Background
Methods
Literature search and selection of studies
Data extraction and quality assessment
Criterion | Original criteria by Clark et al. | Specific criteria |
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1. Defining the Control Group | Control group described for size in relation to case group (n > case group) and ethnicity, in sufficient detail to allow replication. Cohort studies do not get a point. |
Cohort studies are given a point provided that the cohort is described in sufficient detail, namely the ethnicity of a cohort is given. Prospective cohorts regarded as strong design in demonstrating causality between genetic polymorphism and the development of acute kidney injury (AKI).
a
Size of the control group sufficient when essentially equivalent with case group.
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2. Hardy-Weinberg Equilibrium | Case and control groups assessed for Hardy-Weinberg equilibrium (HWE). |
Cohort or control group should be in HWE (p > 0.01). In case of multiple polymorphisms, the majority should be in HWE.
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3. Defining the Case Group | The disease state of interest as well as inclusion and exclusion criteria of the case group defined in sufficient detail to allow replication. |
Studies that aim to investigate predisposition to AKI are given a point only if they describe the phenotype.
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4. Primer Sequence | The priming sequences used for genotyping or references to them provided. |
Whenever a commercial assay was used for genotyping, a point was given as well.
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5. Describing the Methods | Genotyping method described in sufficient detail to allow replication. In addition, second validating assay performed or the accuracy of the assay validated. |
Accepted quality control methods: duplicated samples or control samples included, second independent investigator analyzing the genotype calls, repeating of ambiguous results.
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6. Blinding | Genotyping performed blinded to clinical status. | |
7. Power Calculation | Prospective or retrospective power calculation performed. |
No retrospective power calculations were conducted by the reviewers.
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8. Statistics | Tests of significance presented: such as p values, confidence intervals, or odds ratios. | |
9. Corrected Statistics | Corrected for the increased risk of false-positive error in the case of multiple polymorphisms studied. Should X2 or odds ratio be used, Hardy-Weinberg equilibrium is to be assessed. |
Where there was only one polymorphism studied, a point was given.
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10. Replication | Study performing second, confirmatory study or confirming earlier polymorphism study. |
A point was given only for studies performing exact replication of a polymorphism in association with a phenotype.
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Results
Characteristics of articles
Characteristic | N | References |
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Clinical setting | ||
Post cardiac surgery | 12 | |
ICU treatment | 6 | |
Hospitalization with kidney injury | 5 | |
Dialysis | 1 | [27] |
Other | 4 | |
Study design | ||
Prospective cohort | 23 | |
Prospective case–control | 4 | |
Retrospective case-cohort | 1 | [34] |
Center of data acquisition | ||
Single | 14 | |
Multi | 12 | |
Not applicable | 2 | |
Definition of AKI | ||
RIFLE | 8 | |
AKIN | 7 | |
Renal-SOFA | 1 | [26] |
Administration of RRT | 2 | |
Creatinine level | 4 | |
Not applicable | 6 | |
Studied polymorphisms | ||
1 polymorphism | 11 | |
1 gene, several polymorphisms | 4 | |
Several genes | 12 | |
GWAS | 1 | [34] |
Ethnicity | ||
Caucasian | 9 | |
Mixed | 10 | |
Not applicable | 9 | |
Main outcome | ||
AKI | 26 | |
Other | 2 |