Introduction:Automated peritoneal dialysis (APD) is the predominant peritoneal dialysis (PD) modality in many high-income countries and is increasingly adopted in low- and middle-income settings. Outcome differences between APD and continuous ambulatory PD (CAPD) remain unclear. A clearer understanding could inform clinical and policy decisions. Methods:Patients in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS; N = 9463 patients across 6 countries/regions) who were enrolled within 3 months of starting PD were analyzed in intent-to-treat Cox regression models examining associations between PD modality (CAPD vs. APD) and patient survival, permanent transfer to hemodialysis (HD, HDT), and time to first peritonitis, adjusting for patient and facility-level factors and stratified by country. Results:Of the patients, 87% were prescribed APD (range: 37% in South Korea to 91% in USA). APD patients were younger, had lower urine output, more often used hypertonic solutions, and less often used icodextrin. Overall, there was no evident difference between APD and CAPD in survival (adjusted hazard ratio [AHR]: 0.82, 95% confidence interval [CI]: 0.66-1.03) or HDT (AHR: 0.96, 95% CI: 0.83-1.11), though results varied by country and subgroups (APD had lower death risk in those having assisted PD). APD patients had a lower risk of peritonitis overall (AHR: 0.83, 95% CI: 0.72-0.97), and specifically of gram-positive (AHR: 0.67, 95% CI: 0.52-0.87) and culture-negative (AHR: 0.64, 95% CI: 0.44-0.95) peritonitis. Conclusion:APD and CAPD showed comparable patient and technique survival. APD's lower peritonitis rate highlights the importance of aseptic technique; its benefits in assisted PD patients suggest that it may be suited for those requiring support.

BACKGROUND:There is a large person-to-person variability in ultrafiltration volume with peritoneal dialysis (PD), most of which cannot be accounted for by demographic and clinical differences. Herein we tested the hypothesis that common genetic variants are associated with peritoneal ultrafiltration and explored one mechanistic pathway identified by genetic studies. METHODS:We generated estimates of heritability and undertook genome-wide and gene-wise studies, adjusted for peritoneal solute transfer rate (PSTR), to test associations of genetic variation with ultrafiltration on peritoneal equilibration test (PET) done at PD initiation in 2723 participants in the international Bio-PD study. We used a mouse model of PD to study the mechanistic basis for the association of PTGES gene with peritoneal ultrafiltration. RESULTS:PET was done at a median of 61 days (IQR 38-118) from PD start with a median 4-hour ultrafiltration volume of 250 mL (IQR 25-465). The heritability of peritoneal ultrafiltration was estimated to be 50% (p=0.001). In single nucleotide variant (SNV)-wise multi-ancestry GWAS using TRACTOR software, one SNV reached genome-wide significance in participants with European local ancestry (rs72631501, CRK intron, p=2.6x10-8) and one in participants with South Asian local ancestry (rs1416265, intergenic, p=4.2x10-8). Gene-wise analyses showed significant association of 21 genes at false discovery rates (FDRs) <0.10 in the European strata, notably PTGES (FDR=0.053), SLC24A3 (FDR=0.0003) and CRK (FDR=0.04). SLC24A3 remained significant (FDR=0.03) in meta-analysis of the four ancestry strata. Using scRNAseq, PTGES localized in peritoneal adipocytes. In a mouse PD model, pharmacological modulation of PTGES altered dialysate prostaglandin E2 (PGE2) levels with changes in adipocyte volume, peritoneal small solute transfer rate, and ultrafiltration volume. CONCLUSIONS:Common genetic variants accounted for a substantial proportion of the variability in peritoneal ultrafiltration with potential associations with 21 genes, including CRK, PTGES and SLC24A3. Functional studies substantiated a potential role for PTGES/PGE2 in regulating peritoneal ultrafiltration.

