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Impact of Worsening Renal Function During Hospital Admission
on Resource Utilization in Patients With Heart Failure
Peter M. Herout, PharmDa,*, Qing Harshaw, MD, PhDa, Hemant Phatak, PhDb, Gorkem Saka, PhDc,
Annie McNeill, PhDd, David Wu, PhDb, Vasilisa Sazonov, PhDb, Robert DeSagun, MPHa, and
Jamshid Shirani, MDe
Renal impairment frequently accompanies heart failure (HF) and is a recognized independent risk factor for morbidity and mortality. Few data are available assessing the impact
of worsening renal function (WRF) during hospitalization on health care resource use in
patients with HF. Health Insurance Portability and Accountability Act– compliant, deidentified, clinical, laboratory, and economic data for patients admitted to a tertiary care
medical center with a primary diagnosis of HF were extracted by MedMining and reviewed
retrospectively by the authors. Patients were excluded if they had no previous HF or were
admitted for acute coronary syndrome or coronary artery bypass grafting within 30 days of
index hospitalization. WRF was defined as >0.3 mg/dl increase in serum creatinine from
baseline at any time during hospitalization. Of 5,803 hospitalized patients with primary HF
diagnosis, 827 patients (14%) fulfilled all prespecified inclusion and exclusion criteria (74 ⴞ
14 years of age, 43% men, 98% white, admission serum creatinine 1.4 ⴞ 0.9 mg/dl,
estimated glomerular filtration rate <90 ml/min/1.73 m2 at admission in 83%). During
index hospitalization, WRF was identified in nearly 33%. Compared to patients without
WRF, those with WRF had greater prevalence of diabetes (54% vs 43%), lower estimated
glomerular filtration rate (44 ⴞ 30 vs 62 ⴞ 35 ml/min/1.73 m2), higher serum potassium (4.3 ⴞ
0.7 vs 4.2 ⴞ 0.7 mEq/L), and higher B-type natriuretic peptide (845 ⴞ 821 vs 795 ⴞ 947
pg/ml) at baseline (all p values <0.05). Patients developing WRF incurred higher total
inpatient costs ($10,977, range 671 to 212,819, vs $7,820, range 697 to 269,797, p <0.001)
and longer hospital stay (8.2 ⴞ 6.8 vs 5.7 ⴞ 5.5 days, p <0.001). In conclusion, occurrence
of WRF during HF-related hospitalization is associated with higher hospitalization costs and
longer hospital stay. © 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:1139–1145)
Worsening renal function (WRF) during hospitalization,
defined as an increase in serum creatinine (SCr) value ⱖ0.3
mg/dl, has been reported in nearly 30% of acute heart failure
(HF) admissions.1–3 This has been associated with inpatient
length of stay exceeding 10 days (adjusted risk ratio 3.2,
confidence interval 2.2 to 4.9) and increased in-hospital mortality (adjusted risk ratio 7.5, confidence interval 2.9 to 19.3).2
This study evaluated the costs and resource usage associated
with WRF in a group of patients admitted with HF and a wide
range of renal function in a single integrated health care
system.
Methods
Data were prepared by MedMining (Danville, Pennsylvania), a Geisinger business unit that licenses Health Insurance
a
EPI-Q, Inc., Oak Brook, Illinois; bGlobal Health Outcomes, Merck
and Co., Inc., Whitehouse Station, New Jersey; cHealth Economics Statistics and dEpidemiology, Merck Research Laboratories, Upper Gwynedd,
Pennsylvania; and eDepartment of Cardiology, Geisinger Medical Center,
Danville, Pennsylvania. Manuscript received March 10, 2010; revised
manuscript received and accepted June 2, 2010.
Support of this study was provided by Merck and Co., Inc., Whitehouse
Station, New Jersey.
*Corresponding author: Tel: 630-570-5505; fax: 630-570-5506.
E-mail address: [email protected] (P.M. Herout).
0002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjcard.2010.06.026
Portability and Accountability Act– compliant, de-identified
patient clinical, laboratory, and economic data to promote
research based on data from a real-world setting. After an
approved process for de-identifying the data, MedMining’s
honest broker linked the following data together: (1) clinical
and laboratory data from the electronic medical record system
(Epic Systems Corporation, Madison, Wisconsin) used by Geisinger Health System (GHS) and (2) actual encounter-level
cost data, including direct and indirect costs, from Geisinger’s
financial data warehouse. The GHS consists of 3 hospitals
located primarily in rural Pennsylvania with 791 beds and
nearly 2 million yearly outpatient visits among its 41 community practice sites. These rural communities mostly consist of
Caucasian/European-descent inhabitants.
