Article Figures & Data
Figures
- Figure 1.
Flow diagram of cohort assembly of primary cohort of new users of PPI (n=173,321) and new users of H2 blockers (20,270).
- Figure 2.
Duration of PPI exposure and risk of renal outcomes among PPI users (n=173,321).
Tables
- Table 1.
Baseline characteristics of a cohort of new users of H2 blockers, and new users of PPI
Baseline Characteristics H2 Blockers (n=20,270) PPI (n=173,321) P Value Age (SD) 55.40 (12.81) 56.85 (11.85) P<0.001 Baseline eGFR in ml/min per 1.73 m2 (SD) 86.98 (15.88) 86.56 (15.67) P<0.001 Race White (%) 15,937 (78.62) 137,174 (79.14) P=0.01 Black (%) 3,784 (18.67) 32,018 (18.47) Other (%) 549 (2.71) 4,129 (2.38) Sex Male (%) 18,929 (93.38) 161,259 (93.04) P=0.07 Female (%) 1,341 (6.62) 12,062 (6.96) Diabetes mellitus (%) 8,923 (44.02) 72,309 (41.72) P<0.001 Hypertension (%) 15,814 (78.02) 136,782 (78.92) P<0.01 Chronic lung disease (%) 7,951 (39.23) 66,955 (38.63) P=0.10 Peripheral artery disease (%) 5,009 (24.71) 31,311 (18.07) P<0.001 Cardiovascular disease (%) 8,459 (41.73) 71,807 (41.43) P=0.41 Cerebrovascular disease (%) 4,596 (22.67) 26,457 (15.26) P<0.001 Dementia (%) 5,058 (24.95) 32,380 (18.68) P<0.001 Hyperlipidemia (%) 14,785 (72.94) 127,463 (73.54) P=0.07 Hepatitis C (%) 1,198 (5.91) 14,892 (8.59) P<0.001 HIV (%) 55 (0.27) 678 (0.39) P<0.01 Gastroesophageal reflux disease (%) 3,767 (18.58) 86,804 (50.08) P<0.001 Upper gastrointestinal tract bleeding (%) 246 (1.21) 7,898 (4.56) P<0.001 Ulcer disease (%) 666 (3.29) 26,228 (15.13) P<0.001 H. pylori infection (%) 22 (0.11) 4,052 (2.34) P<0.001 Barrett esophagus (%) 15 (0.07) 3,207 (1.85) P<0.001 Achalasia (%) 1 (0.00) 214 (0.12) P<0.001 Stricture (%) 33 (0.16) 2,299 (1.33) P<0.001 Esophageal adenocarcinoma (%) 3 (0.01) 291 (0.17) P<0.001 Years of follow-up (IQR) 5.00 (5.00, 5.00) 5.00 (5.00, 5.00) P<0.001 Days of having related prescription during follow-up (IQR) 90 (30, 270) 450 (90, 1260) P<0.001 IQR, interquartile range.
Outcome H2 Blockers (n=20,270) PPI (n=173,321) Incident eGFR<60 ml/min per 1.73 m2 Number of events (%) 4,429 (21.85) 48,171 (27.79) Incident rate (95% CI) 5408.24 (5248.96 to 5567.52) 7241.27 (7176.61 to 7305.94) HR (95% CI) 1.0 1.22 (1.18 to 1.26) Incident chronic kidney disease Number of events (%) 2,234 (11.02) 26,193 (15.11) Incident rate (95% CI) 2569.86 (2463.30 to 2676.43) 3683.12 (3638.52 to 3727.72) HR (95% CI) 1.0 1.28 (1.23 to 1.34) Incident rate as incident per 100,000 person-years.
HRs were obtained from Cox models adjusted for baseline eGFR, age, race, sex, diabetes mellitus, hypertension, cardiovascular disease, peripheral artery disease, cerebrovascular disease, chronic lung disease, hepatitis C, HIV, dementia, gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, H. pylori infection, Barrett esophagus, achalasia, stricture, and esophageal adenocarcinoma.
Outcome H2 Blockers (n=20,270) PPI (n=173,321) Doubling of serum creatinine Number of events (%) 759 (3.74) 10,766 (6.21) Incident rate (95% CI) 816.98 (758.86 to 875.10) 1387.02 (1360.81 to 1413.22) HR (95% CI) 1.0 1.53 (1.42 to 1.65) >30% decline in eGFR Number of events (%) 3,949 (19.48) 43,842 (25.30) Incident rate (95% CI) 4533.25 (4391.86 to 4674.64) 6170.27 (6112.51 to 6228.03) HR (95% CI) 1.0 1.32 (1.28 to 1.37) ESRD Number of events (%) 25 (0.12) 329 (0.19) Incident rate (95% CI) 26.50 (16.11 to 36.88) 41.25 (36.79 to 45.70) HR (95% CI) 1.0 1.96 (1.21 to 3.18) ESRD or >50% decline in eGFR Number of events (%) 947 (4.67) 12,952 (7.47) Incident rate (95% CI) 1024.27 (959.03 to 1089.51) 1679.40 (1650.48 to 1708.32) HR (95% CI) 1.0 1.47 (1.38 to 1.57) Incident rate as incident per 100,000 person-years.
