SUPPLEMENTARY MATERIAL
Figure S1. The long-term risk of end-stage renal disease (ESRD) for AKI survivors
by the adjusted Cox regression model. Abbreviations: ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers.
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Figure S2. The long-term risk of all-cause mortality for AKI survivors by the
adjusted Cox regression model. Abbreviations: ACEI, angiotensin-converting enzyme
inhibitors; ARB, angiotensin II receptor blockers.
Table S1. Diagnostic codes for chronic kidney disease, comorbidities, acute kidney
injury etiologies, and causes of death.
Disease ICD-9-CM codes
Chronic kidney disease
016.0x, 042, 095.4, 189.x, 223.x, 236.9, 250.4x, 271.4, 274.1x, 403.x-404.x, 440.1, 442.1, 446.21, 447.3, 572.4, 580.x-589.x, 590.x- 591, 593.x, 642.1x, 646.2x, 753.x, 984.x
Comorbidities
Diabetes mellitus 250.x
Coronary artery disease 411.x, 413.x, 414.x History of heart failure 428.x
History of stroke 430.x – 438.x Atrial fibrillation 427.31
Cirrhosis 571.2, 571.5
Peripheral artery occlusive
disease 440.x, 443.x, 444.2x, 444.8x, 444.9, 447.8, 447.9
Cancer 140.x – 208.x
Acute kidney injury etiologies
Infectious/septic 995.91, 995.92, 785.52, 038.x Cardiovascular 410.x-414.x, 428.x
Post-surgical 351.x, 352.x, 361.x, 392.x, 395.x, 396.x, V42.1 Organophosphate poisoning 989.3
Heavy metal exposure 984.x, 985.x Causes of death
Malignancy death 140-208, C00-C97
Infection death 001.x – 139.x, 320.x, 321.x, 326.x, 421.x, 460.x – 466.x, 480.x – 487.x, 510.x, 513.x, 551.x, 567.x, 590.x, 599.x, 680.x – 686.x, 711.x, 730.x, A00-A84, B15-B19, J11-J21, J20-J21, G00-G03 Cardiovascular death 390.x – 398.x, 410.x – 414.x, 4151, 41511, 41519, 420.x, 422.x –
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429.x, 431.x, 433.x – 436.x, 518.4, 785.51, 250.X, 580-589, I01-I02, I05-I09, I20-I25, I27, I10-I15, I60-I69, I70, I71, N00-N07, N07- N19, N25-N27, E10-E14
Accident death 800-949, 960-969, V01-X59, Y85-Y86, X85-Y09, Y87.1 Other causes Diagnostic codes other than malignancy death, infection death,
cardiovascular death, or accident death
Table S2. Oral antihypertensives and AKI medications analyzed in the study.
Drug classification Generic name/Component Angiotensin-converting
enzyme inhibitors
Benazepril, Captopril, Cilazapril, Enalapril, Fosinopril, Imidapril, Lisinopril, Perindopril, Quinapril, Ramipril
Angiotensin II receptors Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan
β-Blockers Acebutolol, Alprenolol, Atenolol, Betaxolol, Bisoprolol, Carteolol, Carvedilol, Labetalol, Metoprolol, Nadolol, Pindolol, Propranolol, Sotalol
Calcium channel blockers
(non-dihydropyridine) Diltiazem, Verapamil Calcium channel blockers
(dihydropyridine)
Amlodipine, Barnidipine, Felodipine, Isradipine, Lacidipine, Lercanidipine, Nicardipine, Nifedipine, Nitrendipine
Thiazides Benzylhydrocholothiazide, Clopamide, Hydrocholorothiazide, Hydroflumethiazide, Indapamide, Metolazone, Trichlormethiazide Loop diuretics Bumetanide, Furosemide
Potassium-lowering resins Calcium polystyrene sulfonate, Sodium polystyrene sulfonate Alkalinizing agents Sodium bicarbonate
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Table S3. Demographic characteristics of the study cohort after propensity score matching (patient number = 3,093 vs. 3,093).