There is a large person-to-person variability in ultrafiltration with peritoneal dialysis at the time of starting treatment. In this international cohort study, heritability of peritoneal ultrafiltration with peritoneal dialysis was estimated at 50%. In genome-wide association study, two single-nucleotide variants reached genome-wide significance—rs72631501 in CRK intron with European ancestry and rs1416265, intergenic, with South Asian ancestry. There is a large person-to-person variability in ultrafiltration volume with peritoneal dialysis (PD), most of which cannot be accounted for by demographic and clinical differences. In this article, we tested the hypothesis that common genetic variants are associated with peritoneal ultrafiltration and explored one mechanistic pathway identified by genetic studies. We generated estimates of heritability and undertook genome-wide and gene-wise association studies, adjusted for peritoneal solute transfer rate, to test associations of genetic variation with ultrafiltration on peritoneal equilibration test conducted at PD initiation in 2723 participants in the international Biological Determinants of PD (Bio-PD) study. We used a mouse model of PD to study the mechanistic basis for the association of PTGES gene with peritoneal ultrafiltration. The peritoneal equilibration test was conducted at a median of 61 (interquartile range, 38–118) days from PD start with a median 4-hour ultrafiltration volume of 250 (interquartile range, 25–465) ml. The heritability of peritoneal ultrafiltration was estimated to be 50% ( P = 0.001). In single-nucleotide variant–wise multiancestry genome-wide association study using TRACTOR software, one single-nucleotide variant reached genome-wide significance in participants with European local ancestry (rs72631501, CRK intron, P = 2.6×10 −8 ) and one in participants with South Asian local ancestry (rs1416265, intergenic, P = 4.2×10 −8 ). Gene-wise analyses showed significant association of 21 genes at false discovery rates (FDRs) <0.10 in the European strata, notably PTGES (FDR=0.053), SLC24A3 (FDR=0.0003), and CRK (FDR=0.04). SLC24A3 remained significant (FDR=0.03) in meta-analysis of the four ancestry strata. Using single-cell RNA sequencing, PTGES localized in peritoneal adipocytes. In a mouse PD model, pharmacologic modulation of prostaglandin E synthase altered dialysate PGE2 levels with changes in adipocyte volume, peritoneal small solute transfer rate, and ultrafiltration volume. Common genetic variants accounted for a substantial proportion of the variability in peritoneal ultrafiltration with potential associations with 21 genes, including CRK , PTGES , and SLC24A3 . Functional studies substantiated a potential role for prostaglandin E synthase/prostaglandin E2 in regulating peritoneal ultrafiltration. ClinicalTrials.gov, NCT02694068.

BACKGROUND:Mineral bone disorder (MBD) in chronic kidney disease (CKD) is associated with high symptom burden, fractures, vascular calcification, cardiovascular disease and increased morbidity and mortality. CKD-MBD studies have been limited in peritoneal dialysis (PD) patients. Here, we describe calcium and parathyroid hormone (PTH) control, related treatments and mortality associations in PD patients. METHODS:We used data from eight countries (Australia and New Zealand (A/NZ), Canada, Japan, Thailand, South Korea, United Kingdom, United States (US)) participating in the prospective cohort Peritoneal Dialysis Outcomes and Practice Patterns Study (2014-2022) among patients receiving PD for >3 months. We analysed the association of baseline PTH and albumin-adjusted calcium (calciumAlb) with all-cause mortality using Cox regression, adjusted for potential confounders, including serum phosphorus and alkaline phosphatase. RESULTS:Mean age ranged from 54.6 years in South Korea to 63.5 years in Japan. PTH and serum calciumAlb were measured at baseline in 12,642 and 14,244 patients, respectively. Median PTH ranged from 161 (Japan) to 363 pg/mL (US); mean calciumAlb ranged from 9.1 (South Korea, US) to 9.8 mg/dL (A/NZ). The PTH/mortality relationship was U-shaped, with the lowest risk at PTH 300-599 pg/mL. Mortality was nearly 20% higher at serum calciumAlb 9.6+ mg/dL versus 8.4-<9.6 mg/dL. MBD therapy prescriptions varied substantially across countries. CONCLUSIONS:A large proportion of PD patients in this multi-national study have calcium and/or PTH levels in ranges associated with substantially higher mortality. These observations point to the need to substantially improve MBD management in PD to optimise patient outcomes. LAY SUMMARY:Chronic kidney disease-mineral bone disorder (MBD) is a systemic condition, common in dialysis patients, that results in abnormalities in parathyroid hormone (PTH), calcium, phosphorus and vitamin D metabolism. A large proportion of peritoneal dialysis (PD) patients in this current multi-national study had calcium and/or PTH levels in ranges associated with substantially higher risks of death. Our observational study design limits our ability to determine whether these abnormal calcium and PTH levels cause more death due to possible confounding that was not accounted for in our analysis. However, our findings, along with other recent work showing 48-75% higher risk of death for the one-third of PD patients having high phosphorus levels (>5.5 mg/dL), should raise strong concerns for a greater focus on improving MBD management in PD patients.