HRs were obtained from Cox models adjusted for baseline eGFR, age, race, sex, diabetes mellitus, hypertension, cardiovascular disease, peripheral artery disease, cerebrovascular disease, chronic lung disease, hepatitis C, HIV, dementia, gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, H. pylori infection, Barrett esophagus, achalasia, stricture, and esophageal adenocarcinoma.
- Table 4.
Duration of exposure to PPI and risk of renal outcomes among new users of PPI (n=173,321)
Duration Less or Equal to 30 Days 31–90 Days 91–180 Days 181–360 Days 361–720 Days >720 days Incident eGFR<60 ml/min per 1.73 m2 n (%) 25,912 (14.95) 31,192 (18.00) 18,889 (10.90) 20,770 (11.98) 23,446 (13.53) 53,112 (30.64) HR (95% CI) 1 1.94 (1.88 to 2.00) 2.30 (2.22 to 2.39) 2.65 (2.56 to 2.74) 2.75 (2.66 to 2.85) 1.95 (1.87 to 2.02) Incident CKD n (%) 23,621 (13.63) 29,886 (17.24) 18,338 (10.58) 20,148 (11.62) 23,293 (13.44) 58,035 (33.48) HR (95% CI) 1 1.82 (1.74 to 1.89) 2.00 (1.91 to 2.10) 2.16 (2.06 to 2.26) 1.96 (1.87 to 2.06) 0.84 (0.79 to 0.89) Doubling of serum creatinine n (%) 19,602 (11.31) 27,234 (15.71) 16,989 (9.80) 19,116 (11.03) 23,603 (13.62) 66,777 (38.53) HR (95% CI) 1 1.22 (1.13 to 1.30) 1.50 (1.39 to 1.62) 1.74 (1.61 to 1.87) 1.99 (1.85 to 2.14) 1.47 (1.37 to 1.59) >30% decline in eGFR n (%) 22,751 (13.13) 29,291 (16.90) 18,209 (10.51) 20,444 (11.80) 24,371 (14.06) 58,255 (33.61) HR (95% CI) 1 1.76 (1.70 to 1.83) 2.31 (2.22 to 2.40) 2.87 (2.76 to 2.99) 3.48 (3.34 to 3.61) 3.29 (3.17 to 3.42) ESRD n (%) 18,529 (10.69) 26,469 (15.27) 16,649 (9.61) 18,792 (10.84) 23,500 (13.56) 69,382 (40.03) HR (95% CI) 1 1.04 (0.70 to 1.56) 1.80 (1.18 to 2.75) 2.04 (1.33 to 3.12) 3.12 (2.07 to 4.71) 2.25 (1.46 to 3.47) ESRD or >50% decline in eGFR n (%) 19,799 (11.42) 27,349 (15.78) 17,105 (9.87) 19,248 (11.11) 23,695 (13.67) 66,125 (38.15) HR (95% CI) 1 1.23 (1.16 to 1.31) 1.57 (1.47 to 1.69) 1.85 (1.72 to 1.98) 2.13 (1.99 to 2.28) 1.58(1.47 to 1.69) HRs were obtained from Cox models adjusted for PPI duration, baseline eGFR, age, race, sex, diabetes mellitus, hypertension, cardiovascular disease, peripheral artery disease, cerebrovascular disease, chronic lung disease, hepatitis C, HIV, dementia, gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, H. pylori infection, Barrett esophagus, achalasia, stricture, and esophageal adenocarcinoma.
Beginning of follow up (T0) was defined as the date of last use of PPI before event occurrence.
PPI duration was computed between first PPI prescription date and T0.
- Table 5.
Risk of renal events in a 1:1 propensity score-matched cohort of new users of PPI (n=20,270) and new users of H2 blockers (n=20,270)
Outcome H2 Blockers (n=20,270) PPI (n=20,270) Incident eGFR<60 ml/min per 1.73 m2 Number of events (%) 4,429 (21.85) 5,204 (25.67) Incident rate (95% CI) 5408.24 (5249.96 to 5567.52) 6563.33 (6385.01 to 6741.65) HR (95% CI) 1.0 1.23 (1.17 to 1.30) Incident CKD Number of events (%) 2,234 (11.02) 2,776 (13.70) Incident rate (95% CI) 2569.86 (2463.30 to 2676.43) 3294.88 (3172.31 to 3417.44) HR (95% CI) 1.0 1.28 (1.18 to 1.38) Doubling of serum creatinine Number of events (%) 759 (3.74) 1,185 (5.85) Incident rate (95% CI) 816.98 (758.86 to 875.10) 1300.96 (1226.89 to 1375.03) HR (95% CI) 1.0 1.63 (1.47 to 1.81) >30% decline in eGFR Number of events (%) 3,949 (19.48) 4,762 (23.49) Incident rate (95% CI) 4533.25 (4391.86 to 4674.64) 5669.45 (5508.42 to 5830.47) HR (95% CI) 1.0 1.32 (1.25 to 1.39) ESRD Number of events (%) 25 (0.12) 38 (0.19) Incident rate (95% CI) 26.50 (16.11 to 36.88) 40.69 (27.75 to 53.63) HR (95% CI) 1.0 1.48 (0.49 to 4.50) ESRD or >50% decline in eGFR Number of events (%) 947 (4.67) 1433 (7.07) Incident rate (95% CI) 1024.27 (959.03 to 1089.51) 1582.80 (1500.85 to 1664.75) HR (95% CI) 1.0 1.59 (1.45 to 1.74) Incident rate as incident per 100,000 person-years.
