Research

JAMA Internal Medicine | Original Investigation

Implication of Trends in Timing of Dialysis Initiation

for Incidence of End-stage Kidney Disease
Chi-yuan Hsu, MD, MSc; Rishi V. Parikh, MPH; Leonid N. Pravoverov, MD; Sijie Zheng, MD, PhD;
David V. Glidden, PhD; Thida C. Tan, MPH; Alan S. Go, MD

Supplemental content
IMPORTANCE In the last 2 decades, there have been notable changes in the level of estimated
glomerular filtration rate (eGFR) at which patients initiate long-term dialysis in the US and
around the world. How changes over time in the likelihood of dialysis initiation at any given
eGFR level in at-risk patients are associated with the population burden of end-stage kidney
disease (ESKD) has not been not well defined.

OBJECTIVE To examine temporal trends in long-term dialysis initiation by level of eGFR and
to quantify how these patterns are associated with the number of patients with ESKD.

DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study analyzing data obtained
from a large, integrated health care delivery system in Northern California from 2001 to
2018 in successive 3-year intervals. Included individuals, ranging in number from as few as
983 122 (2001-2003) to as many as 1 844 317 (2016-2018), were adult members with 1 or
more outpatient serum creatinine levels determined in the prior year.

MAIN OUTCOMES AND MEASURES One-year risk of initiating long-term dialysis stratified by
eGFR levels. Multivariable logistic regression was performed to assess temporal trends in
each 3-year cohort with adjustment for age, sex, race, and diabetes status. The potential
change in dialysis initiation in the final cohort (2016-2018) was estimated using the relative
difference between the standardized risks in the initial cohort (2001-2003) and the final
cohort.

RESULTS In the initial 3-year cohort, the mean (SD) age was 55.4 (16.3) years, 55.0% were
women, and the prevalence of diabetes was 14.9%. These characteristics, as well as the
distribution of index eGFR, were stable across the study period. The likelihood of receiving
dialysis at eGFR levels of 10 to 24 mL/min/1.73 m2 generally increased over time. For example,
the 1-year odds of initiating dialysis increased for every 3-year interval by 5.2% (adjusted odds
ratio, 1.052; 95% CI, 1.004-1.102) among adults with an index eGFR of 20 to 24 mL/min/1.73
m2, by 6.6% (adjusted odds ratio, 1.066; 95% CI, 1.007-1.130) among adults with an eGFR
of 16 to 17 mL/min/1.73 m2, and by 5.3% (adjusted odds ratio, 1.053; 95% CI, 1.008-1.100)
among adults with an eGFR of 10 to 13 mL/min/1.73 m2, adjusting for age, sex, race, and
diabetes. The incidence of new cases of ESKD was estimated to have potentially been 16%
(95% CI, 13%-18%) lower if there were no changes in system-level practice patterns or other
factors besides timing of initiating long-term dialysis from the initial 3-year interval
(2001-2003) to the final interval (2016-2018) assessed in this study.

CONCLUSIONS AND RELEVANCE The present results underscore the importance the timing
of initiating long-term dialysis has on the size of the population of individuals with ESKD.

Author Affiliations: Author

affiliations are listed at the end of this
article.
Corresponding Author: Chi-yuan
Hsu, MD, MSc, Division of
Nephrology, Department of
Medicine, University of California,
San Francisco, 533 Parnassus Avenue,
JAMA Intern Med. 2020;180(12):1647-1654. doi:10.1001/jamainternmed.2020.5009 Box 0532, U-400, San Francisco, CA
Published online October 12, 2020. 94143 (hsuchi@medicine.ucsf.edu).

