected the mental health of patients during the COVID-19 pandemic. Method This study used data of patients participating in the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). We conducted repeated cross-sectional analyses between ICHD and PD patients from the start of the COVID-19 pandemic in March 2020 until August 2021. For this, we divided the study period into six periods of three months. The year before the pandemic was used as reference period. Mental health-related quality of life (HRQOL) was assessed using the mental component summary (MCS) score of the 12-item Short Form (SF-12) health survey. The presence of mental symptoms was determined using the Dialysis Symptom Index (DSI). Both questionnaires were provided at start of dialysis, at 3 months, 6 months and each 6 months thereafter. Patients were included for analysis if a questionnaire was available in at least one period. MCS scores and the prevalence of mental symptoms between ICHD and PD patients were compared with Student's t-test and Chi-square test, respectively. Moreover, we performed multivariable regression analyses to adjust for possible confounders. Results For this analysis, 1274 patients (968 ICHD and 306 PD) were included. Mean age was 65±14 and 64±14 years, respectively. Most patients were male (ICHD: 68%, PD: 61%). Before the pandemic ICHD patients reported similar MCS scores, yet more often reported feeling nervous (32% vs. 22%, P = .03) and sad (40% vs. 29%, P = .03). During the pandemic, mean MCS scores also did not differ between ICHD and PD patients. In contrast, ICHD patients more often reported feeling nervous during period 3 (27% vs 15%, P = .04), feeling irritable and anxious during period 3 (31% vs 18%, P = .03, 26% vs. 9%, P = .002, resp.) and period 4 (34% vs 22%, P = .04, 22% vs 11%, P = .03, resp.), and feeling sad in period 4 (38% vs 26%, P = .04) and period 5 (37% vs 22%, P = .009). In a multivariable regression analysis, these differences persisted after correction for several confounders. Conclusion ICHD patients experienced more mental symptoms compared to PD patients in the period September 2020 to June 2021, which corresponds with the second lockdown of the COVID-19 pandemic. This higher prevalence of specific mental symptoms in ICHD patients was not reflected by a decrease in mental HRQoL.

#6113 SCRATCHING THE SURFACE? A LONGITUDINAL OBSERVATIONAL STUDY ON PRURITUS AND ITS CURRENT TREATMENT IN INCIDENT DIALYSIS PATIENTS

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in dialysis patients. It is associated with impaired health-related quality of life (HRQoL) and sleep disturbances. The pathophysiology remains unclear resulting in limited treatment options and lack of treatment guidelines. The exact course of CKD-aP after dialysis initiation has not been identified nor the state of current medical treatment. Therefore, the aim of this study was to assess presence and severity of CKD-aP during the first year of dialysis, and to assess how it is currently medically managed. Method Data were used from the ongoing multicentre, prospective, observational Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). This study longitudinally compares HRQoL between different dialysis modalities. Incident dialysis patients (> 18 years) were included, if they completed a HRQoL questionnaire around initiation. Pruritus was assessed using the Dialysis Symptom Index (DSI), using a 5-point Likert scale. Medication data were retrieved from electronic patient files. Outcome parameters were prevalence, severity of pruritus and the use of antipruritic medication, both systemic and topical, all measured at dialysis initiation and after 3,6 and 12 months. The association between pruritus and treatment was studied using logistic regression analysis and adjusted for potential confounders. Results A total of 643 patients were included, 70.8% started with hemodialysis and 29.2% with peritoneal dialysis. The mean (SD) age was 64.0 years (13.8) and 68.3% were men. At dialysis initiation 53.5% of all patients suffered from pruritus with a fluctuation in prevalence following the first year of dialysis (Fig. 1). During the first year 35.7% of the patients had persistent itching, 35.5% had fluctuating itching and 28.8% never experienced itching. There was a small increase in number of patients without itching at 3 months followed by an increase in number of patients with ‘quite some itch’ to ‘severe itch’ over the next months (Fig. 2). At 6 months after start dialysis 10.8% of the dialysis patients received topical antipruritic treatment, 17.2% received systemic antipruritic treatment and 3.3% received both topical and systemic treatment. The majority of patients with topical antipruritic treatment received emollients (58.9%) followed by cutaneous steroids (37.6%). Systemic steroids were the most used systemic antipruritic treatment (58.7%), followed by antihistamines (20.4%) and gabapentoids (17.4%). Patients treated with topical agents at 6 months showed an odds ratio of 3.48 (95%CI: 1.11 – 10.91) on severe itching compared to patients without treatment. Furthermore, patients with systemic antipruritic treatment and with both systemic and topical treatment showed an odds ratio of 1.40 (95%CI: 0.48 – 4.03) and 1.52 (95%CI: 0.41 – 5.70) compared to patients without treatment respectively. Conclusion CKD-aP is highly prevalent in incident dialysis patients. The presence of CKD-aP is fluctuating during the first year of dialysis, with a third of patients experiencing intermittent itching. Starting dialysis may have a small beneficial effect on presence and severity of CKD-aP, but this is lost over time with moderate to severe CKD-aP increasing over the following months. Approximately a third of the patients received treatment for CKD-aP, predominantly as systemic treatment. The use of topical antipruritic treatment is associated with more severe CKD-aP at six months after start dialysis. These findings emphasize the need for further research on the pathophysiology and optimal treatment in dialysis patients.

