Transcript Association of Commonly Used Medications with Prevalence and Renal Recovery after Postoperative Acute Kidney InjuryCPH ; MS ; Shahab Bozorgmehri, MD, MPH, Meghan Brennan,2 Charles.

Association of Commonly Used Medications with Prevalence and Renal Recovery after
Postoperative Acute Kidney Injury
1
CPH ;
2
MS ;
Shahab Bozorgmehri, MD, MPH,
Meghan Brennan,
2
2
Charles E. Hobson, MD, MHA ; Azra Bihorac, MD, MS, FASN
Tezcan Ozrazgat Baslanti,
1Departments
of Epidemiology, College of Public Health & Health Professions;
College of Medicine, University of Florida, Gainesville, FL
Introduction
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Acute kidney injury (AKI) is a common clinical condition in
postoperative patients associated with a significantly increased risk
of morbidity and mortality.1-5
In a significant proportion of patients with AKI, drug intake can be
related to the onset of AKI. 6-8
It is not known to what extent drug intake after the onset of AKI
has an impact on renal outcomes.
Purpose
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Describe the frequency of commonly administered postoperative
medications.
•
Investigate the association between commonly given postoperative
medications and the prevalence of AKI episodes.
•
Describe the frequency of commonly administered postoperative
medications after the onset of AKI episodes.
•
Assess the relationship between complete renal recovery and
common postoperative medications given after the onset of AKI
episodes.
Methods
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•
•
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We retrospectively studied all patients aged 18 years or older, who
were hospitalized for more than 2 days (48 hours) and had any type
of surgery between January 1, 2000 and December 31, 2010 at
Shands Hospital at the University of Florida.
We excluded patients with less than 2 serum creatinine (sCr)
measurements and those who had chronic kidney disease stage 5
[established kidney failure: glomerular filtration rate (GFR) <15
mL/min/1.73 m2, or a need for permanent renal replacement
therapy (RRT)]. We also excluded patients who had a length of
hospital stay over 90 days. The final cohort contained 54,768
patients.
AKI was defined based on the RIFLE (Risk, Injury, Failure, Loss of
kidney function, and End stage renal disease) classification as an
increase in sCr × 1.5 baseline, decrease in GFR ≥25%, or urine
output <0.5 mL/kg/hour × 6 hours. 4
Renal outcome was classified into 3 categories: complete renal
recovery (sCr returning to a level 50% above baseline sCr), partial
renal recovery (a persistent increase in sCr with 50% above
baseline sCr, but no need for RRT), and no renal recovery (a need
for RRT at the time of hospital discharge or death). 4,9
We investigated the frequency of commonly administered
postoperative medications before and after the AKI episodes.
Univariate and multivariate logistic regression models were used to
assess the relationship between commonly given medications and
the prevalence of AKI episodes, and also to investigate the
relationship between common postoperative medications given
after the onset of AKI episodes and renal outcome.
2
Departments of Anesthesiology and Surgery,
Table 1. Sociodemographic and Clinical Characteristics of Study Participants
Characteristics
Sociodemographics
Age ,mean (SD) years
Female Gender, n (%)
Race/ethnicity, n (%)
White
African-American
Hispanic
Baseline eGFR, median (IQR)
Comorbid Conditions, n (%)
Congestive Heart Failure
Myocardial Infarction
Peripheral Vascular Disease
Renal Disease
Chronic Pulmonary Disease
Mild Liver Disease
Diabetes without complications
Cancer
Hospital Complications, n (%)
Sepsis
Shock
Wound complications
Postoperative infections
Pulmonary complications
Hospital Outcomes
In-hospital mortality, n (%)
Days in hospital, median
(IQR)
Days in ICU , median (IQR)
Hospital costs ($,1000),
median (IQR)
Complete Renal Recovery
P-value1
P-value2
Discussion
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The odds of AKI was significantly increased by the use of vancomycin,
aminoglycosides, amphotericin B, antivirals, trimetoprim-sulfametoxazol,
beta-blockers, pressors, inotropes, nesiritide, and diuretics (Table 4).
•
The odds of AKI was significantly decreased by the use of ACE-inhibitors,
aspirin, NSAIDs, and statins (Table 4).
•
The odds of partial or no renal recovery was higher with the use of
amphotericin B, diuretics, pressors, and beta-blockers (Table 5).
•
The impact of NSAIDS on AKI has been documented to be dosedependent, with high plasma concentrations of NSAIDS associated with
renal adverse effect.10 However, in this study, ASA and NSAIDS were
shown to significantly reduce the odds of AKI, irrespective of the baseline
eGFR.