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 Research Original Investigation
I
n the last 2 decades, there have been notable changes in the
estimated glomerular filtration rate (eGFR) at which long-term
dialysis is initiated in the US and around the world.1 For ex-
ample, according to the nationally comprehensive US Renal Data
System registry, the proportion of new patients with end-stage
renal disease in the US with an eGFR of 10 to 15 mL/min/1.73 m2
at the start of dialysis increased from 10% in 1996 to a peak of 28%
in 2010.2 Although several previous publications have examined
dialysis initiation over time, a key remaining knowledge gap is the
distribution of eGFR in the underlying at-risk population from
which the end-stage kidney disease (ESKD) cases are derived.
Thus, secular trends in the likelihood of dialysis initiation at any
given eGFR level could not be defined in previous studies, and
the implications of potential trends in changes in the size of
the at-risk population on the number of patients with ESKD in the
population could not be estimated.
Nationally, the societal and patient burden of ESKD is high,
with Medicare fee-for-service spending for beneficiaries with
ESKD rising from $33.8 billion to $35.4 billion between 2015 and
2016.2 Furthermore,nationalratesofmorbidityanddeatharevery
high surrounding initiation of long-term dialysis.3-5 Initiation of
long-term dialysis can also be associated with declines in cogni-
tive function and functional status6,7 and worsening cardiac
structure.8 The July 2019 Advancing American Kidney Health ini-
tiative issued by the White House targeted as a major national pri-
ority reducing the number of new ESKD cases by 25% by 2030.9
Because ESKD is operationally defined as receiving long-
term dialysis or a kidney transplant, we hypothesized that the
number of patients with incident ESKD can vary consider-
ably depending on decisions between patients and physi-
cians about the choice and timing of kidney replacement
therapy, and particularly of initiating dialysis. Consistent with
this, after publication of the Initiating Dialysis Early and Late
(IDEAL) trial—a randomized clinical trial showing no signifi-
cant difference in death or other outcomes with earlier (eGFR
of 9.0 mL/min/1.73 m2) vs later (eGFR of 7.2 mL/min/1.73 m2)
initiation of dialysis10—a rapid drop in early dialysis initiation
was observed in Canada.11 Although early dialysis initiation was
defined in that study as dialysis initiation at eGFR higher than
10.5 mL/min/1.73 m2, there was no information regarding how
the number of patients with chronic kidney disease (CKD) in
the underlying population with eGFR higher than 10.5 mL/
min/1.73 m2 may have changed during the relevant period.
To date, no study has quantified how secular patterns in
the likelihood of dialysis initiation at any given eGFR level can
impact the number of patients with incident ESKD in a popu-
lation over time. We addressed this important knowledge gap
by examining temporal trends in dialysis initiation by level of
kidney function within a large, community-based population
to provide information relevant for policies supporting the na-
tional advancement of kidney health.
Methods
Source Population
Kaiser Permanente Northern California (KPNC) is a large,
integrated health care delivery system currently providing
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Trends in Timing of Dialysis and Incidence of End-stage Kidney Disease
Key Points
Question How are temporal changes in the level of estimated
glomerular filtration rate (eGFR) at which long-term dialysis is
initiated among at-risk patients associated with the number of
patients with end-stage kidney disease in the population?
Findings This cohort study of 983 122 individuals in the initial
3-year interval (2001-2003) to 1 844 317 individuals in the final
interval (2016-2018) used data from a large, integrated health care
delivery system in Northern California and found that an increase
in the number of individuals starting dialysis with an eGFR of 10
to 24 mL/min/1.73 m2 was associated with changes over time in
the likelihood of receiving dialysis at this eGFR independent of the
number of people in the underlying population who had this same
eGFR. Estimated incidence of new end-stage kidney disease cases
would have been 16% lower with no changes in system-level
practice patterns or other factors besides timing of long-term
dialysis initiation.
Meaning The timing of long-term dialysis initiation is associated
with the number of individuals with end-stage kidney disease.
comprehensive care for more than 4.5 million members. Its
membership is sociodemographically diverse and highly rep-
resentative of the local and statewide population.12 Nearly all
aspects of care are captured through KPNC’s integrated elec-
tronic health record system, with access to clinical data ele-
ments from all practice settings (eg, laboratory test results and
vital signs) as well as previously validated algorithms that in-
corporate relevant diagnostic or procedure codes and phar-
macy dispenses. This study was approved by the KPNC insti-
tutional review board, which also waived the requirement for
obtaining informed consent because this study was a retro-
spective data-only analysis of linked data that were deidenti-
fied before analysis.
Study Sample, Outcome, and Covariates
We assembled cohorts of all adult members (18 years or older)
with at least 1 valid outpatient serum creatinine measure-
ment from 2001 through 2018 grouped into 3-year intervals
(ie, 2001-2003, 2004-2006, 2007-2009, 2010-2012, 2013-
2015, and 2016-2018), which provided more stable and pre-
cise estimates of ESKD rates. Individuals with 12 or more
months of continuous health plan membership were in-
cluded in 3-year cohorts on the first eligible January 1st within
each 3-year interval. Approximately 15% of eligible patients
were excluded in each cohort owing to insufficient prior con-
tinuous membership. Patients with a prior kidney transplant
or who were already undergoing long-term dialysis were also
excluded (approximately 5% of each cohort).
Our primary outcome was initiation of long-term dialysis
within the first eligible year in each 3-year interval, ascer-
tained through a comprehensive, manually validated health
plan ESKD treatment registry.13 Patients are entered into the
registry after manual review to confirm that receipt of dialy-
sis was not temporary or only for acute kidney injury. We re-
moved cases of preemptive kidney transplant (3% of ESKD
