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BMJ Open
Supplemental Table 1 International Classification of Disease 10th (ICD-10) version codes and standardized
procedural codes to identify renal diseases.
Description
ICD-10 code
Acute nephritic syndrome
N00X
Rapidly progressive nephritic syndrome
N01X
Recurrent and persistent haematuria
N02X
Chronic nephritic syndrome
N03X
Nephrotic syndrome
N04X
Unspecified nephritic syndrome
N05X
Isolated proteinuria with specified morphological lesion
N06X
Hereditary nephropathy, not elsewhere classified
N07X
Glomerular disorders in diseases classified elsewhere
N08X
Acute tubulo-interstitial nephritis
N10X
Chronic tubulo-interstitial nephritis
N118, N119
Tubulo-interstitial nephritis, not specified as acute or chronic
N12X
Obstructive and reflux uropathy
N13X
Drug- and heavy-metal-induced tubulo-interstitial and tubular conditions
N14X
Other renal tubulo-interstitial diseases
N15X
Renal tubulo-interstitial disorders in diseases classified elsewhere
N16X
Acute renal failure
N17X
Chronic kidney disease
N18X
Unspecified kidney failure
N19X
Other disorders resulting from impaired renal tubular function
N258
Disorder resulting from impaired renal tubular function, unspecified
N259
Unspecified contracted kidney
N26X
Other disorders of kidney and ureter, not elsewhere classified
N28X
Description
Procedural codes
Hemodialysis, Peritoneal dialysis or renal replacement therapy
C102, J038, J038-2, J039,
J041, J042
Ikuta K, et al. BMJ Open 2021; 11:e041543. doi: 10.1136/bmjopen-2020-041543
Supplemental material
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placed on this supplemental material which has been supplied by the author(s)
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Supplemental Table 2 Definition of the study drugs.
Class or drug name
ATC index code
Proton pump inhibitors (PPIs)
Esomeprazole
(WHO) A02BC05
Lansoprazole
Omeprazole
(WHO) A02BC03, A02BD03, A02BD07, B01AC56
(WHO) A02BC01
Rabeprazole
(WHO) A02BC04, A02BD12, A02BD13
Vonoprazan
Non-steroidal anti-inflammatory drugs
(WHO) A02BC08, A02BD14, A02BD15
(EphMRA) M01A1
(NSAIDs) †
Penicillin antibiotics†
(EphMRA) J01C1, J01C2; (WHO) A02BD03, A02BD07,
A02BD12, A02BD13, A02BD14, A02BD15
Macrolide antibiotics
Cephalosporin antibiotics†
(EphMRA) J01F-; (WHO) A02BD07, A02BD12, A02BD14
(EphMRA) J01D1, J01D2
Fluoroquinolone antibiotics†
(EphMRA) J01G1, J01G2
The study drugs were identified using the ATC index codes developed by the European Pharmaceutical Market
Research Association (EphMRA) or World Health Organization (WHO). †Topical agents were excluded.
Ikuta K, et al. BMJ Open 2021; 11:e041543. doi: 10.1136/bmjopen-2020-041543
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Supplemental Table 3 Drugs suspected to increase risk of AKI.
Class name
EphMRA ATC
index code
Class name
EphMRA ATC index code
H2 blocker
A02B1
Fluoroquinolone antibiotic
J01G1, J01G2
Loop diuretic
Thiazide diuretic
C03A2
C03A3
Aminoglycoside antibiotic
Monobactam antibiotic
J01KJ01P1
Tetracycline antibiotic
J01A-
Carbapenem antibiotic
J01P2
Penicillin antibiotic
Cephalosporin antibiotic
J01C1, J01C2
J01D1, J01D2
NSAIDs
Contrast media
M01A1, M01A3, M02AT01A-, T01B-
Macrolide antibiotic
J01F-
Drug name
Miconazole
Polymyxin B
Amphotericin B
Vancomycin
Sulfasalazine
Hydroxyethyl starch
Mesalazine
Mannitol
Acetylsalicylate
Ephedrine
Dextran
Triamterene
Polidocanol
Trimethoprim-Sulfamethoxazole
Voriconazole
Telaprevir
Oseltamivir
Captopril
Teicoplanin
Rifampicin
Simeprevir
Immunoglobulin
Acyclovir
Fluconazole
Foscarnet
Tenofovir
Ifosfamide
Tacrolimus
Itraconazole
Indinavir
Adefovir
Streptozocin
Methotrexate
Bleomycin
Sunitinib
Interferon beta
Allopurinol
Pemetrexed
Mitomycin C
Sorafenib
Sirolimus
Alendronate
Cytarabine
Cisplatin
Temsirolimus
Cyclosporine
Zoledronic acid
Tegafur
Imatinib
Interferon alfa
Azathioprine
Cocaine
Acetaminophen
Clozapine
Deferasirox
Phenytoin
Lithium
Carbamazepine
Edaravone
Valproic acid
Pentamidine
This list of drugs is based on the formulary described in the ‘Clinical Practice Guideline for Drug-induced
Kidney Injury in Japan 2016’ published by the Japanese Society of Nephrology. To identify the nephrotoxic
drugs in database, the EphMRA ATC codes or the specific drug names were used.
