Background
Methods
Search strategy
Database | Query |
---|---|
Medline | ("Cystatin C"[Mesh] OR "Cystatin C"[TIAB] OR "Post-gamma-Globulin"[TIAB] OR "Post gamma Globulin"[TIAB] OR "Neuroendocrine Basic Polypeptide"[TIAB] OR "Basic Polypeptide, Neuroendocrine"[TIAB] OR "Cystatin 3"[TIAB] OR "gamma-Trace"[TIAB] OR "gamma Trace"[TIAB]) AND ("Acute Kidney Injury"[Mesh] OR "Acute Kidney Injuries"[TIAB] OR "Kidney Injuries, Acute"[TIAB] OR "Kidney Injury, Acute"[TIAB] OR "Acute Renal Injury"[TIAB] OR "Acute Renal Injuries"[TIAB] OR "Renal Injuries, Acute"[TIAB] OR "Renal Injury, Acute"[TIAB] OR "Renal Insufficiency, Acute"[TIAB] OR "Acute Renal Insufficiencies"[TIAB] OR "Renal Insufficiencies, Acute"[TIAB] OR "Acute Renal Insufficiency"[TIAB] OR "Kidney Insufficiency, Acute"[TIAB] OR "Acute Kidney Insufficiencies"[TIAB] OR "Kidney Insufficiencies, Acute"[TIAB] OR "Acute Kidney Insufficiency"[TIAB] OR "Kidney Failure, Acute"[TIAB] OR "Acute Kidney Failures"[TIAB] OR "Kidney Failures, Acute"[TIAB] OR "Acute Renal Failure"[TIAB] OR "Acute Renal Failures"[TIAB] OR "Renal Failures, Acute"[TIAB] OR "Renal Failure, Acute"[TIAB] OR "Acute Kidney Failure"[TIAB] OR "Acute Kidney Tubule Necrosis"[TIAB]) |
Embase | 'cystatin c'/exp OR 'post-gamma-globulin'/exp OR 'post gamma globulin'/exp OR 'neuroendocrine basic polypeptide'/exp OR 'basic polypeptide, neuroendocrine' OR 'cystatin 3'/exp OR 'gamma-trace'/exp OR 'gamma trace'/exp AND ('acute kidney injuries' OR 'kidney injuries, acute' OR 'kidney injury, acute' OR 'acute renal injury'/exp OR 'acute renal injuries' OR 'renal injuries, acute' OR 'renal injury, acute' OR 'renal insufficiency, acute'/exp OR 'acute renal insufficiencies' OR 'renal insufficiencies, acute' OR 'acute renal insufficiency'/exp OR 'kidney insufficiency, acute'/exp OR 'acute kidney insufficiencies' OR 'kidney insufficiencies, acute' OR 'acute kidney insufficiency'/exp OR 'kidney failure, acute'/exp OR 'acute kidney failures' OR 'kidney failures, acute' OR 'acute renal failure'/exp OR 'acute renal failures' OR 'renal failures, acute' OR 'renal failure, acute' OR 'acute kidney failure'/exp OR 'acute kidney tubule necrosis'/exp) |
Selection criteria
Data extraction and quality assessment
Statistical analysis
Results
Characteristics of included studies
Author | Country | Setting | Mean age (year) | Boys (%) | Sample size | AKI definition | Location | Storage degreea
| Timing of CysC (hours) | Timing of SCr (hours) |
---|---|---|---|---|---|---|---|---|---|---|
Ali et al. 2013 [42] | USA | Cardiac surgery | 4 | 47.4 | 19 | Urine output of <0.5 | Serum | NR | 12 | 96 |
Al-Tonbary et al. 2004 [43] | Egypt | Cancer | 5.3 | 63.8 | 47 | Decrease in eCCl by at least 20% from baseline | Serum | -20 | 0 | 720 |
Askenazi et al. 2011 [9] | England | Low Birth Weight Infants | 1 | 46.7 | 30 | 50% increase or rise SCr of at least 0.3 mg/dL | Urine | -20 | 0 | 48 |
Askenazi et al. 2012 [44] | England | ICU admitted | 1 | 51.5 | 33 | 50% increase or rise SCr of at least 0.3 mg/dL | Urine | -20 | 0 | 48 |
Ataei et al. 2014 [45] | Iran | ICU admitted | 1 | 56.1 | 107 | Decrease in eCCl by at least 25% | Serum | -80 | 0 | 48 |
Benzer et al. 2015 [46] | Turkey | Contrast induced nephropathy | 8.8 | 39.7 | 141 | Decrease in eCCl by at least 25% | Serum | -20 | 0 | 24 |