All electronic health record patient-level data were captured for a period of ⱖ12 months before the index hospitalization, throughout the index hospitalization, and for up
to 60 days after hospital discharge to examine preindex
hospitalization health care usage, costs and resource use
related to inpatient care, and short-term follow-up health
care resource use and mortality.
The database contained data of all patients admitted to a
GHS facility with a primary or secondary inpatient HF
diagnosis from January 2004 through August 2008. Patients
were considered for inclusion in the study if they were ⱖ19
years of age and had ⱖ12 months of GHS encounter data
before an index hospitalization with HF based on Internawww.ajconline.org
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Figure 1. Study population. ACS ⫽ acute coronary syndrome; CABG ⫽ coronary artery bypass grafting; IV ⫽ intravenous; LVAD ⫽ left ventricular assist device.
Table 1
Demographic and baseline clinical characteristics in total cohort and those without or with worsening renal function
Variable
Total
(n ⫽ 827)
No WRF
(n ⫽ 515)
WRF
(n ⫽ 252)
Age (years)
Men
White
Body mass index (kg/m2)
Current smoker
Admission through emergency department
Insurance coverage
Medicare
Medicaid
Commercial
Self/other
Preadmission health care use
Hospitalizations
Hospital stay (days)
Annual health care costs ($)
Health care encounters
␤ blocker
Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker
Loop diuretics
Furosemide equivalent diuretic dose
Co-morbidities
Cerebrovascular disease
Hypertension
Atrial fibrillation
Diabetes mellitus
Myocardial infarction
Valvular disease
Renal insufficiency
Serum creatinine increase ⱖ0.3 mg/dl in previous 3 months
Chronic pulmonary disease
73 ⫾ 14
355 (43%)
814 (98%)
30 ⫾ 8
81 (10%)
389 (72%)
74 ⫾ 14
228 (44%)
507 (99%)
30 ⫾ 7
53 (10%)
258 (73%)
74 ⫾ 14
103 (41%)
248 (98%)
30 ⫾ 8
23 (9%)
122 (76%)
434 (53%)
29 (4%)
328 (40%)
35 (4%)
289 (56%)
15 (3%)
195 (38%)
16 (3%)
123 (49%)
9 (4%)
102 (41%)
18 (7%)
1.4 ⫾ 0.8
9.6 ⫾ 9.2
13,518 ⫾ 21,912
49 ⫾ 45
461 (56%)
375 (45%)
518 (63%)
58 ⫾ 56
1.5 ⫾ 0.9
10.3 ⫾ 9.7
13,518 ⫾ 21,912
50 ⫾ 46
288 (56%)
224 (44%)
329 (64%)
55 ⫾ 44
1.3 ⫾ 0.7
8.5 ⫾ 8.5
14,280 ⫾ 22,455
46 ⫾ 41
136 (54%)
117 (46%)
148 (59%)
63 ⫾ 78
Data are presented as mean ⫾ SD or number of patients (percentage).
* p ⬍0.05 for no WRF versus WRF.
