Impacts of Dialysis Adequacy and Intradialytic Hypotension on Changes in Dialysis Recovery Time

doi:10.21203/rs.2.23452/v1

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Impacts of Dialysis Adequacy and Intradialytic Hypotension on Changes in Dialysis Recovery Time

https://doi.org/10.21203/rs.2.23452/v1

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published 07 Dec, 2020

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Background: Patient reported long dialysis recovery time (DRT) is common and associated with higher hospitalization and mortality. The goal of our study was to test the hypothesis that hemodialysis (HD) dose and intradialytic hypotension (IDH) rates are associated with dialysis recovery time (DRT). Methods: We analyzed data from adult HD patients who responded to DRT survey ≤180 days from first date of dialysis (FDD) during 2014 to 2017. DRT survey was administered with annual KDQOL survey. DRT survey asks: “How long does it take you to be able to return to your normal activities after your dialysis treatment?” Answers are: <0.5, 0.5-to-1, 1-to-2, 2-to-4, or >4 hours. An adjusted logistic regression model computed odds ratio for increased/maintained longer DRT (increase above DRT >2 hours) in reference to decreased/maintained shorter DRT (decrease below DRT <2 hours, or from DRT >4 hours). Changes in DRT were calculated from incident (≤180 days FDD) to first prevalent (>365-to-≤545 days FDD) and second prevalent (>730-to-≤910 days FDD) years. Results: Among 98616 incident HD patients (age 62.6±14.4 years, 57.8% male) who responded to DRT survey, a higher spKt/V in the incident period was associated with 13.5% (OR=0.865; 95%CI 0.801-to-0.935) lower risk of longer DRT in the first-prevalent year. A higher number of HD treatments with IDH episodes/month in the incident period was associated with a 0.8% (OR=1.008; 95%CI 1.001-to-1.015) and 1.6% (OR=1.016; 95%CI 1.006-to-1.027) higher probability of a longer DRT in the first- and second-prevalent years, respectively. Consistently, an increased in incidence of IDH episodes/months was associated to longer DRT over time. Conclusions: Incident patients who had higher spKt/V and less sessions with IDH episodes had a lower likelihood of longer DRT in first year of HD. Dose optimization strategies with cardiac stability in fluid removal should be tested.

Urology & Nephrology

Dialysis Recovery Time

Patient Reported Outcomes

Health Related Quality of Life

Adequacy

Intradialytic Hypotension

The healthcare paradigm has begun to shift towards patient centered care, including adoption of various patient reported outcomes (PROs) in the routine clinical assessment in individuals with end stage kidney disease (ESKD), who often suffer a burden resulting not only from their kidney disease and comorbidities, but from the dialysis treatment itself (1–3). Capturing patients’ experiences related to routine dialysis care is an important step towards a more patient focused disease management (4).

Dialysis recovery time (DRT), defined as the perceived time to recover the ability to undertake normal activities after a dialysis, has been proposed as a meaningful variable to assess how the patient feels from and tolerates hemodialysis (HD) (5). DRT has been shown to be a reliable and valid marker of health-related quality of life (HRQOL) (5–15). Prior studies indicated that > 65% of prevalent HD patients report DRT ≥ 2 hours (9, 15). Longer DRTs have been shown to be correlated to an array of symptoms including fatigue, and are predictors of hospitalization and mortality (6–9, 15). Previous studies have shown that DRT is associated with a set of non-modifiable risk factors, such as age, serum albumin, diabetes and psychiatric disorders (15).

The pillars of the HD therapy are fluid removal and solute clearance, which we hypothesize could be modifiable factors associated with DRT (16) via episodes of intradialytic hypotension (IDH) and a reduction in uremic toxicity (17, 18), which has been suggested by studies of frequent HD (5, 12). The extent to which these results are independent of achievements of higher dialysis adequacy and less IDH is unknown.

A limitation of prior research is the characteristics of DRT have not been defined in incident HD patients who recently progressed to ERSD and initiated renal replacement therapy (RRT). Furthermore, longitudinal trajectories of DRT have not been established, and it is unknown if practice patterns affect DRT. Importantly, exploring hypothesis driven potential modifiable risk factors could represent new interventions for improvements in DRT. We hypothesized greater dialysis adequacy and a lower number of HD sessions with IDH episodes would be meaningfully associated to changes towards a shorter DRT. We aimed to longitudinally study the impacts of dialysis adequacy and IDH on DRT, adjusted for multiple confounders, in a cohort of incident ESRD patients treated by HD.