Rationale & Objective: Adverse drug reactions (ADRs) are common in patients with chronic kidney disease (CKD). The impact of kidney function decline on serious ADR risk has been poorly investigated. We comprehensively describe ADRs and assess the relationship between estimated glomerular fi ltration rate (eGFR) and serious ADR risk. Study Design: Prospective cohort study. Setting & Participants: 3,033 participants in French Chronic Kidney Disease -Renal Epidemiology and Information Network (CKD-REIN) cohort study, a nationwide sample of nephrology outpatients with moderate to advanced CKD. Predictors: Demographic and biological data (including eGFR), medication prescriptions. Outcome: ADRs (preventable or not) were prospectively identi fi ed from hospital discharge reports, medical records, and patient interviews. Expert pharmacologists used validated tools to adjudicate ADRs. Analytical Approach: Restricted cubic splines in fully adjusted cause -speci fi c Cox proportional hazard models were used to evaluate the relationship between eGFR and the risk of serious ADRs (overall and by subtype). Results: During a median follow-up period of 4.7 years, 360 patients experienced 488 serious ADRs. Kidney and urinary disorders (n = 170) and hemorrhage (n = 170) accounted for 70% of serious ADRs. The most common medications classes were antithrombotics and renin-angiotensin system inhibitors. The majority of those serious ADRs were associated with hospitalization (n = 467), with 32 directly or indirectly associated with death and 22 associated with a life -threatening event. More than 27% of the 488 serious ADRs were preventable or potentially preventable. The eGFR is a major risk factor for serious ADRs. The risk of acute kidney injury was 2.2% higher and risk of bleeding ADRs was 8% higher for each 1 mL/min/1.73 m(2) lower baseline eGFR. Limitations: The results cannot be extrapolated to patients who are not being treated by a nephrologist. Conclusions: ADRs constitute a major cause of hospitalization in CKD patients for whom lower eGFR level is a major risk factor.

Introduction: Secondary hyperparathyroidism (SHPT) increases the risk of fractures and cardiovascular (CV) disease in patients on hemodialysis (HD). The relationship between parathyroid hormone (PTH) and outcomes has been inconsistent, possibly due to variable bone responsiveness to PTH. The KDIGO guideline suggests monitoring total alkaline phosphatase (ALP), but the role of ALP versus PTH in the management of mineral and bone disorder (MBD) is not clear. Methods: The analysis included 28,888 patients on HD in 9 countries in Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 3 to 7 (2005 - 2021). The primary exposures of interest were normalized ALP and PTH, which are raw values divided by facility upper normal limit, measured at study enrollment. Cox models were used to estimate hazard ratios of all -cause or CV mortality and any or hip fracture adjusted for potential confounders. Linear mixed models, adjusted for potential confounders, were employed to investigate the relationship between normalized ALP levels and patient characteristics. Results: Normalized PTH showed a J-shaped association with all -cause or CV mortality, and a weak linear association with fracture. In contrast, normalized ALP showed a strong association with all outcomes. Factors associated with higher ALP levels after controlling for PTH included Black race, longer dialysis vintage, diabetes mellitus, hypocalcemia, hypophosphatemia, elevated C -reactive protein (CRP), and the use of cinacalcet. Conclusion: Total ALP is a more robust exposure of adverse outcomes than PTH in patients on HD. PTH responsiveness is affected by race, primary renal disease, comorbidities, and mineral metabolism and therapy. Our results indicate that it may be useful to evaluate target organ response, rather than PTH alone when considering the consequences of (SHPT).