Di Nardo et al. 2013 [47] | Italy | Sepsis | 2.5 | 36.4 | 11 | Decrease in eCCl by at least 25% | Serum and urine | -80 | 0 to 24 | 48 |
Elmas et al. 2013 [48] | Turkey | Respiratory distress syndrome | 1 | 45.5 | 28 | Cr > 1.5 mg/dL | Serum | -70 | 0 | 72 |
Hamed et al. 2013 [49] | Egypt | ICU admitted | 7 | 53.1 | 32 | GFR < 80 mL/min/1.73 m2 | Serum | -20 | 0 | 24 |
Hassinger et al. 2012 [50] | USA | Cardiac surgery | 7.6 | 55 | 100 | GFR < 80 mL/min/1.73 m2 | Serum | -70 | 0 to 24 | 96 |
Herbert et al. 2015 [51] | USA | Cardiac surgery | 1 | 58.8 | 17 | NGAL > 150 ng/mL | Serum | -20 | 24 | 72 |
Herrero-Morín et al. 2007 [52] | Spain | ICU admitted | 2.9 | 60 | 25 | GFR < 80 mL/min/1.73 m2 | Serum | NR | 24 | 24 |
Koyner et al. 2013 [53] | USA | Cardiac surgery | 3.8 | 55 | 299 | 100% rise of Cr | Urine | -80 | 0 to 12 | 24 |
Krawczeski et al. 2010 [54] | USA | Cardiac surgery | 3.5 | 53.5 | 374 | 50% increase or rise SCr of at least 0.3 mg/dL | Serum | NR | 0 to 24 | 48 |
Lagos-Arevalo et al. 2014 [55] | Canada | ICU admitted | 4.7 | 60 | 160 | 50% increase or rise SCr of at least 0.3 mg/dL | Urine | -80 | 0 | 48 |
Li et al. 2012 [56] | China | ICU admitted | 0 | 54.8 | 62 | Cr > 1.5 mg/dL | Urine | -80 | Within 240 | 240 |
Mamikonian et al. 2014 [57] | USA | Cardiac surgery | 1.3 | 43 | 40 | Doubling of SCr from baseline | Serum | -80 | 2 to 24 | 24 to 72 |
Maruniak-Chudek et al. 2012 [58] | Poland | ICU admitted | 0 | 62.5 | 32 | 50% increase or rise SCr of at least 0.3 mg/dL | Serum | -70 | 0 to 24 | 24 to 48 |
McCaffrey et al. 2015 [59] | UK | ICU admitted | 3 | 53 | 49 | Decrease in eCCl by at least 25% | Serum | -80 | 0 | 12 to 24 |
Peco-Antić et al. 2013 [60] | Serbia | Cardiac surgery | 1.6 | 58 | 112 | Decrease in eCCl by at least 25% | Serum | -80 | 0 to 24 | 48 |
Polat et al. 2013 [61] | Turkey | ICU admitted | 8.75 | 44 | 52 | 50% increase or rise SCr of at least 0.3 mg/dL | Serum | -80 | 0 | 48 |
Sarafidis et al. 2012 [62] | Greece | Asphyxia | 0 | 76.9 | 13 | 50% increase or rise SCr of at least 0.3 mg/dL | Serum and urine | -80 | 24 | 24 to 72 |
Volpon et al. 2013 [63] | Brazil | ICU admitted | 3.8 | 53.3 | 122 | GFR < 75 mL/min/1.73 m2 | Serum | -80 | 0 to 24 | 72 |
Zhang et al. 2013 [64] | China | Cardiac surgery | 1 | 69.8 | 43 | 50% increase or rise SCr of at least 0.3 mg/dL | Serum | -80 | 0 to 24 | 72 |
Heterogeneity and publication bias
Meta-analysis
Relation between the level of cystatin C with occurrence of AKI
Characteristics |
P
for publication bias
| Model |
P
for heterogeneity (I2) | SMD (95% CI) |
P
for effect size
|
---|---|---|---|---|---|
a) Serum level | |||||
Timing of cystain C assessment | |||||
Overall | 0.44 | REM | <0.001 (89.9%) | 0.96 (0.68-1.24) | <0.001 |
Baseline | 0.37 | REM | <0.001 (91.1%) | 0.98 (0.39-1.57) | <0.001 |
1-6 h | 0.90 | REM | <0.001 (91.2%) | 0.72 (0.09-1.36) | <0.001 |
7-12 h | >0.99 | REM | <0.001 (01.1%) | 1.29 (0.54-2.04) | <0.001 |
13-24 h | 0.66 | REM | <0.001 (83.4%) | 0.99 (0.55-1.43) | <0.001 |
Overall Significant difference among subgroups
| 0.62 | ||||
Timing of AKI definition | |||||
Within 24 h | 0.07 | REM | <0.001 (94.6%) | 0.88 (-0.40-2.17) | 0.18 |
Within 48 h | 0.60 | REM | <0.001 (93.2%) | 1.05 (0.62-1.15) | <0.001 |