Study design:

We conducted an analysis to characterize the profiles and determinants of DRT in incident HD, and investigate associations between dialysis adequacy and IDH versus changes in DRT in the first two years of HD. Research was conducted under a protocol reviewed by New England Independent Review Board, who confirmed the study was secondary research of existing patient data that was anonymized for this study and did not require informed consent per title 45 of the United States Code of Federal Regulations part 46.104-d4ii (Needham Heights, MA; NEIRB#WO1-6614). The study was performed in adherence with the Declaration of Helsinki.

Setting and Participants:

We used data previously collected from ESRD patients during standard-of-care HD at a large dialysis organization (LDO) in North America (Fresenius Kidney Care, Waltham, MA, United States) during January 2014 to December 2017. Analysis included data from adults (age ≥ 18 years at first date of dialysis (FDD)) treated via HD who completed ≥ 1 DRT survey within the first 180 days of RRT. We excluded patients age ≤ 18 years and pregnant females.

DRT Survey:

DRT survey used by the LDO was administered in conjunction with the annual Kidney Disease Quality of Life (KDQOL) survey. DRT survey asks: “How long does it take you to be able to return to your normal activities after your dialysis treatment?” and has five possible answers: 1) “Less than 30 minutes”, 2) “Within 1 hour”, 3) “Within 1–2 hours”, 4) “Within 2–4 hours”, and 5) “More than 4 hours”. DRT survey was chosen by the LDO to be added to the KDQOL to assess additional HRQOL parameters in June of 2013. By 2014 and through 2017, DRT survey was responded to by ≥ 99% of HD patients who completed the KDQOL survey.

Variables:

Dependent variable was DRT. Independent variables assessed as predictors of DRT in incident patients (≤ 180 days from FDD) included demographic, environmental, comorbid, clinical, and laboratory parameters (Table 1). The crude 6-, 12-, and 24-month hospitalization rates were listed by incident DRT category in the population description.

Independent variables included in models assessing predictors of changes in DRT from the incident period (≤ 180 days FDD) to the first prevalent year (> 365-to-≤545 days from FDD) and second prevalent year (> 730-to-≤910 days from FDD) included the incident DRT value, comorbidity burden (age, congestive heart failure (CHF), diabetes, ischemic heart disease (IHD) and number of comorbidities), cardiovascular stability (number of HD treatments with intradialytic hypotension (IDH) episodes per month and changes), dialysis adequacy (incident Kt/V and Δ Kt/V incident to prevalent), and treatment schedule (most HD sessions start before/after 1200 hours and changes).

For continuous variables, we used average values ± 30 days of the DRT survey date. Categorical variables were determined from the most recent record to DRT survey date. UFV was calculated [Δ pre-HD – post-HD weight]. nUFVbw was calculated [((Δ pre-HD – post-HD weight)*1000)/post-HD weight]. UFR was calculated [(((Δ pre-HD – post-HD weight)*1000)/(HD time/60))/post-HD weight]. A treatment with IDH episode was defined as ≥ 1 intradialytic systolic blood pressure (SBP) < 100 mmHg.

Statistical Methods:

Analyses were performed using SAS version 9.4 (SAS, Cary, NC, USA). Sankey diagrams and Forest plots constructed using R version 3.5.2 (R Foundation, Vienna, Austria).

Analysis of Patient Characteristics by Incident DRT:

Categorical and continuous variables were calculated as counts/proportions and mean ± standard deviation (SD). Independent variables were compared in the incident period (≤ 180 days from FDD) between DRT categories in reference to a DRT < 0.5 hours. Comparisons were made using two sample t-tests for means and Chi-Square methods for proportions. Unadjusted Poisson models were used to compare hospital admission rates by DRT category in reference to a DRT < 0.5 hours. Changes from the incident DRT to the first- or second-prevalent year DRT were calculated as proportions and tabulated, as well as visualized via Sankey diagrams.

Analysis of Determinants of Changes in DRT:

A logistic regression model was constructed to calculate the odds ratio and confidence intervals for the incident values of, and changes in, independent variables being associated to increased/maintained longer DRT in the prevalent years in reference to a decreased/maintained shorter DRT. We defined changes in DRT as a binary outcome with: 1) decreased/maintained shorter DRT being any decrease from above to below a DRT category < 2 hours, or a decrease from a DRT > 4 hours to a lower DRT category, and 2) increased/maintained longer DRT being any increase from below to above a DRT category > 2 hours.

The logistic regression model included variables for incident DRT value, age, CHF, diabetes, IHD, number of comorbidities, number of treatments with IDH episodes per month in the incident period and changes from the incident to prevalent periods, Kt/V in the incident period and changes from the incident to prevalent periods, and HD session start before/after 1200 hours and changes from the incident to prevalent periods.

