Inclement Weather and Risk of Missing Scheduled Hemodialysis Appointments among Patients with Kidney Failure.

BACKGROUND: Nonadherence to hemodialysis appointments could potentially result in health complications that can influence morbidity and mortality. We examined the association between different types of inclement weather and hemodialysis appointment adherence. METHODS: We analyzed health records of 60,135 patients with kidney failure who received in-center hemodialysis treatment at Fresenius Kidney Care clinics across the Northeastern US counties during 2001-2019. County-level daily meteorological data on rainfall, hurricane and tropical storm events, snowfall, snow depth, and wind speed were extracted using National Oceanic and Atmosphere Agency data sources. A time-stratified case-crossover study design with conditional Poisson regression was used to estimate the effect of inclement weather exposures within the Northeastern US region. We applied a distributed lag nonlinear model framework to evaluate the delayed effect of inclement weather for up to 1 week. RESULTS: We observed positive associations between inclement weather and missed appointment (rainfall, hurricane and tropical storm, snowfall, snow depth, and wind advisory) when compared with noninclement weather days. The risk of missed appointments was most pronounced during the day of inclement weather (lag 0) for rainfall (incidence rate ratio [RR], 1.03 per 10-mm rainfall; 95% confidence interval [CI], 1.02 to 1.03) and snowfall (RR, 1.02; 95% CI, 1.01 to 1.02). Over 7 days (lag 0-6), hurricane and tropical storm exposures were associated with a 55% higher risk of missed appointments (RR, 1.55; 95% CI, 1.22 to 1.98). Similarly, 7-day cumulative exposure to sustained wind advisories was associated with 29% higher risk (RR, 1.29; 95% CI, 1.25 to 1.31), while wind gusts advisories showed a 34% higher risk (RR, 1.34; 95% CI, 1.29 to 1.39) of missed appointment. CONCLUSIONS: Inclement weather was associated with higher risk of missed hemodialysis appointments within the Northeastern United States. Furthermore, the association between inclement weather and missed hemodialysis appointments persisted for several days, depending on the inclement weather type.

Effectiveness of cold HD for the prevention of HD hypotension and mortality in the general HD population.

BACKGROUND: Cold hemodialysis (HD) prevented intradialysis hypotension (IDH) in small, short-term, randomized trials in selected patients with IDH. Whether this treatments prevents IDH and mortality in the HD population at large is unknown. METHODS: We investigated the relationship between dialysate temperature and the risk of IDH, i.e. nadir blood pressure <90 mmHg (generalized estimating equation model) and all-cause mortality (Cox's regression) in an incident cohort of HD patients (n = 8071). To control for confounding by bias by indication and other factors we applied instrumental variables adjusting for case mix at facility level. RESULTS: Twenty-seven percent of patients in the study cohort were systematically treated with a dialysate temperature ≤35.5°C. Over a median follow-up of 13.6 months (interquartile range 5.2-26.1 months), a 0.5°C reduction of the dialysate temperature was associated with a small (-2.4%) reduction of the risk of IDH [odds ratio (OR) 0.976, 95% confidence interval (CI) 0.957-0.995, P = .013]. In case-mix, facility-level adjusted analysis, the association became much stronger (OR 0.67, 95% CI 0.63-0.72, risk reduction = 33%, P < .001). In contrast, colder dialysate temperature had no effect on mortality both in the unadjusted [hazard ratio (HR) (0.5°C decrease) 1.074, 95% CI 0.972-1.187, P = .16] and case-mix-adjusted analysis at facility level (HR 1.01, 95% CI 0.88-1.16, P = .84). Similar results were registered in additional analyses by instrumental variables applying the median dialysate temperature or the facility percentage of patients prescribed a dialysate temperature <36°C. Further analyses restricted to patients with recurrent IDH fully confirmed these findings. CONCLUSIONS: Cold HD was associated with IDH in the HD population but had no association with all-cause mortality.

Assessing proximate intermediates between ambient temperature, hospital admissions, and mortality in hemodialysis patients.