Within 72 h | 0.57 | REM | <0.001 (76.0%) | 0.74 (0.28-1.10) | 0.002 |
More than 72 h | 0.17 | REM | <0.001 (86.2%) | 1.58 (0.77-2.38) | <0.001 |
Overall Significant difference among subgroups
| 0.44 | ||||
AKI definition | |||||
Decrease in eCCl by at least 20% from baseline | 0.06 | REM | <0.001 (94.5%) | 1.07 (0.29-1.84) | 0.007 |
50% increase or rise SCr of at least 0.3 mg/dL | 0.58 | REM | <0.001 (89.0%) | 0.72 (0.37-1.08) | <0.001 |
GFR < 80 mL/min/1.73 m2 | 0.36 | REM | <0.001 (78.8%) | 1.25 (0.83-1.67) | <0.001 |
Doubling of SCr from baseline | 0.34 | FEM | 0.61 (0.0%) | 0.07 (-0.29-0.44) | 0.69 |
Other | 0.30 | REM | <0.001 (92.4%) | 2.61 (0.24-5.45) | 0.07 |
Overall Significant difference among subgroups
| 0.79 | ||||
Setting | |||||
PICU | 0.69 | REM | <0.001 (82.1%) | 1.50 (1.02-1.99) | <0.001 |
Cardiac surgery | 0.60 | REM | <0.001 (90.5%) | 0.71 (0.41-1.02) | <0.001 |
Other | 0.03 | REM | <0.001 (91.0%) | 1.09 (-1.15-3.33) | 0.34 |
Overall Significant difference among subgroups
|
0.02
| ||||
Sample size | |||||
≤30 | 0.04 | REM | <0.001 (78.0%) | 1.90 (0.98-2.82) | <0.001 |
>30 | 0.91 | REM | <0.001 (92.3%) | 0.80 (0.50-1.10) | <0.001 |
Overall Significant difference among subgroups
| 0.23 | ||||
Storage degree | |||||
-20 | 0.01 | REM | <0.001 (90.0%) | 0.82 (-0.19-1.83) | 0.11 |
-70 | 0.54 | REM | <0.001 (91.7%) | 1.06 (0.66-1.46) | <0.001 |
-80 | 0.60 | REM | <0.001 (90.3%) | 0.97 (0.57-1.41) | <0.001 |
Overall Significant difference among subgroups
|
0.005
| ||||
b) Urine level | |||||
Timing of cystain C assessment | |||||
Overall | 0.09 | REM | 0.04 (49.1%) | 0.54 (0.34-0.75) | <0.001 |
Baseline | 0.07 | REM | 0.01 (63.3%) | 0.70 (0.37-1.03) | <0.001 |
1-12 h | 0.03 | FEM | 0.93 (0.0%) | 0.38 (0.19-0.58) | <0.001 |
13-24 h | 0.11 | REM | >0.99 (0.0%) | 0.55 (-0.61-1.67) | 0.36 |
Overall Significant difference among subgroups
| 0.83 | ||||
AKI definition | |||||
Decrease in eCCl by at least 20% from baseline | 0.32 | FEM | 0.82 (0.0%) | 1.84 (0.78-2.89) | 0.007 |
50% increase or rise SCr of at least 0.3 mg/dL | 0.27 | FEM | 0.06 (52.2%) | 0.56 (0.31-0.82) | <0.001 |
Doubling of SCr from baseline | 0.32 | REM | 0.04 (49.1%) | 0.38 (0.16-0.59) | 0.69 |
Overall Significant difference among subgroups
| 0.11 | ||||
Timing of AKI definition | |||||
Within 24 h | 0.74 | FEM | 0.99 (0.0%) | 0.37 (0.23-0.51) | 0.18 |
Within 48 h | 0.18 | FEM | 0.14 (41.7%) | 1.04 (0.55-1.52) | <0.001 |
Overall Significant difference among subgroups
| 0.11 | ||||
Setting | |||||
PICU | 0.74 | FEM | 0.23 (31.1%) | 0.91 (0.44-0.74) | <0.001 |
Cardiac surgery | 0.38 | FEM | 0.99 (0.0%) | 0.37 (0.23-0.51) | <0.001 |
Other | 0.04 | FEM | 0.12 (52.2%) | 1.20 (0.18-2.23) | 0.02 |
Overall Significant difference among subgroups
| 0.21 | ||||
Sample size | |||||
≤30 | 0.10 | FEM | 0.20 (34.7%) | 0.97 (0.24-1.69) | 0.009 |
>30 | 0.04 | REM | 0.05 (55.2%) | 0.49 (0.30-0.69) | <0.001 |
Overall Significant difference among subgroups
| 0.34 | ||||
Storage degree | |||||
-20 | 0.32 | REM | 0.08 (68.4%) | 0.98 (-0.06-2.02) | 0.11 |
-80 | 0.05 | FEM | 0.11 (40.7%) | 0.48 (0.30-0.66) | <0.001 |
Overall Significant difference among subgroups
| 0.26 |
Variable | Odds ratio | 95% CI | P |
---|---|---|---|
Timing of Cystatin C | |||
Baseline |
Ref.