HRs were obtained from Cox models adjusted for baseline eGFR, age, race, sex, diabetes mellitus, hypertension, cardiovascular disease, peripheral artery disease, cerebrovascular disease, chronic lung disease, hepatitis C, HIV, dementia, gastroesophageal reflux disease, upper GI tract bleeding, ulcer disease, H. pylori infection, Barrett esophagus, achalasia, stricture, and esophageal adenocarcinoma.
- Table 6.
Risk of renal events in a 1:1 propensity matched cohort of new PPI users (173,321) and a control group (n=173,321)
Outcome Control (n=173,321) PPI (n=173,321) Incident eGFR<60 ml/min per 1.73 m2 Number (%) 35,759 (20.63) 48,171 (27.79) Incident rate (95% CI) 5105.97 (5053.05 to 5158.90) 7241.27 (7176.61 to 7305.93) HR (95% CI) 1.0 1.57 (1.54 to 1.60) Incident CKD Number (%) 17,426 (10.05) 26,193 (15.11) Incident rate (95% CI) 2359.99 (2323.96 to 2394.01) 3683.12 (3638.52 to 3727.72) HR (95% CI) 1.0 1.81 (1.76 to 1.86) Doubling of serum creatinine Number (%) 6,039 (3.48) 10,766 (6.21) Incident rate (95% CI) 770.38 (750.95 to 789.81) 1387.02 (1360.81 to 1413.22) HR (95% CI) 1.0 1.86 (1.80 to 1.93) >30% decline in eGFR Number (%) 31,781 (18.34) 43,842 (25.30) Incident rate (95% CI) 4255.67 (4208.88 to 4302.46) 6170.27 (6112.51 to 6228.03) HR (95% CI) 1.0 1.67 (1.64 to 1.70) ESRD Number (%) 219 (0.13) 329 (0.19) Incident rate (95% CI) 27.60 (23.94 to 31.25) 41.25 (36.79 to 45.70) HR (95% CI) 1.0 1.61 (1.26 to 2.04) ESRD or >50% decline in eGFR Number (%) 7,410 (4.28) 12,952 (7.47) Incident rate (95% CI) 949.13 (927.52 to 970.74) 1679.40 (1650.48 to 1708.32) HR (95% CI) 1.0 1.83 (1.77 to 1.89) Incident rate as incident per 100,000 person-years.
HRs were obtained from Cox models adjusted for baseline eGFR, age, race, sex, diabetes mellitus, hypertension, cardiovascular disease, peripheral artery disease, cerebrovascular disease, chronic lung disease, hepatitis C, HIV, dementia, gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, H. pylori infection, Barrett esophagus, achalasia, stricture, and esophageal adenocarcinoma.
- Table 7.
Risk of renal events in models additionally adjusted for AKI during exposure to acid-suppression therapy
Outcome H2 Blockers (n=20,270) PPI (n=173,321) Incident eGFR<60 ml/min per 1.73 m2 Number of patients with AKI during exposure to acid-suppression therapy (%) 690 (3.40) 10,903 (6.29) HR (95% CI) 1 1.20 (1.16 to 1.24) Incident CKD Number of patients with AKI during exposure to acid-suppression therapy (%) 710 (3.50) 12,170 (7.02) HR (95% CI) 1 1.28 (1.22 to 1.34) Doubling of serum creatinine Number of patients with AKI during exposure to acid-suppression therapy (%) 749 (3.70) 14,620 (8.44) HR (95% CI) 1 1.42 (1.32 to 1.54) >30% decline in eGFR Number of patients with AKI during exposure to acid-suppression therapy (%) 720 (3.55) 11,797 (6.81) H R (95% CI) 1 1.28 (1.24 to 1.33) ESRD Number of patients with AKI during exposure to acid-suppression therapy (%) 760 (3.75) 16,063 (9.27) HR (95% CI) 1 1.79 (1.10 to 2.89) ESRD or >50% decline in eGFR Number of patients with AKI during exposure to acid-suppression therapy (%) 748 (3.69) 14,293 (8.25) HR (95% CI) 1 1.38 (1.29 to 1.47) HRs were obtained from Cox models adjusted for AKI during exposure to acid-suppression therapy, baseline eGFR, age, race, sex, diabetes mellitus, hypertension, cardiovascular disease, peripheral artery disease, cerebrovascular disease, chronic lung disease, hepatitis C, HIV, dementia, gastroesophageal reflux disease, upper gastrointestinal tract bleeding, ulcer disease, H. pylori infection, Barrett esophagus, achalasia, stricture, and esophageal adenocarcinoma.
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