Patient Characteristics

We analyzed data from 98616 patients who responded to DRT survey within 180 days from FDD (Fig. 1). Patients were mean age 62.6 ± 14.4 years, 57.8% male, 69.1% white race, 64.7% used a dialysis catheter, 34.8% had diabetes, 14.8% had IHD, and 16.6% had CHF. Mean days to completion of the DRT survey was 112 ± 26 (Table 1).

Profiles of DRT in Incident Patients:

Incident patients in the first 180 days of HD typically had a DRT < 1 hour or > 4 hours. Rates of DRT in incident patients were: 25.2% DRT < 0.5 hour, 19.1% DRT 0.5-to-1 hour, 17.3% 1-to-2 hours, 15.5%, 2-to-4 hours, and 22.9% DRT > 4 hours (Fig. 2).

Patient Characteristics by DRT in Incident Patients:

Most characteristics of incident HD patients were significantly associated with distinctions by DRT category, as compared to a DRT < 0.5 hours (Table 1). A higher proportion of patients used a dialysis catheter in DRT categories > 1 hour (all p < 0.01). There were more comorbidities in patients with increasing DRT categories > 1 hour (all p < 0.05), and a higher proportion of patients with diabetes, IHD, and CHF who reported longer DRT.

Clinical and HD treatment characteristics of incident patients were associated with longer DRTs versus a DRT < 0.5 hour. There were successively lower ultrafiltration rates (UFR) in patients with longer DRTs (all p < 0.05), and lower ultrafiltration volumes (UFV) in the DRT categories of 1-to-2 and > 4 hours (both p < 0.05). Patients with longer DRTs typically had had higher pre-/post-HD weights, especially in DRT categories > 2 hours (all p < 0.001). The number of HD treatments with IDH episodes (SBP < 100 mmHg) per month was higher in longer DRT categories (all p < 0.01). A higher proportion of patients treated before noon (1200 hours) had a longer DRT (all p < 0.001).

Longer DRTs in incident HD patients tended to be associated to laboratory measures compared to a DRT of < 0.5 hour, with only the exception of phosphate levels. Kt/V was slightly higher in patients with longer DRTs (all p < 0.001). Patients had successive changes in laboratories with increasing DRT categories (Table 1)

In an assessment of hospital admission rates associated with DRT categories, we observed 6-, 12-, and 24-month crude admission rates rose with each longer DRT category (all p < 0.001), as compared to rates in patients with a DRT < 0.5 hour.

Trajectories of DRT:

Changes in DRT categories from the incident period (≤ 180 days from FDD) to subsequent periods in the first prevalent year (> 365-to-≤545 days from FDD) or the second prevalent year (> 730-to-≤910 days from FDD) are presented in Table 2 and visualized with Sankey diagram river plots in Fig. 1 and Supplemental Fig. 1. About 40% of patients with an incident DRT < 0.5 hour, and about 50% of patients with incident DRT > 4 hour, remained in the same DRT category in the first- and second-year prevalent periods. In the Sankey diagram, this is shown via the thickest rivers/flows remaining in the same DRT category. DRT typically changes into categories < 0.5 hour or > 4 hour, with the largest proportion of patients changing into the > 4 hour category; this can be seen in the Sankey diagram by thicker rivers increasing, thinner rivers decreasing, and the thickest river section at the right of the graphics.

Determinants of Changes in DRT Over Time:

For logistic regression modeling, we categorized the changes as: 1) decreased/maintained shorter DRT (green shaded cells; Table 2), or 2) increased/maintained longer DRT (orange shaded cells; Table 2). The model was designed to determine the probability of covariates being associated with changing to an increased/maintained longer DRT in reference to a decreased/maintained shorter DRT.

The adjusted logistic regression models to test our hypothesis revealed a higher dialysis adequacy in the incident period was associated with a 13.5% (OR = 0.865 ;95%CI 0.801-to-0.935) lower odds of an increased/maintained longer DRT in the first prevalent year of HD (Figs. 4; Tables 3 and 4). A higher number of HD treatments with IDH episodes/month in the incident period was associated with a 0.8% (OR = 1.008 ;95%CI 1.001-to-1.015) and 1.6% (OR = 1.016 ;95%CI 1.006-to-1.027) higher probability of an increased/maintained longer DRT in the first- and second-prevalent years, respectively. Consistently, a change to a higher number of treatments with IDH episodes/month in the incident to prevalent periods was associated with a 2.2% (OR = 1.022 ;95%CI 1.015-to-1.028) and 2.8% (OR = 1.028 ;95%CI 1.019-to-1.036) higher likelihood of an increased/maintained longer DRT in the first- and second-prevalent years, respectively.