142 (17%)
691 (84%)
420 (51%)
382 (46%)
151 (18%)
418 (51%)
213 (26%)
91 (11.0%)
399 (48%)
90 (18%)
426 (89%)
252 (49%)
222 (43%)
87 (17%)
250 (49%)
121 (24%)
66 (12.8%)
249 (48%)
45 (18%)
220 (87%)
141 (56%)
136 (54%)*
55 (22%)
141 (56%)
88 (35%)*
24 (9.5%)
125 (50%)
Heart Failure/Economic Impact of WRF in HF Admissions
1141
Table 2
Laboratory values obtained at index admission in total cohort and in those without or with worsening renal function
Laboratory Variable
Serum creatinine (mg/dl)
Estimated glomerular filtration rate (ml/min/1.73 m2)
Serum urea nitrogen (mg/dl)
Serum sodium (mEq/L)
Serum potassium (mEq/L)
B-type natriuretic peptide (pg/ml)
ⱕ250
251–400
⬎400
Total
(n ⫽ 827)
No WRF
(n ⫽ 515)
WRF
(n ⫽ 252)
1.39 ⫾ 0.93
57 ⫾ 35
32 ⫾ 22
139 ⫾ 4
4.2 ⫾ 0.7
814 ⫾ 901 (n ⫽ 422)
111 (26%)
79 (19%)
232 (55%)
1.36 ⫾ 0.86
62 ⫾ 36
32 ⫾ 23
139 ⫾ 4
4.2 ⫾ 0.7
795 ⫾ 947 (n ⫽ 254)
76 (30%)
49 (19%)
129 (51%)
1.48 ⫾ 1.01*
44 ⫾ 30*
33 ⫾ 21
139 ⫾ 4
4.3 ⫾ 0.7*
845 ⫾ 821* (n ⫽ 157)
31 (20%)
28 (18%)
98 (62%)
Data are presented as mean ⫾ SD or number of patients (percentage).
* p ⬍0.05 for no WRF versus WRF.
tional Classification of Diseases, Ninth Revision, Clinical
Modification codes. Patients were excluded if they had no
documentation of HF before the index hospitalization (i.e.,
de novo HF), died within 24 hours of the index admission,
or had no documented baseline (within 1 day of hospital
admission) SCr. To limit the confounding effect of procedures or drug exposures known to be associated with acute
renal dysfunction, additional criteria for exclusion included
admission with a primary diagnosis of cardiogenic shock or
acute coronary syndrome; exposure to radiographic contrast
agents during the index hospitalization; current or previous
use of a left ventricular assist device; chemotherapy or
coronary artery bypass grafting surgery during or within 30
days of the index hospitalization; solid organ transplantation
before or during the index hospitalization; or diagnosed
end-stage renal disease on long-term dialysis.
Of the original 12,277 patients admitted with a primary
or secondary diagnosis of HF during the prespecified period,
5,803 met all inclusion criteria (Figure 1). Of the latter,
4,976 (85.7%) were also excluded due to the presence of ⱖ1
exclusion criterion. The remaining 827 patients (14.3%)
who fulfilled all inclusion and exclusion criteria are the
subjects of this evaluation.
The primary outcome measurement was total cost of the
index hospitalization for patients stratified to the no-WRF
and WRF groups. Costs are reported as the actual cost of
care derived from the GHS Eclipsys cost accounting system
database. All costs were adjusted to 2007 price levels using
the medical care component of the consumer price index.
Among inpatient costs, the following were evaluated: medication costs, costs for physician services, costs for procedures and laboratory tests, and costs for general hospital
services. Inpatient usage variables included length of stay
(total, intensive care unit, telemetric monitoring), number of
procedures or laboratory tests performed, number of medication orders written, and total amount of intravenous loop
diuretic (in furosemide equivalents) administered. The following doses of diuretics were considered equivalent: furosemide 40 mg, bumetanide 1 mg, and torsemide 10 mg.
Hospital mortality and 30- and 60-day health care outcomes
and usage were also evaluated.
The descriptive analysis includes population demographics, co-morbidities, information related to treatment
such as the site where treatment was provided (e.g.,
Figure 2. Distribution of admission eGFR for total study population (n ⫽
827) (left column), population not developing WRF (n ⫽ 515) (center
column), and population developing WRF (n ⫽ 252) (right column). eGFR
(milliliters per minute per 1.73 m2) was calculated using the Modification
of Diet in Renal Disease Study equation and admission study variables and
reported as percentage of study group within the ranges ⬎90 (A), 60 to 89
(B), 30 to 59 (C), 15 to 29 (D), and ⬍15 (E).
