Table 2.
Biomarkers of Diabetic Nephropathy Pathophysiology.
| Class | Biomarkers | Clinical importance | Method of detection | Ref. |
|---|---|---|---|---|
| Oxidative stress | Pentosidine | Predictor of progression; influenced by glycemic levels and renal function; biomarker of microvascular complications and diabetic cardiovascular risk. | Serum/urine | 77,78 |
| 8-OHdG | Predictor of advanced stage; related to the severity of DN, associated with macroalbuminuria. | Urine | 79,80 | |
| Uric acid | Predictor of progression; associated with various stages of DN, onset and progression; potential target for therapeutic intervention in diabetes. | Serum | 81,82 | |
| Fibrosis | TGF-β1 | Predictor of advanced stage DN; positively correlates with micro- and macroalbuminuria | Serum/urine | 31 |
| CTGF | Predictor of ESRD; correlates with the rate of decline in GFR. | Serum/urine | 83,84 | |
| VEGF | Predictor of progression; increased during the earlier stage of DN and shown to significantly correlate with urinary albumin excretion. | Serum/urine | 85,86 | |
| Glomerular damage | Transferrin | Predictor of early stage; increased before development of microalbuminuria. | Urine | 87 |
| Type IV collagen | Predictor of advanced stage of DN; associated with a faster decline in eGFR. | Urine | 88,89 | |
| Cystatin C | Predictor of early stage DN; raised early in DN and pre-DN; increased in patients with microalbuminuria without any other urinary abnormality. | Serum/urine | 90,91 | |
| Tubular damage | L-FABP | Predictor of early stage and progression of DN; increased from the microalbuminuric stage; elevated in patients with reduced eGFR. | Urine | 92,93 |
| NGAL | Predictor of early stage and progression of DN; found in diabetic patients without early signs of glomerular damage (normoalbuminuric). | Urine | 94,95 | |
| KIM-1 | Predictor of early stage DN; increased even before the onset of albuminuria and proteinuria. | Serum/urine | 96,97 | |
| ACE2 | Biomarker of increased metabolism of Ang II in DN; its downregulation or excretion in urine predicts tubular injury and reduced renal function. | Serum/urine | 98,99 | |
| Angiotensinogen | Predictor of early and development of kidney injury; levels correlated with albuminuria, biomarker of the intrarenal RAAS. | Urine | 100,101 | |
| NAG | Predictor of early stage DN; associated with normoalbuminuric and microalbuminuric stages; increased in parallel with the severity of disease. | Urine | 102,103 | |
| α1-microglobulin | Predictor of early stage DN; directly correlates with albuminuria and severity of the disease. | Urine | 104,105 | |
| FGF23 | Predictor of DN progression to ESRD; associated with macroalbuminuria and risk of mortality. | Serum | 106,107 | |
| Inflammation | TNF-α;TNFR1/2 | Predictor of DN progression to ESRD and GFR loss; associated with the presence and severity of microalbuminuric stage. | Serum/urine | 108,109 |
| MCP-1 | Predictor of progressive renal disease; correlated significantly with albuminuria levels; accelerate nephropathy by increasing inflammation and fibrosis; potential for therapeutic target for treating DN. | Urine | 110,111 | |
| IL-18, IL-1, IL-6, IL-8 | Predictor of DN progression; strongly associated with future risk of early progressive renal decline. | Serum/urine | 18,112-114 |
Note. 8-OHdG = 8-hydroxy-2′-deoxyguanosine; DN = diabetic nephropathy; TGF-β1 = transforming growth factor-β1; CTGF = connective tissue growth factor; ESRD = end-stage renal disease; GFR = glomerular filtration rate; VEGF = vascular endothelial growth factor; eGFR = estimated glomerular filtration rate; L-FABP = liver-type fatty acid-binding protein; NGAL = neutrophil gelatinase-associated lipocalin; KIM-1 = kidney injury molecule-1; ACE2 = angiotensin-converting enzyme-2; Ang II = angiotensin II; RAAS = renin-angiotensin-aldosterone system; NAG = N-acetyl-beta-d-glucosaminidase; FGF23 = fibroblast growth factor 23; TNF-α = tumor necrosis factor-α; TNFR1/2 = tumor necrosis factor receptor 1/2; MCP-1 = monocyte chemoattractant protein-1; IL = interleukin.