The covariates included in the adjusted analysis further identified the predominant determinant of an increased/maintained longer DRT in both prevalent periods was the incident DRT value. Patients with an incident DRT category of > 0.5 hour had > 50%, and up to a fivefold higher probability of changing to an increased/maintained longer DRT category in both prevalent periods (all p < 0.001). An increased/maintained longer DRT was also associated with higher age in both years (both p < 0.01), CHF in the first-prevalent year (p < 0.05), and a higher number of comorbidities in the first-prevalent year (p ≤ 0.05). Diabetes and IHD were not associated to changes in DRT.

Patients with most of their HD start times after noon (1200 hours) at the incident and prevalent periods had a 15% (OR = 0.846 ; 95%CI 0.801-to-0.894) and a 12% (OR = 0.879 ;95%CI 0.807-to-0.959) lower likelihood of an increased/maintained longer DRT in both prevalent years. However, changing from a HD start time before 1200 hours in the incident period to after 1200 hours in the first- and second-prevalent periods, and vice versa, was not associated to changes in DRT.

In this retrospective study, DRT was most commonly reported to be < 1 hour or > 4 hours in the first 180 days after initiation of RRT. Longer incident DRT categories were associated to most demographic, environmental, treatment, clinical and laboratory variables. Patients typically progressed to a longer DRT in the first two years of HD. For our hypothesis-derived endpoints, we found a higher dialysis adequacy and less episodes/month of IDH in the incident period are associated with a lower likelihood of longer DRT over time. It appears that it will be important for clinicians and providers to strive to achieve a high removal of retention solutes without causing IDH to optimize how patients feel from their HD treatments.

Consistent with previous studies in the prevalent HD population, we found longer DRT categories in the cross sectional analysis of the incident period were associated with several markers of comorbidity burden and poor fluid control (11, 15, 19). BMI and female sex were associated with longer DRTs reported in incident HD patients. Incident DRT levels were found to be predictors of higher unadjusted 6-, 12- and 24-month hospitalization rates, which is similar to prior findings in prevalent HD (15). Interestingly, we also observed that patients who start HD before 1200 hours reported longer incident DRT. Although HD schedule may influence DRT, findings could be confounded and patients being treated in the evening/night shifts may represent a subgroup with better functional status who perceive shorter DRT. Sleep patterns may also contribute to the findings, given late shift patients may sleep soon after HD and perceive a shorter DRT, albeit this relationship remains underexplored (16).

We described longitudinal trajectories of DRT in patients who survived the follow-up periods after initiation of HD. Most patients remained in the same DRT category or progressed to longer DRT categories in the first 2-years of HD. This unfortunately suggests patients tend to feel progressively worse from their lifesaving HD treatments over time.

To consider the cumulative nature of cardiovascular and inflammatory dysfunctions over time in ESRD, we postulated hypothetical drivers of longer DRT and constructed longitudinal models considering modifiable variables to improve DRT (2, 16, 20). In that sense, this study focused on solute clearance and IDH as important modifiable factors. Ultimately, we found achievement of higher spKt/V and less episodes of IDH would provide a higher probability of a decreased DRT from the incident to 1-year prevalent HD period. A study of DRT over time in 364 HD patients (mean vintage 2.4 years) suggested an HD vintage > 6 months, high BMI, low post-HD SBP, and intradialytic cramping, post-SBP < 115 mmHg was associated with a higher DRT over time, albeit the study did not disclose any precise window of exposure (10). Contrary to our findings, a cross sectional analysis of the DOPPS data did not identify an association between Kt/V and DRT (21).

Modalities such as frequent HD and hemodiafiltration (HDF) can achieve a high adequacy and more fluid removal while maintaining hemodynamic stability, which may lead to better DRT (5, 12–14). The Frequent Hemodialysis Network (FHN) trial and observational studies have demonstrated frequent HD leads to lower DRT compared to thrice weekly HD (5, 12). The effect sizes for reductions in DRT from frequent HD in the FHN trial were up to 60 minutes, which translates into meaningful improvements for patients (12). A randomized cross-over trial found HDF does not promote better DRT compared to HD (14). Interestingly, the Kt/V and ultrafiltration volume was similar between the HDF and HD groups and the symptomatic IDH rate was higher in HDF versus HD, which might have influenced the trial’s overall negative findings (14).

Limitations of our study include not accounting for dialysate sodium, which has been found to be inversely associated to DRT presumably on account of higher hemodynamic instability (15, 22, 23). However, the gradient in blood/dialysate sodium and potential variations in intradialytic tonicity might be independently associated to longer DRT. Also, higher sodium dialysate may cause more residual fluid overload, which could longitudinally associate with longer DRT. Residual kidney function was not taken into account, which may lead to better fluid control, solute clearance and a shorter DRT (24, 25). Moreover, our model may not have optimized ordinal information provided by DRT categorization, which could restrict our power to detect smaller, but still clinically meaningful changes. Finally, in this longitudinal study design, we cannot rule out selection bias conditioned by survival.

