Ultrafiltration Fee and Mortality in Upkeep Hemodialysis Sufferers

Ultrafiltration Rate and Mortality in Maintenance Hemodialysis Patients
June 6, 2021 0 Comments

Hemodialysis (HD) sufferers have excessive charges of morbidity and mortality.1 Fluid elimination practices possible contribute to those poor outcomes. Present information assist an affiliation between extra speedy fluid elimination throughout dialysis and higher mortality.2–4 Finish-organ ischemia of the center, mind and intestine from overt and subclinical hemodynamic instability plausibly underlie this affiliation.5–8 Ultrafiltration (UF) fee is quantifiable and represents a modifiable fluid-related facet of the HD prescription that’s probably inside dialysis facility management. At present, the Facilities for Medicare & Medicaid Providers (CMS) is contemplating an UF fee threshold of 13 mL/h/kg as a top quality measure to evaluate dialysis facility fluid administration, and such a threshold has been integrated into the CMS 2016 Finish Stage Renal Illness Core Survey.9,10

Three observational investigations have demonstrated hurt from higher UF charges.2–4 Nonetheless, the research are modestly sized, precluding strong analyses amongst key subgroups with plausibly totally different UF fee–end result associations. The UF fee threshold delineating heightened threat might fluctuate by affected person kind, which, if true, would make a single UF fee benchmark inappropriate as a top quality measure. Affected person traits reminiscent of physique dimension and composition affect complete physique water distribution and plasma refill, making physique dimension and its correlating elements of race and intercourse believable modifiers of the UF fee–end result affiliation. Moreover, UF charges are sometimes normalized to physique weight. Nonetheless, UF fee normalization to different anthropometric measures which will seize metabolic mass higher has not been evaluated. Lastly, potential shortcomings in prior analyses might have biased threat estimates. Investigators included interdialytic weight acquire (IDWG), session length, and weight, all UF fee calculation parts, in multivariable fashions. Such inclusion might obscure the true affiliation between UF charges and outcomes.11 The aforementioned uncertainties, together with the observational nature of the information, have led to reluctance by guideline our bodies reminiscent of NKF-KDOQI (Nationwide Kidney Basis–Kidney Illness Outcomes High quality Initiative) to problem agency UF fee tips and questions in regards to the appropriateness of a single, weight-based UF fee threshold for all sufferers.12,13

We undertook this examine to additional examine the affiliation of UF fee and mortality in a big, prevalent HD affected person cohort. We examined the UF fee–mortality affiliation throughout physique dimension, intercourse, race, dialysis classic, and HD session length subgroups. We additionally investigated the robustness of the UF fee–mortality affiliation throughout UF fee calculations normalized to totally different anthropometric measures.

METHODS

Examine Design

Knowledge have been obtained from a cohort of 337,863 sufferers receiving HD at a single giant dialysis group (LDO) from June 2008 by means of December 2012. shows examine design. Sufferers have been included in the event that they have been age 18 years or older, obtained in-center HD, and had been on dialysis for ≥90 days at examine entry. Exclusion standards included the incidence of loss of life or censoring occasion through the publicity interval, <7 in-center HD therapies through the publicity interval, and lacking UF fee information. We recognized all in-center HD sufferers who met examine eligibility standards as of June 1, 2008 (examine begin date). For sufferers coming into the LDO database later in calendar time, eligibility standards was assessed on the primary outpatient HD remedy date within the information. This date was the examine entry date for sufferers coming into the cohort after June 1, 2008.

An external file that holds a picture, illustration, etc.
Object name is nihms805509f1.jpg

Examine design schematic

a Supply cohort consisted of 337,863 in-center hemodialysis sufferers with full age, intercourse, race and ethnicity information.

Demographic traits (age, intercourse, race, peak, and dialysis classic) and comorbid situations (diabetes, coronary heart failure, coronary illness) have been thought of as of cohort entry. Laboratory and HD remedy information have been captured in a 30-day baseline interval. Laboratory covariates (urea discount ratio [URR], albumin, sodium, creatinine, hemoglobin, and phosphate) have been thought of because the final non-missing values within the baseline interval. Pre-dialysis systolic blood strain (SBP) was thought of because the imply of values within the baseline interval. Ultrafiltration charges have been assessed in a 30-day publicity interval following the baseline interval. Sufferers surviving the baseline and publicity durations (to check day 60) have been adopted ahead in historic time to loss of life, censoring occasion, or examine finish (December 31, 2013).

This examine was authorized by the College of North Carolina at Chapel Hill Institutional Evaluate Board (IRB quantity 15–2100). Given the big cohort dimension, information anonymity, and nonintrusive analysis, knowledgeable consent necessities have been exempted.

Knowledge Assortment

All information have been obtained from the LDO’s medical file. Demographics have been recorded upon admission to a company facility. Comorbid situations have been decided by a nephrologist on the time of affected person entry to the LDO and up to date primarily based upon scientific course. Laboratory outcomes have been measured biweekly or month-to-month. Dialysis remedy information together with session length and pre- and post-dialysis weights have been recorded on a treatment-to-treatment foundation. Interdialytic weight acquire was outlined as pre-dialysis weight (kg) minus post-dialysis weight (kg) from the earlier remedy. Based mostly on evaluate of related medical information and per standardized LDO protocol, loss of life dates have been recorded by facility personnel.

