Table 6.
Overview of molecular and physiological information on the identified kidney biomarkers.
| Molecular Information | Physiological Information | References | |||||
|---|---|---|---|---|---|---|---|
| Type of Molecule | Size | Origin | Function in the Body | Kidney Physiology | Extra Renal Factors Influencing Biomarker in Other Species | ||
| Functional biomarkers | |||||||
| SDMA | Methylated aminoacid | 202.25 | Generated intracellularly during protein degradation as analogues of L-arginine; enantiomer of ADMA | Methylation of arginine residues appears to be required for RNA processing, protein shuttling and signal transduction. SDMA has an indirect effect on NO synthesis by interfering with tubular arginine absorption | Almost all SDMA is excreted by kidneys, concentration proportional to GFR. Some hepatic clearance also occurs | Factors that impact GFR | [12,52,53,54] |
| Cystatin C | Cationic and non-glycosylated protein | 13 kDa | Produced by all nucleated cells of the body and is released into the intravascular compartment at a constant rate | Protease inhibitor | Filtered from the blood through the glomerulus and catabolized, but not secreted, by the proximal tubular cells. Concentration proportional to GFR. | Inflammation, metabolic diseases, and even the interval between feeding and serum collection. