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Original ArticlesAcute Kidney Injury /Acute Renal Failure
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Predictors of Death and Dialysis in Severe AKI: The UPHS-AKI Cohort

Francis Perry Wilson, Wei Yang and Harold I. Feldman
CJASN April 2013, 8 (4) 527-537; DOI: https://doi.org/10.2215/CJN.06450612
Francis Perry Wilson
*Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania. Philadelphia, Pennsylvania;
‡Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Wei Yang
‡Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
†Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and
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Harold I. Feldman
*Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania. Philadelphia, Pennsylvania;
‡Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
†Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and
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    Figure 1.

    Rates of dialysis, death, and the combined endpoint in the full cohort (n=6119). Patients initiated on dialysis are considered to be AKIN stage 3 at initiation. Patient-days are analyzed distinctly, allowing patients to contribute to multiple AKIN stages. AKIN, Acute Kidney Injury Network.

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    Table 1.

    Baseline characteristics and unadjusted analyses of patients in the derivation and validation cohorts

    CharacteristicDerivation Cohort HUP (n=4263)Validation PAH (n=758)Validation PMC (n=1098)P Value
    HUP versus PAHHUP versus PMC
    Male sex2366 (55.5)332 (43.8)561 (51.1)<0.0010.01
    Black1011 (23.7)238 (31.4)445 (40.5)<0.001<0.001
    Surgical service2355 (55.2)278 (36.7)217 (19.8)<0.001<0.001
    HIV/AIDS63 (1.5)33 (4.4)46 (4.2)<0.001<0.001
    Malignancy408 (9.6)144 (19.0)135 (12.3)<0.0010.01
    Congestive heart failure1478 (34.7)239 (31.5)501 (45.6)0.09<0.001
    Cardiovascular disease433 (10.2)49 (6.5)121 (11.0)0.0010.40
    Dementia22 (0.5)7 (0.9)31 (2.8)0.17<0.001
    Diabetes mellitus1037 (24.3)227 (29.9)388 (35.3)0.001<0.001
    Hemiplegia1112 (2.6)19 (2.5)22 (2.0)0.840.24
    Metastatic solid tumor399 (9.4)89 (11.7)65 (5.9)0.04<0.001
    Myocardial infarction538 (12.6)109 (14.4)219 (19.9)0.18<0.001
    Liver disease847 (19.9)102 (13.5)140 (12.8)<0.001<0.001
    Pulmonary disease302 (7.1)195 (25.7)414 (37.7)<0.001<0.001
    Peripheral vascular disease594 (13.9)94 (12.4)167 (15.2)0.260.28
    Rheumatic disease124 (2.9)31 (4.1)41 (3.7)0.080.16
    Peptic ulcer disease113 (2.7)17 (2.2)27 (2.5)0.520.72
    Age (SD)59.1 (16.3)64.0 (16.5)65.6 (14.9)<0.001<0.001
    Baseline creatinine, mg/dl (SD)0.80 (0.26)0.79 (0.26)0.84 (0.26)0.35<0.001
    Hospital stay before AKI (d), median (IQR)3 (2–8)3 (2–7)3 (1–6)0.26<0.001
    Onset of AKI to doubling of creatinine (d), median (IQR)1 (0–2)1 (0–1)1 (0–2)<0.0010.15
    Time from AKI to RRT( d), median (IQR)a4 (1–9)6 (2–9)3.5 (1–9)0.090.39
    • Data expressed as n (%) except where noted. HUP, Hospital of the University of Pennsylvania; PAH, Pennsylvania Hospital; PMC, Presbyterian Medical Center; RRT, renal replacement therapy.

    • ↵a Among patients receiving RRT.

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    Table 2.

    Intention-to-treat Cox proportional hazards model of associations between key covariates and time to initiation of dialytic therapy

    CovariateUnivariable Analysis, Derivation CohortParsimonious Multivariable Model, Derivation CohortShort Multivariable Model, Derivation Cohort
    HR (95% CI)P Value HR (95% CI)P Value HR (95% CI)P Value
    Demographics
     Age (per 10 yr)0.96 (0.90–1.02)0.20
     Male sex1.52 (1.20–1.92)0.001
     Black (versus other races)0.53 (0.39–0.74)<0.0010.63 (0.46–0.86)0.004
    Hospital location
     Surgical service (versusmedical service)1.05 (0.83–1.33)0.660.70 (0.55–0.90)0.01
     ICU (versus other hospital location)5.68 (4.55–7.09)<0.0011.93 (1.52–2.45)<0.0012.98 (2.35–3.78)<0.001
    Comorbidities (present at admission)
     HIV0.15 (0.03–0.76)0.02
     Congestive heart failure1.19 (0.95–1.50)0.13
     Diabetes1.06 (0.82–1.37)0.641.27 (1.00–1.62)0.05
     Liver disease3.70 (2.95–4.63)<0.0012.45 (1.94–3.09)<0.0012.75 (2.18–3.47)<0.001
     Malignancy0.72 (0.46–1.11)0.14
     Metastatic solid tumor0.86 (0.53–1.42)0.56
     Myocardial infarction1.13 (0.82–1.55)0.46
     Peptic ulcer disease2.15 (1.32–3.50)0.002
     Peripheral vascular disease1.10 (0.81–1.49)0.54
     Pulmonary disease0.73 (0.45–1.20)0.22
    Laboratory values
     Baseline creatinine (per 0.1 mg/dl)1.19 (1.14–1.24)<0.001
     Bicarbonate (per mEq/L)0.86 (0.84–0.88)<0.0010.95 (0.93–0.98)<0.001
     BUN (per 10 mg/dl)1.27 (1.24–1.30)<0.0011.07 (1.03–1.10)<0.001
     Change in creatinine from day prior (per 0.1 mg/dl)1.09 (1.08–1.11)<0.0011.02 (1.02–1.03)<0.0011.02 (1.01–1.03)<0.001
     Creatinine (per mg/dl)1.86 (1.75–1.99)<0.0011.53 (1.41–1.67)<0.0011.64 (1.54–1.76)<0.001
     Potassium (per mEq/L)2.08 (1.94–2.23)<0.0011.27 (1.16–1.40)<0.0011.35 (1.23–1.48)<0.001
    Medications
     Number of sedatives (per drug)1.81 (1.68–1.94)<0.0011.14 (1.04–1.26)0.01
     Prior aminoglycoside exposure1.20 (0.95–1.53)0.13
     Number of antibiotics (per drug)1.42 (1.35–1.49)<0.0011.12 (1.06–1.19)<0.001
     Number of pressors (per drug)2.12 (1.98–2.26)<0.0011.28 (1.18–1.40)<0.0011.44 (1.33–1.55)<0.001
     Paralytic exposure4.55 (3.50–5.92)<0.0011.40 (1.03–1.90)0.03
     Thiazide diuretic2.25 (1.83–2.76)<0.0011.63 (1.33–2.00)<0.001
    Other orders
     Ventilated3.71 (3.07–4.49)<0.0011.22 (0.99–1.51)0.06
    • n=35,462 patient-days, 3951 patients, and 471 outcome events. Data were censored at discharge, death, or 14 days from the onset of AKI, whichever came first. Data excludes patient-days after placement of a do not resuscitate order. HR, hazard ratio; CI, confidence interval; ICU, intensive care unit.

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    Table 3.

    Intention-to-treat Cox proportional hazards model of associations between key covariates and time to all-cause mortality