Correction: Arrhythmia and Sudden Death in Hemodialysis Patients: Protocol and Baseline Characteristics of the Monitoring in Dialysis Study.

Charytan, David M; Foley, Robert; McCullough, Peter A.; Rogers, John D; Zimetbaum, Peter; Herzog, Charles A.; Tumlin, James A

Blood Pressure and Mortality in the 4D Study

Introduction: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) are risk factors for cardiovascular mortality (CVM). Pulse pressure (PP) is an easily available parameter of vascular stiffness, but its impact on CVM in chronic dialysis patients with diabetes is unclear. Methods: Therefore, we have examined the predictive value of baseline, predialytic PP, SBP, DBP, and MAP in the German Diabetes and Dialysis (4D) study, a prospective, randomized, double-blind trial enrolling 1,255 patients with type 2 diabetes on hemodialysis in 178 German dialysis centers. Results: Mean age was 66.3 years, mean blood pressure 146/76 mm Hg, mean time suffering from diabetes 18.1 years, and mean time on maintenance dialysis 8.3 months. Considered as continuous variables, PP, MAP, SBP, and DBP could not provide a significant mortality prediction for either cardiovascular or all-cause mortality. After dividing the cohort into corresponding tertiles, we also did not detect any significant mortality prediction for PP, SBP, DBP, or MAP, both for all-cause mortality and CVM after adjusting for age and sex. Nevertheless, when comparing the HR plots of the corresponding blood pressure parameters, a pronounced U-curve was seen for PP for both all-cause mortality and CVM, with the trough range being 70–80 mm Hg. Discussion: In patients with end-stage renal disease and long-lasting diabetes mellitus predialytic blood pressure parameters at study entry are not predictive for mortality, presumably because there is a very high rate of competing mortality risk factors, resulting in overall very high rates of all-cause and CVM that may no longer be significantly modulated by blood pressure control.

Effect of residual kidney function and dialysis adequacy on chronic pruritus in dialysis patients.

Chronic kidney disease-associated pruritus (CKD-aP) is common in dialysis patients, and is associated with lower quality of life and increased risk of death. We investigated the association between residual estimated glomerular filtration rate (eGFR), dialysis adequacy or serum phosphate level and CKD-aP in incident dialysis patients. A total of 1256 incident hemodialysis (HD) and 670 peritoneal dialysis (PD) patients (>18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) study were included (1997-2007) and followed until death, transplantation or a maximum of 10 years. CKD-aP was measured using a single item of the Kidney Disease Quality of Life Instrument-36. The associations were studied by logistic and linear regression analyses, adjusted for potential baseline confounders. At baseline mean (standard deviation) age was 60 (16) years, 62% were men and median (interquartile range) residual eGFR was 3.4 (1.7; 5.3) mL/min/1.73 m2. The prevalence of CKD-aP (∼70%) was similar in HD and PD. It was observed that 12months after starting dialysis (after multivariable adjustment) each 1 mL/min/1.73 m2 higher residual eGFR, one unit higher total weekly Kt/V, or 1mmol/L lower serum phosphate level was associated with lower burden of CKD-aP in HD and PD patients of -0.05 (95% CI -0.09; -0.02) and -0.09 (95% CI -0.13; -0.05), -0.15 (95% CI -0.26; -0.05) and -0.35 (95% CI -0.54; -0.16), and of -0.34 (95%CI: -0.51; -0.17) and -0.45 (95%CI: -0.71; -0.19), respectively. We found no association between dialysis Kt/V and CKD-aP. Higher residual eGFR and lower serum phosphate level, but not the dialysis dose, were related with lower burden of CKD-aP in dialysis patients.

