Association of Commonly Used Medications with Prevalence and Renal Recovery after Postoperative Acute Kidney Injury

Shahab Bozorgmehri, MD, MPH, CPH 1; Meghan Brennan, MS 2; Tezcan Ozrazgat Baslanti, PhD 2; Charles E. Hobson, MD, MHA 3; Azra Bihorac, MD, MS, FASN 2
1

Department of Epidemiology, College of Public Health and Health Professions, College of Medicine, University of Florida; 2 Department of Anesthesiology, College of Medicine, University of Florida 3 Department of Surgery, College of Medicine, University of Florida ;

INTRODUCTION
Acute kidney injury (AKI) is a common clinical condition in postoperative patients associating 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. 6-7 It is not known to what extent drug intake after the onset of AKI has an impact on renal outcomes.
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 All (n=54,768) 54 (18) 26,134 (47.7) 44,388 (82.5) 6,829 (12.7) 1,613 (3.0) 91 (69,107) 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) 2,758 (5.0) 1,622 (2.9) 3,358 (6.1) 2,787 (5.1) 5,061 (9.2) 2,186 (4.0) 7 (4,13) 0 (0,3) 48 (29,93) n/a No AKI(n=33,407) 53 (18) 16,214(48.5) 27,297 (83.0) 3,941 (12.0) 979 (3.0) 95 (77,109) 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) 221 (0.6) 307 (0.9) 1,355 (4.1) 1,165 (3.5) 1,394 (4.2) 251 (0.7) 5 (4,8) 0 (0,1) 37 (25,57) n/a

RESULTS
All AKI(n=21,361) 55(18) 9,920 (46.5) 17,091 (81.6) 2,888 (13.8) 634 (3.0) 84(54,103) 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) 2,537 (11.9) 1,315 (6.2) 2,003 (9.4) 1,622 (7.6) 3,667 (17.2) 1,935 (9.1) 13 (7,24) 2 (0,9) 93 (51,178) 18,306 (85.7) AKI RIFLE-R(n=11,664) 55 (18) 5,575 (47.8) 9,489 (83.0) 1,424 (12.4) 336 (2.9) 89 (65,106) 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) 447 (3.8) 292 (2.5) 898 (7.7) 710 (6.1) 1,380 (11.8) 450 (3.8) 10 (7,17) 1 (0,5) 71 (42,119) 10,795 (92.5) RIFLE-I(n=5,666) 55 (18) 2,662 (47.0) 4,512 (81.2) 774 (13.9) 180 (3.2) 78 (50,101) 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) 790 (13.9) 366 (6.4) 584 (10.3) 509 (9.0) 1,263 (22.3) 551 (9.7) 17 (10,29) 4 (0,13) 123 (65,217) 4,707 (83.1) RIFLE-F(n=4,031) 55 (17) 1,683 (41.7) 3090 (78.3) 690 (17.5) 118 (3.0) 63 (27,96) 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) 1,300 (32.2) 657 (16.3) 521 (12.9) 403 (10.0) 1,024 (25.4) 934 (23.2) 25 (12,45) 9 (1,24) 194 (89,366) 2,804 (69.5) P-value1 P-value2

DISCUSSION
The odds of AKI was significantly increased by use of vancomycin, aminoglycosides, amphotericin B, antivirals, trimetoprim-sulfametoxazol, beta-blockers, pressors, inotropes, nesiritide and diuretics (Table 3). The odds of AKI was significantly decreased by use of ACEinhibitors, aspirin, NSAIDs and statins (Table 3). The odds of partial or no renal recovery was higher with use of amphotericin B, diuretics, pressors and beta-blockers (Table 2). The impact of NSAIDS on AKI has been documented to be dose dependent, with high plasma concentration of NSAIDS associated with renal adverse effect 10. However, in this study ASA and NSAIDS were shown to significantly reduce the odds of AKI, and this was irrespective of the baseline eGFR.

