Introduction
Pathogenesis of DKD (Fig. 1)
Glomerular injury
Tubular injury
Oxidative stress injury
Inflammatory injury
Existing biomarkers
Novel biomarkers in DKD
Glomerular biomarkers | Tubular biomarkers | Biomarkers of oxidative stress | Biomarkers of inflammation |
---|---|---|---|
Type IV collagen | NGAL | 8oxodG | Tumor necrotic factor-α |
Fibronectin | Urinary cystatin C | Pentosidine | Tumor necrotic factor-α receptors |
Laminin | KIM-1 | Uric acid | MCP-1 |
Serum cystatin C | RBP4 | TGF- β | |
Glycosaminoglycans | L-FABP | CTGF | |
Immunoglobulin G | IL-6 | ||
Ceruloplasmin | |||
L-PGDS | |||
Transferrin |
Glomerular biomarkers
Type IV collagen
Fibronectin (FN)
Laminin
Cystatin C (CysC)
Glycosaminoglycans (GAG)
Immunoglobulin G (IgG)
Ceruloplasmin
Lipocalin-type prostaglandin D synthase (L-PGDS)
Transferrin
Tubular markers
Neutrophil gelatinase-associated lipocalin (NGAL)
Urinary cystatin C (uCysC)
Kidney injury molecule-1 (KIM-1)
Retinol-binding protein-4 (RBP4)
Liver-type fatty acid-binding protein (L-FABP)
Biomarker of oxidative stress
8-Oxo-7,8-dihydro-2’-deoxyguanosine(8-oxodG)
Pentosidine
Uric acid
Biomarkers of inflammation
Tumor necrotic factor-alpha (TNF-α)
Tumor necrotic factor-alpha receptors
Monocyte chemoattractant protein-1 (MCP-1)
Transforming growth factor-beta (TGF- β)
Connective tissue growth factor (CTGF)
Interleukins-6 (IL-6)
Type of biomarkers | Name of biomarkers | Utility in DKD prediction | Prediction of retinopathy | Prediction of cardiovascular risk |
---|---|---|---|---|
Glomerular marker | Fibronectin | Yes [22] | Yes [24] | |
Type IV collagen | Onset (T1DM, T2DM) [16] Progression (T2DM) [17] | Yes [20] | n/a | |
Serum laminin | Onset (T2DM) [26] Progression (T2DM) [27] | Yes [28] | n/a | |
Serum cystatin C | Progression (T1DM, T2DM) [32] | Yes [33] | Yes [34] | |
GAG | Onset and progression (T1DM, T2DM) [38] | Yes [39] | n/a | |
Transferrin | Progression (T2DM) [53] | Yes [54] | Yes [55] | |
Tubular markers | NGAL | Onset and progression (T2DM) [57] | n/a | n/a |
RBP-4 | Yes [75] | Yes [72] | ||
KIM-1 | Onset (T2DM) [69] Progression (T1DM) [90] | n/a | n/a | |
L-FABP | Progression (T2DM) [99] | n/a | Yes [79] | |
Oxidative marker | 8-OxodG | Progression (T2DM) [104] | Yes [84] | Yes [86] |
Pentosidine | Yes [128] | Yes [91] | ||
Inflammation | MCP-1 | Progression (T2DM) [113] | Yes [115] | n/a |
TNF-α | Progression (T2DM) [98] | Yes [100] | Yes [101] | |
TNF-α Receptors | Yes [107] | n/a | ||
CTGF | Predictor of ESRD (T1DM) [123] | Yes [124] | n/a | |
IL-6 | Onset and progression (T2DM) [127] | n/a | Yes [101] |
Study | Biomarkers | Patients | Cut-off value | AUC | Sensitivity (%) | Specificity (%) | Method |
---|---|---|---|---|---|---|---|
Rashid et al. 2021 [27] | Serum laminin | 96 | 135.7 pg/ml | 0.913 | 85 | 80 | ELISA |
Kaul et al. 2018 [57] | Urine NGAL | 198 | 21.31 mg/dl | 0.996 | 95 | 100 | ELISA |
Qamar et al. 2018 [31] | Serum cystatin C | 119 | 1.26 mg/L | 0.914 | 88.2 | 84.8 | Turbidimetric |
Xian et al. 2017 [61] | Urine cystatin C | 146 | 0.525 ng/ml | 0.803 | 0.76 | 0.80 | Turbidimetric |
Ali et al. 2018 [69] | uKIM-1 | 89 | 88.5 ng/l | – | 91.6 | 84 | ELISA |
Abbasi et al. 2020 [62] | uRBP-4 | 133 | 46.1 ng/mg | 0.744 | 84.6 | 62.5 | ELISA |
Shoukry et al. 2015 [113] | uMCP-1 | 100 | 110 pg/mg | 0.98 | 92 | 100 | ELISA |