Designation of Exposures and Final result

In major analyses, prescribed UF fee normalized to physique weight (mL/h/kg) was calculated as follows: IDWG (kg)/prescribed session length (h)/post-HD weight (kg) for every publicity interval HD remedy. Prescribed UF fee was assumed fixed throughout every remedy and was thought of as a imply of UF fee values over the 30-day publicity interval. A 30-day publicity interval was chosen a priori to restrict survivorship bias and to reflect prior analyses.3,4 Sixty and 90-day durations have been thought of in sensitivity analyses, and outcomes have been analogous (Desk S1, obtainable as on-line supplementary materials). Extra sensitivity analyses thought of time-updated UF fee and mortality.

In major analyses, prescribed UF fee was handled as binary (≤10 versus >10 mL/h/kg and ≤13 versus >13 mL/h/kg, individually) to reflect the dichotomized strategy of high quality measures.14 Secondary analyses thought of categorized UF charges (<10, 10–13, and >13 mL/h/kg) in step with prior research2,4 and extra granular UF fee classes (<6, 6–<8, 8–<10, 10–<12, 12–<14, and ≥14 mL/h/kg). To evaluate for a dose-response relationship, we constructed a frequency-based UF rate exposure definition. We considered the proportion of HD treatments in the exposure period with UF rates >13 mL/h/kg: <25%, 25–50%, and >50% of therapies. We chosen a threshold of 13 mL/h/kg to reflect the CMS surveyor software cut-point.10 We carried out extra analyses contemplating delivered UF charges. Delivered UF fee listed to physique weight (mL/h/kg) was calculated as: UF quantity (mL)/delivered session length (h)/post-HD weight (kg).

Secondary analyses have been carried out contemplating UF fee normalized to physique mass index (BMI, kg/m2) and physique floor space (BSA, m2), individually. To reflect major analyses, BMI and BSA have been calculated primarily based on post-HD weight. The BSA was calculated in keeping with Du Bois.15 In these analyses, UF fee to BMI (mL/h/kg/m2) and UF fee to BSA (mL/h/m2) have been dichotomized on the 80th percentiles. The 80th percentile threshold was chosen to reflect the first evaluation, as 13 mL/h/kg represented the 80th percentile of UF fee normalized to physique weight.

The result of curiosity was all-cause mortality. Sufferers have been thought of at-risk for the examine end result following the publicity interval and remained at-risk till loss of life or censoring for loss to follow-up or examine finish (December 31, 2013). Dialysis modality change and kidney transplantation have been handled as competing dangers.16

Statistical Analyses

Analyses have been carried out utilizing SAS model 9.4 (SAS Institute Inc, Cary, NC). Baseline affected person traits have been described throughout UF fee teams as counts and proportions for categorical variables and as means ± commonplace deviations for steady variables.

Time-to-event analyses have been carried out utilizing unadjusted and adjusted Wonderful and Grey proportional subdistribution hazards regression fashions to estimate hazard ratios (HRs). The proportionality assumption was confirmed through Schoenfeld residual testing. Lacking values of laboratory variables have been imputed utilizing the Markov chain Monte Carlo technique with 10 imputations (albumin, n=2,184; creatinine, n=7,473; phosphorus, n=1,430; hemoglobin, n=627; and URR, n=1,642).17 Implausible values of pre- and post-HD weight, session length, and post-HD weight have been thought of lacking. Collinearity of publicity and mannequin covariates was evaluated by the variance inflation issue. Interdialytic weight acquire, session length, and post-HD weight demonstrated reasonable collinearity with UF fee and have been excluded from the mannequin (variance inflation issue ≥1.3 versus =1.0 for all different mannequin variables).

Impact modification of the UF fee–mortality affiliation on the idea of intercourse, race (black versus non-black), ethnicity (Hispanic versus non-Hispanic), physique weight (<20th versus >80th percentile of post-HD weight), dialysis classic (<4 versus ≥4 years), and session length (<4 versus ≥4 h) was explored by means of restriction subgroup analyses. Significance of interplay was assessed by the Wald check of nested fashions that did and didn't embrace two-way cross product phrases. Restricted analyses, utilizing the identical analytic strategies as major analyses, have been carried out in subgroups of curiosity (session length ≥4 h and dialysis classic ≥4 years). In secondary analyses the Vuong check was used to check the relative mortality predictive worth of UF charges normalized to physique weight, mL/h/kg, (versus BMI, mL/h/kg/m2, and BSA, mL/h/m2, individually) primarily based on the cumulative incidence operate of totally adjusted fashions.18

In sensitivity analyses, we assessed the affiliation between time-updated UF fee (mL/h/kg) and mortality utilizing marginal structural proportional hazards fashions. Marginal structural fashions estimate the impact of a time-varying publicity on an end result by controlling for the consequences of time-dependent confounders.19,20
Desk a and determine a of Merchandise S1 present detailed strategies.