Factor ACEI/ARB User
(n = 3,093)
ACEI/ARB Non- user (n = 3,093)
p Value
Age, mean (SD), year 65.9 (13.8) 66.7 (13.5) 0.017
20-39 136 (4.4) 131 (4.2) 0.75
40-64 1,143 (37) 1,125 (36.4) 0.63
65-74 874 (28.3) 863 (27.9) 0.76
75-100 940 (30.4) 974 (31.5) 0.35
Male gender 1,521 (49.2) 1,561 (50.5) 0.31
Primary care by the
nephrologist at AKI 2,050 (66.3) 2,072 (67.0) 0.55 Comorbidities
Diabetes mellitus 2,143 (69.3) 2,142 (69.3) 0.98
Coronary artery disease 922 (29.8) 982 (31.7) 0.10 Congestive heart failure 755 (24.4) 754 (24.4) 0.98
Prior stroke 573 (18.5) 584 (18.9) 0.72
COPD 381 (12.3) 367 (11.9) 0.59
Malignancy 308 (10.0) 295 (9.5) 0.58
Medications Before AKI
ACEI/ARB 2,285 (73.9) 2,292 (74.1) 0.84
β-blocker 1,601 (51.8) 1,608 (52.0) 0.86
During AKI
Potassium-lowering resin 1,053 (34) 1,070 (34.6) 0.65
Sodium bicarbonate 881 (28.5) 885 (28.6) 0.91
Loop diuretics 2,426 (78.4) 2,427 (78.5) 0.98
Thiazides 526 (17.0) 527 (17.0) 0.97
After AKI
β-blockers 1,486 (48.0) 1,524 (49.3) 0.33
Calcium channel blockers 2,623 (84.8) 2,631 (85.1) 0.78 Glycemic control
Insulin 187 (6.0) 182 (5.9) 0.79
Statins 583 (18.8) 577 (18.7) 0.85
Hospitalization of the index
AKI
Hospitalization days 18.7 (17.9) 19.5 (18.3) 0.07 ICU days/hospitalization
days (%) 50.2 (31.7) 52.9 (31.5) 0.81
HD duration (hour) 19.1 (22.5) 19.2 (21.8) 0.78
CRRT/SLEDD use 11 (0.4) 12 (0.4) 0.83
CRRT duration (hour) 34.2 (17.2) 42 (43.3) 0.59
Chronic kidney disease
No 194 (6.3) 185 (6.0) 0.63
Stages 1-4 1,791 (57.9) 1,792 (57.9) 0.98
Stage 5 with anemia 1,108 (35.8) 1,116 (36.1) 0.83 Acute kidney injury etiologies
Infectious/septic 224 (7.2) 217 (7.0) 0.73
Cardiovascular 535 (17.3) 532 (17.2) 0.92
Post-surgical 15 (0.5) 16 (0.5) 0.86
Organophosphate poisoning 6 (0.2) 5 (0.2) 0.76
Heavy metal exposure 10 (0.3) 13 (0.4) 0.53
Unless otherwise indicated, data are expressed as number (percentage) of patients or mean (standard deviation). Abbreviations: ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; AKI, acute kidney injury; COPD, chronic obstructive pulmonary disease; ICU, intensive care unit; HD, hemodialysis;
CRRT, continuous renal replacement therapy; SLEDD, sustained low-efficiency daily dialysis.
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Table S4. Multivariate Cox regression analysis of the ACEI/ARB use on patient outcomes after propensity score matching (patient number = 3,093 vs. 3,093).
Outcomes Crude
HR
95% CI
p Value Adjusted HR#
95% CI
p Value
Lower Upper Lower Upper
ESRD 0.99 0.93 1.05 0.81 0.99 0.94 1.05 0.82
All-cause death## 0.94 0.88 1.01 0.51 0.94 0.88 1.01 0.08
Malignancy death 0.80 0.68 0.94 0.08 0.78 0.66 0.92 0.003
Infection death 0.86 0.67 1.10 0.24 0.87 0.67 1.11 0.26
Cardiovascular death 0.97 0.87 1.09 0.62 0.98 0.88 1.10 0.78
Accident death 0.89 0.75 1.06 0.18 0.89 0.75 1.06 0.19
Other death 1.04 0.91 1.19 0.58 1.05 0.92 1.20 0.47
Abbreviations: ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; HR, hazard ratio; CI, confidence interval; ESRD, end-stage renal disease.