Association of Bradycardia and Asystole Episodes with Dialytic Parameters: An Analysis of the Monitoring in Dialysis (MiD) Study.

Bradycardia and asystole events are common among patients treated with maintenance hemodialysis. However, triggers of these events in patients on maintenance hemodialysis (HD), particularly during the long interdialytic period when these events cluster, are uncertain. The Monitoring in Dialysis Study (MiD) enrolled 66 patients on maintenance HD who were implanted with loop recorders and followed for 6 months. We analyzed associations of predialysis laboratory values with clinically significant bradyarrhythmia or asystole (CSBA) during the 12 hours before an HD session. Associations with CSBA were analyzed with mixed-effect models. Adjusted negative binomial mixed-effect regression was used to estimate incidence rate ratios (IRR) for CSBA. We additionally evaluated associations of CSBA at any time during follow-up with time-averaged dialytic and laboratory parameters and associations of peridialytic parameters with occurrence of CSBA from the start of one HD session to the beginning of the next. There were 551 CSBA that occurred in the last 12 hours of the interdialytic interval preceding 100 HD sessions in 12% of patients and 1475 CSBA events in 23% of patients overall. We did not identify significant associations between dialytic parameters or serum electrolytes and CSBA in the last 12 hours of the interdialytic interval in adjusted analyses. Median time-averaged ultrafiltration rate was significantly higher in individuals without CSBA (9.8 versus 8, P=0.04). Use of dialysate sodium concentrations ≤135 (versus 140) mEq/L was associated with a reduced risk of CSBA from the start of one session to the beginning of next. Although a few factors had modest associations with CSBA in some analyses, we did not identify any robust associations of modifiable parameters with CSBA in the MiD Study. Further investigation is needed to understand the high rates of arrhythmia in the hemodialysis population.

Tunable ultraviolet laser induces high signal-to-noise ratio in intrinsic fluorescence titration for protein- ligand interaction studies

Protein intrinsic fluorescence emitted by tryptophan residues is widely used for macromolecular mechanism studies, such as the protein binding by ligands and enzyme kinetics. However, modifications in fluorescence intensity can be weak using the intrinsic fluorescence in many proteins containing few tryptophan residues, or with their weak involvement in the binding. A low signal to noise ratio is a main drawback, due to the weak intensity of Xenon lamp illumination in the spectrofluorometer at the ultraviolet (UV) range, in addition to the small intrinsic fluorescence modifications with ligand binding, in many cases. We report herein the montage and the utilization of a laser light source in a spectrofluorometer in the UV range for the titration of protein intrinsic fluorescence. A significantly stronger modification of the protein intrinsic fluorescence was obtained with the titrations represented by E. coli Arginyl tRNA synthetase and human 17β-hydroxysteroid dehydrogenase type 7 with their natural ligands using a wavelength-tunable UV laser source. Also, a higher signal to noise ratio was obtained with the laser source. Finally, a similar KD was obtained with the titration using the two light sources. These results are supported by the direct binding study of equilibrium dialysis, showing that the laser source yields a reliable binding analysis. Thus, the utilization of a laser source in the intrinsic fluorescence titration and related usage can give a significant opening for the wider applications of the spectroscopy and photo technology to many new proteins with limited intrinsic fluorescence signals, while their mechanisms are critical to understand biochemistry and will facilitate medical applications. This study includes fundamental, applied, and interdisciplinary areas of physics.