RESULTS

Cohort Traits

shows a flowchart of affected person choice. shows cohort traits throughout prescribed UF fee teams. In contrast with sufferers with UF charges ≤13 mL/h/kg, sufferers with UF charges >13 mL/h/kg had smaller physique sizes, have been youthful, and have been extra more likely to be feminine, non-black, Hispanic, and have comorbid coronary heart failure, longer dialysis classic, shorter session durations, and bigger IDWGs. Desk S2 shows comparisons of included and excluded sufferers.

An external file that holds a picture, illustration, etc.
Object name is nihms805509f2.jpg

Stream-chart of cohort choice.

Desk 1

Baseline traits throughout prescribed ultrafiltration fee teams.

Whole (N=118,394)b 30-d imply prescribed UF fee


<10 mL/h/kg (n=69,865 [59.0%]b 10–13 mL/h/kg (n=26,794 [22.6%])b >13 mL/h/kg (n=21,735 [18.4%])b
UF fee
 pmL/h/kg 9.4 ± 4.3 6.6 ± 2.5 11.4 ± 0.9 16.0 ± 2.9
 mL/h/kg/m2 27.2 ± 13.2 (n=118,215) 19.5 ± 8.5 (n=69,743) 32.8 ± 6.4 (n=26,765) 45.0 ± 10.8 (n=21,707)
 mL/h/m2 377.2 ± 154.2 (n=118,215) 286.3 ± 107.7 (n=69,768) 451.1 ± 70.0 (n=26,765) 578.3 ± 111.8 (n=21,707)
Age (y) 61 ± 15 62 ± 15 61 ± 15 58 ± 16
Feminine intercourse 53,307 (45.0) 30,964 (44.3) 11,554 (43.1) 10,789 (49.6)
Black race 45,289 (38.3) 28,584 (40.9) 9,713 (36.3) 6,992 (32.2)
Hispanic ethnicity 19,520 (16.5) 9,823 (14.1) 5,108 (19.1) 4,589 (21.1)
Historical past of coronary heart failure 31,534 (26.6) 16,775 (24.0) 7,911 (29.5) 6,848 (31.5)
Historical past of CVD 66,988 (56.6) 37,999 (54.4) 15,864 (59.2) 13,125 (60.4)
Historical past of diabetes 61,721 (52.1) 36,085 (51.6) 14,467 (54.0) 11,169 (51.4)
Dialysis classic
 <1 y 25,283 (21.4) 16,874 (24.2) 4,963 (18.5) 3,446 (15.9)
 1–2 y 39,411 (33.3) 23,995 (34.3) 8,788 (32.8) 6,628 (30.5)
 3–4 y 22,718 (19.2) 12,842 (18.4) 5,404 (20.2) 4,472 (20.6)
 ≥5 y 30,982 (26.2) 16,154 (23.1) 7,639 (28.5) 7,189 (33.1)
Vascular entry
 Graft 25,743 (21.7) 14,323 (20.5) 6,184 (23.1) 5,236 (24.1)
 Fistula 61,991 (52.4) 35,226 (50.4) 14,784 (55.2) 11,981 (55.1)
 Catheter 30,660 (25.9) 20,316 (29.1) 5,826 (21.7) 4,518 (20.8)
Put up-HD weight (kg) 79.2 ± 22.4 84.6 ± 23.7 75.6 ± 18.3 73.5 ± 6.5
IDWG (kg) 2.9 ± 2.2 2.5 ± 2.1 3.3 ± 2.0 3.6 ± 2.2
BMI (kg/m2) 27.7 ± 7.3 (n=118,215) 29.3 ± 7.8 (n=69,743) 26.6 ± 6.1 (n=26,765) 23.9 ± 5.1 (n=21,707)
BSA (m2) 1.9 ± 0.3 (n=118,215) 2.0 ± 0.3 (n=69,768) 1.9 ± 0.2 (n=26,765) 1.7 ± 0.2 (n=21,707)
Prescribed session length (min) 218 ± 36 223 ± 39 214 ± 28 205 ± 28
Pre-HD SBP
 ≤130 m Hg 28,766 (24.3) 17,419 (24.9) 6,403 (23.9) 4,944 (22.7)
 131–150 mm Hg 34,102 (28.8) 20,217 (28.9) 7,783 (29.0) 6,102 (28.1)
 151–170 mm Hg 30,279 (25.6) 17,640 (25.2) 6,934 (25.9) 5,705 (26.2)
 ≥171 mm Hg 25,247 (21.3) 14,589 (20.9) 5,674 (21.2) 4,984 (22.9)
Missed classes ≥3 23,590 (19.9) 13,590 (19.5) 5,183 (19.3) 4,817 (22.2)
Albuminc
 ≤3.0 g/dL 6,390 (5.4) 3,932 (5.6) 1,216 (4.5) 1,242 (5.7)
 3.1–3.5 g/dL 19,852 (16.8) 11,829 (16.9) 4,255 (15.9) 3,768 (17.3)
 3.6–4.0 g/dL 56,005 (47.3) 33,335 (47.7) 12,785 (47.7) 9,885 (45.5)
 >4.0 g/dL 36,147 (30.5) 20,769 (29.7) 8,538 (31.9) 6,840 (31.5)
Serum sodium (mEq/L)c 138.2 ± 2.1 138.4 ± 2.0 138.2 ± 2.1 137.8 ± 2.3
Creatinine (mg/dL)c 8.3 ± 3.1 8.1 ± 3.1 8.6 ± 3.1 8.6 ± 3.1
Phosphorousc
 ≤4.0 mg/dL 23,431 (19.8) 14,849 (21.3) 4,815 (18.0) 3,767 (17.3)
 4.1–5.0 mg/dL 33,958 (28.7) 20,981 (30.0) 7,553 (28.2) 5,424 (25.0)
 5.1–6.0 mg/dL 29,464 (24.9) 17,376 (24.9) 6,754 (25.2) 5,334 (24.5)
 >6.0 mg/dL 31,541 (26.6) 16,659 (23.8) 7,672 (28.6) 7,210 (33.2)
Hemoglobinc
 <10.0 g/dL 12,805 (10.8) 7,373 (10.6) 2,713 (10.1) 2,719 (12.5)
 10.0–11.9 g/dL 56,405 (47.6) 33,526 (48.0) 12,680 (47.3) 10,199 (46.9)
 ≥12.0 g/dL 49,184 (41.5) 28,966 (41.5) 11,401 (42.6) 8,817 (40.6)
Urea discount ratio (%)c 73.0 ± 6.8 72.8 ± 7.0 73.2 ± 6.5 73.5 ± 6.5