cases). Initial dialysis modality (hemodialysis vs peritoneal di-
alysis) was ascertained from registry files. We defined urgent
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 Trends in Timing of Dialysis and Incidence of End-stage Kidney Disease
dialysis starts as being preceded by an episode of dialysis-
requiring acute kidney injury13 within 28 days before long-
term dialysis initiation. All cases not meeting this definition
were considered elective starts.
Age, sex, and self-reported race were obtained from elec-
tronic health records to calculate eGFR and to account for po-
tential changes in the source population. Targeted comorbidi-
ties in the study population were defined using validated
International Classification of Diseases, Ninth Revision and Tenth
Revision diagnostic codes, laboratory results, and receipt of
medications using electronic health record–based data that
were cleaned and linked at the individual-patient level into the
KPNC Virtual Data Warehouse as previously described and
validated.14-17 We ascertained outpatient laboratory test re-
sults, including the CKD Epidemiology Collaboration equation–
based eGFR and proteinuria.18
Statistical Analysis
For each 3-year cohort, we calculated the 1-year risk of initi-
ating long-term dialysis, overall and by urgent vs elective
starts, directly standardized to the 2001 to 2003 KPNC popu-
lation by age, sex, and index eGFR (ie, most recent outpa-
tient measurement before cohort entry). We estimated a
potential change in dialysis initiation in the final cohort
(2016-2018) using the relative difference between the stan-
dardized risks and associated 95% CIs in the initial cohort
(2001-2003) and the final cohort.
We next stratified the study population into a priori se-
lected index eGFR levels of 60 to 150, 30 to 59, 25 to 29, 20 to
24, 18 to 19, 16 to 17, 14 to 15, 10 to 13, 6 to 9, and 0 to 5 mL/
min/1.73 m2. Within each eGFR stratum, we calculated the
1-year risk of receiving long-term dialysis across each 3-year
interval. All crude temporal trends were evaluated using
Cochrane-Armitage tests for trend. To assess multivariable-
adjusted temporal trends, we evaluated the significance and
odds ratios (95% CIs) of an ordinal 3-year cohort term in a
logistic regression model adjusting for age, sex, race, and dia-
betes status and used a generalized estimating equations ap-
proach to account for correlations between repeated individu-
als across calendar cohorts.
To enhance comparability with previous studies, we also
report the mean (SD) eGFR at dialysis initiation in each time
interval, using the most recent outpatient eGFR measure-
ment before dialysis initiation.2 This eGFR value is separate
from the index eGFR value used for assembly of calendar year
cohorts.
All data were analyzed using SAS, version 9.4 (SAS Insti-
tute Inc). A 2-sided P < .05 was considered statistically
significant.
Results
Patient Characteristics
Between 2001 and 2018, the size of the eligible population in-
creased consistent with growth in overall KPNC enrollment and
more frequent outpatient serum creatinine testing per pa-
tient (Table 1). In the first 3-year interval (2001-2003) the mean
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Original Investigation Research
(SD) age in the eligible population was 55.4 (16.3) years, 55.0%
were women, and the prevalence of diabetes was 14.9%. These
characteristics as well as the distribution of index eGFR were
stable across the study period. The prevalence of docu-
mented hypertension and dyslipidemia increased since 2001,
although this was largely due to increased detection and chang-
ing systemwide practice guidelines. In later years, we also
observed a higher prevalence of Asian/Pacific Islander and
Hispanic patients.
Temporal Trends in eGFR at Dialysis Initiation
Overall, the temporal trend in mean eGFR at dialysis initia-
tion mirrored that seen in the general US population,19 with
a progressively higher mean eGFR through the first decade
of the 21st century, followed by a plateau (Figure 1). Mean
(SD) eGFR at dialysis initiation for patients starting long-
term dialysis was 12.4 (13.1) mL/min/1.73 m2 in 2001 to 2003,
rose to 16.3 (17.7) mL/min/1.73 m2 in 2010 to 2012, and did
not further increase through 2016 to 2018. These temporal
trends were similar for elective starts and for all patients
undergoing peritoneal dialysis or hemodialysis (eFigure 1 in
the Supplement).
Temporal Trends in Dialysis Initiation
In our study population, the number of eligible patients who
started dialysis was 847 (0.086% of 983 122 at risk) in 2001
to 2003, 917 (0.074% of 1 241 537) in 2004 to 2006, 1011
(0.072% of 1 411 690) in 2007 to 2009, 1013 (0.068% of
1 482 883) in 2010 to 2012, 1092 (0.068% of 1 607 737) in
2013 to 2015, and 1224 (0.066% of 1 844 317) in 2016 to 2018.
The proportion of elective ESKD cases was 85.6% in 2001 to
2003, 89.2% in 2004 to 2006, 94.1% 2007 to 2009, 74.9% in
2010 to 2012, 87.2% in 2013 to 2015, and 84.0% in 2016 to
2018. In addition, the proportion of new ESKD cases initiat-
ing peritoneal dialysis was 13.7% in 2001 to 2003, 14.2% in
2004 to 2006, 11.0% in 2007 to 2009, 13.4% in 2010 to 2012,
21.7% in 2013 to 2015, and 20.8% in 2016 to 2018. As
recently reported,20 KPNC has made a concerted system-
wide effort to increase peritoneal dialysis as the preferred
initial modality since approximately 2008.
The likelihood of long-term dialysis initiation within
1 year increased from 0.086% (95% CI, 0.080%-0.092%) in
2001 to 2003, to 0.103% (95% CI, 0.099%-0.107%) in 2016
to 2018 (P < .001 for trend) (Figure 2). When examining the
annual risk of initiating long-term dialysis by index eGFR
between 2001 and 2018, the most prominent secular trends
were noted in those with an index eGFR of 20 to 24 mL/min/
1.73 m2 (from 3.2% to 5.1%; P = .001), those with an index
eGFR of 18 to 19 mL/min/1.73 m 2 (from 8.3% to 11.0%;
P = .03), those with an index eGFR of 16 to 17 mL/min/1.73
m2 (from 12.4% to 17.9%; P = .005), and those with an index
eGFR of 10 to 13 mL/min/1.73 m 2 (from 34.2% to 40.3%;
P = .03) (Figure 3; eFigure 2 in the Supplement). After
adjustment for age, sex, race, and diabetes, statistically sig-
nificant temporal increases in 1-year odds of initiating dialy-
sis persisted among eGFR categories of 20 to 24, 16 to 17, and
10 to 13 mL/min/1.73 m2 (Table 2). Among patients with an
index eGFR of 20 to 24 mL/min/1.73 m2, the 1-year odds of
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 Research Original Investigation Trends in Timing of Dialysis and Incidence of End-stage Kidney Disease