<0.0001 <0.0001 <0.0001

0.9572 <0.0001 <0.0001

<0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 0.0556 0.1123 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

<0.0001 <0.0001 <0.0001 0.0005 <0.0001 0.26 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001

PURPOSE
Describe the frequency of common postoperative medications Investigate the association between the common postoperative

medications and the prevalence of AKI episodes

Describe the frequency of common postoperative medications

CONCLUSION
Our findings demonstrate that several commonly used postoperative medications may be associated not only with increased risk for AKI but also decrease the likelihood of renal recovery after AKI episode. 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 in patients at risk of AKI or with new onset of AKI.

after the onset of AKI episodes

Assess the relationship between the complete renal recovery and

the common postoperative medication that were given after the onset of AKI episodes

METHODS
We retrospectively studied all patients aged 18 years or older, 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 University of Florida. We excluded patients with less than two serum creatinine measurements and those who had chronic kidney disease stage 5 (established kidney failure (GFR <15 mL/min/1.73 m2, or a need for permanent renal replacement therapy (RRT)). We also excluded patients who had length of hospital stay more than 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 serum creatinine 1.5 baseline; decrease in GFR of 25%; or urine output <0.5ml/kg/hour 6hours.4 Renal outcome were classified into three categories: complete renal recovery (sCr returning to a level less than 50% above baseline sCr), partial renal recovery (a persistent increase in sCr with more than 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 common postoperative medications before and after the AKI episodes . Univariate and multivariate logistic regression models were used to assess the relationship between common 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.

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. Association between Common Medications and Partial or No Renal Recovery Drug Use Pressors Amphotericin B Diuretics Betablockers Nesiritide ASA Aminoglycosides Vancomycin TMP-SMX Antiviral Inotropes Statin ACE inhibitors NSAIDs
1Adjusted

Table 3. Association between Common Medications and AKI Drug Use Amphotericin B Nesiritide Inotropes Pressors Diuretic Vancomycin Betablockers TMP-SMX Aminoglycosides Antiviral NSAIDs ACE inhibitors Statin ASA
1Adjusted

Adjusted1 Odds Ratio (95% Confidence Interval) 1.75 (1.54-1.98) 1.71 (1.31-2.24) 1.53 (1.35-1.74) 1.18 (1.04-1.35) 1.20 (0.89-1.60) 1.13 (0.98-1.32) 1.11 (0.92-1.35) 1.09 (0.96-1.24) 1.07 (0.90-1.26) 1.05 (0.87-1.26) 1.02 (0.83-1.24) 1.00 (0.81-1.23) 0.90 (0.75-1.06) 0.83 (0.67-1.03)

P-value <.0001 <.0001 <.0001 0.01 0.238 0.098 0.275 0.18 0.453 0.624 0.868 0.998 0.216 0.089

Unadjusted Odds Ratio (95% Confidence Interval) 10.64 (8.09-14.00) 9.38 (7.31-12.03) 6.72 (6.03-7.49) 3.58 (3.41-3.75) 2.62 (2.53-2.72) 2.22 (2.14-2.30) 1.94 (1.87-2.00) 2.65 (2.45-2.85) 1.31 (1.24-1.38) 3.62 (3.30-3.97) 0.71 (0.67-0.74) 1.16 (1.18-1.21) 1.16 (1.11-1.21) 1.10 (1.06-1.14)

P-value <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001

Adjusted1 Odds Ratio (95% Confidence Interval) 4.46 (3.31-6.01) 2.43 (1.85-3.19) 2.35 (2.08-2.67) 2.05 (1.93-2.17) 1.72 (1.65-1.80) 1.60 (1.53-1.67) 1.38 (1.33-1.44) 1.31 (1.19-1.44) 1.28 (1.20-1.36) 1.24 (1.11-1.39) 0.91 (0.81-0.96) 0.88 (0.84-0.92) 0.79 (0.75-0.84) 0.74 (0.70-0.77)

P-value <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 0.0002 0.0006 <.0001 <.0001 <.0001

ACKNOWLEDGEMENTS
This study was funded by NIH NIGMS K23GM087709.