Background:Individuals with kidney disease are at a high risk of bleeding and as such tools that identify those at highest risk may aid mitigation strategies. Objective:We set out to develop and validate a prediction equation (BLEED-HD) to identify patients on maintenance hemodialysis at high risk of bleeding. Design:International prospective cohort study (development); retrospective cohort study (validation). Settings:Development: 15 countries (Dialysis Outcomes and Practice Patterns Study [DOPPS] phase 2-6 from 2002 to 2018); Validation: Ontario, Canada. Patients:Development: 53 147 patients; Validation: 19 318 patients. Measurements:Hospitalization for a bleeding event. Methods:Cox proportional hazards models. Results:Among the DOPPS cohort (mean age, 63.7 years; female, 39.7%), a bleeding event occurred in 2773 patients (5.2%, event rate 32 per 1000 person-years), with a median follow-up of 1.6 (interquartile range [IQR], 0.9-2.1) years. BLEED-HD included 6 variables: age, sex, country, previous gastrointestinal bleeding, prosthetic heart valve, and vitamin K antagonist use. The observed 3-year probability of bleeding by deciles of risk ranged from 2.2% to 10.8%. Model discrimination was low to moderate (c-statistic = 0.65) with excellent calibration (Brier score range = 0.036-0.095). Discrimination and calibration of BLEED-HD were similar in an external validation of 19 318 patients from Ontario, Canada. Compared to existing bleeding scores, BLEED-HD demonstrated better discrimination and calibration (c-statistic: HEMORRHAGE = 0.59, HAS-BLED = 0.59, and ATRIA = 0.57, c-stat difference, net reclassification index [NRI], and integrated discrimination index [IDI] all P value <.0001). Limitations:Dialysis procedure anticoagulation was not available; validation cohort was considerably older than the development cohort. Conclusion:In patients on maintenance hemodialysis, BLEED-HD is a simple risk equation that may be more applicable than existing risk tools in predicting the risk of bleeding in this high-risk population.

Interest in incremental peritoneal dialysis (PD) has risen dramatically since the publication of the International Society for Peritoneal Dialysis (ISPD) delivery of high-quality PD practice recommendations in 2020. Click or tap here to enter text. These focus on goal-directed care and patients’ quality of life. Incremental PD is a means of delivering a personalised PD prescription, which can be intensified over time in response to clinical symptoms and residual kidney function (RKF) decline. Given that no PD prescription can ever fully take the place of native kidney function, including the spectrum of uraemic toxin removal, ‘Kidney replacement therapy’ may be a misnomer for PD. In this regard, ‘Kidney Addition Therapy’ may be at times a more relevant term to describe a philosophy of PD prescribing commensurate with the level of RKF while respecting the importance of strategies aimed at its preservation. Intensification of an incremental PD prescription is often triggered by worsening uraemic symptoms, volume status changes and biochemical perturbations. It stands to reason that perhaps the relevant question is not should the PD prescription be intensified over time but where and how do we start? In other words, is less more when it comes to the approach to the initial PD prescription where the presence of RKF may allow for a less intensive prescription thereby reducing the burden of PD at initiation. Over 20 years ago, lines of investigation by the PD community including landmark studies such as the Canada-USA Peritoneal Dialysis multicentre trial (CANUSA) and Adequacy of Peritonal Dialysis in Mexico (ADEMEX) were designed around fears that ‘underdialysis’ may negatively impact patient outcomes. These studies tested the hypothesis that increasing peritoneal small solute removal in PD might improve patient survival. In fact, both studies cemented the notion that targeting higher small solute clearance in PD did not specifically improve patient outcomes. Now, modern PD therapy, in an era of initiatives such as choosing wisely, turns to the question as to whether there are adverse consequences to ‘overdialysis’. In addition to lowering costs, initial lower intensity PD prescriptions have been postulated to be associated with a host of potential clinical benefits including less peritoneal membrane glucose exposure, slower RKF decline, a lower risk of peritonitis, lower risks of early mechanical complications and less dialysis waste generation. However, perhaps most compelling of all is: Can a lower intensity initial dialysis prescription personalise PD delivery in a patient-centric way to help lower the burden of therapy and improve the patient and/or care partner experience starting on PD? In this issue of Peritoneal Dialysis International, two observational reports evaluating the impact of lower initial weekly volume PD prescriptions on patient outcomes in Australia and New Zealand (ANZ) are published. The first is a reanalysis of the balANZ data, a multicentre randomized controlled trial (RCT) comparing low glucose degradation product (GDP), neutral pH PD solutions to standard solutions. The second is a review of the ANZ dialysis and transplant registry also known as the ANZDATA between 2007 and 2017. The original balANZ study was an RCT looking at the impact of low GDP, neutral pH PD solutions compared to standard solution among 161 patients. They found no difference in the rate of decline in RKF between the two arms, but time to anuria and peritonitis rates were lower in the low GDP, neutral pH solution arm. Hayat et al. reanalysed these data, defining incremental PD as <56 L per week, which the authors justified was equivalent to less than four daily 2 L continuous ambulatory PD (CAPD) exchanges a day (7 days per week) and compared it to