General, 118,394 sufferers underwent 1,511,740 therapies through the publicity interval. Of those, 69,865 (59.0%) sufferers had UF charges <10 mL/h/kg, 26,794 (22.6%) had UF rates 10–13 mL/h/kg, and 21,735 (18.4%) had UF rates >13 mL/h/kg. The median followup time was 2.3 (interquartile vary [IQR], 1.0–4.4) years, and there have been 310,064 patient-years of complete follow-up time. Mortality occurred at a fee of 15.3 deaths per 100 patient-years.

Main Analyses

Unadjusted and adjusted associations between prescribed UF fee listed to physique weight and mortality are offered in . Prescribed UF charges >13 (versus ≤13) mL/h/kg have been related to higher mortality (adjusted HR, 1.31; 95% CI, 1.28–1.34). At a decrease threshold, prescribed UF charges >10 (versus ≤10) mL/h/kg have been additionally related to higher mortality (adjusted HR, 1.22; 95% CI, 1.20–1.24). As we lacked information on residual urine output, we carried out analyses restricted to sufferers with dialysis vintages ≥4 years (n= 40,706). Outcomes have been analogous to these of the total cohort (). We noticed a dose-response affiliation between UF fee and mortality, with extra frequent publicity to elevated UF charges related to elevated hurt. In contrast with <25% of treatments above the threshold, incrementally greater proportions of treatments with UF rates >13 mL/h/kg have been related to incrementally higher mortality (adjusted HRs of 1.26 [95% CI, 1.23–1.29] for 25%–49% of therapies and 1.40 [95% CI, 1.36–1.43] for ≥50% of therapies).

Desk 2

Associations between prescribed ultrafiltration fee and all-cause mortality amongst all sufferers and sufferers with longer dialysis classic.

n (%) Unadjusted HR (95percentCI) Adjustedb HR (95% CI)
Full Cohort (N=118,394)


Imply UF fee dichotomized at 10 mL/h/kg
 ≤10 mL/h/kg 69,865 (59.0) 1.00 (reference) 1.00 (reference)
 >10 mL/h/kg 48,529 (41.0) 1.10 (1.08–1.12) 1.22 (1.20–1.24)
Imply UF fee dichotomized at 13 mL/h/kg
 ≤13 mL/h/kg 96,659 (81.6) 1.00 (reference) 1.00 (reference)
 >13 mL/h/kg 21,735 (18.4) 1.15 (1.12–1.17) 1.31 (1.28–1.34)
Imply UF fee categorized
 <10 mL/h/kg 69,865 (59.0) 1.00 (reference) 1.00 (reference)
 10–13 mL/h/kg 26,794 (22.6) 1.05 (1.03–1.07) 1.12 (1.10–1.15)
 >13 mL/h/kg 21,735 (18.4) 1.16 (1.14–1.19) 1.35 (1.32–1.39)

Restricted Cohort: Dialysis Classic ≥4 Y (n=40,706)


Imply UF fee dichotomized at 10 mL/h/kg
 ≤10 mL/h/kg 21,470 (52.7) 1.00 (reference) 1.00 (reference)
 >10 mL/h/kg 19,236 (47.3) 1.03 (1.00–1.06) 1.19 (1.15–1.23)
Imply UF fee dichotomized at 13 mL/h/kg
 ≤13 mL/h/kg 31,488 (77.4) 1.00 (reference) 1.00 (reference)
 >13 mL/h/kg 9,218 (22.6) 1.05 (1.02–1.09) 1.26 (1.21–1.30)
Imply UF fee categorized
 <10 mL/h/kg 21,470 (52.7) 1.00 (reference) 1.00 (reference)
 10–13 mL/h/kg 10,018 (24.6) 1.00 (0.97–1.04) 1.10 (1.06–1.15)
 >13 mL/h/kg 9,218 (22.6) 1.05 (1.02–1.10) 1.30 (1.25–1.35)

Sensitivity Analyses Associated to Publicity Specification

In secondary analyses contemplating extra finely categorized UF charges, mortality threat elevated incrementally throughout successively higher UF fee classes (). When UF fee was thought of repeatedly, mortality threat rose by 3% for each 1 mL/h/kg UF fee improve.