    CovariateUnivariable Analysis, Derivation CohortParsimonious Multivariable Model, Derivation CohortShort Multivariable Model, Derivation Cohort
    HR (95% CI)P ValueHR (95% CI)P Value HR (95% CI)P Value
    Demographics
     Age (per 10 yr)1.05 (0.99–1.12)0.081.11 (1.04–1.19)0.003
     Male sex1.19 (0.99–1.43)0.06
     Black (versus other races)0.70 (0.55–0.89)0.0030.81 (0.63–1.03)0.09
    Hospital location
     Surgical service (versus medical service)0.51 (0.42–0.61)<0.0010.39 (0.32–0.47)<0.0010.36 (0.30–0.43)<0.001
     ICU (versus other hospital location)4.39 (3.70–5.21)<0.0012.07 (1.69–2.53)<0.0012.97 (2.46–3.59)<0.001
    Comorbidities (present at admission)
     HIV0.87 (0.36–2.09)0.75
     Congestive heart failure0.93 (0.77–1.12)0.450.80 (0.65–0.99)0.04
     Diabetes0.75 (0.59–0.94)0.01
     Liver disease1.90 (1.56–2.32)<0.0011.48 (1.21–1.81)<0.001
     Malignancy1.91 (1.47–2.48)<0.0011.31 (0.99–1.73)0.06
     Metastatic solid tumor2.64 (2.06–3.40)<0.0012.18 (1.67–2.84)<0.0012.79 (2.16–3.61)<0.001
     Myocardial infarction1.13 (0.87–1.48)0.35
     Peptic ulcer disease1.23 (0.71–2.12)0.46
     Peripheral vascular disease1.02 (0.78–1.33)0.91
     Pulmonary disease0.95 (0.92–0.99)0.02
    Laboratory values
     Baseline creatinine (per 0.1 mg/dl)1.04 (1.00–1.08)0.05
     Bicarbonate (per mEq/L)0.88 (0.86–0.89)<0.0010.95 (0.93–0.97)<0.001
     BUN (per 10 mg/dl)1.18 (1.16–1.21)<0.0011.14 (1.10–1.18)<0.0011.12 (1.09–1.15)<0.001
     Change in creatinine from day prior (per 0.1 mg/dl)1.06 (1.05–1.07)<0.0011.05 (1.04–1.06)<0.0011.05 (1.04–1.05)<0.001
     Creatinine (per mg/dl)1.31 (1.24–1.39)<0.0010.81 (0.73–0.90)<0.001
     Potassium (per mEq/L)1.70 (1.57–1.83)<0.0011.16 (1.06–1.26)0.001
    Medications
     Number of sedatives (per drug)1.69 (1.59–1.79)<0.001
     Prior aminoglycoside exposure0.92 (0.74–1.13)0.420.77 (0.61–0.96)0.01
     Number of antibiotics (per drug)1.42 (1.36–1.48)<0.0011.08 (1.02–1.14)0.01
     Number of pressors (per drug)1.83 (1.72–1.94)<0.0011.38 (1.26–1.50)<0.0011.55 (1.43–1.67)<0.001
     Paralytic exposure4.60 (3.64–5.80)<0.0011.95 (1.53–2.50)<0.001
     Thiazide diuretic0.67 (0.52–0.87)0.0020.60 (0.47–0.78)<0.001
    Other orders
     Ventilated3.65 (3.12–4.27)<0.0011.43 (1.20–1.70)<0.001
    • n=35,028 patient-days, 3901 patients, and 778 outcome events. Data were censored at 14 days from the onset of AKI or August 31, 2010, whichever came first. Data excludes patient-days after initiation of dialysis or placement of a do not resuscitate order. HR, hazard ratio; CI, confidence interval; ICU, intensive care unit.

    • View popup
    Table 4.

    Intention-to-treat Cox proportional hazards model of associations between key covariates and time to all-cause mortality or initiation of dialysis