Despite some limitations, this evaluation of novel modifiable determinants of longitudinal changes in DRT has many strengths. Variables were selected in an a priori model in which dialysis adequacy and IDH were hypothesized to be consistent and clinically meaningful variables influencing DRT, thereby mapping potential interventions (26). The longitudinal design minimizes systematic errors, particularly reverse causality in association between IDH and DRT. We adjusted for key confounders and described longitudinal associations that warrant interventional testing.

In conclusion, this novel description of trajectories and determinants of changes in DRT in incident HD patients found targeting higher spKt/V while limiting IDH may have the potential to lead to a shorter DRT from the incident to prevalent years. The majority of incident HD patients tend to report longer DRT after two years. Our findings support the concept that higher solute removal and optimal fluid control may improve DRT in HD patients, which may be tested in appropriately designed clinical trials in the future.

DRT

Dialysis Recovery Time

Hemodialysis

IDH

Intra-dialytic hypotension

FDD

First day of dialysis

HDF

Hemodiafiltration

FHN

Frequent Hemodialysis Network

UFV

Ultra filtration volumes

UFR

Ultra filtration rates

HRQOL

Health-related quality of life

RRT

Renal replacement therapy

Disclosures:

MG, JEGL, JWL are students at Pontifícia Universidade Católica do Paraná. YJ, LAU, FWM, JWL are employees of Fresenius Medical Care. JGR, PK are employees of Renal Research Institute, a wholly owned subsidiary of Fresenius Medical Care. LAU, PK, FWM have share options/ownership in Fresenius Medical Care. PK receives honorarium from Up-To-Date and is on the Editorial Board of Blood Purification and Kidney and Blood Pressure Research. TPM, RPF are employed by Pontifícia Universidade Católica do Paraná, and are recipients of scholarships from the Brazilian Council for Research (CNPq). RT is employed by Partners HealthCare, is a consultant for Fresenius Medical Care North America, Biogen Idec, Pfizer, Shire Human Genetics, and Celgene, has ownership interests in Aggamin LLC, receives research funding from the National Institutes of Health, Kaneka Corp, Diasorin, and ThermoFisher, receives honoraria from Roche Diagnostics and ZS Pharma, has patents and invention interests that include ThermoFisher and Up-To-Date, and is a scientific advisor for Aggamin LLC. FWM has directorships in Fresenius Medical Care Management Board, Goldfinch Bio, and Vifor Fresenius Medical Care Renal Pharma. RPF is employed by Arbor Research Collaborative for Health, and receives research grants, consulting fees, and honoraria from Baxter Healthcare and Fresenius Medical Care.

Declarations:

Consent to publish:

Not applicable.

Ethics approval and consent to participate:

This study was conducted under a protocol reviewed by a central ethics review board (New England Independent Review Board, Needham Heights, MA; protocol IRB # WO1-6614), who confirmed the study was secondary research of existing patient data that was anonymized for this research analysis and did not require informed consent per title 45 of the United States Code of Federal Regulations part 46.104-d4ii. This study was performed in accordance with the Declaration of Helsinki.

Availability of data and materials:

The datasets and coding utilized for this study are not publicly available. The datasets were obtained from the Fresenius Medical Care North America Knowledge Center Data Warehouse, which is restricted to use by only authorized employees and is not publicly available.

Competing interests:

MG, JEGL, JWL are students at Pontifícia Universidade Católica do Paraná. YJ, LAU, FWM, JWL are employees of Fresenius Medical Care. JGR, PK are employees of Renal Research Institute, a wholly owned subsidiary of Fresenius Medical Care. LAU, PK, FWM have share options/ownership in Fresenius Medical Care. PK receives honorarium from Up-To-Date and is on the Editorial Board of Blood Purification and Kidney and Blood Pressure Research. TPM, RPF are employed by Pontifícia Universidade Católica do Paraná, and are recipients of scholarships from the Brazilian Council for Research (CNPq). RT is employed by Partners HealthCare, is a consultant for Fresenius Medical Care North America, Biogen Idec, Pfizer, Shire Human Genetics, and Celgene, has ownership interests in Aggamin LLC, receives research funding from the National Institutes of Health, Kaneka Corp, Diasorin, and ThermoFisher, receives honoraria from Roche Diagnostics and ZS Pharma, has patents and invention interests that include ThermoFisher and Up-To-Date, and is a scientific advisor for Aggamin LLC. FWM has directorships in American National Bank & Trust and is chairman of Pacific Care Renal Foundation 501(c)(3) nonprofit. RPF is employed by Arbor Research Collaborative for Health, and receives research grants, consulting fees, and honoraria from Baxter Healthcare and Fresenius Medical Care.