BACKGROUND: Typical thermoregulatory responses to elevated temperatures among healthy individuals include reduced blood pressure and perspiration. Individuals with end-stage kidney disease (ESKD) are susceptible to systemic fluctuations caused by ambient temperature changes that may increase morbidity and mortality. We investigated whether pre-dialysis systolic blood pressure (preSBP) and interdialytic weight gain (IDWG) can independently mediate the association between ambient temperature, all-cause hospital admissions (ACHA), and all-cause mortality (ACM). METHODS: The study population consisted of ESKD patients receiving hemodialysis treatments at Fresenius Medical Care facilities in Philadelphia County, PA, from 2011 to 2019 (n = 1981). Within a time-to-event framework, we estimated the association between daily maximum dry-bulb temperature (TMAX) and, as separate models, ACHA and ACM during warmer calendar months. Clinically measured preSBP and IDWG responses to temperature increases were estimated using linear mixed effect models. We employed the difference (c-c') method to decompose total effect models for ACHA and ACM using preSBP and IDWG as time-dependent mediators. Covariate adjustments for exposure-mediator and total and direct effect models include age, race, ethnicity, blood pressure medication use, treatment location, preSBP, and IDWG. We considered lags up to two days for exposure and 1-day lag for mediator variables (Lag 2-Lag 1) to assure temporality between exposure-outcome models. Sensitivity analyses for 2-day (Lag 2-only) and 1-day (Lag 1-only) lag structures were also conducted. RESULTS: Based on Lag 2- Lag 1 temporal ordering, 1 °C increase in daily TMAX was associated with increased hazard of ACHA by 1.4% (adjusted hazard ratio (HR), 1.014; 95% confidence interval, 1.007-1.021) and ACM 7.5% (adjusted HR, 1.075, 1.050-1.100). Short-term lag exposures to 1 °C increase in temperature predicted mean reductions in IDWG and preSBP by 0.013-0.015% and 0.168-0.229 mmHg, respectively. Mediation analysis for ACHA identified significant indirect effects for all three studied pathways (preSBP, IDWG, and preSBP + IDWG) and significant indirect effects for IDWG and conjoined preSBP + IDWG pathways for ACM. Of note, only 1.03% of the association between temperature and ACM was mediated through preSBP. The mechanistic path for IDWG, independent of preSBP, demonstrated inconsistent mediation and, consequently, potential suppression effects in ACHA (-15.5%) and ACM (-6.3%) based on combined pathway models. Proportion mediated estimates from preSBP + IDWG pathways achieved 2.2% and 0.3% in combined pathway analysis for ACHA and ACM outcomes, respectively. Lag 2 discrete-time ACM mediation models exhibited consistent mediation for all three pathways suggesting that 2-day lag in IDWG and preSBP responses can explain 2.11% and 4.41% of total effect association between temperature and mortality, respectively. CONCLUSION: We corroborated the previously reported association between ambient temperature, ACHA and ACM. Our results foster the understanding of potential physiological linkages that may explain or suppress temperature-driven hospital admissions and mortality risks. Of note, concomitant changes in preSBP and IDWG may have little intermediary effect when analyzed in combined pathway models. These findings advance our assessment of candidate interventions to reduce the impact of outdoor temperature change on ESKD patients.

Combined effects of air pollution and extreme heat events among ESKD patients within the Northeastern United States.

