Frailty, Dialysis Initiation, and Mortality in End-Stage Renal Disease
Frailty, Dialysis Initiation, and Mortality in End-Stage Renal Disease
Frailty, Dialysis Initiation, and Mortality in End-Stage Renal Disease
odds of frailty (odds ratio [OR], 1.44 [95% CI, 1.231.68] per 5 mL/min/1.73 m2; P .001). Frailty was
indepen- dently associated with mortality (hazard ratio
[HR], 1.57 [95% CI, 1.25-1.97]; P .001) and time to
first hospital- ization (HR, 1.26 [95% CI, 1.09-1.45]; P
.001). While higher eGFR at dialysis initiation was
associated with mor- tality (HR, 1.12 [95% CI, 1.021.23] per 5 mL/min/1.73 m2; P = .02), the association
was no longer statistically sig- nificant after frailty was
accounted for (HR, 1.08 [95% CI,
0.98-1.19] per 5 mL/min/1.73 m2; P = .
11).
Conclusions: Frailty is extremely common among pa-
tients starting dialysis in the United States and is associated with higher eGFR at dialysis initiation. Recognition of signs and symptoms of frailty by clinicians may
prompt earlier initiation of dialysis and may explain, at
least in part, the well-described association between
eGFR at dialysis initiation and mortality.
Arch Intern Med. 2012;172(14):10711077. Published online June 25, 2012.
doi:10.1001/archinternmed.2012.3020
Rehabilitation/Quality of Life
Special Studies Center,
Atlanta, Georgia (Dr
Johansen).
ARCH INTERN MED/ VOL 172 (NO. 14), JULY 23, 2012
47
WWW.
ARCHINTERNMED.COM
ARCH INTERN MED/ VOL 172 (NO. 14), JULY 23, 2012
48
ARCHINTERNMED.COM
the hypothesis that frailty is associated with earlier initiation of dialysis. We also aimed to determine whether
the association between eGFR and mortality
described in large registry studiesmight be explained,
at least in part, by frailty.
METHODS
PATIENTS
The CDS is a special study of the US Renal Data System (USRDS), and the details of its study design have been previously
published.7 Briefly, the CDS was designed as a prospective
study of incident patients receiving maintenance dialysis at
335 di- alysis units throughout the United States. From
September 1,
2005, through June 1, 2007, a total of 1678 eligible adult incident maintenance dialysis patients were enrolled (only 296
of the 335 dialysis units participated). Institutional review
boards at the Nutrition Special Study Center (SSC) (University
of Cali- fornia, San Francisco, and University of California,
Davis), the Rehabilitation/Quality of Life SSC (Emory
University), and the USRDS Coordinating Center (University
of Minnesota) ap- proved the study. All participants provided
informed consent. For the current analysis, those with
missing data to determine frailty status (n = 49) or eGFR (n =
14) were excluded, as well as those participants who were
unable to ambulate or transfer (n = 39), leaving 1576
participants from 295 dialysis units in the analytic cohort.
FRAILTY DEFINITION
The phenotype of frailty was established using criteria similar
to the earlier modification of Frieds criteria (Fried et al12) by
Johansen et al6 (eTable; http://www.archinternmed.com). However, since the CDS did not have data on weight loss, this vari-
STATISTICAL ANALYSIS
We a priori selected a set of baseline characteristics, including
eGFR at the time of dialysis initiation, based on our clinical
sus- picion that they might be associated with frailty (Table
1). These factors were compared among frail and nonfrail
pa- tients using t test for continuous variables and the 2 test
for categorical variables. We converted serum albumin and
hemo- globin concentrations to categorical variables based on
clini- cally meaningful cut points; we also created a category
of miss- ing values. We assessed model discrimination
using the concordance (C) statistic, equivalent to the area
under the receiver operating characteristic curve. We used the
Hosmer- Lemeshow test to assess model goodness of fit. We
also as- sessed the relations among each of the frailty
components and the same predictors using multivariate
logistic regression.
We used proportional hazards Cox regression to evaluate the
outcomes of mortality or time to first hospitalization. We built
3 multivariate models. In addition to the variables selected a
priori to study frailty, we included erythropoietin use prior to
dialysis initiation and early nephrology referral in all 3 models.
We in- cluded either frailty or eGFR at the time of dialysis
initiation in each of the first 2 models. In the final model, we
included both frailty and eGFR at the time of dialysis
initiation simultane- ously. We examined log (log) plots and
Schoenfeld residuals to test the proportionality assumption.
To test whether frailty or eGFR at the time of dialysis
initiation predicts mortality and hospitalization independent of
each other, we tested the inter- action between frailty and
eGFR in our models.
We accounted for clustering by dialysis centers as previ15
the results were altered by excluding patients with missing values for serum albumin and hemoglobin. We considered 2-tailed P
.05 as
statistically significant. We conducted all analyses using STATA statistical
software (version 11.1; StataCorp).
RESULTS
Table 1. Baseline Characteristics of Included Participants of the Comprehensive Dialysis Study (CDS) a
No. (%)
Characteristic
Age, mean (SD), y
Male sex
White race
Current smoker
Medicaid vs other payer
eGFR, mean (SD), mL/min/1.73 m2
Albumin, mean (SD), g/dL b
Hemoglobin, mean (SD), g/dL c
Hemodialysis
Comorbidity
Diabetes mellitus
Congestive heart failure
Atherosclerotic heart disease
CVA/TIA
Peripheral vascular disease
COPD
Cancer
Cohort
(n = 1576)
Frail
(n = 1155)
Not Frail
(n = 421)
P Value
59.6 (14.2)
874 (55.5)
1084 (68.8)
111 (7.0)
373 (23.7)
10.0 (4.45)
3.18 (0.71)
10.08 (1.77)
1411 (89.3)
60.0 (14.0)
594 (51.4)
809 (70.0)
89 (7.7)
307 (26.6)
10.4 (4.52)
3.15 (0.70)
10.14 (1.76)
1038 (89.9)
58.3 (14.6)
280 (66.5)
275 (65.3)
22 (5.2)
66 (15.7)
8.8 (4.04)
3.26 (0.71)
9.92 (1.77)
373 (88.6)
.03
.001
.07
.09
.001
.001
.02
.04
.53
820 (52.0)
474 (30.1)
367 (23.3)
112 (7.1)
226 (14.3)
120 (7.6)
95 (6.0)
650 (56.3)
381 (33.0)
288 (24.9)
96 (8.3)
189 (16.4)
104 (9.0)
71 (6.2)
170 (40.4)
93 (22.1)
79 (18.8)
16 (3.8)
37 (8.8)
16 (3.8)
24 (5.7)
.001
.001
.01
.002
.001
.001
.74
Abbreviations: COPD, chronic obstructive pulmonary disease; CVA/TIA, cerebrovascular accident/transient ischemic attack; eGFR, estimated glomerular
filtration rate.
SI conversion factors: To convert albumin to grams per liter, multiply by 10; to convert hemoglobin to grams per liter, multiply by 10.
a
Data are presented as number (percentage) except where noted.
b
n = 1199.
c n = 1412.
morbidities, tobacco
insurance status, se-
use,
Medicaid