|
Ref.
| --- |
1-6 h | 2.34 | 0.86-6.34 | 0.09 |
7-12 h | 1.92 | 0.60-6.15 | 0.26 |
13-24 h | 1.52 | 0.65-3.56 | 0.32 |
Timing of AKI definition | |||
Within 24 h |
Ref.
|
Ref.
| --- |
Within 48 h | 0.44 | 0.07-3.00 | 0.39 |
Within 72 h | 0.16 | 0.02-1.46 | 0.10 |
More than 72 h | 0.58 | 0.05-6.8 | 0.65 |
AKI definition | |||
Other |
Ref.
|
Ref.
| --- |
Decrease in eCCl by at least 20% from baseline | 0.08 | 0.002-2.32 | 0.13 |
50% increase or rise SCr of at least 0.3 mg/dL | 0.06 | 0.004-1.07 | 0.09 |
GFR < 80 mL/min/1.73 m2 | 0.07 | 0003-1.97 | 0.12 |
Doubling of SCr from baseline | 0.11 | 0.01-1.3 | 0.08 |
Setting | |||
Other |
Ref.
|
Ref.
| --- |
Cardiac surgery | 2.52 | 0.45-14.17 | 0.24 |
PICU admitted | 5.45 | 1.23-24.10 |
0.03
|
Sample size | |||
≤30 |
Ref.
|
Ref.
| --- |
>30 | 0.43 | 0.10-1.80 | 0.23 |
Storage degree | |||
-20 |
Ref.
|
Ref.
| --- |
-70 | 10.03 | 1.61-62.27 |
0.02
|
-80 | 11.69 | 1.13-121.08 |
0.04
|
Diagnostic performance characteristics of cystatin C in AKI
Characteristics | TP | FP | FN | TN | P for publication bias
| Model | P for heterogeneity (I2) | Effect size (95% CI) |
---|---|---|---|---|---|---|---|---|
a) Serum level | 543 | 445 | 206 | 1102 | ||||
Overall area under the curve | 0.08 | REM | <0.001 (80.0) | 0.83 (0.80-0.86) | ||||
0.4-1 mg/L | 314 | 361 | 53 | 386 | ||||
Sensitivity | 0.29 | REM | <0.001 (77.6) | 0.85 (0.78-0.90) | ||||
Specificity | 0.29 | REM | <0.001 (94.6) | 0.61 (0.48-0.73) | ||||
Positive likelihood ratio | 0.29 | REM | <0.001 (92.8) | 2.18 (1.66-2.88) | ||||
Negative likelihood ratio | 0.29 | REM | 0.01 (60.3) | 0.24 (0.18-0.34) | ||||
1.01-2.5 mg/L | 229 | 84 | 153 | 716 | ||||
Sensitivity | 0.01 | REM | <0.001 (87.1) | 0.65 (0.49-0.77) | ||||
Specificity | 0.01 | REM | <0.001 (87.8) | 0.88 (0.79-0.94) | ||||
Positive likelihood ratio | 0.01 | REM | <0.001 (64.5) | 5.56 (3.62-8.53) | ||||
Negative likelihood ratio | 0.01 | REM | <0.001 (85.5) | 0.40 (0.28-0.56) | ||||
b) Urine level | 93 | 37 | 128 | 295 | ||||
Overall area under the curve | 0.07 | REM | <0.001 (83.3) | 0.85 (0.81-0.88) | ||||
Sensitivity | 0.07 | REM | <0.001 (83.3) | 0.47 (0.29-0.66) | ||||
Specificity | 0.07 | REM | 0.09 (54.3) | 0.89 (0.83-0.93) | ||||
Positive likelihood ratio | 0.07 | FEM | 0.24 (0.0) | 4.24 (2.93-6.13) | ||||
Negative likelihood ratio | 0.07 | REM | 0.04 (63.2) | 0.60 (0.43-0.83) |