inpatient, outpatient), medications, and select baseline
laboratory values. Health care resource units (e.g., readmissions, emergency department visits, office visits, procedures, length of stay) and costs are stratified and compared by the presence of WRF defined as an increase in
SCr ⱖ0.3 mg/dl from hospital admission to any time
during the index hospitalization. Univariate analysis was
conducted between the no-WRF and WRF groups for
primary outcomes and secondary outcomes using chisquare test for categorical variables and t test or MannWhitney U test for continuous variables based on variable characteristics and data distribution. Comparison of
continuous variables among ⱖ3 groups was performed
by Kruskal-Wallis analysis of variance. Multivariable
analysis was performed for the primary outcome. A generalized linear regression model with log-link function
and ␥ distribution was performed to estimate total costs
associated with the WRF and no-WRF groups. Variables
that were found to have a difference at the significance
level ⱕ0.10 during univariate analysis and those identified as clinically important from the relevant literature
were included in the model to adjust for baseline differences. Correlations between variables were evaluated before modeling. If the correlation coefficient for 2 variables was ⬎0.65 and statistically significant, then only 1
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Table 3
Index hospitalization costs for total cohort and for patients without or with worsening renal function
Cost Variable ($)
Total
Mean ⫾ SD
Hospital services
Mean ⫾ SD
Physician services
Mean ⫾ SD
Medications administered
Mean ⫾ SD
Procedures
Mean ⫾ SD
Total
(n ⫽ 827)
No WRF
(n ⫽ 515)
WRF
(n ⫽ 252)
8,825 (671–269,797)
16,195 ⫾ 22,675
7,570 (1,154–246,067)
13,961 ⫾ 19,735
1,193 (12–29,850)
2,355 ⫾ 3,532
393 (3–52,980)
1,396 ⫾ 3,862
552 (2–11,014)
900 ⫾ 1,102
7,820 (697–269,797)
13,445 ⫾ 20,392
6,878 (1,251–246,067)
11,532 ⫾ 17,812
1,071.53 (12–29,850)
2,030 ⫾ 3,254
352.43 (3–52,980)
1,145 ⫾ 3,532
501 (2–9,333)
773 ⫾ 858
10,977 (671–212,819)*
20,829 ⫾ 26,686
9,478 (1,866–183,872)*
17,752 ⫾ 22,791
1,627.46 (46–28,947)*
3,218 ⫾ 4,327
680 (15–41,163)*
2,184 ⫾ 4,729
911 (28–11,014)*
1,309 ⫾ 1,465
Data are presented as median (range) or mean ⫾ SD where noted.
* p ⬍0.05 for no WRF versus WRF.
Table 4
Index hospitalization resource usage for total cohort and for patients without or with worsening renal function
Usage Variable
Total length of stay (days)
Intensive care
Telemetry unit
Length of stay ⬎4 days
Total procedures performed
Medication orders
Laboratory results
Intravenous loop diuretic doses given
Total intravenous loop diuretic (mg)
Total
(n ⫽ 827)
No WRF
(n ⫽ 515)
WRF
(n ⫽ 252)
6.2 ⫾ 6.0
5.1 ⫾ 3.9 (n ⫽ 81)
4.5 ⫾ 3.5 (n ⫽ 351)
416 (50%)
33 ⫾ 39
37 ⫾ 37
76 ⫾ 79
0.97 ⫾ 0.91
270.57 ⫾ 1,085.21
5.7 ⫾ 5.5
5.9 ⫾ 4.3 (n ⫽ 36)
4.0 ⫾ 2.8 (n ⫽ 214)
246 (48%)
28 ⫾ 29
34 ⫾ 36
66 ⫾ 67
0.84 ⫾ 0.86
190.62 ⫾ 640.25
8.2 ⫾ 6.8*
4.5 ⫾ 3.4 (n ⫽ 44)
6.0 ⫾ 4.2* (n ⫽ 117)
164 (65%)*
48 ⫾ 53*
47 ⫾ 39*
104 ⫾ 94*
1.42 ⫾ 0.89*
487.26 ⫾ 1,719.53*
Data are presented as mean ⫾ SD or number of patients (percentage).
* p ⬍0.05 for no WRF versus WRF.
variable was included in the model to avoid multicollinearity. In addition, we used the general linear regression model for sensitivity analysis by looking at the
association between level of SCr change and cost. The
level of significance for all comparisons was set at a p
value ⱕ0.05. All analyses were performed using SAS 9.1
(SAS Institute, Cary, North Carolina) and STATA 9
(STATA Corp. LP, College Station, Texas).
Results
Baseline clinical and demographic characteristics of the
827 patients and those of the 2 subgroups, without and with
WRF, are presented in Table 1. Approximately 55% of
patients (n ⫽ 453) were ⱖ75 years of age at the index
admission. Laboratory data obtained at admission are presented in Table 2. All subjects had all laboratory values
available on admission except where noted. Sixty subjects
had no follow-up SCr value during the index admission and
therefore are not represented within the no-WRF or WRF
subgroup.