SELECTED REFERENCES
1. Bihorac A, Yavas S, Subbiah S, Hobson CE, Schold JD, Gabrielli A, Layon AJ, Segal MS. Long-Term Risk of Mortality and Acute Kidney Injury During Hospitalization After Major Surgery. Annals of Surgery Issue 2009;249(5):851-858. 2. Hobson CE, Yavas S, Segal MS, Schold JD, Tribble CG, Layon AJ, Bihorac A: Acute Kidney Injury Is Associated With Increased Long-Term Mortality After Cardiothoracic Surgery. Circulation 2009;119(18):2444-2453. 3. Zavada J, Hoste1 E, Cartin-Ceba R, Calzavacca P, Gajic O, Clermont G, Bellomo R, Kellum JA. A comparison of three methods to estimate baseline creatinine for RIFLE classification. Nephrol Dial Transplant 2010;25:3911-3918. 4. Bagshaw SM, George C, Bellomo R. A comparison of the RIFLE and AKIN criteria for acute kidney injury in critically ill patients. Nephrol Dial Transplant 2008;23: 15691574 5. Abelha FJ, Botelho M, Fernandes V, Barros H. Determinants of postoperative acute kidney injury. Critical Care 2009, 13:R79 6. Khutsishivili K, Okusa MD. Distant organ effects of acute kidney injury. Nephrology SelfAssessment Program 2009;8(3). 7. Naughton CA. Drug-Induced Nephrotoxicity. Am Fam Physician. 2008;78(6):743-750. 8. Schetza M, Dastab J, Goldsteinc S, Golperd T. Drug-induced acute kidney injury. Current Opinion in Critical Care 2005;11:555565. 9. Bihorac A, Delano MJ, Schold JD, Lopez MC, Nathens AB, Maier RV, Layon AJ, Baker HV, Moldawer LL.Incidence, clinical predictors, genomics, and outcome of acute kidney injury among trauma patients. Ann Surg. 2010;252(1):158-65. 10. Harirforoosh S, Jamali F. Renal adverse effects of non steroidal anti-inflamatory drugs. Expert Opinion on Drug Safety 2009;8(6):669-681.

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

for age, sex, race, admission service, routine elective vs. emergency admission, weekend vs. weekdays admission, Charlson comorbidity index, and baseline eGFR

Table 4. Frequency of Common Medications prior to AKI No AKI during AKI during hospitalization hospitalization Drug Use, n (%) (n=33407) (n=21361) Betablockers 15292 (45.8) 13256 (62.1) Diuretic Vancomycin ASA ACE inhibitors Statin NSAIDs
1P-value

P-value <.0001 <.0001 <.0001 <.0001 <.0001 <.0001 <.0001

11191 (33.5) 8786 (26.3) 8768 (26.2) 7598 (22.7) 6892 (20.6) 6173 (18.5)

12158 (56.9) 9445 (44.2) 6020 (28.2) 5441 (25.5) 4957 (23.2) 2940 (13.8)

Table 5. 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 Diuretic Betablocker ASA TMP-SMX ACE inhibitors,
1P-value

2153 (10) 1984 (9.3) 1829 (8.5) 1321 (6.2) 1183 (5.5) 1059 (4.9)

1576 (8.6) 1441 (7.9) 1376 (7.5) 993 (5.4) 895 (4.9) 835 (4.6)

367 (15) 409 (16.7) 322 (13.2) 219 (9) 211 (8.6) 163 (6.7)

210 (34.3) 134 (21.9) 131 (21.4) 109 (17.8) 77 (12.6) 61 (9.9)

<.0001 <.0001 <.0001 <.0001 <.0001 <.0001

CONTACT INFORMATION
For more information regarding the study, please contact Shahab Bozorgmehri at s.bozorgmehri@ufl.edu.

for comparison between AKI and No AKI, by chi-square test

for comparison across renal outcome categories, by chi-square test

RESEARCH POSTER PRESENTATION DESIGN 2011

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