All (n=54,768)
No AKI(n=33,407)
All AKI(n=21,361)
AKI
RIFLE-R(n=11,664)
54 (18)
26,134 (47.7)
53 (18)
16,214(48.5)
55(18)
9,920 (46.5)
55 (18)
5,575 (47.8)
55 (18)
2,662 (47.0)
55 (17)
1,683 (41.7)
<0.0001
<0.0001
0.9572
<0.0001
44,388 (82.5)
6,829 (12.7)
1,613 (3.0)
91 (69,107)
27,297 (83.0)
3,941 (12.0)
979 (3.0)
95 (77,109)
17,091 (81.6)
2,888 (13.8)
634 (3.0)
84(54,103)
9,489 (83.0)
1,424 (12.4)
336 (2.9)
89 (65,106)
4,512 (81.2)
774 (13.9)
180 (3.2)
78 (50,101)
3090 (78.3)
690 (17.5)
118 (3.0)
63 (27,96)
<0.0001
<0.0001
<0.0001
<0.0001
4,761 (8.7)
3,919 (7.1)
7,385 (13.5)
3,904 (7.1)
9,394 (17.1)
2,686 (4.9)
8,687 (15.8)
9,377 (17.1)
1,797 (5.4)
1,990 (6.0)
3,991 (11.9)
1,315 (3.9)
5,175 (15.5)
1,072 (3.2)
5,219 (15.6)
5,788 (17.3)
2,964 (13.9)
1,929 (9.0)
3,394 (15.9)
2,589 (12.1)
4,219 (19.7)
1,614 (7.6)
3,468 (16.2)
3,589 (16.8)
1,259 (10.8)
1,005 (8.6)
1,835 (15.7)
869 (7.4)
2,282 (19.5)
619 (5.3)
2,050 (17.6)
2,167 (18.6)
882 (15.6)
515 (9.1)
979 (17.3)
715 (12.6)
1,160 (20.5)
434 (7.6)
953 (16.8)
825 (14.5)
823 (20.4)
409 (10.1)
580 (14.4)
1,005 (24.9)
777 (19.3)
561 (13.9)
465 (11.5)
97 (14.8)
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
0.0556
0.1123
<0.0001
<0.0001
0.0005
<0.0001
0.26
<0.0001
<0.0001
<0.0001
2,758 (5.0)
1,622 (2.9)
3,358 (6.1)
2,787 (5.1)
5,061 (9.2)
221 (0.6)
307 (0.9)
1,355 (4.1)
1,165 (3.5)
1,394 (4.2)
2,537 (11.9)
1,315 (6.2)
2,003 (9.4)
1,622 (7.6)
3,667 (17.2)
447 (3.8)
292 (2.5)
898 (7.7)
710 (6.1)
1,380 (11.8)
790 (13.9)
366 (6.4)
584 (10.3)
509 (9.0)
1,263 (22.3)
1,300 (32.2)
657 (16.3)
521 (12.9)
403 (10.0)
1,024 (25.4)
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<.0001
<0.0001
<0.0001
Conclusion
2,186 (4.0)
251 (0.7)
1,935 (9.1)
450 (3.8)
551 (9.7)
934 (23.2)
<0.0001
<0.0001
•
7 (4,13)
5 (4,8)
13 (7,24)
10 (7,17)
17 (10,29)
25 (12,45)
<0.0001
<0.0001
0 (0,3)
0 (0,1)
2 (0,9)
1 (0,5)
4 (0,13)
9 (1,24)
<0.0001
<0.0001
48 (29,93)
37 (25,57)
93 (51,178)
71 (42,119)
123 (65,217)
194 (89,366)
<0.0001
<0.0001
Our findings demonstrate that several commonly administered
postoperative medications may be associated not only with an increased
risk for AKI, but with a decreased likelihood of renal recovery after an AKI
episode.
n/a
n/a
18,306 (85.7)
10,795 (92.5)
4,707 (83.1)
2,804 (69.5)
•
While some of these findings could be explained, further research is
required to corroborate them. These findings may be useful to determine
risks versus benefits of common medications given to patients at risk of
AKI or with new onset of AKI.