Prehospitalization SCr (within 3 months) was available
in 337 patients and was acutely increased in 27% (n ⫽ 92).
The percentage of the patients without or with WRF who
had increased prehospitalization SCr was not significantly
different (12.8% vs 9.5%, p ⫽ 0.183). A coded diagnosis of
renal insufficiency before the index hospitalization was
present in 26% of the total cohort. Overall, 36% presented
with an increased SCr on admission to the hospital (defined
as SCr ⬎1.3 mg/dl) and 82% had an estimated glomerular
filtration rate (eGFR) ⬍90 ml/min as calculated by the
Modification of Diet in Renal Disease method. Decreased
eGFR at admission was significantly more prevalent in
those who would eventually show WRF during the index
hospitalization (203, 81%, vs 285, 55%). Of 767 patients
with a follow-up SCr level during the index hospitalization,
252 (32.6%) had increased SCr ⱖ0.3 mg/dl anytime during
hospitalization. Severity of WRF was proportional to the
interval from admission to SCr measurement such that SCr
increases of 0.30 to 0.39 mg/dl occurred in 3.0 ⫾ 1.9 days
and increases ⱖ0.5 g/dl occurred in 5.3 ⫾ 5.9 days. Patients
with an admission eGFR range of 30 to 59 ml/min represented the largest proportion of patients who developed
WRF (Figure 2).
The median of total cost of the index hospitalization was
$8,826 (671 to 269,797) for the entire cohort (Table 3) and
was significantly lower in those without WRF compared to
those with WRF ($7,820, 697 to 269,797, vs $10,977, 671
to 212,819, p ⬍0.0001). Patients without WRF also had a
shorter total length of stay; a smaller proportion remaining
hospitalized ⬎4 days; fewer procedures, medication orders,
and laboratory tests; and lower usage of intravenous loop
diuretics (Table 4).
Heart Failure/Economic Impact of WRF in HF Admissions
1143
Table 5
Generalized linear regression model of total cost of index hospitalization
Parameter
Estimate
SE
95% Confidence Interval
Wald Chi-Square
p Value
Intercept
Age 65–74 years
Age ⱖ75 years
Male gender
New emergency admission
Worsening renal function
Previous hypertension*
Admission B-type natriuretic peptide (pg/ml)
Previous diabetes*
Previous renal insufficiency*
Total intravenous loop dose†
Admission serum sodium
Emergency department admission, age 65–74 years
Emergency department admission, age ⱖ75 years
Scale
10.6206
⫺0.0498
⫺0.8150
⫺0.0228
⫺0.2204
0.4767
⫺0.0504
0.0001
⫺0.0787
0.0727
0.0001
⫺0.0065
⫺0.2177
0.4106
1.6954
1.0659
0.1465
0.1281
0.0682
0.1472
0.0715
0.1016
0.0000
0.0696
0.0778
0.0000
0.0076
0.2049
0.1725
0.0947
8.5314 to 12.7098
⫺0.3369 to 0.2374
⫺1.0661 to ⫺0.5638
⫺0.1564 to 0.1108
⫺0.5088 to 0.0681
0.3366 to 0.6168
⫺0.2495 to 0.1486
⫺0.0000 to 0.0001
⫺0.2151 to 0.0577
⫺0.0797 to 0.2252
0.0001 to 0.0002
⫺0.0215 to 0.0084
⫺0.6193 to 0.1840
0.0725 to 0.7488
1.5197 to 1.8915
99.28
0.12
40.46
0.11
2.24
44.47
0.25
2.49
1.28
0.87
15.91
0.73
1.13
5.67
⬍0.0001
0.7340
⬍0.0001
0.7382
0.1343
⬍0.0001
0.6195
0.1148
0.2580
0.3497
⬍0.0001
0.3938
0.2881
0.0173
* From the International Classification of Diseases, Ninth Revision, Clinical Modification codes before index hospitalization.
Total amount of intravenous loop diuretic during index hospitalization.