Funding:

Fresenius Medical Care funded this study.

Authors' contributions:

The design and conduct of the study was performed by: MG, JEGL, YJ, JGR, PK, TPM, LAU, RT, FWM, RPF, JWL. The data collection and analysis for this study was performed by: YJ, LAU, JWL. The interpretation, drafting and revision of this manuscript was conducted by all authors. The decision to submit this manuscript for publication was jointly made by all authors and the manuscript was confirmed to be accurate and approved by all authors.

Acknowledgements:

Not applicable.

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Table 1: Profiles and Determinants of Dialysis Recovery Time in Incident HD Patients
Parameter	Overall Mean (SD) or N (%)	Dialysis Recovery Time ≤180 Days FDD (hours) Mean (SD), Column %, or Rate PPY
Demographics:		<0.5 (Reference)	0.5-1	1-2	2-4	>4
Patient (n)	98616 (100%)	25.2%	19.1%	17.3%	15.5%	22.9%
Age (years)	62.6 (14.4)	62.9 (14.5)	62.7 (14.5)	62.4* (14.5)**	62.1* (14.4)**	62.8 (13.9)
Male (%)	56991 (57.8%)	62.6%	57.3%***	56.7%***	55.5%***	55.3%***
Race white (%)	58528 (69.1%)	66.5%	66.4%	68.3%***	69.1%***	74.6%***
Non-Hispanic ethnicity (%)	72293 (87.6%)	86.7%	86.2%	87.2%	88.5%***	89.6%***
BMI (kg/m²)	29.4 (9.2)	28.9 (8.9)	29.1 (9.2)	29.3* (9.2)**	29.7* (9.3)**	30.0* (9.6)**
Days from FDD to survey	112 (26)	110 (26)	112 (26)	112 (26)	*113 (26)**	113 (26)**
Employed	11643 (15.3%)	18.2%	15.7%***	14.7%***	13.9%***	13.0%***
Environmental Parameters:
Resides in same zip code as clinic (%)	25707 (26.1%)	25.7%	26.8%*	26.6%*	26.4%	25.4%
Season: spring (%)	25957 (26.3%)	26.0%	27.0%^a	26.4%	26.4%	26.0%
Season: summer (%) (Reference)	26425 (26.8%)	26.7%	26.2%	27.0%	26.8%	27.2%
Season: fall (%)	24397 (24.7%)	24.6%	24.5%	24.9%	24.4%	25.2%
Season: winter (%)	21837 (22.1%)	22.7%	22.3%	21.7%^a	22.4%	21.6%^aa
Differences in columns between all 4 seasons	P-Value	Reference	0.131	0.086	0.808	0.014*
Comorbidities:
Number of comorbidities (n)	1.92 (1.49)	1.88 (1.47)	1.89 (1.47)	*1.91 (1.48)**	1.92 (1.49)**	2.00* (1.55)**
Diabetes (%)	34325 (34.8%)	33.6%	34.3%	35.2%***	35.0%**	36.1%***
Ischemic Heart Disease (%)	14560 (14.8%)	14.7%	14.1%	14.5%	14.3%	16.0%***
Congestive Heart Failure (%)	16377 (16.6%)	16.0%	16.5%	16.5%	16.2%	17.7%***
Treatment Parameters:
HD start before 1200 hours (%)	65876 (66.8%)	63.1%	65.3%***	69.2%***	72.3%***	66.6%***
UFV (L)	2.16 (0.92)	2.17 (0.92)	2.17 (0.90)	*2.15 (0.91)**	2.16 (0.91)	2.14* (0.93)**
Normalized UFV by body weight (nUFVbw) (mL/kg)	26.6 (10.8)	26.9 (10.8)	27.1 (10.9)	26.6 (10.8)*	26.5 (10.9)***	25.9 (10.8)***
UFR (mL/hour/kg)	7.06 (2.92)	7.14 (2.90)	*7.19 (2.93)**	*7.07 (2.92)**	7.03* (2.93)**	6.87* (2.91)**
HD treatment time (hours)	3.82 (0.44)	3.82 (0.43)	3.82 (0.42)	3.82 (0.42)	3.83 (0.45)	3.83 (0.45)
Number of treatments ±30 days of DRT survey (n)	24.55 (3.92)	24.71 (3.85)	*24.61 (3.84)**	*24.62 (3.65)**	24.61(3.94)**	24.23* (4.20)**
Clinical Parameters:
Catheter (%)	62220 (64.7%)	63.4%	64.2%	65.3%***	64.8%**	65.8%***
Pre-HD weight (kg)	85.5 (23.7)	84.8 (22.9)	*84.2 (23.2)**	85.1 (23.8)	86.2* (23.9)**	87.1* (24.7)**
Post-HD weight (kg)	83.3 (23.3)	82.6 (22.5)	*82.1 (22.8)**	83.0 (23.3)	84.0* (23.4)**	85.0* (24.2)**
IDWG (kg)	2.21 (0.93)	2.22 (0.94)	2.22 (0.92)	2.20 (0.92)	2.22 (0.92)	2.20 (0.95)
Treatments with IDH episodes (SBP<100) per month (n)	3.01 (3.32)	2.87 (3.28)	2.96 (3.29)**	3.04* (3.29)**	3.09* (3.37)**	3.15* (3.39)**
Laboratories:
Pre-HD BUN (mg/dL)	53.9 (16.6)	54.5 (16.5)	*54.2 (16.6)**	53.6* (16.6)**	53.6* (16.4)**	53.3* (16.7)**
Post-HD BUN (mg/dL)	14.1 (5.7)	14.4 (5.8)	14.1* (5.8)**	13.9* (5.7)**	13.9* (5.5)**	13.9* (5.7)**
Kt/V	1.624 (0.318)	1.609 (0.313)	1.630* (0.319)**	1.632* (0.321)**	1.627* (0.315)**	1.625* (0.322)**
Albumin (g/dL)	3.67 (0.42)	3.71 (0.41)	3.68* (0.41)**	3.67* (0.42)**	3.66* (0.42)**	3.64* (0.43)**
Sodium (mmol/L)	137.9 (3.1)	138.0 (3.1)	137.9* (3.1)**	137.8* (3.1)**	137.8* (3.1)**	137.7* (3.2)**
Potassium (mmoI/L)	4.54 (0.55)	4.56 (0.55)	4.55 (0.55)	4.54* (0.55)**	4.53* (0.54)**	*4.54 (0.55)**
Glucose (mg/dL)	183.5 (88.0)	177.3 (84.1)	181.3 (86.2)**	185.0* (88.6)**	184.9* (87.7)**	189.8* (92.7)**
Calcium (mg/dL)	8.95 (0.60)	8.93 (0.59)	*8.95 (0.60)**	*8.95 (0.59)**	8.96* (0.60)**	8.95 (0.60)**
Phosphate (mg/dL)	5.21 (1.32)	5.21 (1.33)	5.20 (1.32)	5.19 (1.32)	5.24 (1.31)	5.23 (1.33)
iPTH (pg/mL)	386.5 (287.7)	396.1 (291.1)	390.7 (290.0)	*389.5 (292.9)**	383.7* (283.7)**	372.1* (280.0)**
Hemoglobin (g/dL)	10.83 (0.99)	10.87 (0.98)	10.82* (0.99)**	10.83* (1.00)**	10.82* (0.98)**	10.80* (1.01)**
White blood cells (10⁹/L)	7.18 (2.51)	6.98 (2.38)	7.11* (2.60)**	7.20* (2.62)**	7.25* (2.38)**	7.41* (2.57)**
Neutrophil to lymphocyte ratio	4.21 (3.16)	4.12 (3.02)	4.17 (3.06)	4.17 (3.07)	4.24 (3.30)**	4.37* (3.36)**
Hospitalization:
6-month admission rate (ppy)	39996 (40.6%)	1.50	1.62***	1.70***	1.76***	2.00***
12-month admission rate (ppy)	55719 (56.5%)	1.61	1.72***	1.79***	1.86***	2.11***
24-month admission rate (ppy)	69125 (70.1%)	1.76	1.85***	1.95***	2.02***	2.26***
Differences in means/proportions/rates with DRT of <0.5 hours as the reference. , p<0.05; , p<0.01; , p<0.001; Differences between seasons were made with summer as the reference and are in reference to a DRT of <0.5 hours. ^a, p<0.05; ^aa**, p<0.01