Exploring experiences and health-related quality of life of caregivers of patients who start home dialysis: study protocol for a prospective, multicentre cohort study

IntroductionStarting dialysis not only has a major impact on the life of patients but also on their informal caregivers. Previous research shows greater burden and lower quality of life among...

Theoretical and Experimental Study of Neutralization Dialysis of Phenylalanine–Mineral Salt Equimolar Mixture of Different Concentrations

Theoretical and Experimental Study of Neutralization Dialysis of Phenylalanine–Mineral Salt Equimolar Mixture of Different Concentrations

Impact of phosphate binders on quality of life in dialysis patients: Results from the prospective Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes study.

Phosphate binders cause high pill burden for dialysis patients, complicate medication regimens, and have unpleasant taste and large size which may affect patients' quality of life. This study explores the association between phosphate binder pill burden and health-related quality of life (HRQoL) in dialysis patients. We conducted a cross-sectional multi-centre cohort study in 21 Dutch dialysis centres. Phosphate binder pill burden was extracted from electronic patient records. Primary outcome was HRQoL measured with the Short Form 12 physical and mental component summary scores (PCS and MCS). Secondary endpoints were severity of gastro-intestinal symptoms, itching, dry mouth, and mental health symptoms, measured with the Dialysis Symptom Index. Of 388 included patients, aged 62 ± 16 years, 77% underwent haemodialysis. PCS scores were comparable for patients with and without phosphate binders. Patients using 1-3 pills reported lower scores for decreased appetite (β -0.5; 95%CI -0.9 to -0.2), implying better appetite, than patients without phosphate binders. Patients using 4-6 pills also reported lower scores for decreased appetite (β -0.5; 95%CI -0.8 to -0.1) and for itching (β -0.5; 95%CI -0.9 to -0.1). Patients using >6 pills reported lower MCS (β -2.9; 95%CI -6.2-0.4) and higher scores for feeling nervous (β 0.6; 95%CI 0.1-1.1) and feeling sad (β 0.4; 95%CI 0.0-0.9). Phosphate binder pill burden is not associated with physical quality of life. A higher pill burden is associated with better appetite and less itching. Patients using >6 pills per day report lower mental quality of life and felt nervous and sad more often.

Association of Peritonitis With Cardiovascular Mortality Over Time in the Peritoneal Dialysis Population: An Australia and New Zealand Dialysis and Transplant Registry Study

Though peritonitis is associated with increased mortality in patients receiving peritoneal dialysis (PD), its association with cardiovascular mortality remains uncertain. The study participants included adult patients (≥18 years old) commencing PD in Australia (from October 2003 to December 2019) using the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Association between peritonitis and cardiovascular mortality was evaluated using Cox proportional hazards analysis and competing risks analysis. Associations between peritonitis rates between different eras and cardiovascular mortality were also compared using Jointpoint regression model to determine the time point when a significant change in peritonitis trend occurred to define the era for cardiovascular mortality. Subgroup analysis dividing the groups into 0, 1 and≥2 episodes of peritonitis and sensitivity analysis censoring at 90 days post-transfer to hemodialysis (HD) were performed. The study included 9699 incident PD patients. The overall peritonitis rate was 0.37 episodes per patient-year and declined by 4.7% (95% confidence interval [CI] 3.6-5.8%) during the study period. Peritonitis was associated with increased cardiovascular mortality risk (subdistribution hazard ratio [SHR] 1.53, 95% CI 1.39-1.69, P< 0.001) with increasing peritonitis episodes associated with higher risk (1 episode of peritonitis SHR 1.41, 95%CI 1.24-1.61;≥2 episodes of peritonitis SHR 1.69, 95% CI 1.47-1.93, P< 0.001). Patients who commenced PD between 2012 and 2019 had a lower risk of cardiovascular mortality (SHR 0.60, 95% CI 0.50-0.72, P< 0.001), compared to patients who commenced between 2003 and 2011. Results were consistent in the sensitivity analysis. Peritonitis is independently associated with an increased risk of cardiovascular mortality, and the association is episode-dependent. Prevention and adequate treatment of PD peritonitis may improve cardiovascular outcomes among patients receiving PD.