ABSTRACT Background Elevated serum urea levels are common in moderate-to-advanced chronic kidney disease (CKD). Several studies have shown that urea is a direct and indirect uraemic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before renal replacement therapy (RRT) in patients with CKD. Methods CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 <10.5, T2 10.5–15.1 and T3 ≥15.1 mmol/L). Cox proportional hazard models were used to estimate hazard ratios (HRs) for first atheromatous or non-atheromatous cardiovascular (CV) events and all-cause mortality before RRT. The models were adjusted for baseline comorbidities, laboratory data and medications. Findings Of the 2507 included patients {median [interquartile range (IQR)] age: 69 [61–77]; mean (standard deviation) estimated glomerular filtration rate (eGFR) 33.5 (11.6) mL/min/1.73 m²}, 54% had a history of cardiovascular disease. After multiple adjustments for CV risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and non-atheromatous CV events than patient in T1 (n events = 451, HR [95% CI]: 1.93 [1.39; 2.69]). The adjusted HRs for death before RRT (n events = 407) were 1.31 [0.97; 1.76] and 1.73 [1.22; 2.45] for patients T2 and those in T3, respectively. Interpretation Our data suggested that urea is a predictor of CV outcomes beyond CV risk factors including eGFR.

Background In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. Methods We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014–2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. Results LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France ( p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients ( p < 0.0001) and differed significantly by country ( p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage ( p = 0.09 LDL-C and p = 0.24 statin use). Between 7—23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7–17% of nephrologists believed that LDL-C should be < 70 mg/dL. Conclusion There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment.

Abstract BACKGROUND AND AIMS Loop diuretic use during maintenance haemodialysis (HD), including use of very high doses in Europe, is thought to maintain diuresis and reduce interdialytic weight gain, but is based on little evidence, with impact on clinical outcomes unclear. To help better inform international therapeutic strategies, we investigate regional variation in loop diuretic use and dosing strategies. METHOD This study included 71 756 HD patients from the international Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 2–5 (2002–15), including 27 759 patients with dialysis vintage (time since HD initiation) <1 year. We report the proportion of patients in each country prescribed a diuretic (loop, thiazide or other) by dialysis vintage. Among patients with vintage < 1 year at enrollment and prescribed a loop diuretic, we report the distribution of loop diuretic dose (mg/day) by country. Doses of torsemide (4:1) and bumetanide (80:1) were converted to oral furosemide-equivalent dose. RESULTS Diuretic use varied widely by country, ranging at vintage < 3 months from >80% in Germany and Sweden to < 35% in the US, Spain, and Gulf Cooperation Council (GCC) countries (Figure 1). The proportion of patients prescribed a diuretic decreased with dialysis vintage in all countries. At vintage >5 years, diuretic use was 30%–35% in Germany and Sweden and < 20% in other countries. In all countries, >90% of diuretic prescriptions were for loop diuretics. Loop diuretic dose varied widely across countries. Among patients with vintage < 1 year, median dose ranged from 400–500 mg/day in Belgium, France, Germany and Sweden to < 100 mg/day in the GCC, Japan, Spain and the US (Figure 2). CONCLUSION We observed substantial international differences in diuretic prescription patterns to HD patients, with usage and doses much higher in some European countries than the US, where high-dose formulations are not available. The potential impact of diuretic prescription patterns on outcomes, including residual urine volume, volume-related complications and others should be investigated.