BACKGROUND: Increasing number of studies have linked air pollution exposure with renal function decline and disease. However, there is a lack of data on its impact among end-stage kidney disease (ESKD) patients and its potential modifying effect from extreme heat events (EHE). METHODS: Fresenius Kidney Care records from 28 selected northeastern US counties were used to pool daily all-cause mortality (ACM) and all-cause hospital admissions (ACHA) counts. County-level daily ambient PM2.5 and ozone (O3) were estimated using a high-resolution spatiotemporal coupled climate-air quality model and matched to ESKD patients based on ZIP codes of treatment sites. We used time-stratified case-crossover analyses to characterize acute exposures using individual and cumulative lag exposures for up to 3 days (Lag 0-3) by using a distributed lag nonlinear model framework. We used a nested model comparison hypothesis test to evaluate for interaction effects between air pollutants and EHE and stratification analyses to estimate effect measures modified by EHE days. RESULTS: From 2001 to 2016, the sample population consisted of 43,338 ESKD patients. We recorded 5217 deaths and 78,433 hospital admissions. A 10-unit increase in PM2.5 concentration was associated with a 5% increase in ACM (rate ratio [RRLag0-3]: 1.05, 95% CI: 1.00-1.10) and same-day O3 (RRLag0: 1.02, 95% CI: 1.01-1.03) after adjusting for extreme heat exposures. Mortality models suggest evidence of interaction and effect measure modification, though not always simultaneously. ACM risk increased up to 8% when daily ozone concentrations exceeded National Ambient Air Quality Standards established by the United States, but the increases in risk were considerably higher during EHE days across lag periods. CONCLUSION: Our findings suggest interdependent effects of EHE and air pollution among ESKD patients for all-cause mortality risks. National level assessments are needed to consider the ESKD population as a sensitive population and inform treatment protocols during extreme heat and degraded pollution episodes.

Deciphering the core elements around haemodialysis therapy.

The projected future demand for renal replacement therapies for patients with end-stage renal failure requires preparedness at different levels. The deliberations focus predominantly on the disproportionately high financial burden of care for patients on routine dialysis therapy compared with other chronic conditions. However, even today there are concerns regarding the shortage of healthcare workers in the field of nephrology. A substantial increase in trained healthcare professionals is needed for the future delivery and care of patients requiring haemodialysis (HD) that 89% of patients on dialysis receive; a sustainable health workforce is the cornerstone of any healthcare system. The multimorbid nature of chronic kidney disease as well as the complexity-especially the technical aspects-of HD are deterrents for pursuing nephrology as a career. An educational platform that critically examines the essential issues and components of HD therapy was thus considered appropriate to create or renew interest in nephrology. By providing broader and newer perspectives of some of the core principles around which HD evolves, with this set of articles we seek to facilitate a better appreciation of HD. We believe that such a reappraisal of either poorly understood or ill-defined principles, including usage of terminology that is imprecise, will help facilitate a better understanding of the functioning principles of HD.

Informed decision-making in delivery of dialysis: combining clinical outcomes with sustainability.

As the prevalence of chronic kidney disease is expected to rise worldwide over the next decades, provision of renal replacement therapy (RRT), will further challenge budgets of all healthcare systems. Most patients today requiring RRT are treated with haemodialysis (HD) therapy and are elderly. This article demonstrates the interdependence of clinical and sustainability criteria that need to be considered to prepare for the future challenges of delivering dialysis to all patients in need. Newer, more sustainable models of high-value care need to be devised, whereby delivery of dialysis is based on value-based healthcare (VBHC) principles, i.e. improving patient outcomes while restricting costs. Essentially, this entails maximizing patient outcomes per amount of money spent or available. To bring such a meaningful change, revised strategies having the involvement of multiple stakeholders (i.e. patients, providers, payers and policymakers) need to be adopted. Although each stakeholder has a vested interest in the value agenda often with conflicting expectations and motivations (or motives) between each other, progress is only achieved if the multiple blocs of the delivery system are advanced as mutually reinforcing entities. Clinical considerations of delivery of dialysis need to be based on the entire patient disease pathway and evidence-based medicine, while the non-clinical sustainability criteria entail, in addition to economics, the societal and ecological implications of HD therapy. We discuss how selection of appropriate modes and features of delivery of HD (e.g. treatment modalities and schedules, selection of consumables, product life cycle assessment) could positively impact decision-making towards value-based renal care. Although the delivery of HD therapy is multifactorial and complex, applying cost-effectiveness analyses for the different HD modalities (conventional in-centre and home HD) can support in guiding payability (balance between clinical value and costs) for health systems. For a resource intensive therapy like HD, concerted and fully integrated care strategies need to be urgently implemented to cope with the global demand and burden of HD therapy.

Delayed conversion from central venous catheter to non-catheter hemodialysis access associates with an increased risk of death: A retrospective cohort study based on data from a large dialysis provider.