Table 1. Characteristics of Adults With Valid Serum Creatinine Measurements Receiving Care at Kaiser Permanente Northern California, 2001-2018

Adults, No. (%)

2001-2003 2004-2006 2007-2009 2010-2012 2013-2015 2016-2018
Characteristic (n = 983 122) (n = 1 241 537) (n = 1 411 690) (n = 1 482 883) (n = 1 607 737) (n = 1 844 317)
Age, mean (SD), y 55.4 (16.3) 54.7 (16.3) 54.2 (16.3) 54.6 (16.4) 54.9 (16.7) 54.7 (16.9)
Age categories, y
18-40 179 731 (18.3) 240 543 (19.4) 286 716 (20.3) 295 446 (19.9) 328 504 (20.4) 399 867 (21.7)
41-60 416 351 (42.3) 539 286 (43.4) 615 565 (43.6) 622 535 (42.0) 638 647 (39.7) 705 825 (38.3)
61-75 259 110 (26.4) 310 287 (25.0) 346 504 (24.5) 390 589 (26.3) 447 649 (27.8) 524 846 (28.5)
>75 127 930 (13.0) 151 421 (12.2) 162 905 (11.5) 174 313 (11.8) 192 937 (12.0) 213 779 (11.6)
Women 540 490 (55.0) 682 077 (54.9) 773 307 (54.8) 817 276 (55.1) 883 892 (55.0) 1 007 674 (54.6)
Self-reported race
White 573 225 (58.3) 697 084 (56.1) 769 082 (54.5) 797 395 (53.8) 850 849 (52.9) 927 541 (50.3)
Black/African American 79 894 (8.1) 94 415 (7.6) 103 164 (7.3) 108 548 (7.3) 115 687 (7.2) 129 088 (7.0)
Asian/Pacific Islander 121 761 (12.4) 173 116 (13.9) 221 400 (15.7) 257 561 (17.4) 299 665 (18.6) 370 711 (20.1)
Other/unknown 208 242 (21.2) 276 922 (22.3) 318 044 (22.5) 319 379 (21.5) 341 536 (21.2) 416 977 (22.6)
Hispanic ethnicity 129 213 (13.1) 178 716 (14.4) 222 922 (15.8) 238 701 (16.1) 269 953 (16.8) 334 194 (18.1)
Smoking status
Current 103 728 (10.6) 169 502 (13.7) 156 589 (11.1) 134 965 (9.1) 134 051 (8.3) 140 041 (7.6)
Former 13 477 (1.4) 48 476 (3.9) 243 301 (17.2) 352 580 (23.8) 403 922 (25.1) 457 932 (24.8)
CKD-EPI eGFR, mean (SD), 85.3 (21.5) 86.0 (21.4) 85.1 (21.3) 88.2 (21.2) 87.5 (21.0) 88.6 (21.2)
mL/min/1.73 m2
CKD-EPI eGFR category,
mL/min/1.73 m2
60-150 863 987 (87.88) 1 098 418 (88.5) 1 240 252 (87.9) 1 336 995 (90.2) 1 447 191 (90.0) 1 672 049 (90.7)
30-59 110 721 (11.3) 133 503 (10.8) 160 126 (11.3) 135 829 (9.2) 150 083 (9.3) 161 204 (8.7)
25-29 3865 (0.39) 4507 (0.36) 5654 (0.40) 4927 (0.33) 5055 (0.31) 5255 (0.28)
20-24 2260 (0.23) 2684 (0.22) 3035 (0.21) 2755 (0.19) 2855 (0.18) 2990 (0.16)
18-19 604 (0.06) 709 (0.06) 782 (0.06) 720 (0.05) 713 (0.04) 809 (0.04)
16-17 468 (0.05) 536 (0.04) 610 (0.04) 536 (0.04) 607 (0.04) 649 (0.04)
14-15 369 (0.04) 408 (0.03) 444 (0.03) 427 (0.03) 438 (0.03) 496 (0.03)
10-13 553 (0.06) 515 (0.04) 563 (0.04) 490 (0.03) 542 (0.03) 611 (0.03)
6-9 264 (0.03) 220 (0.02) 201 (0.01) 178 (0.01) 220 (0.01) 222 (0.01)
0-5 31 (0.00) 37 (0.00) 23 (0.00) 26 (0.00) 33 (0.00) 32 (0.00)
Medical history
Acute myocardial infarction 14 415 (1.5) 16 256 (1.3) 16 703 (1.2) 14 693 (1.0) 12 878 (0.8) 11 974 (0.6)
Atrial fibrillation/flutter 24 511 (2.5) 33 494 (2.7) 40 430 (2.9) 47 405 (3.2) 56 902 (3.5) 66 575 (3.6)
Ischemic stroke or transient 14 146 (1.4) 16 883 (1.4) 16 211 (1.1) 14 892 (1.0) 16 176 (1.0) 23 080 (1.3)
ischemic attack
Heart failure 19 853 (2.0) 24 918 (2.0) 30 433 (2.2) 31 475 (2.1) 31 440 (2.0) 34 018 (1.8)
Mitral or aortic valvular 15 789 (1.6) 25 266 (2.0) 31 274 (2.2) 30 817 (2.1) 31 171 (1.9) 36 021 (2.0)
disease
Venous thromboembolism 4656 (0.5) 5377 (0.4) 6118 (0.4) 6822 (0.5) 8927 (0.6) 13 127 (0.7)
Diabetes 146 298 (14.9) 185 806 (15.0) 219 498 (15.5) 237 431 (16.0) 262 638 (16.3) 312 960 (17.0)
Hypertension 307 243 (31.3) 446 279 (35.9) 544 853 (38.6) 588 694 (39.7) 614 317 (38.2) 660 973 (35.8)
Dyslipidemia 321 948 (32.7) 516 220 (41.6) 644 239 (45.6) 706 601 (47.7) 774 987 (48.2) 857 073 (46.5)
Hyperthyroidism 26 761 (2.7) 36 463 (2.9) 40 837 (2.9) 42 933 (2.9) 47 680 (3.0) 56 325 (3.1)
Hypothyroidism 101 838 (10.4) 127 484 (10.3) 144 472 (10.2) 156 335 (10.5) 172 232 (10.7) 195 849 (10.6)
Chronic liver disease 17 136 (1.7) 29 510 (2.4) 39 983 (2.8) 47 458 (3.2) 55 878 (3.5) 76 039 (4.1)
Chronic lung disease 273 959 (27.9) 238 618 (19.2) 268 455 (19.0) 320 192 (21.6) 334 295 (20.8) 359 858 (19.5)
Diagnosed dementia 11 718 (1.2) 16 908 (1.4) 23 404 (1.7) 25 442 (1.7) 28 665 (1.8) 31 160 (1.7)
Diagnosed depression 108 859 (11.1) 159 655 (12.9) 190 748 (13.5) 201 285 (13.6) 200 943 (12.5) 218 521 (11.8)

Abbreviations: CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFR, estimated glomerular filtration rate.

initiating dialysis increased for every 3-year interval by 5.2% odds of initiating dialysis increased by 6.6% (adjusted odds
(adjusted odds ratio, 1.052; 95% CI, 1.004-1.102); among ratio, 1.066; 95% CI, 1.007-1.130); and among patients with
patients with an eGFR 16 to 17 mL/min/1.73 m2, the 1-year an eGFR of 10 to 13 mL/min/1.73 m2, the 1-year odds of initi-

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 Trends in Timing of Dialysis and Incidence of End-stage Kidney Disease Original Investigation Research

Figure 1. Mean Estimated Glomerular Filtration Rate (GFR) Figure 2. Age-, Sex-, and Estimated Glomerular Filtration Rate–
at Dialysis Initiation Among Patients Initiating Dialysis Standardized Annual Risk of Initiating Long-term Dialysis Among Adults
Between 2001 and 2018, by 3-Year Intervals With Serum Creatinine Measurements at Kaiser Permanente Northern
California, 2001-2018, Overall and by Elective vs Urgent Dialysis Start
20
18 Overall Urgent Elective
0.12
Estimated GFR, mL/min/1.73 m2

1-y Risk of initiating long-term dialysis, %

16
a
14 0.10
12 a

10 0.08

8
0.06
6
4 0.04
2
0 0.02
2001-2003 2004-2006 2007-2009 2010-2012 2013-2015 2016-2018
3-y Interval 0
2001-2003 2004-2006 2007-2009 2010-2012 2013-2015 2016-2018
No. initiating 847 917 1011 1013 1092 1224
dialysis 3-y Interval
No. at risk 983 122 1 241 537 1 411 690 1 482 883 1 607 737 1 844 317
Data are based on outpatient, nonemergency department serum creatinine
level closest to dialysis initiation date. Error bars indicate 95% CIs. Error bars indicate 95% CIs.
a
P < .001 for trend.

ating dialysis increased by 5.3% (adjusted odds ratio, 1.053;