Ikuta K, et al. BMJ Open 2021; 11:e041543. doi: 10.1136/bmjopen-2020-041543
Supplemental material
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance
placed on this supplemental material which has been supplied by the author(s)
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Supplemental Table 4 Characteristics of current PPI users in cases and controls.
Current PPI users
Characteristics
Cases (n = 148)
Controls (n = 655)
54 (13)
55 (13)
Female, n (%)
43 (29.1)
195 (29.8)
Duration of follow-up, days, mean (SD)
313 (404)
319 (431)
Hypertension
40 (27.0)
225 (34.4)
Congestive heart failure
12 (8.1)
39 (6.0)
Diabetes
22 (14.9)
122 (18.6)
Liver disease
15 (10.1)
78 (11.9)
Pulmonary disease
10 (6.8)
48 (7.3)
Cancer
32 (21.6)
38 (5.8)
1 (0 to 3)
0 (0 to 2)
Lansoprazole
54 (36.5)
222 (33.9)
Esomeprazole
48 (32.4)
180 (27.5)
Rabeprazole
29 (19.6)
140 (21.4)
Omeprazole
10 (6.8)
59 (9.0)
Vonoprazan
7 (4.7)
54 (8.2)
113 (77.9)
349 (53.3)
Age, years, mean (SD)
Comorbidity, n (%)
Charlson comorbidity index, median (IQR)
PPIs prescribed at the last time, n (%)
Current use of nephrotoxic drugs, n (%)†
SD, standard deviation; IQR, interquartile range. †Three cases (2.0%) had missing data.
Ikuta K, et al. BMJ Open 2021; 11:e041543. doi: 10.1136/bmjopen-2020-041543
Supplemental material
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance
placed on this supplemental material which has been supplied by the author(s)
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Supplemental Table 5 Sensitivity analyses.
Current drug use
Cases
Controls
Matched odds ratio (95% CI) †
Setting the index date 1 week before the diagnosis (Cases, n = 294; Controls, n = 2,920)
Current use of PPIs
With NSAIDs (Yes/No)
44/82
75/422
4.04 (2.27 to 7.42)
With penicillins (Yes/No)
12/114
41/456
1.54 (0.65 to 3.59)
With macrolides (Yes/No)
8/118
50/447
0.76 (0.29 to 1.79)
With cephalosporins (Yes/No)
16/110
25/472
2.63 (1.25 to 5.56)
With fluoroquinolones (Yes/No)
7/119
19/478
1.66 (0.59 to 4.36)
Following patients for up to 120 days from the cohort entry (Cases, n = 99; Controls, n = 990)
Current use of PPIs
With NSAIDs (Yes/No)
29/41
66/318
3.50 (1.91 to 6.53)
With penicillins (Yes/No)
10/60
98/286
0.49 (0.23 to 0.98)
With macrolides (Yes/No)
7/63
94/290
0.32 (0.12 to 0.72)
With cephalosporins (Yes/No)
16/54
36/348
3.44 (1.61 to 7.40)
With fluoroquinolones (Yes/No)
12/58
21/363
4.65 (1.87 to 12.10)
Including patients diagnosed with AIN into cases (Cases, n = 475; Controls, n = 4,721)
Current use of PPIs
With NSAIDs (Yes/No)
68/142
186/824
2.01 (1.35 to 2.99)
With penicillins (Yes/No)
40/170
118/892
1.50 (0.95 to 2.35)
With macrolides (Yes/No)
34/176
138/872
1.16 (0.74 to 1.78)
With cephalosporins (Yes/No)
30/180
77/933
2.00 (1.17 to 3.40)
With fluoroquinolones (Yes/No)
20/190
44/966
2.11 (1.09 to 3.96)
Including patients with previous renal diseases into the study cohort (Cases, n = 517; Controls, n = 5,143)
Current use of PPIs
With NSAIDs (Yes/No)
80/164
180/943
2.80 (1.96 to 4.02)
With penicillins (Yes/No)
27/217
129/994
1.12 (0.68 to 1.80)
With macrolides (Yes/No)
23/221
160/963
0.69 (0.41 to 1.11)
With cephalosporins (Yes/No)
54/190
80/1,043
3.81 (2.46 to 5.92)
With fluoroquinolones (Yes/No)
28/216
60/1,063
2.24 (1.31 to 3.80)
CI, confidence interval. †Odds ratios of AKI for current drug combinations compared with PPIs alone were
estimated using the conditional logistic regression model.
Ikuta K, et al. BMJ Open 2021; 11:e041543. doi: 10.1136/bmjopen-2020-041543
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