†
Table 6
Impact of worsening renal function on total cost of index hospitalization
Change in SCr
Estimated Parameter
⬍0.3 mg/dl
ⱖ0.3 mg/dl
⬍0.1 mg/dl
ⱖ0.1–⬍0.2 mg/dl
ⱖ0.2–⬍0.3 mg/dl
ⱖ0.3–⬍0.4 mg/dl
ⱖ0.4–⬍0.5 mg/dl
ⱖ0.5 mg/dl
reference group
0.4764
reference group
⫺0.0322
0.1152
⫺0.0175
0.3144
0.7382
95% CI
Mean Incremental Cost ($)
0.3366 to 0.6168
5,846
⫺0.2248 to 0.1604
⫺0.0927 to 0.3231
⫺0.2509 to 0.2158
0.0264 to 0.6024
0.5520 to 0.9245
⫺813
442
⫺1,603
2,806
8,456
95% CI of Cost ($)
p Value
5,827 to 5,864
⬍0.0001
⫺843 to ⫺784
411 to 473
⫺1,640 to ⫺1,565
2,765 to 2,847
8,434 to 8,479
0.7428
0.2774
0.8828
0.0324
⬍0.0001
CI ⫽ confidence interval.
Of the 809 patients with hospital discharge information,
42 (5.2%) died, 391 (48.3%) were discharged home, 363
(44.9%) were discharged to another medical facility or rehabilitation center, and 13 (1.6%) were discharged to endof-life care. Patients without WRF had significantly lower
hospital mortality compared to those with WRF (16, 3.1%,
vs 25, 9.9%, p ⬍0.0001). Thirty- and 60-day outcomes
including mortality, all-cause and HF-related hospital readmissions, ambulatory encounters, and total health care costs
were not significantly different between those without and
those with WRF.
By multivariate analysis, WRF, total intravenous loop
diuretic dose, and admission through the emergency department of those ⱖ75 years of age were independent predictors
of hospitalization costs, although the overall cost of hospitalization was lower in those ⱖ75 years old at admission
(Table 5). The impact of WRF on total index hospitalization
cost is presented in Table 6. After adjusting for confounding
variables, adjusted mean cost of hospitalization was $5,846
higher for those with WRF compared to patients without.
The corresponding difference between the adjusted mean
hospital costs of those with an increase in SCr ⱖ0.5 mg/dl
compared to those with an increase ⬍0.1 mg/dl was $8,456.
Analysis indicated that a threshold of an increase of SCr of
0.3 mg/dl is associated with a statistically significant increase in hospital cost per patient.
Discussion
The present study provides further data in support of the
observed high prevalence and negative impact of baseline
renal impairment and WRF on the hospital course and
outcome of patients with established HF who are hospitalized with acute decompensated HF. Thus, moderate to severe decrease in eGFR was noted in ⬎60% of the patients
at admission and nearly 1/3 showed an increase in SCr of
ⱖ0.3 mg/dl during the course of their hospital stay. Such
deterioration in renal function was found to be associated
with longer hospital stay, and greater resource use, cost of
hospitalization, and in-hospital mortality. Prominent among
the predisposing factors for WRF were pre-existing renal
dysfunction and diabetes mellitus.