#The clustered Cox model was adjusted for age, gender, diabetes mellitus, coronary artery disease, congestive heart failure, prior stroke, COPD, malignancy, pre-AKI ACEI/ARB or β-blocker use, medication use during AKI (potassium-lowering resin, sodium bicarbonate, loop diuretics, thiazides), post-AKI use of antihypertensive drugs other than ACEI/ARBs (β-blockers, calcium channel blockers), insulin, and statins, hospitalization days of the index AKI, intensive care unit days/total hospitalization days, hemodialysis duration, CRRT/SLEDD use, CRRT duration, stages of CKD, etiologies of AKI (infectious, cardiovascular, post-surgical, or intoxication).
##dialysis and dialysis duration as time-dependent covariates.
*p < 0.05.
Table S5. Multivariate Cox regression analysis of the ACEI/ARB use on patient outcomes by different defined daily doses (DDD).
Outcomes
Before propensity score matching After propensity score matching Adjusted
HR#
95% CI
p Value Adjusted HR#
95% CI
p Value
Lower Upper Lower Upper
Long-term dialysis
DDD < 0.70 1.09 1.02 1.16 0.014 1.09 1.01 1.17 0.024
DDD 0.70≧ 0.84 0.78 0.89 <0.001 0.84 0.78 0.90 <0.001
P for trend 0.09 0.26
All-cause death##
DDD < 0.70 1.04 0.97 1.12 0.30 1.06 0.98 1.14 0.18
DDD 0.70≧ 0.83 0.77 0.90 <0.001 0.83 0.76 0.90 <0.001
P for trend <0.001 <0.001
Malignancy death
DDD < 0.70 0.93 0.78 1.12 0.46 0.89 0.74 1.09 0.27
DDD 0.70≧ 0.69 0.57 0.85 <0.001 0.67 0.54 0.83 <0.001
P for trend 0.001 <0.001
Infectious death
DDD < 0.70 0.95 0.73 1.25 0.72 1.04 0.77 1.40 0.80
DDD 0.70≧ 0.71 0.52 0.96 0.03 0.69 0.49 0.97 0.033
P for trend 0.06 0.08
Cardiovascular death
DDD < 0.70 1.01 0.90 1.14 0.84 1.02 0.89 1.16 0.81
DDD 0.70≧ 0.97 0.86 1.10 0.60 0.95 0.83 1.09 0.49
P for trend 0.65 0.58
Accident death
DDD < 0.70 1.01 0.84 1.21 0.92 1.06 0.86 1.29 0.59
DDD 0.70≧ 0.73 0.59 0.90 0.003 0.73 0.58 0.92 0.007
P for trend 0.007 0.020
Other death
DDD < 0.70 1.17 1.02 1.35 0.02 1.24 1.06 1.45 0.008
DDD 0.70≧ 0.83 0.71 0.98 0.02 0.86 0.72 1.03 0.10
P for trend 0.12 0.32
Abbreviations: ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; DDD, defined daily dose; HR, hazard ratio; CI, confidence interval.
#The clustered Cox model was adjusted for age, gender, diabetes mellitus, coronary artery disease, congestive heart
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failure, prior stroke, COPD, malignancy, pre-AKI ACEI/ARB or β-blocker use, medication use during AKI (potassium-lowering resin, sodium bicarbonate, loop diuretics, thiazides), post-AKI use of antihypertensive drugs other than ACEI/ARBs (β-blockers, calcium channel blockers), insulin, and statins, hospitalization days of the index AKI, intensive care unit days/total hospitalization days, hemodialysis duration, CRRT/SLEDD use, CRRT duration, stages of CKD, etiologies of AKI (infectious, cardiovascular, post-surgical, or intoxication).
##dialysis and dialysis duration as time-dependent covariates.
*p < 0.05.