Desk 3

Associations between steady and finely categorized prescribed ultrafiltration fee and all-cause mortality.

n (%) HR (95% CI)


Unadjusted Adjustedb
Imply UF fee, mL/h/kg 118,394 (100.0%) 1.01 (1.01–1.02) 1.03 (1.02–1.03)
Imply UF fee
 <6 mL/h/kg 23,813 (20.1%) 1.00 (reference) 1.00 (reference)
 6–<8 mL/h/kg 21,729 (18.4%) 0.99 (0.96–1.02) 1.03 (1.00–1.07)
 8–<10 mL/h/kg 24,323 (20.5%) 1.01 (0.98–1.04) 1.09 (1.06–1.12)
 10–<12 mL/h/kg 19,457 (16.4%) 1.04 (1.01–1.07) 1.15 (1.12–1.19)
 12–<14 mL/h/kg 13,086 (11.1%) 1.08 (1.05–1.12) 1.23 (1.18–1.27)
 ≥14 mL/h/kg 15,986 (13.5%) 1.19 (1.15–1.23) 1.43 (1.39–1.48)

Delivered and prescribed UF charges have been extremely correlated (r=0.96; p<0.005). Outcomes from analyses contemplating the delivered UF fee–mortality affiliation have been analogous to major prescribed UF fee outcomes (Desk S3). To research the affiliation of UF charges and mortality with out affect from threat incurred through the lengthy interdialytic interval, we carried out analyses excluding HD therapies following the 72 hour interdialytic interval. Outcomes have been in step with full cohort findings (Desk S4). Outcomes from fashions investigating time-updated prescribed UF fee and mortality have been additionally analogous to major findings (Merchandise S1).

Subgroup Analyses

shows outcomes from subgroup analyses. Larger prescribed UF fee (throughout all specs) was related to considerably higher mortality in all subgroups studied. When UF fee was dichotomized at 13 mL/h/kg, this affiliation was extra pronounced in blacks versus non-blacks, non-Hispanics versus Hispanics, sufferers with dialysis classic ≥4 years versus <4 years, sufferers with session durations ≥ 4 hours versus <4 hours, and heavier versus lighter sufferers (p for interplay <0.05 for all, indicating that subgroup impact dimension variations have been important). Equally, prescribed UF fee thought of repeatedly (per 1 mL/h/kg) was related to higher mortality throughout all subgroups. Impact sizes have been considerably higher amongst females versus males, non-Hispanics versus Hispanics, sufferers with dialysis classic <4 years versus ≥4 years, and heavier versus lighter sufferers (p for interplay < 0.05 for all).

Desk 4

Associations between prescribed ultrafiltration fee and mortality inside subgroups of curiosity.