BACKGROUND: Hemodialysis initiation using a central venous catheter (CVC) poses an increased risk of death. Conversion to an arterio-venous graft or fistula (AVF, AVG) improves outcomes. The relationship of primary dialysis access and timing of conversion from CVC to either AVF or AVG to all-cause mortality was investigated. METHODS: Two retrospective analyses in incident hemodialysis patients commencing treatment from January 2010 to December 2014 in dialysis clinics in the United States were conducted. Analysis 1 stratified as per access at initiation and those commencing with CVC were further stratified into (a) those that had a CVC, AVF, or AVG the entire year; (b) those that were converted to either AVF or AVG within either (i) the first or (ii) the second 6 months. Kaplan Meier analysis and Cox regression analysis were employed. Analysis 2 included all CVC patients investigating the relationship between access conversion time and mortality risk using a Cox proportional hazards model depicting the hazard ratio (HR) as a spline function over time. RESULTS: Two subsets from initial 78,871 patients were studied. In Analysis 1 both AVF (referent) and AVG [HR 1.12 (0.97 to 1.30)] associated with a better outcome than CVC [HR 1.55 (1.38 to 1.74)] during follow-up. Lower mortality risk was seen for early switch from a CVC to AV access within the first 6 months [HR = 1.04 (0.97-1.13)] compared to a later switch [HR = 1.23 (1.10-1.38)]. Analysis 2 indicated that a CVC to AVF switch resulted in improved survival. Analysis 2 indicated early conversion to confer a survival benefit for CVC to AVG switch. DISCUSSION AND CONCLUSION: AVF and AVG show a survival benefit over CVC. Early conversion from CVC to either access improves survival. This emphasizes the importance of early preparation for dialysis by creation of an AVF or AVG and to convert CVCs early.

The renal replacement therapy landscape in 2030: reducing the global cardiovascular burden in dialysis patients.

Despite the significant progress made in understanding chronic kidney disease and uraemic pathophysiology, use of advanced technology and implementation of new strategies in renal replacement therapy, the clinical outcomes of chronic kidney disease 5 dialysis patients remain suboptimal. Considering residual suboptimal medical needs of short intermittent dialysis, it is our medical duty to revisit standards of dialysis practice and propose new therapeutic options for improving the overall effectiveness of dialysis sessions and reduce the burden of stress induced by the therapy. Several themes arise to address the modifiable components of the therapy that are aimed at mitigating some of the cardiovascular risks in patients with end-stage kidney disease. Among them, five are of utmost importance and include: (i) enhancement of treatment efficiency and continuous monitoring of dialysis performances; (ii) prevention of dialysis-induced stress; (iii) precise handling of sodium and fluid balance; (iv) moving towards heparin-free dialysis; and (v) customizing electrolyte prescriptions. In summary, haemodialysis treatment in 2030 will be substantially more personalized to the patient, with a clear focus on cardioprotection, volume management, arrhythmia surveillance, avoidance of anticoagulation and the development of more dynamic systems to align the fluid and electrolyte needs of the patient on the day of the treatment to their particular circumstances.

Association of Extreme Heat Events With Hospital Admission or Mortality Among Patients With End-Stage Renal Disease.