Alirocumab and Lipid Levels, Inflammatory Biomarkers, Metabolomics, and Safety in Patients Receiving Maintenance Dialysis: The ALIrocumab in DIALysis Study (A Phase 3 Trial to Evaluate the Efficacy and Safety of Biweekly Alirocumab in Patients on a Stable Dialysis Regimen)

Rationale & ObjectiveThe proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab is used in the general population to treat dyslipidemia, but little is known about the effects of alirocumab on lipid levels, biomarkers, the metabolome, and safety in individuals receiving maintenance dialysis.Study DesignPatients receiving maintenance dialysis for at least 3 months and with a low-density lipoprotein cholesterol level of >70 mg/dL were treated with alirocumab for 12 weeks. Laboratory measurements, drug levels, and safety assessments were obtained at baseline and every 4 weeks during the trial.Setting & ParticipantsIn an outpatient setting, 14 patients completed the trial.InterventionThe patients were treated with alirocumab at a full dose of 150 mg every 2 weeks for 12 weeks. The patients were asked to report any adverse events every 2 weeks.OutcomesThere were no unexpected adverse events or laboratory abnormalities in this population receiving dialysis. The drug levels were the same as those for a population not receiving dialysis.ResultsAlirocumab resulted in a 45% reduction in the low-density lipoprotein cholesterol level (P = 0.005) and a 35% reduction in the apolipoprotein B level (P = 0.06). There were no significant decreases in the levels of triglycerides, C-reactive protein, fibrinogen, or other inflammatory biomarkers tested. There were significant decreases in the levels of 7 ceramide, 5 sphingomyelin, and 5 cholesterol ester species.LimitationsThis study was performed in only 14 patients who were administered alirocumab for only 12 weeks. This study did not address alirocumab treatment in patients with chronic kidney disease not receiving maintenance dialysis.ConclusionsIndividuals receiving maintenance dialysis had a similar response to the PCSK9 inhibitor alirocumab as patients not receiving dialysis. The levels of inflammatory biomarkers were not clearly decreased by alirocumab, but the levels of ceramides, sphingomyelins, and cholesterol esters were significantly reduced.Trial RegistrationClinical Trials.gov as NCT03480568.

Soluble suppression of tumorigenesis-2 is a strong predictor of all-cause, cardiovascular and infection-related mortality risk in haemodialysis patients with diabetes mellitus

ABSTRACTBackgroundSoluble suppression of tumorigenesis-2 (sST2) is a strong prognostic biomarker of cardiovascular (CV) disease. End-stage kidney disease (ESKD) patients are at high risk of CV events and infections. Herein we investigated the utility of sST2 to predict all-cause and cause-specific mortality in haemodialysis (HD) patients with diabetes mellitus.MethodssST2 concentrations were measured in plasma samples of 1196 participants of the German Diabetes and Dialysis (4D) study who had type 2 diabetes mellitus and received maintenance HD for ESKD. Hazard ratios (HRs) for prespecified, adjudicated endpoints were determined according to sST2 levels at baseline by multivariate Cox proportional hazards analysis.ResultsParticipants (mean age 66 years, 54% male) had a median sST2 concentration of 25 ng/mL and were followed up for 4 years. After adjustment for possible confounders, participants with sST2 concentrations in the highest (>32.6 ng/mL) compared with the lowest (<20.1 ng/mL) quartile exhibited a 2-fold higher all-cause mortality risk {[HR 2.06 95% confidence interval (CI) 1.61–2.61]; P < .001}. High sST concentrations (fourth versus first quartile) were strongly associated with the risk of cardiac death [HR 2.29 (95% CI 1.55–3.39); P < .001]. Analysis of individual components of cardiac causes of death showed an increased risk of sudden death [HR 2.24 (95% CI 1.33–3.77); P < .001], death due to myocardial infarction [HR 2.12 (95% CI 0.9–5.0); P = .087] and heart failure [HR 3.34 (95% CI 1.15–9.75); P = .027] in participants with sST2 levels in the highest compared with the lowest quartile. Likewise, participants with the highest sST2 levels had an increased risk of fatal stroke [HR 1.92 (95% CI 1.17–3.14); P = .009] and fatal infections [HR 2.01 (95% CI 1.2–3.37); P = .008]. In contrast to fatal CV events, sST2 was not associated with the risk of non-fatal myocardial infarction [HR 0.68 (95% CI 0.41–1.12); P = .132] or non-fatal stroke [HR 1.28 (95% CI 0.64–2.53); P = .485].ConclusionsIn HD patients with diabetes mellitus, high concentrations of sST2 were strongly and independently associated with an increased risk of all-cause mortality, CV mortality and death due to infection but not non-fatal CV events.