RIFLE-I(n=5,666)
RIFLE-F(n=4,031)
<0.0001
IQR=Inter quarter range; eGFR= Estimated glomerular filtration rate, GFR was estimated by means of CKD-EPI equation
1 P value for comparison across AKI and No AKI, by analysis of variance (continuous variables) and chi-square (categorical variables)
2 P value for comparison across AKI-RIFLE categories, by analysis of variance (continuous variables) and chi-square (categorical variables)
3Specialty surgeries include orthopedics, urology, ENT, OB/GYN, and plastic surgery
4Others include transplant, ophthalmology, burn, non-operative, and trauma
Table 2. Frequency of Common Medications Given prior to AKI
No AKI during
AKI during
Drug Use, n (%)
hospitalization
hospitalization
(n=33407)
(n=21361)
Beta-blockers
15292 (45.8)
13256 (62.1)
P-value
Diuretic
11191 (33.5)
12158 (56.9)
<.0001
Vancomycin
8786 (26.3)
9445 (44.2)
<.0001
ASA
8768 (26.2)
6020 (28.2)
<.0001
ACE inhibitors
7598 (22.7)
5441 (25.5)
<.0001
Statin
6892 (20.6)
4957 (23.2)
<.0001
NSAIDs
6173 (18.5)
2940 (13.8)
<.0001
1P-value
<.0001
for comparison between AKI and No AKI, by chi-square test
Table 4. Association between Common Medications Used and AKI
Unadjusted Odds
Adjusted1 Odds Ratio
Ratio (95%
Drug Use
P-value
(95% Confidence
P-value
Confidence
Interval)
Interval)
Amphotericin B
10.64 (8.09-14.00) <.0001
4.46 (3.31-6.01)
<.0001
Nesiritide
9.38 (7.31-12.03)
<.0001
2.43 (1.85-3.19)
<.0001
6.72 (6.03-7.49)
<.0001
2.35 (2.08-2.67)
<.0001
Inotropes
3.58 (3.41-3.75)
<.0001
2.05 (1.93-2.17)
<.0001
Pressors
Diuretic
2.62 (2.53-2.72)
<.0001
1.72 (1.65-1.80)
<.0001
Vancomycin
2.22 (2.14-2.30)
<.0001
1.60 (1.53-1.67)
<.0001
Beta-blockers
1.94 (1.87-2.00)
<.0001
1.38 (1.33-1.44)
<.0001
TMP-SMX
2.65 (2.45-2.85)
<.0001
1.31 (1.19-1.44)
<.0001
Aminoglycosides
1.31 (1.24-1.38)
<.0001
1.28 (1.20-1.36)
<.0001
Antiviral
3.62 (3.30-3.97)
<.0001
1.24 (1.11-1.39)
0.0002
NSAIDs
0.71 (0.67-0.74)
<.0001
0.91 (0.81-0.96)
0.0006
ACE inhibitors
1.16 (1.18-1.21)
<.0001
0.88 (0.84-0.92)
<.0001
Statin
1.16 (1.11-1.21)
<.0001
0.79 (0.75-0.84)
<.0001
ASA
1.10 (1.06-1.14)
<.0001
0.74 (0.70-0.77)
<.0001
1Adjusted
2
PhD ;
for age, sex, race, admission service, routine elective vs. emergency admission,
weekend vs. weekdays admission, Charlson comorbidity index, and baseline eGFR
Table 3. Common Medications Given after the Onset of AKI, Stratified by Renal
Outcome
Complete
Partial Renal
No Renal
All AKI
Renal
PDrug Use, n (%)
Recovery
Recovery
(n=21361)
Recovery
value1
(n=2442)
(n=613)
(n=18306)
2362 (11)
1573 (8.6)
Pressors
467 (19.1)
322 (52.5) <.0001
Vancomycin
2153 (10)
1576 (8.6)
367 (15)
210 (34.3) <.0001
Diuretic
1984 (9.3)
1441 (7.9)
409 (16.7)
134 (21.9) <.0001
Beta-blocker
1829 (8.5)
1376 (7.5)
322 (13.2)
131 (21.4) <.0001
ASA
1321 (6.2)
993 (5.4)
219 (9)
109 (17.8) <.0001
TMP-SMX
1183 (5.5)
895 (4.9)
<.0001
211 (8.6)
77 (12.6)
ACE inhibitors,
1059 (4.9)
835 (4.6)
163 (6.7)
61 (9.9)
<.0001
1P-value
for comparison across renal outcome categories, by chi-square test
Table 5. Association between Common Medications Used and Partial or No Renal
Recovery
Adjusted1 Odds Ratio (95%
Confidence Interval)
P-value
Pressors
Amphotericin B
1.75 (1.54-1.98)
<.0001
1.71 (1.31-2.24)
<.0001
Diuretics
1.53 (1.35-1.74)
<.0001
Beta-blockers
1.18 (1.04-1.35)
0.01
Nesiritide
1.20 (0.89-1.60)
0.238
ASA
1.13 (0.98-1.32)
0.098
Aminoglycosides
1.11 (0.92-1.35)
0.275
Vancomycin
1.09 (0.96-1.24)
0.18
TMP-SMX
1.07 (0.90-1.26)
0.453
Antiviral
1.05 (0.87-1.26)
0.624
Inotropes
Statin
1.02 (0.83-1.24)
0.868
1.00 (0.81-1.23)
0.998
ACE inhibitors
0.90 (0.75-1.06)
0.216
NSAIDs
0.83 (0.67-1.03)
0.089
Drug Use
1Adjusted
for age, sex, race, admission service, routine elective vs. emergency admission, weekends
vs. weekdays admission, Charlson comorbidity index, and severity of AKI by RIFLE classification
Acknowledgement
This study was funded by NIH NIGMS K23GM087709.
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For more information regarding the study, please contact Shahab Bozorgmehri
at: [email protected].