95% CI, 1.008-1.100) (Table 2). By contrast, among patients Figure 3. Annual Risk of Initiating Long-term Dialysis by Calendar Year
with very low index eGFR (≤9 mL/min/1.73 m2), we observed and Index Estimated Glomerular Filtration Rate, 2001-2018
stable or decreased unadjusted and adjusted odds of initiat-
ing dialysis over time. These patterns were similar among 0-5 mL/min/1.73 m2 16-17 mL/min/1.73 m2
6-9 mL/min/1.73 m2 18-19 mL/min/1.73 m2
the subset of patients with elective dialysis starts (eTable in 10-13 mL/min/1.73 m2 20-24 mL/min/1.73 m2
the Supplement). 14-15 mL/min/1.73 m2 25-29 mL/min/1.73 m2

Overall, we estimated that incidence of ESKD could have 70

1-y Risk of initiating long-term dialysis, %

potentially been 16% (95% CI, 13%-18%) lower if there were no

60
changes in system-level practice patterns or other factors be-
sides timing of initiation of long-term dialysis from the initial 50

3-year interval (2001-2003) to the final 3-year interval (2016- a

40
2018) assessed in this study.
30

20 b

Discussion 10
a

b
In this study using a large, integrated health care delivery sys-
0
tem that facilitated accurate determination of the size and eGFR 2001-2003 2004-2006 2007-2009 2010-2012 2013-2015 2016-2018
distribution of the underlying source population, we estimated 3-y Interval

that incidence of ESKD could have potentially been 16% (95% CI,
13%-18%) lower if there were no changes in system-level prac-
tice patterns or other factors besides timing of initiation of long-
term dialysis from the initial 3-year interval (2001-2003) to the
final 3-year interval (2016-2018) assessed in this study.
The optimal time to initiate long-term dialysis in patients
with kidney disease remains unclear,10,21-27 with a high de-
gree of variability in practice patterns over time and across
health systems.1 Among 11 215 older US veterans with sus-
tained eGFR lower than 15 mL/min/1.73 m2, Tamura et al28 ob-
served that patients exclusively using fee-for-service Medi-
care for nephrology care had 28% higher frequency of dialysis
initiation compared with those exclusively using Depart-
ment of Veterans Affairs nephrology care. Based on US Renal
Data System data, the percentage of patients with incident kid-
ney failure who initiated dialysis at an eGFR of 10 mL/min/
See Table 2 for unadjusted P values.
a
P < .05 for trend.
b
P < .01 for trend.
1.73 m2 or higher increased steadily from the mid-1990s (13%)
until 2010 (43%), when it remained stable or slightly declined.2
Similar temporal trends have been observed in the Veterans
Affairs health system29 and in other countries, such as the
United Kingdom.30
We hypothesize that the level of eGFR at which long-
term dialysis was started during the 2 decades internation-
ally has been influenced by a variety of system-, physician-,
and patient-level factors.1 On a national level, perspectives from
opinion leaders31 combined with high-profile, consensus-
based clinical practice guidelines32,33 contributed to an em-

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 Research Original Investigation
Table 2. Unadjusted and Adjusted Associations for Calendar Year Trend in the Annual Risk of Initiating Dialysis
by Index eGFR Category at Kaiser Permanente Northern California, 2001-2018, by 3-Year Interval
P value
eGFR category,
mL/min/1.73 m2 No. Unadjusteda
60-150 7 658 892 .89
30-59 851 466 .14
25-29 29 263 .17
20-24 16 579 .001
18-19 4337 .03
16-17 3406 .005
14-15 2582 .08
10-13 3274 .03
6-9 1305 .21
0-5 182 .47
phasis on recommending a “healthy/timely” dialysis,1 which
included efforts to promote the placement of arteriovenous fis-
tulas at higher eGFR levels.34 This may have contributed to pa-
tients accepting dialysis at relatively higher eGFR levels dur-
ing the present study period, especially if they had a mature
arteriovenous fistula and symptoms that are challenging to
manage medically. In addition, because KPNC promoted the
use of peritoneal dialysis as the initial modality during the study
period, the need for a significant amount of time to train pa-
tients and caregivers may have also contributed, in part, to our
observed patterns of dialysis starts at a higher eGFR. The con-
current expansion of educational efforts to raise awareness of
kidney disease and empower patients with CKD regarding their
options may have affected patterns in timing of initiation of
dialysis. Of note, as a fully integrated health care delivery
system, KPNC had no financial incentives to initiate dialysis
earlier vs later.
An alternative possibility that would also lead to the iden-
tical observation of an increase in the number (and percent-
age) of individuals starting dialysis with an eGFR of 10 to
24 mL/min/1.73 m2 is that there are relatively more people in
the underlying source population who had an eGFR of 10 to
24 mL/min/1.73 m2 in more recent years, with no change over
time in the likelihood of receiving dialysis at this eGFR.29 A re-
cent interrupted time series analysis provided circumstantial
evidence that the progressive increase in mean eGFR level at
the start of dialysis may likely be driven more by secular trends
in practice patterns or other factors and not by secular trends
in the distribution of eGFR in the underlying at-risk popula-
tion. Ferguson et al11 showed that after publication of the IDEAL
trial in 2010, which found no systematic clinical benefit for
initiation of earlier vs later dialysis, there was an immediate
decrease in the proportion of early dialysis starts (ie, at eGFR
>10.5 mL/min/1.73 m2) in Canada. However, Ferguson et al did
not have data on the underlying at-risk Canadian population.
By contrast, a major strength of our study is that we captured
the underlying at-risk population whose distribution of eGFR
was known.
Few prior studies have attempted to quantify the public
health and cost implications of changes in timing of dialysis
initiation. Using US Renal Data System data and observed rates
of eGFR loss from a CKD cohort, O’Hare et al35 estimated that
1652 JAMA Internal Medicine December 2020 Volume 180, Number 12 (Reprinted)
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Trends in Timing of Dialysis and Incidence of End-stage Kidney Disease
Adjustedb AOR (95% CI)
.70 0.989 (0.934-1.047)
.74 1.007 (0.966-1.049)
.68 1.012 (0.955-1.073)
.03 1.052 (1.004-1.102) Abbreviations: AOR, adjusted odds
.07 1.060 (0.996-1.129) ratio; eGFR, estimated glomerular
filtration rate.
.03 1.066 (1.007-1.130) a
Cochrane-Armitage test for trend.
.13 1.044 (0.987-1.105) b
Reflects the significance of an
.02 1.053 (1.008-1.100) ordinal 3-year cohort term in
.06 0.938 (0.878-1.002) a logistic regression model for
end-stage kidney disease adjusting
.97 0.996 (0.825-1.201)
for age, sex, race, and diabetes.
long-term dialysis was initiated nationally a mean of approxi-
mately 5 months earlier (and approximately 8 months earlier
for those aged ≥75 years) in 2007 vs 1997, leading to more than
$1.5 billion of cost annually. However, that study did not con-
sider the association of changes in timing of dialysis initia-
tion with the number of incident ESKD cases, which our pre-
sent analysis showed is notable. To put the observed relative
16% change between 2001 and 2018 in context, this is approxi-
mately two-thirds of the target relative 25% reduction in new
ESKD cases by 2030 called for in the 2019 White House Ad-
vancing American Kidney Health initiative.9 In addition, if there
was a 16% smaller ESKD population, the estimated cost dif-
ference could be up to $2.2 billion because Medicare Part B
spending for total outpatient dialysis–related services was
$13.7 billion in 2016 to 2017.36 This cost is likely an underes-
timate because it does not include indirect costs of care (eg,
patient and caregiver travel time; costs associated with creat-
ing and maintaining functioning dialysis access; potential
loss of employment; and costs associated with caregiver and
patient burnout).
Our study has several important implications. Given the
lack of strong evidence that earlier initiation of long-term di-
alysis has net clinical benefit,10,21-27 careful evaluation of con-
temporary dialysis initiation practices is needed,35 along with
ongoing improved shared decision-making efforts to person-
alize the approach with patients.34 Dialysis is currently rec-
ommended when kidney function is “low” and a patient has
symptoms or signs consistent with kidney failure. However,
some symptoms and signs (eg, fatigue or pruritus) may be non-
specific and caused by comorbid conditions, whereas others
(eg, anorexia or hypoalbuminemia) can change over time and
may improve spontaneously without dialysis therapy. In most
cases, long-term dialysis is initiated not to treat an immedi-
ately life-threatening condition (eg, uremic pericarditis or re-
fractory hyperkalemia). As noted previously, the aggressive
promotion of earlier arteriovenous fistula placement in pa-
tients with CKD may also affect patient and physician expec-
tations about the timing of initiating dialysis. Thus, decisions
about when to start dialysis are not always fully objective, and
policy decisions that have encouraged systematic earlier di-
alysis initiation can be adjusted. For example, O’Hare et al29
suggested reimposing scrutiny by the Health Care Financing
jamainternalmedicine.com
 Trends in Timing of Dialysis and Incidence of End-stage Kidney Disease Original Investigation Research