Abstract BACKGROUND AND AIMS The burden of chronic kidney disease-associated pruritus (CKD-aP) in hemodialysis (HD) patients, and its association with adverse clinical events and patient-reported outcomes (PROs) has been well-established. However, most studies focus on a single baseline CKD-aP assessment. In this study, we quantify the extent to which pruritus symptoms vary >1 year, and relationship with associated clinical and patient-reported outcomes. METHOD We included 7976 HD patients across 21 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4–6 (2009–18) who had 2 CKD-aP assessments 12 months (±6 months) apart, with concurrent PRO collection. CKD-aP intensity was assessed by a single question in the KDQOL-36 asking about the extent patients were bothered by itch over the past 4 weeks. We categorized patients into 4 groups—those at least moderately (versus somewhat or not at all) bothered by itchy skin in Year 1 only (Yes/No), Year 2 only (No/Yes), neither (No/No), or both (Yes/Yes) time points. Difference-in-difference analyses were used to estimate changes in laboratory values and PROs between Years 1 and 2, by within-patient changes in CKD-aP severity. Cox regression was used to estimate rates of mortality and hospitalization, with follow-up starting after the Year 2 CKD-aP assessment, across the 4 exposure groups, adjusted for confounders. RESULTS Half of the patients were at least moderately bothered by pruritus over the course of 1 year: 22% of patients were at least moderately bothered by CKD-aP at each annual assessment (Yes/Yes); 14% each were bothered at Year 1 only (Yes/No) or Year 2 only (No/Yes); 49% were not bothered at either CKD-aP assessment (No/No). These proportions were similar across DOPPS regions. Changes in laboratory values—including calcium, phosphorus, parathyroid hormone (PTH), albumin, hemoglobin, single pool Kt/V—between Years 1 and 2 varied minimally by within-patient changes in CKD-aP. Changes in some targeted PROs (depression, sleep quality, feeling faint or drained) tracked closely with changes in CKD-aP: the proportion of patients reporting > = 3 nights/week of restless sleep increased from 38% to 48% in the No/Yes group, decreased from 48% to 40% in the Yes/No group, and was unchanged between Years 1 and 2 in the No/No and Yes/Yes groups (Table 1). Changes in more general PROs (physical [PCS] and mental [MCS] component summary scores) were modest, and only varied by 2–3 points across the 4 CKD-aP exposure groups. The all-cause mortality HR (95% confidence interval), compared with the No/No reference group, was 1.22 (0.99–1.51) for Yes/No, 1.32 (1.07–1.63) for No/Yes and 1.31 (1.11–1.56) for Yes/Yes. Results for hospitalization and other clinical outcomes are shown in Figure 1. CONCLUSION Our findings indicate that half of chronic HD patients were at least moderately bothered by CKD-aP at some point over the course of 1 year, reflecting an unmet medical need, and that CKD-aP symptoms remained unresolved 12 months later for the majority of HD patients who were bothered by itchy skin at baseline, highlighting the chronic nature of the condition. The trend towards worse patient-reported outcomes for those affected in Year 2 but not Year 1 implicates the consequences of patients’ significant adjustment to this new, often unrelenting, symptom. Those with chronic pruritus had higher rates of hospitalization and cardiovascular events, underscoring the impact of patients with chronic pruritus on hospital systems. Moreover, those affected by pruritus at any point in the year had higher rates of mortality, further highlighting the importance of diagnosing pruritus and investigating its effect on cardiovascular events. Future research should investigate potential causes of CKD-aP symptoms more systematically and focus on how potential treatments can aide in patients’ relief.