MO716: A Different Pet Test: The Relationship between Pet Ownership and Peritonitis Risk in the Peritoneal Dialysis Outcomes and Practice Patterns Study

Abstract BACKGROUND AND AIMS In the USA, 64% of homes have dogs or cats (38% dogs and 25% cats in 2017-8). As a home-based treatment, peritoneal dialysis (PD) patients run the risk of developing zoonotic diseases from their pets. The 2016 International Society for Peritoneal Dialysis Guidelines recommend that domestic animals should not be in the area while the PD exchange is performed. The primary aim of this study was to see how common it was for PD patients to have pets and to examine the association between pet ownership and peritonitis risk in the Peritoneal Dialysis and Outcomes Practice Patterns Study (PDOPPS). METHOD PDOPPS is an international prospective cohort study of adult PD patients across eight countries—Australia, Canada, Japan, New Zealand, South Korea, Thailand, the UK, and the USA. Patient demographics and comorbid conditions were collected at study enrolment and patient questionnaires collected information on household pets. Peritonitis episodes were collected using uniform and standardized data collection tools, procedures and processes. Risk of peritonitis was modelled using a Cox proportional hazards regression adjusted for patient demographics, 14 comorbid conditions, serum albumin, and residual urine volume and stratifying on country and prior peritonitis episodes during follow-up. RESULTS In total, 3655 PD patients provided information about household pets (out of a total of 4473 participants who filled out patient questionnaires amongst a total of 12 447 eligible patients). Among patients who reported on pet ownership, the percentage of patients owning only dogs was 19%, only cats 7%, and 6% with dogs and cats. Most countries, including the USA, had less than 50% of PD patient households having pets, lower than the US general population. Notable differences could be seen between countries in the profile of pets at home, including low numbers of pet ownership in South Korea and greater numbers of dogs than cats in the USA, Thailand, Japan and the UK (Fig. 1). Over a median follow-up for this cohort of 14 months and a total exposure time of 55 475 patient-months, 1347 peritonitis episodes were detected with an overall peritonitis rate of 0.29 episodes/patient-year. Having pets was associated with a hazard ratio of 1.09 (95% confidence interval 0.96–1.25) compared to no pet ownership. Figure 2 compares various combinations of pet ownership to PD patients with no pets as the reference group. However, among patients who lived alone, the peritonitis risk associated with pet ownership versus no pets appeared elevated, especially for people who owned both dogs and cats, although the P-value for the interaction was 0.72 (Fig. 2). CONCLUSION Utilizing this large cohort study, our results suggest limited increased peritonitis risk with pet ownership was seen among patients who live with others. However, our findings do suggest that for patients who live alone, higher peritonitis rates may be seen in those who have a pet. While it would be prudent to ensure maintenance of a high level of hygiene, our results suggest that pet ownership should not be an obstacle to choosing PD.

MO484: Gender Differences in the Incidence of End-Stage of Renal Disease in Okinawa