    CovariateUnivariable Analysis, Derivation CohortParsimonious Multivariable Model, Derivation CohortShort Multivariable Model, Derivation Cohort
    HR (95% CI)P Value HR (95% CI)P Value HR (95% CI)P Value
    Demographics
     Age (per 10 yr)1.01 (0.96–1.06)0.891.05 (0.99–1.11)0.08
     Male sex1.31 (1.12–1.54)0.001
     Black (versus other races)0.60 (0.49–0.74)<0.0010.68 (0.55–0.84)<0.001
    Hospital location
     Surgical service (versus medical service)0.68 (0.58–0.79)<0.0010.48 (0.41–0.57)<0.0010.45 (0.39–0.53)<0.001
     ICU (versus other hospital location)4.82 (4.16–5.57)<0.0011.91 (1.61–2.27)<0.0013.12 (2.67–3.65)<0.001
    Comorbidities (present at admission)
     HIV0.47 (0.20–1.08)0.22
     Congestive heart failure1.07 (0.91–1.25)0.370.86 (0.73–1.02)0.08
     Diabetes0.93 (0.77–1.11)0.23
     Liver disease2.61 (2.22–3.07)<0.0011.92 (1.63–2.27)<0.0012.12 (1.81–2.50)<0.001
     Malignancy1.35 (1.06–1.72)0.01
     Metastatic solid tumor1.78 (1.40–2.26)<0.0011.67 (1.31–2.13)<0.001
     Myocardial infarction1.13 (0.91–1.42)0.33
     Peptic ulcer disease1.61 (1.08–2.39)0.02
     Peripheral vascular disease1.11 (0.89–1.37)0.61
     Pulmonary disease0.82 (0.59–1.13)0.25
    Laboratory values
     Baseline creatinine (per 0.1 mg/dl)1.11 (1.07–1.14)<0.001
     Bicarbonate (per mEq/L)0.87 (0.85–0.88)<0.0010.96 (0.94–0.97)<0.001
     BUN (per 10 mg/dl)1.23 (1.21–1.26)<0.0011.09 (1.06–1.12)<0.001
     Change in creatinine from day prior (per 0.1 mg/dl)1.08 (1.07–1.10)<0.0011.04 (1.03–1.04)<0.0011.04 (1.03–1.05)<0.001
     Creatinine (per mg/dl)1.66 (1.58–1.76)<0.0011.26 (1.17–1.35)<0.0011.42 (1.35–1.50)<0.001
     Potassium (per mEq/L)1.92 (1.81–2.03)<0.0011.24 (1.16–1.33)<0.001
    Medications
     Number of sedatives (per drug)1.73 (1.64–1.82)<0.0011.08 (1.01–1.16)0.02
     Prior aminoglycoside exposure1.03 (0.86–1.22)0.83
     Number of antibiotics (per drug)1.42 (1.37–1.47)<0.0011.09 (1.05–1.14)<0.001
     Number of pressors (per drug)1.98 (1.88–2.09)<0.0011.32 (1.24–1.42)<0.0011.52 (1.44–1.61)<0.001
     Paralytic exposure4.39 (3.60–5.34)<0.0011.61 (1.30–1.99)<0.001
     Thiazide diuretic1.35 (1.13–1.61)0.002
    Other orders
     Ventilated3.62 (3.17–4.14)<0.0011.34 (1.15–1.56)<0.001
    • n=35,462 patient-days, 3951 patients, and 1031 outcome events. Data censored at 14 days from the onset of AKI or August 31, 2010, whichever came first. Data exclude patient-days after placement of a do not resuscitate order. HR, hazard ratio; CI, confidence interval; ICU, intensive care unit.

    • View popup
    Table 5.

    c-statistics for derivation and validation cohorts, stratified by outcome of prediction

    Parsimonious Model
(95% CI)Short Model
(95% CI)P Value (Short versus Parsimonious)
    Dialysis
     Derivation cohort (HUP 2004–2010)0.89 (0.88–0.91)0.88 (0.87–0.89)<0.001a
     Validation (PAH 2006–2010)0.89 (0.85–0.93)0.89 (0.85–0.93)0.48
     Validation (PMC 2004–2010)0.89 (0.86–0.92)0.88 (0.85–0.91)0.23
    Death
     Derivation cohort (HUP 2004–2010)0.83 (0.82–0.84)0.80 (0.79–0.81)<0.001a
     Validation (PAH 2006–2010)0.83 (0.80–0.86)0.79 (0.76–0.83)<0.001
     Validation (PMC 2004–2010)0.82 (0.79–0.85)0.79 (0.75–0.82)<0.001
    Dialysis or death
     Derivation cohort (HUP 2004–2010)0.85 (0.84–0.86)0.82 (0.81–0.83)<0.001a
     Validation (PAH 2006–2010)0.83 (0.80–0.86)0.77 (0.73–0.80)<0.001
     Validation (PMC 2004–2010)0.84 (0.82–0.86)0.80 (0.78–0.83)<0.001
    • P value reflects difference in predictive ability between short and parsimonious models. CI, confidence interval; HUP, Hospital of the University of Pennsylvania; PAH, Pennsylvania Hospital; PMC, Presbyterian Medical Center.

    • ↵a P values may be unreliable in cohort from which model was derived

    • View popup
    Table 6.