Table 2: Changes in Dialysis Recovery Time in the First Years on HD
Table 2 A:		1^st Year Prevalent Dialysis Recovery Time >365-to-≤545 Days FDD
Table 2 A:		<0.5 hrs	0.5-1 hrs	1-2 hrs	2-4 hrs	>4 hrs
Incident Dialysis Recovery Time ≤180 Days FDD	<0.5 hrs	44.3%	20.1%	14.28%	9.82%	11.5%
	0.5-1 hrs	22.3%	27.9%	21.44%	13.9%	14.4%
	1-2 hrs	13.14%	17.5%	28.38%	20.8%	20.2%
	2-4 hrs	10.13%	11.5%	19.54%	29.2%	29.7%
	>4 hrs	8.5%	8.0%	12.4%	18.8%	52.4%
Table 2 B:		2^nd Year Prevalent Dialysis Recovery Time >730-to-≤910 Days FDD
Table 2 B:		<0.5 hrs	0.5-1 hrs	1-2 hrs	2-4 hrs	>4 hrs
Incident Dialysis Recovery Time ≤180 Days FDD	<0.5 hrs	40.0%	20.7%	15.7%	11.2%	12.47%
	0.5-1 hrs	22.3%	24.4%	21.8%	15.8%	15.76%
	1-2 hrs	14.9%	17.1%	25.1%	21.9%	20.9%
	2-4 hrs	11.5%	12.2%	19.2%	27.2%	29.98%
	>4 hrs	9.3%	8.9%	14.0%	19.6%	48.21%
Shaded cells denote method used for categorizing DRT changes for the logistic regression models. Green shaded cells denote patient group with decreased/maintained shorter DRT. Orange shaded cells denote patient group with increased/maintained longer DRT