Importance: Extreme heat events (EHEs) are increasing in frequency, duration, and intensity, and this trend is projected to continue as part of ongoing climate change. There is a paucity of data regarding how EHEs may affect highly vulnerable populations, such as patients with end-stage renal disease (ESRD). Such data are needed to inform ESRD patient management guidelines in a changing climate. Objectives: To investigate the association between EHEs and the risk of hospital admission or mortality among patients with ESRD and further characterize how this risk may vary among races/ethnicities or patients with preexisting comorbidities. Design, Setting, and Participants: This study used hospital admission and mortality records of patients with ESRD who underwent hemodialysis treatment at Fresenius Kidney Care clinics in Boston, Massachusetts; Philadelphia, Pennsylvania; or New York, New York, from January 1, 2001, to December 31, 2012. Data were analyzed using a time-stratified case-crossover design with conditional Poisson regression to investigate associations between EHEs and risk of hospital admission or mortality among patients with ESRD. Data were analyzed from July 1, 2017, to March 31, 2019. Exposures: Calendar day- and location-specific 95th-percentile maximum temperature thresholds were calculated using daily meteorological data from 1960 to 1989. These thresholds were used to identify EHEs in each of the 3 cities during the study. Main Outcomes and Measures: Daily all-cause hospital admission and all-cause mortality among patients with ESRD. Results: The study included 7445 patients with ESRD (mean [SD] age, 61.1 [14.1] years; 4283 [57.5%] men), among whom 2953 deaths (39.7%) and 44 941 hospital admissions (mean [SD], 6.0 [7.5] per patient) were recorded. Extreme heat events were associated with increased risk of same-day hospital admission (rate ratio [RR], 1.27; 95% CI, 1.13-1.43) and same-day mortality (RR, 1.31; 95% CI, 1.01-1.70) among patients with ESRD. There was some heterogeneity in risk, with patients in Boston showing statistically significant increased risk for hospital admission (RR, 1.15; 95% CI, 1.00-1.31) and mortality (RR, 1.45; 95% CI, 1.04-2.02) associated with cumulative exposure to EHEs, while such risk was absent among patients with ESRD in Philadelphia. While increases in risks were similar among non-Hispanic black and non-Hispanic white patients, findings among Hispanic and Asian patients were less clear. After stratifying by preexisting comorbidities, cumulative lag exposure to EHEs was associated with increased risk of mortality among patients with ESRD living with congestive heart failure (RR, 1.55; 95% CI, 1.27-1.89), chronic obstructive pulmonary disease (RR, 1.60; 95% CI, 1.24-2.06), or diabetes (RR, 1.83; 95% CI, 1.51-2.21). Conclusions and Relevance: In this study, extreme heat events were associated with increased risk of hospital admission or mortality among patients with ESRD, and the association was potentially affected by geographic region and race/ethnicity. Future studies with larger populations and broader geographic coverage are needed to better characterize this variability in risk and inform ESRD management guidelines and differential risk variables, given the projected increases in the frequency, duration, and intensity of EHEs.

Detection of Atherosclerotic Cardiovascular Disease in Patients with Advanced Chronic Kidney Disease in the Cardiology and Nephrology Communities.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality among patients with chronic kidney disease (CKD) with a glomerular filtration rate of < 60 mL/min/1.73 m2 body surface area. The availability of high-quality randomized controlled trial data to guide management for the population with CKD and ASCVD is limited. Understanding current practice patterns among providers caring for individuals with CKD and CVD is important in guiding future trial questions. METHODS: A qualitative survey study was performed. An electronic survey regarding the diagnosis and management of CVD in patients with CKD was conducted using a convenience sample of 450 practicing nephrology and cardiology providers. The survey was administered using Qualtrics® (https://www.qualtrics.com). RESULTS: There were a total of 113 responses, 81 of which were complete responses. More than 90% of the respondents acknowledged the importance of CVD as a cause of morbidity and mortality in patients with CKD. Outside the kidney transplant evaluation setting, 5% of the respondents would screen an asymptomatic patient with advanced CKD for ASCVD. Outside the kidney transplant evaluation scenario, the respondents did not opt for invasive management strategies in advanced CKD. CONCLUSIONS: The survey results reveal a lack of consensus among providers caring for patients with advanced CKD about the management of ASCVD in this setting. Future randomized controlled trials will be needed to better inform the clinical management of ASCVD in these patients. The limitations of the study include its small sample size and the relatively low response rate among the respondents.

Improving clinical outcomes among hemodialysis patients: a proposal for a "volume first" approach from the chief medical officers of US dialysis providers.