Intercourse Feminine (n=53,307) Male (n=65,087) P for interplayb
Imply UF fee dichotomized at 10 mL/h/kg <0.001
 ≤10 mL/h/kg 1.00 (reference) 1.00 (reference)
 >10 mL/h/kg 1.26 (1.23–1.30) 1.18 (1.15–1.21)
Imply UF fee dichotomized at 13 mL/h/kg 0.2
 ≤13 mL/h/kg 1.00 (reference) 1.00 (reference)
 >13 mL/h/kg 1.33 (1.29–1.37) 1.29 (1.25–1.33)
Imply UF fee steady (mL/h/kg) 1.03 (1.03–1.03) 1.02 (1.02–1.03) 0.004
Race Non-Black (n=73,105) Black (n=45,289) P for interplayb
Imply UF fee dichotomized at 10 mL/h/kg 0.6
 ≤10 mL/h/kg 1.00 (reference) 1.00 (reference)
 >10 mL/h/kg 1.21 (1.19–1.24) 1.23 (1.19–1.27)
Imply UF fee dichotomized at 13 mL/h/kg 0.004
 ≤13 mL/h/kg 1.00 (reference) 1.00 (reference)
 >13 mL/h/kg 1.28 (1.24–1.31) 1.38 (1.32–1.43)
Imply UF fee steady (mL/h/kg) 1.03 (1.02–1.03) 1.03 (1.03–1.03) 0.2
Ethnicity Non-Hispanic (n=98,874) Hispanic (n=19,520) P for interplayb
Imply UF fee dichotomized at 10 mL/h/kg 0.1
 ≤10 mL/h/kg 1.00 (reference) 1.00 (reference)
 >10 mL/h/kg 1.23 (1.20–1.25) 1.17 (1.12–1.23)
Imply UF fee dichotomized at 13 mL/h/kg 0.002
 ≤13 mL/h/kg 1.00 (reference) 1.00 (reference)
 >13 mL/h/kg 1.33 (1.29–1.36) 1.20 (1.14–1.27)
Imply UF fee steady (mL/h/kg) 1.03 (1.02–1.03) 1.02 (1.01–1.03) 0.03
Dialysis Classic <4 y (n=77,688) ≥4 y (n=40,706) P for interplayb
Imply UF fee dichotomized at 10 mL/h/kg <0.001
 ≤10 mL/h/kg 1.00 (reference) 1.00 (reference)
 >10 mL/h/kg 1.17 (1.13–1.21) 1.25 (1.22–1.28)
Imply UF fee dichotomized at 13 mL/h/kg <0.001
 ≤13 mL/h/kg 1.00 (reference) 1.00 (reference)
 >13 mL/h/kg 1.23 (1.19–1.28) 1.37 (1.33–1.41)
Imply UF fee steady (mL/h/kg) 1.03 (1.02–1.03) 1.02 (1.02–1.03) 0.007
Session Length <4 h (n=78,504) ≥4 h (n=39,890) P for interplayb
Imply UF fee dichotomized at 10 mL/h/kg 0.9
 ≤10 mL/h/kg 1.00 (reference) 1.00 (reference)
 >10 mL/h/kg 1.22 (1.20–1.25) 1.23 (1.19–1.27)
Imply UF fee dichotomized at 13 mL/h/kg 0.02
 ≤13 mL/h/kg 1.00 (reference) 1.00 (reference)
 >13 mL/h/kg 1.30 (1.26–1.33) 1.39 (1.32–1.46)
Imply UF fee steady (mL/h/kg) 1.03 (1.02–1.03) 1.03 (1.02–1.03) 0.09
Put up-HD Weight <20th percentilec
(n=23,524)
>80th percentilec
(n=23,646)
P for interplayb
Imply UF fee dichotomized at 10 mL/h/kg 0.2
 ≤10 mL/h/kg 1.00 (reference) 1.00 (reference)
 >10 mL/h/kg 1.14 (1.10–1.19) 1.22 (1.16–1.29)
Imply UF fee dichotomized at 13 mL/h/kg <0.001
 ≤13 mL/h/kg 1.00 (reference) 1.00 (reference)
 >13 mL/h/kg 1.15 (1.11–1.20) 1.36 (1.22–1.51)
Imply UF fee steady (mL/h/kg) 1.01 (1.01–1.02) 1.02 (1.02–1.03) <0.001

Physique Measurement Affect

When prescribed UF fee was normalized to BMI, UF charges >37 (versus ≤37 [the 80th percentile]) mL/h/kg/m2 have been related to elevated mortality (adjusted HR, 1.27; 95% CI, 1.24–1.30). When normalized to BSA, UF charges >500 (versus ≤500 [the 80th percentile]) mL/h/m2 have been related to elevated mortality (adjusted HR, 1.23; 95% CI, 1.20–1.26). Utilizing the Vuong check, modeling UF fee normalized to weight (in comparison with BMI and BSA, individually) was most predictive of mortality (p<0.001 for each).18

To additional discover the UF fee–mortality affiliation throughout physique sizes, we categorized physique dimension as <20th, 20th–80th, and >80th percentile of post-HD physique weight, BMI and BSA (individually). Once more, UF charges >13 (versus ≤13) mL/h/kg have been related to higher loss of life threat in every subgroup. The affiliation was strongest amongst sufferers with larger versus decrease physique weight and at larger versus decrease BMI. The magnitude of affiliation was comparable throughout BSA strata ().

An external file that holds a picture, illustration, etc.
Object name is nihms805509f3.jpg

Associations between prescribed ultrafiltration fee and mortality by percentile of post-dialysis weight, physique mass index and physique floor space

Wonderful and Grey proportional subdistribution hazards regression fashions with kidney transplantation and dialysis modality change handled as competing dangers have been used to estimate the ultrafiltration fee and all-cause mortality affiliation evaluating imply UF charges >13 mL/h/kg to these ≤13 mL/h/kg inside strata of physique weight, BMI and BSA (individually). Fashions have been adjusted for age (steady), intercourse (feminine vs. male), race (black vs. non-black), ethnicity (Hispanic vs. non-Hispanic), dialysis classic (1–2, 3–4, ≥5 vs. <1 year), vascular access (graft, fistula vs. catheter), history of heart failure (yes vs. no), history of cardiovascular disease (yes vs. no), history of diabetes (yes vs. no), albumin (3.1–3.5, 3.6–4.0, >4.0 vs. ≤3.0 g/dL), creatinine (steady), phosphorous (4.1–5.0, 5.1–6.0, >6.0 vs. ≤4.0 mg/dL), hemoglobin (10.0–11.9, ≥12.0 vs. <10.0 g/dL), urea reduction ratio (continuous), pre-HD systolic blood pressure (131–150, 151–170, >170 vs. ≤130 mmHg), and missed classes (≥3 vs. <3).

Put up-dialysis weight was used to calculate normalized UF charges for weight, BMI and BSA. 20th/80th percentile for post-weight = 60.9/95.3 kg; 21.8/32.8 kg/m2 for BMI; 1.66/2.10 m2 for BSA. 80th percentile for UF fee normalized to BMI = 37 mL/h/(kg/m2); UF fee normalized to BSA = 500 mL/h/m2. 80th percentile chosen for BMI and BSA primarily based on 13 mL/h/kg being the 80th percentile of UF fee when normalized to post-HD weight.