Table 3: Odds Ratio of Increased/Maintained Longer DRT Incident to First Prevalent Year
Parameter	Odds Ratio	95% Confidence Limits
Incident DRT 0.5-1 hour	1.557	1.463 to 1.657
Incident DRT 1-2 hour	2.698	2.536 to 2.871
Incident DRT 2-4 hour	5.661	5.309 to 6.037
Incident DRT >4 hour	4.388	4.137 to 4.655
Age	1.003	1.002 to 1.004
Congestive heart failure	1.07	1.003 to 1.141
Diabetes	1.044	0.995 to 1.095
Ischemic heart disease	1.019	0.947 to 1.097
Number of comorbidities	1.024	1.001 to 1.048
HD start after 1200 hours incident and prevalent	0.846	0.801 to 0.894
HD start before 1200 hours incident and after 1200 hours prevalent	0.999	0.906 to 1.101
HD start after 1200 hours incident and before 1200 hours prevalent	0.97	0.917 to 1.026
Kt/V incident	0.865	0.801 to 0.935
Δ Kt/V incident to prevalent	0.946	0.872 to 1.025
Treatments with IDH episodes per month incident	1.008	1.001 to 1.015
Δ Treatments with IDH episodes per month incident to prevalent	1.022	1.015 to 1.028

Table 4: Odds Ratio of Increased/Maintained Longer DRT Incident to Second Prevalent Year
Parameter	Odds Ratio	95% Confidence Limits
Incident DRT 0.5-1 hour	1.512	1.388 to 1.646
Incident DRT 1-2 hour	2.500	2.294 to 2.725
Incident DRT 2-4 hour	4.434	4.057 to 4.846
Incident DRT >4 hour	3.192	2.939 to 3.467
Age	1.004	1.002 to 1.006
Congestive heart failure	1.057	0.963 to 1.160
Diabetes	1.058	0.988 to 1.133
Ischemic heart disease	1.001	0.900 to 1.113
Number of comorbidities	1.03	0.995 to 1.066
HD start after 1200 hours incident and prevalent	0.879	0.807 to 0.959
HD start before 1200 hours incident and after 1200 hours prevalent	1.024	0.907 to 1.156
HD start after 1200 hours incident and before 1200 hours prevalent	0.944	0.876 to 1.017
Kt/V incident	0.912	0.816 to 1.020
Δ Kt/V incident to prevalent	1.072	0.957 to 1.200
Treatments with IDH episodes per month incident	1.016	1.006 to 1.027
Δ Treatments with IDH episodes per month incident to prevalent	1.028	1.019 to 1.036

Supplemental Figure 1: Sankey diagram river plot of the changes in DRT from ≤180 days FDD to >730-to-≤910 days FDD. (I)= incident DRT from ≤180 days FDD on left; (P)=second year prevalent DRT from >730-to-≤910 days FDD on right.

SupplementalFigure1DRT.docx

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published 07 Dec, 2020

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Editorial decision: Major revision
16 Jun, 2020
Review #2 received at journal
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Reviewer #1 agreed at journal
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Impacts of Dialysis Adequacy and Intradialytic Hypotension on Changes in Dialysis Recovery Time

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Journal Publication

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Abstract

Figures

Background

Methods

Study design:

Setting and Participants:

DRT Survey:

Variables:

Statistical Methods:

Analysis of Patient Characteristics by Incident DRT:

Analysis of Determinants of Changes in DRT:

Results

Patient Characteristics

Profiles of DRT in Incident Patients:

Patient Characteristics by DRT in Incident Patients:

Trajectories of DRT:

Determinants of Changes in DRT Over Time:

Discussion

Conclusion

Abbreviations

Declarations

References

Tables

Supplemental Figure 1

Supplementary Files

Status:

Journal Publication

Version 1