Community-Health Workers Community-health workers (CHWs), such as patient navigators and promotoras, are lay, nonmedical individuals who are trusted and share the lived experience and characteristics of the community they serve (e.g., race and ethnicity, language, immigration status, socioeconomic challenges, medical illness).1CHWs typically provide support with social- and health-related challenges. CHW interventions became an important community-based strategy to address health disparities after landmark research demonstrated their efficacy in reducing breast cancer screening and treatment disparities.1 CHW interventions deserve consideration to reduce kidney health disparities, particularly for individuals who experience poverty, and members of racial and ethnic minority groups who face a disproportionate burden of social and structural challenges. Characteristics and Training of CHWs Ideally, CHWs should mirror the demographics and language characteristics of their target community, and share experiences in facing social and structural challenges. A culture- and language-concordant CHW may more easily earn an individual’s trust, serve as a source of information, and provide a bridge to health care clinicians and services. A CHW with personal experience with kidney disease may be valuable, because they can empathize with patients and understand the health challenges imposed by kidney disease. The preferability of support from someone with personal experience with kidney disease was confirmed with qualitative findings that assessed the needs and preferences of Latinx individuals with kidney failure, and of interdisciplinary clinicians on how to best support Latinx individuals with kidney failure.2,3 Training for CHWs should be guided by, and specific to, the target community and intended outcomes. Training may include: (1) social risk assessment and how to identify resources and support for individuals with social and structural challenges; (2) behavioral training such as motivational interviewing and patient activation; (3) basic CHW skills (e.g., professional conduct, health promotion, care coordination, health care system overview, electronic health record, or computer training); (4) kidney-specific education and experience that may include clinical shadowing of interdisciplinary clinicians treating kidney disease.4 Opportunities for CHWs to Reduce Kidney Health Disparities Health disparities in using home dialysis and receiving kidney transplant are especially prevalent among racial and ethnic minority groups and individuals who experience poverty.5 Challenges to increasing home dialysis and transplant include clinician, health-system, and patient-related factors. The Advancing American Kidney Health Initiative is a 2019 executive order that challenged the community to increase the number of individuals with kidney failure who receive either home dialysis or a kidney transplant.6 In response, the Centers for Medicare and Medicaid Services implemented the ESRD Treatment Choices and the Kidney Care Choices models.7 CHWs trained in RRT options can provide emotional support, educate patients with low health literacy, support them in dealing with competing social challenges and language interpretation, accompany patients to key encounters, such as the first transplant center visit, or home-based clinician evaluation for home dialysis. CHWs can use their training in motivational interviewing and patient activation to strengthen a patient’s engagement in preparing for, and responding to, the demands related to RRT choice. CHWs can also be active in: (1) supporting efforts to screen patients at risk for kidney disease to reduce the prevalence; (2) connecting patients with kidney disease to clinical care to reduce the progression of kidney disease to kidney failure; (3) providing support to patients with advanced kidney disease for shared decision-making regarding choice of RRT; and (4) improving the transition to transplant or dialysis for patients with kidney failure (Figure 1).Figure 1.: Contributors to disparities and opportunities for CHW interventions.Example of CHW Intervention We partnered with a community-advisory panel to create and pilot test a one-arm feasibility study of a CHW intervention in response to Latinx community members, indicating that socioeconomic challenges compounded by low health literacy and lack of language interpretation were the most distressing aspects of living with kidney failure.2,8 We are now conducting a small (140 Latinx participants) randomized trial of the CHW intervention at five inner-city dialysis centers in Denver. The CHWs consent for participants, and those randomized to the intervention receive at least five visits over 3 months. The CHW provides support with social challenges, language interpretation during key clinical visits, and uses motivational interviewing and patient activation to support patient-centered decision making. Visits occur at the dialysis center, at home, or at clinical encounters. The CHW works in partnership with social workers, who are often overwhelmed by the demand in urban dialysis centers. They are also often integrated into the interdisciplinary dialysis team meetings, because they can provide a deeper understanding of the social and structural challenges that may be influencing kidney care and adherence. We achieved a recruitment rate of approximately 80% for both studies because the CHW is not rushed, describes the study in a culturally and language concordant manner, and develops a personalized relationship. Our preliminary findings confirm the many social challenges that participants face, and demonstrate where a CHW has been crucial to improving patient-centered outcomes (i.e., outcomes that matter to, and are prioritized by, patients) such as support with social challenges and communication. Building Sustainability As we build an evidence base to demonstrate the effectiveness of CHW interventions, a key element will be research to demonstrate the cost effectiveness of CHWs in reducing kidney health disparities. Strategic advocacy will also require a policy analysis that describes legislative options. In 2021, the National Academy for State Health Policy released a report describing state-level approaches and financing strategies across the United States. The report stresses that CHWs are a “critical segment of the community-based workforce that is increasingly central to state workforce and equity planning.”9 As the evidence base for CHWs grows, there may be an opportunity to partner with the Centers for Medicare and Medicaid Services and include reimbursement for CHWs through value-based payment systems, bundled reimbursement, or alternative payment models. Additionally, as the effects of the ESRD Treatment Choices and Kidney Care Choices models on underserved populations are monitored, there may be an opportunity, even imperative, to integrate CHWs to further improve patient experiences and outcomes. CHW interventions are a promising community-based approach to reduce kidney health disparities for racial and ethnic minorities and people that experience poverty along the kidney care continuum. Effectiveness, policy, and reimbursement considerations for CHW support must be prioritized to create sustainable change and meaningfully reduce disparities. Disclosures B. Robinson reports receiving research funding as the Principal Investigator of the Dialysis Outcomes and Practice Patterns Study Program, which is funded by a consortium of private industry, public funders, and professional societies, all support is provided without restrictions on publications; all funds are made to Arbor Research Collaborative for Health and not directly to Dr. Robinson; the full Dialysis Outcomes and Practice Patterns Study Program support and additional support for specific projects and countries can be found at https://www.dopps.org/AboutUs/Support.aspx; reports receiving honoraria from consultancy fees or travel reimbursement in the last 3 years from AstraZeneca, GlaxoSmithKline, Kyowa Kirin Co., and Monogram Health, all paid directly to the institution of employment; and reports having an advisory or leadership role on the Editorial Board of the American Journal of Kidney Diseases. L. Cervantes reports receiving research funding from Retrophin; reports having an advisory or leadership role with Retrophin/Travere; reports other interests or relationships with the National Kidney Foundation; and reports receiving general research funds from DaVita, paid directly to the foundation at the institution of employment. L. Myaskovsky reports having an advisory or leadership role as Associate Editor for Clinical Transplantation; and reports other interests or relationships as the Director of the Center for Healthcare Equity in Kidney Disease, which is funded by Dialysis Clinic Inc., a national nonprofit dialysis provider. All remaining authors have nothing to disclose. Funding This work was supported in part by National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK117018, Robert Wood Johnson Foundation Clinical Scholars grant 77887 (to L. Cervantes), NIH, National Institute of Minority Health and Health Disparities grant R01MD013752, and Dialysis Clinic Inc., a national nonprofit dialysis provider, grant C-3924 (to L. Myaskovsky).