Abstract BACKGROUND AND AIMS The incidence of chronic kidney disease (CKD) and its progression to end-stage renal disease (ESRD) differ between genders, so it can be surmised that the incidence of ESRD is different between males and females. Acceptance of dialysis therapy may not necessarily be equal to the incidence of ESRD. Factors such as socio-economic conditions of the family, residential area, risk factors and compliance to the treatment of CKD are not equal among gender. We accessed the gender difference in incidence of ESRD and its risk factors in Okinawa, Japan, a major ESRD epidemic area. METHOD The Okinawa Dialysis Study (OKIDS) registry included all chronic dialysis patients treated in Okinawa, Japan, since 1971. We defined the ESRD as those who survived at least one month on scheduled dialysis therapy (hemodialysis and peritoneal dialysis) to exclude acute kidney injury. We analyzed the annual incidence of ESRD by gender for 30 years from 1971 to 2000. The incidence rate of ESRD was calculated as the number of incident dialysis patients divided by the census population of the previous year in each gender and expressed per million population (pmp). The number of dialysis facilities increased from 1 (1971) to 50 (2000). The census population was increased from 939 742 (1971) to 1 318 220 (2000) in Okinawa. RESULTS A total of 5264 patients, 2981 males and 2265 females, have initiated maintenance hemodialysis during the study period. The incidence rate of ESRD increased from 8.9 to 370 pmp in males and from 0 to 227 pmp in females between 1971 and 2000. The growth was fast and consistent throughout the period in males, while in females, the growth has become slower since 1990. After age-standardized, a similar trend was observed, which increased from 41 to 224 pmp in males and from 36 to 154 pmp in females between 1975 and 2000. For males and females, the age-specific incidence rate in the 60–79 year and &amp;gt;80 year groups increased rapidly, and that in the 40–59 year group increased gradually, whereas in the 0–39 year group have been flat. The age-specific rate in the 60–79 year and &amp;gt;80 year groups for males continued to increase throughout the period, while that for females peaked between 1990 and 1995. In the cause-specific incidence rate, the following trends were observed in males and females. The incident rate caused by chronic glomerular nephropathy increased from the 1970s to the 1980s and then leveled off, while that by diabetic nephropathy increased from the 1980s and that by nephrosclerosis increased from the 1990s. The marked growth was seen in the incident rate caused by diabetic nephropathy for both males and females. The rate increased 31 times for males and 12 times for females in the 20 years from 1981 to 2000. The age- and cause-specific incidence rate has risen remarkably among male diabetic nephropathy in &amp;gt;60 years. CONCLUSION In Okinawa, the incidence rate of ESRD has increased significantly in males compared with females, and the gender difference has been widening. It was suggested that the increase in the number of males with diabetic nephropathy over the age of 60 contributed to this widening of the gender difference.

Organometallic Folate Gold Nanoparticles Ameliorate Lipopolysaccharide-Induced Oxidative Damage and Inflammation in Zebrafish Brain.

Synthesized organometallic gold-based folate nanoparticles (FAuNPs) were characterized, and its defense against lipopolysaccharide (LPS)-induced brain inflammation in Zebra fish was proven. Vitamin entrapment efficiency of these particles was found to be nearly 70%. The in vitro pH-dependent drug release dialysis study of FAuNPs confirmed a slow, sustained, and gradual release of folate for a period of 24 h. Both AuNPs and FAuNPs did not cause any marked changes in food intake, body weight, color, behavioral pattern, blood parameters, and hepatotoxicity. Histology of liver showed no changes between treated and control groups of fishes. The ex vivo study showed significant uptake of FAuNPs to free folate in folate receptor negative Hek293 cells, confirming a strategy to overcome folate deficiency in the brain. Antioxidant status and activities of few crucial brain enzymes were also measured to assess the brain function and found to be returned to the basal level, following FAuNP treatment. The transcription factor NRF2-Keap 1 expression pattern was also noted, and a prominent modulation was observed in the LPS-treated and FAuNP-administered group. Decisive brain enzymes like AChE and Na+K+ATPase were decreased significantly after LPS treatment, which is restored with FAuNP treatment. Caspases increased sharply after LPS treatment and diminished following FAuNP treatment. We conclude that FAuNP due to its high physical stability and uptake could be utilized against severe brain inflammation, leading to brain injury and neurodegeneration.

Technique failure in peritoneal dialysis: Modifiable causes and patient-specific risk factors.

