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Manuscript title: Acute kidney injury development and impact on clinical and economic outcomes in patients with cirrhosis: an observational cohort study over a 10-year period

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Manuscript title: Acute kidney injury development and impact on clinical and economic outcomes in patients with cirrhosis: an observational cohort study over a 10-year period

Supplementary Table 1: Comorbid conditions among study subjects by AKI status

Comorbidity Total Sample With AKI Without AKI P value

N= 380 n= 106 (27.9%) n= 274 (72.1%)

Myocardial infarction 1 (0.26) 0 (0.0) 1 (0.36) 0.533

Congestive heart failure 22 (5.79) 9 (8.49) 13 (4.74) 0.161

Peripheral vascular disease 0 (0.0) 0 (0.0) 0 (0.0) Cerebrovascular accident or transient

Ischemic attacks 12 (3.16) 5 (4.72) 7 (2.55) 0.28

Dementia 0 (0.0) 0 (0.0) 0 (0.0)

Chronic obstructive pulmonary disease 6 (1.58) 2 (1.89) 4 (1.46) 0.765

Connective tissue disease 0 (0.0) 0 (0.0) 0 (0.0)

Peptic ulcer disease 0 (0.0) 0 (0.0) 0 (0.0)

Diabetes mellitus 180 (47.37) 63 (59.43) 117 (42.70) 0.003

Hemiplegia 1 (0.26) 0 (0.0) 1 (0.36) 0.533

Chronic kidney disease 15 (3.95) 6 (5.66) 9 (3.28) 0.286

Solid tumor 21 (5.53) 8 (7.55) 13 (4.74) 0.284

Leukemia 2 (0.53) 0 (0.0) 2 (0.73) 0.378

Lymphoma 0 (0.0) 0 (0.0) 0 (0.0)

AIDS 0 (0.0) 0 (0.0) 0 (0.0)

Charlson Comorbidity Index* 5.66 ± 2.11 6.48 ± 2.20 5.35 ± 1.99 <0.001 Data are presented as n (%) unless otherwise indicated

*Data are presented as mean ± standard deviation

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Supplementary Table 2: The frequency of prescription per the total number of admissions for selected medications in cirrhosis

Medication % of total

admissions#

Lanzoprazole capsule 89.5

Furosemide tab 71.6

Spironolactone tab 67.1

Lactulose syrup 63.2

Human albumin 20% 51.3

Propranolol tab 38.7

Omeprazole inj 36.6

Ceftriaxone inj 30.5

Carvidolol tab 31.5

Ciprofloxacin tab 25.5

Furosemide injection 24.7

Piperacilin+Tazobactam inj 20.5

Metronidazole tab 18.9

Octreotide inj 10.3

Metronidazole inj 8.2

Isosorbide dinitrate 7.6

Cefotaxime inj 2.4

#The total number of admissions was 380.

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Supplementary Table 3: Patients demographics and clinical characteristics by discharge status (death vs alive)

Variable Total Sample Death Alive P value

N= 380 n= 72 (18.9%) n= 308 (81.1%)

Age 59.42 ± 19.88 63.56 ± 17.22 58.45 ± 20.36 0.049

Older adults (65 years or

older)* 161 (42.37) 36 (50.0) 125(40.58) 0.145

Gender* 0.932

Male 197 (51.84) 37 (51.39) 160 (51.95)

Female 183 (48.16) 35 (48.61) 148 (48.05)

Body mass index (Kg/m2) 29.10 ± 7.35 29.02 ± 7.89 29.11 ± 7.26 0.9444

Smoking Status* 0.755

Smoker 79 (20.79) 14 (19.44) 65 (21.10)

Non-smoker 301 (79.21) 58 (80.56) 243 (78.90)

