Table 1

Data to be extracted from included studies, stratified by study characteristics and outcome measures

Study characteristics
CategoryDescription
Study ID
  • Authors

  • Year

  • Journal

  • Language

Study design
  • Experimental groups, including type of control group(s)

  • Number of animals per group

  • Duration of follow-up

  • Number of experiments and replications

Animal model
  • Species

  • Strain

  • Age

  • Gender

  • Weight

  • Comorbidities:

    • Obesity—yes/no

    • Diabetes—yes/no (if yes, type 1 or type 2 diabetes mellitus model)

    • Dyslipidaemia—yes/no

    • Hypertension—yes/no

  • Kidney disease characteristics:

    • AKI model vs CKD model vs acute-on-chronic renal injury model vs renal transplant model

    • Kidney disease manifests as part of natural history or induced

    • Modality of kidney disease induction

Intervention
  • PPAR isotypes pharmacologically targeted:

    • PPARα

    • PPARβ/δ

    • PPARγ

    • Two PPAR isotypes

    • Three PPAR isotypes

  • Route of administration:

    • Oral

    • Intravenous

    • Subcutaneous

    • Intraperitoneal

  • Dose of PPAR-targeting pharmacological agent

  • Timing of intervention

    • Preventative if given before or during kidney disease induction

    • Rescue if given after kidney disease induction

  • Frequency of intervention (n times per day, once daily, once every n number of days, once weekly)

  • Duration of intervention (in days/weeks/months)

Other
  • Study quality indicators (adapted from CAMARADES study quality checklist)68 69:

    • Publication in a peer-reviewed journal—yes/no

    • Species/strain of animals reported in title or abstract and in full-text—yes/no

    • Provision of author conflict of interest statements—yes/no

    • Statement of compliance with animal welfare regulations—yes/no

    • Basic animal and housing characteristics reported—yes/no

    • Sample size calculation reported—yes/no

    • Randomisation of treatment allocation reported—yes/no

    • Concealment of treatment allocation reported—yes/no

    • Statement on blinded outcome assessment provided—yes/no

    • Criteria for inclusion and/or exclusion of data provided—yes/no

  • Risk of bias assessment using the SYRCLE risk of bias tool

    • 10 items will be recorded as ‘yes’, ‘no’ or ‘unclear’

Outcome measures
CategoryDescription (data type; unit)
PrimaryRenal injury and function indices:
  • Plasma/serum creatinine (continuous; mg/dL or μmol/L)

  • Plasma/serum urea or blood urea nitrogen (continuous; mg/dL or μmol/L)

  • Creatinine clearance (continuous; mL/min)

  • Glomerular filtration rate (continuous; mL/min)

  • Urinary albumin/protein excretion (continuous; μg/hour (excretion rate) or μg/mg (normalised to urinary creatinine))

  • Histological parameters of renal injury (continuous; arbitrary units)

  • Kidney size parameters (continuous; grams (kidney weight) or percentage (kidney weight/body weight ratio))

  • Kidney cyst size parameters (continuous; mL (kidney cyst volume) or percentage (kidney cystic index)

SecondaryMechanistic mediators explored (all categorical; yes/no)
  • Renal fibrosis

  • Renal inflammation

  • Renal oxidative stress

  • Renal apoptosis

  • Renal epithelial-to-mesenchymal transition

  • Renal lipotoxicity

  • Renal glucotoxicity

  • Renal nicotinamide adenine dinucleotide metabolism


Urinary biochemical evidence of renal injury (biomarkers)
  • Neutrophil gelatinase-associated lipocalin (continuous; μg/hour (excretion rate) or μg/mg (normalised to urinary creatinine))

  • Kidney injury molecule-1 (continuous; μg/hour (excretion rate) or μg/mg (normalised to urinary creatinine))


Metabolic parameters
  • Body weight (continuous; g)

  • Glycaemia

    • Circulating glucose (continuous; mg/dL or mmol/L)

    • HbA1c (continuous; % or mmol/mol)

    • Fructosamine (continuous; mg/dL or mmol/L)

  • Dyslipidaemia (all continuous; mg/dL or mmol/L)

    • Circulating total cholesterol

    • LDL-cholesterol

    • HDL-cholesterol

    • Triglycerides

  • Blood pressure (all continuous; mm Hg)

    • Systolic blood pressure

    • Diastolic blood pressure

    • Mean arterial blood pressure


Safety outcomes
  • Hepatotoxicity

    • Liver enzyme elevation (continuous; mg/dL or mmol/L)

    • Histological evidence of liver injury (categorical; yes/no)

  • Cardiotoxicity

    • Ejection fraction (continuous; %)

    • Heart failure (categorical; yes/no)

    • Histological evidence of cardiac injury (categorical; yes/no)

  • Carcinogenicity

    • Tumour development (categorical; yes/no)

    • Tumour site (categorical; organ)

  • Mortality

    • Mortality (categorical; yes/no)

    • Number who died (continuous; n)

    • Timing of death from start of intervention (continuous; days/weeks/months)

  • AKI, acute kidney injury; CAMARADES, Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies; CKD, chronic kidney disease; HbA1c, glycated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; PPAR, peroxisome proliferator-activated receptor; SYRCLE, Systematic Review Centre for Laboratory Animal Experimentation.