Administration and renal networks of an upper eGFR limit at
which elective dialysis initiation would trigger a review. Fol-
lowing publication of the IDEAL trial, there have also been calls
for starting dialysis later.37 The United Kingdom National In-
stitute for Health and Care Excellence now recommends wait-
ing until an eGFR of 5 to 7 mL/min/1.73 m2 or the presence of
symptoms affecting daily life before starting dialysis.38 Fur-
thermore, the Japanese Society of Nephrology guidelines rec-
ommend patients “endure under conservative treatment un-
til the GFR is <8 mL/min/1.73 m2 even when the symptoms
of renal failure are observed.”39(p97)
Our results also support the perspective that practice pat-
terns or other factors beyond just population CKD burden may
impact the number of new ESKD cases. Thus, incidence of
ESKD (as currently defined) in a population may not be an
entirely optimal quality metric to reflect the success or fail-
ure of renoprotective efforts, and policy makers and public
health officials should consider other metrics as well.40
Limitations
Our study was limited in that we only assessed the associa-
tion between the timing of dialysis initiation and incident ESKD
rates within an integrated health care delivery system in
California. However, the KPNC membership is sociodemo-
graphically diverse and highly representative of the local and
statewide population.12 Supporting the external validity of
our findings is the observation that the temporal trend in
mean eGFR at the start of dialysis among KPNC members—
progressively increasing through the first decade of this
century (Figure 1)—matches that reported by the US Renal
Data System,2 US Department of Veterans Affairs,29 Canadian
Organ Replacement Register,11 and United Kingdom Renal
Registry.30 We did not have information on the specific sys-
tem-, physician-, and patient-level reasons that may have con-
tributed to the observed trends, nor did we analyze how chang-
ing the timing and threshold for dialysis initiation may have
affected clinical outcomes (including in frail25 or older41 per-
sons). However, previous studies do not provide convincing
evidence that systematically starting dialysis earlier confers
net benefits,10,26,27,42 including the only large randomized trial
performed to date.10
Conclusions
In conclusion, choices regarding the timing of dialysis initia-
tion should be made on a patient-by-patient basis to maximize
the net benefit for individual patients with kidney disease,
including taking into account the results of large randomized
clinical trials, such as the IDEAL trial.10 Our results underscore
the importance the timing of initiating long-term dialysis has
on the size of the population of patients with ESKD.