Baseline serum creatinine

(mg/dl) 1.16 ± 0.75 1.41 ± 0.86 1.10 ± 0.72 0.001

Length of hospital stay

(median (IQR), days) 4 (2-8) 8 (3-12.5) 3 (2-7) <0.001

AKI* 106 (27.89) 55 (76.39) 51 (16.56) <0.001

Hospital complications*

ICU Transfer 28 (7.37) 28 (38.89) 0 (0.0) <0.001

Hospital acquired

infection 11 (2.89) 6 (8.33) 5 (1.62) 0.002

Acid-base disturbance 96 (25.26) 47 (65.28) 49 (15.91) <0.001 Sodium abnormalities 116 (30.53) 45 (62.50) 71(23.05) <0.001 Potassium abnormalities 87 (22.89) 37 (51.39) 50 (16.23) <0.001 Calcium abnormalities 68 (17.89) 20 (27.78) 48 (15.58) 0.015 Phosphorus abnormalities 53 (13.95) 27 (37.50) 26 (8.44) <0.001 Magnesium abnormalities 27 (7.11) 10 (13.89) 17 (5.52) 0.013

Needs for RRT* 18 (4.7) 5 (6.94) 13 (4.22) 0.327

Comorbidities*

Myocardial infarction 1 (0.26) 1 (1.39) 0 (0.0) 0.038

Congestive heart failure 22 (5.79) 5 (6.94) 17 (5.52) 0.641 Peripheral vascular

disease 0 (0.0) 0 (0.0) 0 (0.0)

Cerebrovascular accident or transient ischemic

attacks 12 (3.16) 2 (2.78) 10 (3.25) 0.838

Dementia 0 (0.0) 0 (0.0) 0 (0.0)

Chronic obstructive

pulmonary disease 6 (1.58) 2 (2.78) 4 (1.3) 0.365

Connective tissue disease 0 (0.0) 0 (0.0) 0 (0.0)

Peptic ulcer disease 0 (0.0) 0 (0.0) 0 (0.0)

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Diabetes mellitus 180 (47.37) 34 (47.22) 146 (47.40) 0.978

Hemiplegia 1 (0.26) 0 (0.0) 1 (0.32) 0.628

Chronic kidney disease 15 (3.95) 5 (6.94) 10 (3.25) 0.147

Solid tumor 21 (5.53) 6 (8.33) 15 (4.87) 0.247

Leukemia 2 (0.53) 0 (0.0) 2 (0.65) 0.493

Lymphoma 0 (0.0) 0 (0.0) 0 (0.0)

AIDS 0 (0.0) 0 (0.0) 0 (0.0)

Charlson Comorbidity

Index 5.66 ± 2.11 6.16 ± 2.22 5.54 ± 2.07 0.025

Cirrhosis duration 3.52 ± 4.46 2.67 ± 2.62 3.71 ± 4.75 0.092 Cirrhosis complications*

Ascites 277 (72.89) 56 (77.78) 221 (71.75) 0.3

Portal Hypertension 346 (91.05) 63 (87.50) 283 (91.88) 0.241 Hepatic Encephalopathy 249 (65.53) 50 (69.44) 199 (64.61) 0.437 Spontaneous Bacterial

Peritonitis (SBP) 54 (14.21) 13 (18.06) 41 (13.31) 0.299

Varices 255 (67.11) 40 (55.56) 215 (69.81) 0.021

Cirrhosis etiology*

Hepatitis B 65 (17.11) 14 (19.44) 51 (16.56) 0.558

Hepatitis C 50 (13.16) 15 (20.83) 35 (11.36) 0.032

Nonalcoholic

steatohepatitis 40 (10.53) 5 (6.94) 35(11.36) 0.271

Cirrhosis severity scores

Child Pugh Score 8.60 ± 2.08 9.92 ± 1.56 8.30 ± 2.07 <0.001

MELD-Na 21.81 ± 8.52 30.07 ± 7.5 19.91 ± 7.56 <0.001

Patients’ labs during the admission

Sodium (mmol/l) 135.8 ± 6.14 134.44 ± 7.67 136.11 ± 5.68 0.0383 Potassium (mmol/l) 4.51 ± 0.86 4.83 ± 0.91 4.43 ± 0.83 <0.001 Serum creatinine (mg/dl) 1.49 ± 1.13 2.45 ± 1.36 1.27 ± 0.94 <0.001 Blood urea nitrogen