    Intention-to-treat Cox proportional hazards model of associations between key covariates and time to all-cause mortality or initiation of dialysis based on covariates measured on the day creatinine doubled from baseline (AKIN stage 2 criteria)

    CovariateUnivariable Analysis, Derivation CohortParsimonious Multivariable Model, Derivation CohortShort Multivariable Model, Derivation Cohort
    HR (95% CI)P ValueHR (95% CI)P ValueHR (95% CI)P Value
    Demographics
     Age (per 10 yr)1.00 (0.96–1.04)0.98
     Male sex1.33 (1.17–1.52)<0.001
     Black (versus other races)0.64 (0.55–0.76)<0.0010.80 (0.67–0.95)0.01
    Hospital location
     Surgical service (versus medical service)0.82 (0.72–0.93)0.0020.57 (0.49–0.66)<0.0010.64 (0.55–0.74)<0.001
     ICU (versus other hospital location)4.48 (3.86–5.19)<0.0011.82 (1.51–2.20)<0.001
    Comorbidities (present at admission)
     HIV0.64 (0.33–1.22)0.17
    Congestive heart failure1.17 (1.03–1.33)0.020.88 (0.76–1.01)0.06
     Diabetes0.85 (0.73–0.99)0.04
     Liver disease2.37 (2.08–2.69)<0.0011.60 (1.39–1.85)<0.0011.61 (1.40–1.86)<0.001
     Malignancy1.47 (1.22–1.78)<0.001
     Metastatic solid tumor1.57 (1.31–1.89)<0.0011.58 (1.25–2.01)<0.001
     Myocardial infarction1.28 (1.07–1.52)<0.001
     Peptic ulcer disease1.73 (1.27–2.34)<0.001
     Peripheral vascular disease1.18 (1.00–1.40)0.06
     Pulmonary disease0.84 (0.65–1.09)0.19
    Laboratory values
     Baseline creatinine (per 0.1 mg/dl)1.12 (1.10–1.14)<0.001
     Bicarbonate (per mEq/L)0,86 (0,85–0.87)<0.0010.93 (0.92–0.95)<0.0010.91 (0.89–0.92)<0.001
     BUN (per 10 mg/dl)1.17 (1.15–1.20)<0.0011.12 (1.09–1.15)<0.0011.15 (1.12–1.18)<0.001
     Change in creatinine from day prior (per 0.1 mg/dl)1.05 (1.04–1.06)<0.0011.03 (1.02–1.04)<0.0011.03 (1.02–1.04)<0.001
     Creatinine (per mg/dl)1.58 (1.44–1.73)<0.001
     Potassium (per mEq/L)1.80 (1.69–1.91)<0.0011.23 (1.13–1.33)<0.001
    Medications
     Number of sedatives (per drug)1.66 (1.57–1.74)<0.001
     Prior aminoglycoside exposure1.19 (1.03–1.38)0.02
     Number of antibiotics (per drug)1.39 (1.34–1.44)<0.0011.07 (1.02–1.12)0.003
     Number of pressors (per drug)1.87 (1.78–1.97)<0.0011.34 (1.25–1.44)<0.0011.69 (1.59–1.80)<0.001
     Paralytic exposure3.53 (2.89–4.30)<0.0011.48 (1.19–1.85)<0.001
     Thiazide diuretic1.17 (0.98–1.40)0.09
    Other orders
     Ventilated3.78 (3.33–4.28)<0.0011.58 (1.35–1.86)<0.001
    • n=3848 patient-days, 3848 patients, and 954 outcome events. Data were censored at 14 days from the onset of AKI or August 31, 2010, whichever came first. AKIN, Acute Kidney Injury Network; HR, hazard ratio; CI, confidence interval; ICU, intensive care unit.

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Clinical Journal of the American Society of Nephrology: 8 (4)
Clinical Journal of the American Society of Nephrology
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April 05, 2013
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Predictors of Death and Dialysis in Severe AKI: The UPHS-AKI Cohort
Francis Perry Wilson, Wei Yang, Harold I. Feldman
CJASN Apr 2013, 8 (4) 527-537; DOI: 10.2215/CJN.06450612

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Predictors of Death and Dialysis in Severe AKI: The UPHS-AKI Cohort
Francis Perry Wilson, Wei Yang, Harold I. Feldman
CJASN Apr 2013, 8 (4) 527-537; DOI: 10.2215/CJN.06450612
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