Addressing fluid intake and volume control requires alignment and coordination of patients, providers, dialysis facilities, and payers, potentially necessitating a "Volume First" approach. This article reports the consensus opinions achieved at the March 2013 symposium of the Chief Medical Officers of 14 of the largest dialysis providers in the United States. These opinions are based on broad experience among participants, but often reinforced by only observational and frequently retrospective studies, highlighting the lack of high-quality clinical trials in nephrology. Given the high morbidity and mortality rates among dialysis patients and the absence of sufficient trial data to guide most aspects of hemodialysis therapy, participants believed that immediate attempts to improve care based on quality improvement initiatives, physiologic principles, and clinical experiences are warranted until such time as rigorous clinical trial data become available. The following overarching consensus opinions emerged. (1) Extracellular fluid status should be a component of sufficient dialysis, such that approaching normalization of extracellular fluid volume should be a primary goal of dialysis care. (2) Fluid removal should be gradual and dialysis treatment duration should not routinely be less than 4 hours without justification based on individual patient factors. (3) Intradialytic sodium loading should be avoided by incorporating dialysate sodium concentrations set routinely in the range of 134-138 mEq/L, avoidance of routine use of sodium modeling, and avoidance of hypertonic saline solution. (4) Dietary counseling should emphasize sodium avoidance.

Early outcomes among those initiating chronic dialysis in the United States.

BACKGROUND AND OBJECTIVES: Approximately one million Americans initiated chronic dialysis over the past decade; the first-year mortality rate reported by the U.S. Renal Data System was 19.6% in 2007. This estimate has historically excluded the first 90 days of chronic dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To characterize the mortality and hospitalization risks for patients starting chronic renal replacement therapy, we followed all patients initiating dialysis in 1733 facilities throughout the United States (n = 303,289). Mortality and hospitalizations within the first 90 days were compared with outcomes after this period, and the results were analyzed. Standard time-series analyses were used to depict the weekly risk estimates for each outcome. RESULTS: Between 1997 and 2009, >300,000 patients initiated chronic dialysis and were followed for >35 million dialysis treatments; the highest risk for morbidity and mortality occurred in the first 2 weeks of treatment. The initial 2-week risk of death for a typical dialysis patient was 2.72-fold higher, and the risk of hospitalization was 1.95-fold higher when compared to a patient who survived the first year of chronic dialysis (week 53 after initiation). Similarly, over the first 90 days, the risk of mortality and hospitalization remained elevated. Thereafter, between days 91 and 365, these risks decreased considerably by more than half. Surviving these first weeks of dialysis was most associated with the type of vascular access. Initiating dialysis with a fistula was associated with a decreased early death risk by 61%, whereas peritoneal dialysis decreased the risk by 87%. CONCLUSIONS: The first 2 weeks of chronic dialysis are associated with heightened mortality and hospitalization risks, which remain elevated over the ensuing 90 days.

Access survival amongst hemodialysis patients referred for preventive angiography and percutaneous transluminal angioplasty.

BACKGROUND AND OBJECTIVES: Referring hemodialysis patients for elective access angiography and percutaneous transluminal angioplasty (PTA) is commonly done to prevent access failure, yet the effectiveness of this procedure remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASURES: An observational matched cohort analysis among 40,132 Medicare beneficiaries receiving hemodialysis with a fistula or graft was performed. Cox regression was used to determine whether access intervention was associated with improved 1-year access survival. RESULTS: Nonsurgical access intervention was found to be frequent at a rate of 20.9 procedures per 100 access years. In the 1-year period after intervention using angiography and PTA, the overall access failure rate was 53.7 per 100 access years in the intervention group and 49.6 in the nonintervention group (HR = 1.02; 95% CI, 0.96 to 1.08). Similar findings were also seen when the analysis was repeated in only fistulas (HR = 1.06; 95% CI, 0.98 to 1.15) and grafts (HR = 0.95; 95% CI, 0.86 to 1.05). In patients with a low intra-access flow rate (HR = 0.86; 95% CI, 0.75 to 0.99) or a new access (HR = 0.79; 95% CI, 0.71 to 0.89), angiography and PTA significantly increased access survival when compared with nonintervention (P for interaction was <0.0001). Angiography-PTA-related upper-extremity hematoma, vessel injury, or embolism-thrombosis occurred in 1.1% of all patients. CONCLUSIONS: Access characteristics significantly modify the survival benefits of angiography and PTA intervention where the benefits of these interventions are most seen in newer accesses or accesses with insufficient flow.