ARTICLE INFORMATION
Accepted for Publication: August 4, 2020.
Published Online: October 12, 2020.
doi:10.1001/jamainternmed.2020.5009
Author Affiliations: Division of Nephrology,
Department of Medicine, University of California,
San Francisco, San Francisco (Hsu, Go); Division of
Research, Kaiser Permanente Northern California,
Oakland (Hsu, Parikh, Zheng, Tan, Go); Department
of Nephrology, Kaiser Permanente Oakland Medical
Center, Oakland, California (Pravoverov, Zheng);
Division of Medical Education, Department of
Medicine, University of California, San Francisco,
San Francisco (Zheng); Department of
Epidemiology and Biostatistics, University of
California, San Francisco, San Francisco (Glidden,
Go); Department of Medicine, Stanford University,
Stanford, California (Go); Department of Health
Research and Policy, Stanford University, Stanford,
California (Go).
Author Contributions: Dr Go and Mr Parikh had full
access to all of the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis.
Concept and design: Hsu, Tan, Go.
Acquisition, analysis, or interpretation of data: Hsu,
Parikh, Pravoverov, Zheng, Glidden, Go.
Drafting of the manuscript: Hsu, Parikh, Go.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Hsu, Parikh, Glidden, Go.
Obtained funding: Hsu.
Administrative, technical, or material support: Hsu,
Parikh, Pravoverov, Zheng, Tan, Go.
Supervision: Pravoverov, Tan, Go.
Conflict of Interest Disclosures: Dr Hsu is the
medical director of the San Francisco Wellbound
dialysis unit. He reported receiving research
funding from Satellite Healthcare Inc to support an
investigator-initiated research project and grants
from the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) during the
conduct of the study. Dr Zheng reported being a
senior partner of The Permanente Medical Group,
outside the submitted work. Dr Go reported
receiving grants from NIDDK during the conduct of
the study. No other disclosures were reported
Funding/Support: This study was supported by
award K24 DK092291 from NIDDK and funding
from the Kaiser Permanente Northern California
Division of Research.
Role of the Funder/Sponsor: The funders had no
role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
REFERENCES
1. Johansen KL. Time to rethink the timing of
dialysis initiation. Arch Intern Med. 2011;171(5):382-
383. doi:10.1001/archinternmed.2010.413
2. Saran R, Robinson B, Abbott KC, et al. US Renal
Data System 2018 Annual Data Report:
Epidemiology of Kidney Disease in the United
States. Am J Kidney Dis. 2019;73(3)(suppl 1):A7-A8.
doi:10.1053/j.ajkd.2019.01.001
3. Ivory SE, Polkinghorne KR, Khandakar Y, et al.
Predicting 6-month mortality risk of patients
commencing dialysis treatment for end-stage
kidney disease. Nephrol Dial Transplant. 2017;32(9):
1558-1565. doi:10.1093/ndt/gfw383
4. Chan KE, Maddux FW, Tolkoff-Rubin N,
Karumanchi SA, Thadhani R, Hakim RM. Early
outcomes among those initiating chronic dialysis in
the United States. Clin J Am Soc Nephrol. 2011;6(11):
2642-2649. doi:10.2215/CJN.03680411
5. Foley RN, Chen SC, Solid CA, Gilbertson DT,
Collins AJ. Early mortality in patients starting
dialysis appears to go unregistered. Kidney Int.
2014;86(2):392-398. doi:10.1038/ki.2014.15
6. Kurella Tamura M, Vittinghoff E, Hsu CY, et al;
CRIC Study Investigators. Loss of executive function
after dialysis initiation in adults with chronic kidney
disease. Kidney Int. 2017;91(4):948-953. doi:10.
1016/j.kint.2016.11.015
7. Kurella Tamura M, Covinsky KE, Chertow GM,
Yaffe K, Landefeld CS, McCulloch CE. Functional
status of elderly adults before and after initiation of
dialysis. N Engl J Med. 2009;361(16):1539-1547.
doi:10.1056/NEJMoa0904655
8. Bansal N, Keane M, Delafontaine P, et al; CRIC
Study Investigators. A longitudinal study of left
ventricular function and structure from CKD to
ESRD: the CRIC study. Clin J Am Soc Nephrol. 2013;8
(3):355-362. doi:10.2215/CJN.06020612
9. Patel S, Boehler A, Uehlecke N. A vision for
advancing American kidney health: view from the
US Department of Health and Human Services. Clin
J Am Soc Nephrol. 2019;14(12):1789-1791. doi:10.
2215/CJN.10460919
10. Cooper BA, Branley P, Bulfone L, et al; IDEAL
Study. A randomized, controlled trial of early versus
late initiation of dialysis. N Engl J Med. 2010;363
(7):609-619. doi:10.1056/NEJMoa1000552
11. Ferguson TW, Garg AX, Sood MM, et al.
Association between the publication of the
Initiating Dialysis Early and Late Trial and the timing

jamainternalmedicine.com (Reprinted) JAMA Internal Medicine December 2020 Volume 180, Number 12 1653