Given the inequities in access to COVID-19 vaccination and the heightened vulnerability of patients living with advanced chronic kidney disease (CKD) or kidney transplant (KT), it is important to ascertain the availability, readiness, and prioritization of COVID-19 vaccines for this population globally.

BACKGROUND:Acute-on-chronic kidney disease (ACKD) is poorly understood and often overlooked. We studied its incidence, circumstances, determinants and outcomes in patients with CKD.METHODS:We used the Kidney Disease: Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) events in 3033 nephrology outpatients with CKD Stages 3-5 participating in the CKD-Renal Epidemiology and Information Network cohort study (2013-20), and cause-specific Cox models to estimate hazard ratios [HRs; 95% confidence intervals (CIs)] of AKI-associated risk factors.RESULTS:At baseline, 22% of the patients [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] had a history of AKI. Over a 3-year follow-up, 443 had at least one AKI event: 27% were Stage 2 or 3 and 11% required dialysis; 74% involved hospitalization including 47% acquired as hospital inpatients; and a third were not reported in hospital discharge reports. Incidence rates were 10.1 and 4.8/100 person-years in patients with and without an AKI history, respectively. In 2375 patients without this history, male sex, diabetes, cardiovascular disease, cirrhosis, several drugs, low eGFR and serum albumin levels were significantly associated with a higher risk of AKI, as were low birth weight (<2500 g) (adjusted HR 1.98; 95% CI 1.35-2.91) and haemoglobin level (HR 1.21; 1.12-1.32 per 1 g/dL decrease). Within 1 year, only 63% of the patients had recovered their previous kidney function, 13.7% had started kidney replacement therapy and 12.7% had died.CONCLUSIONS:The study highlights the high rate of hospital-acquired AKI events in patients with CKD, and their underreporting at hospital discharge. It also reveals low birth weight and anaemia as possible new risk factors in CKD patients.

Background Spiritual well-being (SWB), an individual's understanding of the meaning and purpose of life, may help patients with chronic or terminal illnesses cope with their diseases. This study aimed to assess SWB in patients on peritoneal dialysis (PD), as well as its relationship with patient characteristics and patient-reported outcomes (PRO). Methods The data were obtained from questionnaires that formed part of the PD Outcomes and Practice Patterns Study (PDOPPS). Measures used in this study were SWB scores derived from the WHO quality of life, spirituality, religiousness and personal beliefs (WHOQOL-SRPB) tool including 32 items from eight facets; physical (PCS) and mental component summary (MCS) scores of the 12-Item Short-Form Health Survey (SF-12), Center of Epidemiologic Studies Depression Scale-10 (CES-D-10) scores, burden of kidney disease scores and functional status scores. Results Overall, 529 out of 848 participants (62%) completely responded to the questionnaires and were included in the analysis. Over two-thirds of PD patients (70%) had moderate or higher SWB scores. The SWB scores were significantly lower in patients with age >65 years and unemployed status. SWB scores positively correlated with higher PCS, MCS, burden of kidney disease scores and functional status scores, while negatively correlated with depression scores by CES-D-10 scale. Patients who reported significant depressive symptoms (CES-D-10 score >= 10) had significantly lower SWB scores. Conclusion Better SWB was significantly associated with better health-related QOL (HRQOL) and the absence of depressive symptoms. SWB may be an essential consideration in the delivery of high-quality PD.