The patients included in this study had the general characteristics of patients treated at other tertiary care medical centers
but differed from those by being taken care of in a primarily
rural setting and having had established HF. Prevalences of
concomitant diseases and pre-existing chronic kidney disease
in our patients were similar to those in previous studies.4 –10
Impaired renal function is frequently seen in hospitalized
patients with HF and is a powerful independent determinant
of outcomes.1– 4 In recent years, there has been a trend
toward higher SCr and lower eGFR in patients with HF
admitted to the hospital.5 Based on recent reports, some
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degree of renal impairment is present in ⬎50% of patients
hospitalized for HF and moderate to severe renal dysfunction is observed in 1/3 of such patients.1,6,7,11 Chronic kidney disease was reported as present in 30% of the 105,388
hospitalization episodes in the Acute Decompensated Heart
Failure National Registry (ADHERE) and documentation of
a SCr exceeding 2.0 mg/dl occurred in 1/5 of cases.8 Of
patients enrolled in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM)
study, severity of renal dysfunction was a strong independent predictor of hospitalization and mortality.9 It is important to note that the presence of renal dysfunction is also a
strong predictor of future development of HF in those with
acute myocardial infarction.12
We used a largely accepted definition of WRF, that is, an
absolute increase in SCr of ⱖ0.3 mg/dl (26.5 ␮mol/L) at
any time during hospitalization compared to the value obtained at admission. Others have used different criteria including requirements for relative increases in SCr compared
to baseline, achievement of a minimum level of SCr, or use
of eGFR rather than SCr.4,13–15 For 2 reasons, the criterion
used in our study appears appropriate. First, it has been used
in many previous studies, is shown to be a clinically relevant and appropriate choice, and provides a basis for direct
comparison of the findings.1–3,16 –20 Second, a stricter criterion may yield lower incidences of WRF and exclude many
patients with heightened risk for adverse outcome from
consideration.13 Importantly, the threshold of 0.3 mg/dl
used in this study had the best discriminating power for
identifying the highest increase in hospital cost per patient
(Table 6). Others have also shown that a threshold of a ⱖ0.3
mg/dl increase in SCr has the best overall diagnostic accuracy for identification of patients at high risk for in-hospital
mortality and prolonged hospital stay.6 This is unlike the
finding of another study indicating that a relative increase
ⱖ25% from the admission SCr value (rather than an absolute increase) lacked sensitivity and showed a relatively
small effect size for predicting mortality.7 In general, WRF
occurs relatively early in the course of hospitalization.21
However, as shown in our study, the magnitude of SCr
increase increases with length of hospitalization.
As defined in this study, WRF occurs in 1/6 of patients
with HF in the ambulatory setting and 1/3 of those admitted
with acute decompensated HF.1–3,20 The major predisposing
factors to WRF can be generally categorized into demographic (age, male gender), systemic (hypertension, diabetes, vascular disease), renal (pre-existing kidney dysfunction), medication related (diuretics, calcium channel blockers),
and cardiac (atrial fibrillation, increased ventricular filling
pressures).1–3,13,17,19,20,22 Importantly, several studies have
indicated a lack of relation between cardiac output and
WRF.1,2,13,17,19 The latter has been specifically addressed in
the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE)
trial that demonstrated a lack of relation between baseline
renal function and cardiac index, thus indicating that impaired renal function in patients with HF may not necessarily be a direct consequence of low cardiac output.18 Occurrence of WRF during hospitalization in patients with acute
decompensated HF has been associated with increased risk
of in-hospital mortality, rehospitalization, and postdischarge
mortality.1,6,7,15 Although we did observe a statistically significantly greater unadjusted in-hospital mortality in patients meeting the criteria for WRF versus those who did
not, our study was not designed or powered to detect differences in short- or long-term clinical outcomes. Total
intravenous loop diuretic dose was significantly greater in
the WRF group and independently associated with higher
hospitalization costs; however, no causal relation between
loop diuretic use and WRF can be assumed.
We used strict criteria for patient selection to assure
uniformity and to decrease clinical heterogeneity in our
patients. The selection process limited the size of the final
cohort and may have thus decreased the power of the study
to identify other factors that may have influenced renal
function, length of hospital stay, hospital cost, and the
outcome of our patients. Nevertheless, the present sample
size was sufficient to detect important differences between
those with and without WRF and to support our conclusions. Due to the retrospective nature of the study, measurements of SCr and other relevant laboratory parameters were
not uniform and variations in the timing of these measurements may have introduced unknown biases in the study.
In-hospital management choices in individual patients may
have differed significantly in this study depending on the
year and place of admission and the specialty of the treating
physician. This study reports the results of HF referral and
management in a primarily rural setting and a relatively
homogenous patient population and thus may not be generalizable to other clinical settings.
HF is a costly condition and has an increasing economic
impact on the national health care system. More than 1/2 of
the total cost of the management of HF is related to hospitalization. Factors that precipitate hospitalization, increased
hospital stay, and need for resource usage can add to the
economic impact of HF. Limited information is available
regarding the impact of WRF on cost of hospitalization and
its economic attributes in patients with acute decompensated HF. In the present study, WRF is shown to be an
independent predictor of hospitalization costs. After adjusting for confounding variables, the calculated cost of hospitalization was $5,846 higher for those with WRF compared
to patients without. Considering the large number of annual
hospital admissions for HF (⬎1 million) and the current
prevalence of WRF (roughly 30% of patients), this estimate
of additional hospital cost would translate into a projected
total cost of nearly $2 billion.
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