© 2020 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ on 07/01/2023

 Research Original Investigation
of dialysis initiation in Canada. JAMA Intern Med.
2019;179(7):934-941. doi:10.1001/jamainternmed.
2019.0489
12. Kaiser Permanente. Sociodemographic and
health-related characteristics of members in Kaiser
Permanente’s Northern California region,
2014/2015: internal report, division of research,
Kaiser Permanente medical care program, Oakland,
CA. Published October 2017. Accessed August 28,
2020. https://divisionofresearch.
kaiserpermanente.org/projects/
memberhealthsurvey/SiteCollectionDocuments/
mhs11reg.pdf
13. Lo LJ, Go AS, Chertow GM, et al.
Dialysis-requiring acute renal failure increases the
risk of progressive chronic kidney disease. Kidney Int.
2009;76(8):893-899. doi:10.1038/ki.2009.289
14. Ross TR, Ng D, Brown JS, et al. The HMO
Research Network Virtual Data Warehouse: a public
data model to support collaboration. EGEMS (Wash
DC). 2014;2(1):1049. doi:10.13063/2327-9214.1049
15. Go AS, Hsu CY, Yang J, et al. Acute kidney injury
and risk of heart failure and atherosclerotic events.
Clin J Am Soc Nephrol. 2018;13(6):833-841. doi:10.
2215/CJN.12591117
16. Gurwitz JH, Magid DJ, Smith DH, et al.
Treatment effectiveness in heart failure with
comorbidity: lung disease and kidney disease. J Am
Geriatr Soc. 2017;65(12):2610-2618. doi:10.1111/jgs.
15062
17. Go AS, Magid DJ, Wells B, et al.
The Cardiovascular Research Network: a new
paradigm for cardiovascular quality and outcomes
research. Circ Cardiovasc Qual Outcomes. 2008;1
(2):138-147. doi:10.1161/CIRCOUTCOMES.108.801654
18. Levey AS, Stevens LA, Schmid CH, et al;
CKD-EPI (Chronic Kidney Disease Epidemiology
Collaboration). A new equation to estimate
glomerular filtration rate. Ann Intern Med. 2009;
150(9):604-612. doi:10.7326/0003-4819-150-9-
200905050-00006
19. Rivara MB, Mehrotra R. Timing of dialysis
initiation: what has changed since IDEAL? Semin
Nephrol. 2017;37(2):181-193. doi:10.1016/j.
semnephrol.2016.12.008
20. Pravoverov LV, Zheng S, Parikh R, et al. Trends
associated with large-scale expansion of peritoneal
dialysis within an integrated care delivery model.
JAMA Intern Med. 2019;179(11):1537-1542. doi:10.
1001/jamainternmed.2019.3155
21. Korevaar JC, Jansen MA, Dekker FW, et al;
Netherlands Cooperative Study on the Adequacy of
Dialysis Study Group. When to initiate dialysis:
effect of proposed US guidelines on survival. Lancet.
1654 JAMA Internal Medicine December 2020 Volume 180, Number 12 (Reprinted)
© 2020 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 07/01/2023
Trends in Timing of Dialysis and Incidence of End-stage Kidney Disease
2001;358(9287):1046-1050. doi:10.1016/S0140-
6736(01)06180-3
22. Traynor JP, Simpson K, Geddes CC, Deighan CJ,
Fox JG. Early initiation of dialysis fails to prolong
survival in patients with end-stage renal failure.
J Am Soc Nephrol. 2002;13(8):2125-2132. doi:10.
1097/01.ASN.0000025294.40179.E8
23. Rosansky SJ, Clark WF, Eggers P, Glassock RJ.
Initiation of dialysis at higher GFRs: is the apparent
rising tide of early dialysis harmful or helpful?
Kidney Int. 2009;76(3):257-261. doi:10.1038/ki.
2009.161
24. Rosansky SJ, Eggers P, Jackson K, Glassock R,
Clark WF. Early start of hemodialysis may be
harmful. Arch Intern Med. 2011;171(5):396-403.
doi:10.1001/archinternmed.2010.415
25. Bao Y, Dalrymple L, Chertow GM, Kaysen GA,
Johansen KL. Frailty, dialysis initiation, and
mortality in end-stage renal disease. Arch Intern Med.
2012;172(14):1071-1077. doi:10.1001/archinternmed.
2012.3020
26. Crews DC, Scialla JJ, Boulware LE, et al; DEcIDE
Network Patient Outcomes in End Stage Renal
Disease Study Investigators. Comparative
effectiveness of early versus conventional timing of
dialysis initiation in advanced CKD. Am J Kidney Dis.
2014;63(5):806-815. doi:10.1053/j.ajkd.2013.12.010
27. Crews DC, Scialla JJ, Liu J, et al; Developing
Evidence to Inform Decisions about Effectiveness
(DEcIDE) Patient Outcomes in End Stage Renal
Disease Study Investigators. Predialysis health,
dialysis timing, and outcomes among older United
States adults. J Am Soc Nephrol. 2014;25(2):370-379.
doi:10.1681/ASN.2013050567
28. Kurella Tamura M, Thomas IC,
Montez-Rath ME, et al. Dialysis initiation and
mortality among older veterans with kidney failure
treated in Medicare vs the Department of Veterans
Affairs. JAMA Intern Med. 2018;178(5):657-664.
doi:10.1001/jamainternmed.2018.0411
29. O’Hare AM, Wong SP, Yu MK, et al. Trends in
the timing and clinical context of maintenance
dialysis initiation. J Am Soc Nephrol. 2015;26(8):
1975-1981. doi:10.1681/ASN.2013050531
30. Renal Association: UK Renal Registry.
2017—The twentieth annual report. Accessed March
10, 2020. https://www.renalreg.org/reports/2017-
twentieth-annual-report/
31. Hakim RM, Lazarus JM. Initiation of dialysis.
J Am Soc Nephrol. 1995;6(5):1319-1328.
32. National Kidney Foundation. NKF-DOQI clinical
practice guidelines for peritoneal dialysis adequacy.
Am J Kidney Dis. 1997;30(3)(suppl 2):S67-S136.
doi:10.1016/S0272-6386(97)70028-3
33. National Kidney Foundation. 2006 Updates:
clinical practice guidelines and recommendations:
peritoneal dialysis adequacy. Published 2006.
Accessed March 10, 2020. https://www.kidney.org/
sites/default/files/docs/12-50-0210_jag_dcp_
guidelines-pd_oct06_sectionb_ofc.pdf
34. Kalloo S, Blake PG, Wish J. A patient-centered
approach to hemodialysis vascular access in the era
of fistula first. Semin Dial. 2016;29(2):148-157.
doi:10.1111/sdi.12465
35. O’Hare AM, Choi AI, Boscardin WJ, et al. Trends
in timing of initiation of chronic dialysis in the
United States. Arch Intern Med. 2011;171(18):1663-
1669. doi:10.1001/archinternmed.2011.436
36. Medicare Medical Payment Advisory
Commission March 2019 report. Accessed March
10, 2020. http://medpac.gov/docs/default-source/
reports/mar19_medpac_ch6_sec.pdf?sfvrsn=0
37. Di Micco L, Torraca S, Pota A, et al. Setting
dialysis start at 6.0 ml/min/1.73 m2 eGFR—a study
on safety, quality of life and economic impact.
Nephrol Dial Transplant. 2009;24(11):3434-3440.
doi:10.1093/ndt/gfp281
38. Gilbert J, Lovibond K, Mooney A, Dudley J;
Guideline Committee. Renal replacement therapy:
summary of NICE guidance. BMJ. 2018;363:k4303.
doi:10.1136/bmj.k4303
39. Watanabe Y, Yamagata K, Nishi S, et al;
“Hemodialysis Initiation for Maintenance
Hemodialysis” Guideline Working Group, Japanese
Society for Dialysis Therapy. Japanese society for
dialysis therapy clinical guideline for “hemodialysis
initiation for maintenance hemodialysis”. Ther
Apher Dial. 2015;19(S1)(suppl 1):93-107. doi:10.1111/
1744-9987.12293
40. Office of Disease Prevention and Health
Promotion: Healthy People 2020. Chronic kidney
disease. Accessed June 4, 2019. https://www.
healthypeople.gov/2020/topics-objectives/topic/
chronic-kidney-disease/objectives
41. Kurella Tamura M, Desai M, Kapphahn KI,
Thomas IC, Asch SM, Chertow GM. Dialysis versus
medical management at different ages and levels of
kidney function in veterans with advanced CKD.
J Am Soc Nephrol. 2018;29(8):2169-2177. doi:10.
1681/ASN.2017121273
42. Scialla JJ, Liu J, Crews DC, et al; DEcIDE
Network Patient Outcomes in End Stage Renal
Disease Study Investigators. An instrumental
variable approach finds no associated harm or
benefit with early dialysis initiation in the United
States. Kidney Int. 2014;86(4):798-809. doi:10.
1038/ki.2014.110
jamainternalmedicine.com