(mmol/l) 11.53 ± 9.31 19.10 ± 9.88 9.72 ± 8.21 <0.001

Total protein (g/l) 66.08 ± 10.38 60.83 ± 12.10 67.27 ± 9.58 <0.001 Albumin (g/l) 30.82 ± 6.74 27.83 ± 5.64 31.50 ± 6.79 <0.001 Total bilirubin (µmol/l) 85.68 ± 128.14 179.71 ± 223.74 64.17 ± 79.80 <0.001 Direct bilirubin (µmol/l) 61.58 ± 113.82 140.81 ± 200.66 42.38 ± 67.50 <0.001 Alkaline phosphatase (u/l) 269.26 ± 268.67 259.30 ± 234.59 271.56 ± 276.22 0.731 Alanine aminotransferase

(u/l) 38.23 ± 65.55 62.81 ± 122.44 32.47 ± 40.70 <0.001

Aspartate

aminotransferase (u/l) 83.74 ± 206.43 177.18 ± 443.37 61.84 ± 67.36 <0.001 Gamma Glutamyl

Transferase (u/l) 126.11 ± 158.88 92.51 ± 112.63 133.90 ± 166.98 0.049 White blood cells

(*103/mm3) 7.39 ± 5.92 10.35 ± 6.34 6.69 ± 5.60 <0.001

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Red blood cells

(*106/mm3) 3.56 ± 1.41 3.51 ± 2.70 3.58 ± 0.86 0.718

Hemoglobin (g/dl) 10.51 ± 2.14 9.88 ± 2.06 10.66 ± 2.14 0.004 Hematocrit (%) 31.12 ± 7.36 28.78 ± 6.49 31.67 ± 7.46 0.002 Platelets (*103/mm3) 115.86 ± 82.01 122.93 ± 109.74 114.16 ± 73.94 0.416

INR 1.83 ± 1.04 2.24 ± 0.78 1.74 ± 1.07 <0.001

PTT (s) 36.66 ± 11.78 40.33 ± 12.12 35.83 ± 11.57 0.014

PT (s) 22.78 ± 9.72 27.11 ± 8.96 21.76 ± 9.63 < 0.001

D-dimer (μg/ml) 6.67 ± 9.21 7.47 ± 5.74 5.71 ± 12.33 0.593 Last labs during admission

Sodium (mmol/l) 137.35 ± 6.58 140.06 ± 10.70 136.71 ± 4.99 <0.001 Potassium (mmol/l) 4.35 ± 0.74 4.80 ± 1.06 4.24 ± 0.59 <0.001 Serum creatinine (mg/dl) 1.51 ± 1.32 2.99 ± 1.87 1.16 ± 0.85 <0.001 Blood Urea Nitrogen 11.36 ± 10.41 22.59 ± 13.45 8.70 ± 7.39 <0.001 AKI Stage*#

Stage I 74 (69.81) 35 (63.64) 39 (76.47) 0.042

Stage II 19 (17.92) 9 (16.36) 10 (19.61)

Stage III 13 (12.26) 11 (20.00) 2 (3.92)

AKI Source*#

Community acquired 68 (64.15) 33 (60.00) 35 (68.63) 0.497

Hospital acquired 26 (24.53) 14 (25.45) 12 (23.53)

ICU acquired 12 (11.32) 8 (14.55) 4 (7.84)

Abbreviations: AKI: acute kidney injury, MELD-Na: Model for End Stage Liver Disease-sodium score, ICU:

intensive care unit, RTT: renal replacement therapy, INR: international normalized ratio, PTT: partial thromboplastin time, PT: prothrombin time.

Data are presented as mean ± standard deviation or median (interquartile range) unless otherwise indicated

*Data are presented as n (%)

#among AKI patients only

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