Abbreviations: HR=hazard ratio, CI=confidence interval, HD=hemodialysis

Ultrafiltration Fee High quality Measure Concerns

Because the proposed CMS High quality Incentive Program (QIP) UF fee measure excludes sufferers with prescribed session durations ≥4 h from the metric numerator, we carried out analyses restricted to sufferers with prescribed session durations ≥4h (n=39,890). Amongst sufferers with session durations ≥4h, prescribed UF charges >13 (versus ≤13) mL/h/kg and prescribed UF charges >10 (versus ≤10) mL/h/kg have been related to higher mortality, no matter physique dimension. These associations have been extra pronounced in heavier sufferers (>80th percentile of physique weight) versus lighter sufferers ().

Desk 5

Associations between prescribed ultrafiltration fee and mortality general and by percentile of post-HD weight in sufferers with prescribed session durations ≥4 hours.

All Put up-HD weight


<20th percentile: <70.9 kg 20th–80th percentile: 70.9–110.2 kg >eightieth percentile:>110.2 kg
No. of sufferers 39,890 7,925 24,009 7,956
IDWG (kg) 3.5 ± 2.3 2.8 ± 2.2 3.4 ± 2.2 4.3 ± 2.4
Prescribed session length (min) 253 ± 34 247 ± 31 250 ± 31 265 ± 42
Associations**
 Imply UF fee dichotomized at 10 mL/h/kg
  ≤10 mL/h/kg 1.00 (reference) 1.00 (reference) 1.00 (reference) 1.00 (reference)
  >10 mL/h/kg 1.23 (1.18–1.27) 1.08 (1.01–1.16)* 1.18 (1.13–1.24)* 1.39 (1.24–1.55)*
 Imply UF fee dichotomized at 13 mL/h/kg
  ≤13 mL/h/kg 1.00 (reference) 1.00 (reference) 1.00 (reference) 1.00 (reference)
  >13 mL/h/kg 1.38 (1.31–1.45) 1.21 (1.12–1.31)* 1.32 (1.23–1.43)* 1.76 (1.41–2.18)*
 Imply UF fee categorized
  <10 mL/h/kg 1.00 (reference) 1.00 (reference) 1.00 (reference) 1.00 (reference)
  10–13 mL/h/kg 1.14 (1.09–1.18) 0.98 (0.90–1.06)* 1.12 (1.06–1.18)* 1.31 (1.16–1.48)*
  >13 mL/h/kg 1.42 (1.35–1.50) 1.20 (1.11–1.31)* 1.36 (1.26–1.48)* 1.81 (1.45–2.25)*

DISCUSSION

Prior research have proven associations between speedy fluid elimination and mortality amongst HD sufferers, however questions on examine design and potential variations throughout subpopulations stay. Within the largest to-date observational cohort, we demonstrated an affiliation between higher UF fee and mortality, exhibiting incrementally higher hurt from UF charges beginning at 6 mL/h/kg. Our outcomes recommend that notable UF-related hurt begins earlier than 10 mL/h/kg, considerably decrease than the proposed high quality measure threshold of 13 mL/h/kg. The UF fee–mortality affiliation was important throughout all physique sizes, with bigger sufferers having higher mortality threat from larger UF charges. Ultrafiltration fee normalized to physique weight had a stronger affiliation with mortality (versus normalization to BMI or BSA). Findings have been strong throughout key sub-populations.

Thus far, three observational research have examined the UF fee–mortality affiliation. There have been no randomized-controlled trials. In a DOPPS (Dialysis Outcomes Observe Patterns Examine) evaluation, Saran et al. demonstrated a modest affiliation between UF charges >10 mL/h/kg and all-cause mortality.2 In an Italian cohort, Movilli et al. recognized a UF fee threshold of 12.2 mL/h/kg as essentially the most predictive cut-point of mortality.3 In a post-hoc evaluation of the Hemodialysis (HEMO) Examine, Flythe et al. discovered that UF charges >13 mL/h/kg (versus <10 mL/h/kg) have been related to higher mortality.4 Impact modification on the idea of coronary heart failure was noticed, suggesting that threat might happen at charges of 10 mL/h/kg in some populations. Actually, spline analyses confirmed that the UF fee threat started to rise at 10 mL/h/kg amongst all sufferers.4 Mechanistic research evaluating intradialytic echocardiography, troponin and endotoxin have established hemodynamic-induced end-organ ischemia as a possible mediator of the UF fee–mortality affiliation.5,6,8,21

Regardless of constant findings throughout current epidemiologic research, the methodological shortcomings of those investigations have tempered enthusiasm for UF fee scientific tips.22–24 We sought to handle these uncertainties. The IDWG (or UF quantity), session length, and post-HD weight all contribute to the UF fee calculation and have been included in prior multivariable fashions, probably introducing impact dimension inaccuracies. In our new analyses, we didn’t alter for these elements as controlling for these variables obscures interpretation of findings. Said in any other case, accepting that prime UF fee should outcome from excessive IDWG, low session length, low physique weight, or some mixture thereof, we didn’t artificially constrain these elements analytically however accepted their inherent contributions to UF fee. Moreover, concern for confounding from residual kidney operate has led to scrutiny of prior research as urine output is a crucial confounder.23 To handle this, we carried out analyses restricted to sufferers on dialysis for ≥4 years, a inhabitants with usually low urine output.