Technique survival is a core outcome for peritoneal dialysis (PD), according to Standardized Outcomes in Nephrology-Peritoneal Dialysis. This study aimed to identify modifiable causes and risk factors of technique failure in a large Dutch cohort using standardised definitions. Patients who participated in the retrospective Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes cohort study and started PD between 2012 and 2016 were included and followed until 1 January 2017. The primary outcome was technique failure, defined as transfer to in-centre haemodialysis for ≥ 30 days or death. Death-censored technique failure was analysed as secondary outcome. Cox regression models and competing risk models were used to assess the association between potential risk factors and technique failure. A total of 695 patients were included, of whom 318 experienced technique failure during follow-up. Technique failure rate in the first year was 29%, while the death-censored technique failure rate was 23%. Infections were the most common modifiable cause for technique failure, accounting for 20% of all causes during the entire follow-up. Leakage and catheter problems were important causes within the first 6 months of PD treatment (both accounting for 15%). APD use was associated with a lower risk of technique failure (hazard ratio 0.66, 95% confidence interval 0.53-0.83). Infections, leakage and catheter problems were important modifiable causes for technique failure. As the first-year death-censored technique failure rate remains high, future studies should focus on infection prevention and catheter access to improve technique survival.

Differences in hospitalisation between peritoneal dialysis and haemodialysis patients.

BackgroundDialysis is associated with frequent hospitalisations. Studies comparing hospitalisations between peritoneal dialysis (PD) and haemodialysis (HD) report conflicting results and mostly analyse data of patients that remain on their initial dialysis modality. This cohort study compares hospitalisations between PD and HD patients taking into account transitions between modalities.MethodsThe Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes collected hospitalisation data of patients who started dialysis between 2012 and 2017. Primary outcome was hospitalisation rate, analysed with a multi‐state model that attributed each hospitalisation to the current dialysis modality.ResultsIn total, 695 patients (252 PD, 443 HD) treated in 31 Dutch hospitals were included. The crude hospitalisation rate for PD was 2.3 ( ± 5.0) and for HD 1.4 ( ± 3.2) hospitalisations per patient‐year. The adjusted hazard ratio for hospitalisation rate was 1.1 (95%CI 1.02–1.3) for PD compared with HD. The risk for first hospitalisation was 1.3 times (95%CI 1.1–1.6) higher for PD compared with HD during the first year after dialysis initiation. The number of hospitalisations and number of hospital days per patient‐year were significantly higher for PD. The most common causes of PD and HD hospitalisations were peritonitis (23%) and vascular access‐related problems (33%).ConclusionPD was associated with higher hospitalisation rate, higher risk for first hospitalisation and higher number of hospitalisations compared with HD. Since the PD hospitalisations were mainly caused by peritonitis, more attention to infection prevention is necessary for reducing the number of hospitalisations in the future.

Outcomes and predictors of skin sodium concentration in dialysis patients.

ABSTRACTBackgroundSodium-23 magnetic resonance imaging (23Na MRI) allows the measurement of skin sodium concentration ([Na+]). In patients requiring dialysis, no data are available relating to the clinical outcomes associated with skin sodium accumulation or the determinants of increasing deposition.MethodsThis was an exploratory, observational study of adult hemodialysis (HD) and peritoneal dialysis (PD) patients. Participants underwent skin [Na+] quantification with leg 23Na MRI at the study’s beginning. Outcomes of interest were all-cause mortality and composite all-cause mortality plus major adverse cardiovascular events. Cumulative total and event-free survival were assessed using the Kaplan–Meier survival function after stratification into skin [Na+] quartiles. Cox proportional hazards regression was used to model the association between skin [Na+] and outcomes of interest. Multiple linear regression was used to model the predictors of skin [Na+].ResultsA total of 52 participants (42 HD and 10 PD) underwent the study procedures. The median follow-up was 529 days (interquartile range: 353–602). Increasing skin [Na+] quartiles were associated with significantly shorter overall and event-free survival (log-rank χ2(1) = 3.926, log-rank χ2(1) = 5.685; P for trend <0.05 in both instances). Skin [Na+] was associated with all-cause mortality {hazard ratio (HR) 4.013, [95% confidence interval (95% CI) 1.988–8.101]; P < 0.001} and composite events [HR 2.332 (95% CI 1.378–3.945); P < 0.01], independently of age, sex, serum [Na+] and albumin. In multiple regression models, dialysate [Na+], serum albumin and congestive heart failure were significantly associated with skin [Na+] in HD patients (R2adj = 0.62).ConclusionsHigher skin [Na+] was associated with worse clinical outcomes in dialysis patients and may represent a direct therapeutic target.