Our current analyses exhibit that prescribed (and delivered) UF charges >10 mL/h/kg are related to higher mortality. This discovering is in step with Saran et al. and the Flythe et al. spline evaluation exhibiting a steep rise in UF fee–associated mortality threat at 10 mL/h/kg.2,4 An UF fee threshold of 13 mL/h/kg, as instituted within the Core Survey and as proposed for the 2019 CMS QIP, is probably going conservative.9,10 Moreover, the Nationwide High quality Discussion board–endorsed UF fee measure features a session size restriction. The metric numerator consists of solely sufferers with UF charges ≥13 mL/h/kg and delivered session durations <4 hours. Whereas this restriction could also be in-line with affected person desire information exhibiting aversion to longer session lengths,25 our information exhibit that sufferers with longer session durations incur higher mortality threat at larger UF charges. We additionally noticed a dose-response affiliation between UF fee and mortality: extra frequent publicity to larger UF charges is related to an incrementally larger loss of life threat. Frequency-based definitions of UF charges might higher seize threat than single remedy or mean-based UF fee definitions. Reassuringly, we noticed the UF fee–mortality affiliation to be strong throughout subgroups, rendering a single mean-based threshold strategy affordable. We additionally noticed comparable associations between prescribed and delivered UF charges and mortality, offering reassurance relating to the proposed high quality measure’s seize of delivered UF charges. Collectively, these information present sturdy observational proof supporting an affiliation between higher UF charges and mortality.

Fluid elimination–associated hurt happens when the UF fee exceeds the plasma refill fee and subclinical or scientific hemodynamic compromise happens. Vascular refill is influenced by many elements together with physique dimension, intercourse, dietary standing, complete physique quantity standing and distribution, and blood movement distribution.26 It’s believable that the UF fee–end result affiliation varies throughout physique varieties. Due to this fact, we thought of fluid elimination normalized to physique weight, BMI and BSA. Ultrafiltration fee normalized to weight had the strongest affiliation with mortality, however, when UF fee was modeled repeatedly, the impact dimension diversified throughout intercourse and physique dimension with females (versus males) and heavier (versus lighter) sufferers having higher mortality threat. Related impact dimension variations have been noticed when UF fee was normalized to BMI. Normalizing UF fee to BSA produced extra secure impact estimates throughout BSA strata. The perfect indexing technique would possibly yield comparable strengths of affiliation throughout physique sizes as noticed with BSA. Nonetheless, the impact dimension variations throughout physique sizes when UF fee was normalized to each weight and BMI have been modest, and all three normalization strategies revealed considerably higher mortality with larger UF charges throughout all physique sizes. As physique weight is available for UF fee calculation within the clinic and impact sizes solely modestly totally different throughout physique dimension strata, UF fee normalization to physique weight is affordable.

A number of limitations of our examine needs to be acknowledged. That is an observational evaluation and should include uncontrolled confounding. To attenuate confounding from difficult-to-measure elements reminiscent of well being standing, we managed for variables together with albumin, phosphate, creatinine, albumin, and weight. Associated, we carried out analyses restricted to sufferers of superior dialysis classic to reduce confounding from residual urine output. Nonetheless, we can not rule out the potential for confounding from these elements or different unconsidered elements. For instance, physique dimension, clearance, and session length are intently associated. Regardless of together with URR and physique dimension (through UF fee) in our fashions, we can not rule-out residual confounding from clearance and physique size-related elements. We additionally lacked information on dialysate and dietary sodium, potential confounders of the UF fee–mortality affiliation. Reassuringly, the addition of serum sodium to multivariable fashions didn’t considerably alter UF fee–mortality impact estimates (Desk S5), however residual confounding from these and different elements can’t be excluded. Potential examine of UF fee and outcomes is warranted. Second, we have been unable to research cause-specific mortality attributable to lack of adjudicated loss of life causes in our database. Third, we have been unable to contemplate intradialytic signs attributable to lack of symptom information. Fourth, our information have been derived from a single LDO and will not be consultant of different dialysis suppliers. Lastly, our examine included grownup, in-center upkeep HD sufferers with dialytic classic ≥90 days. Outcomes shouldn’t be extrapolated to excluded populations reminiscent of incident HD sufferers.

In conclusion, we demonstrated an affiliation between UF charges >10 mL/h/kg (versus ≤10) and all-cause mortality and confirmed an incremental rise in UF-related threat starting at a UF fee of 6 mL/h/kg. Moreover, we discovered the UF fee–end result affiliation to be strong throughout physique dimension, intercourse, and racial subgroups and offered proof supporting normalization of UF fee to weight versus different anthropometric metrics. The richness of the UF fee–end result observational proof base and the regulatory curiosity in adoption of an UF fee high quality measure requires a randomized managed trial investigation of UF charges and outcomes.

Leave a Reply

Your email address will not be published. Required fields are marked *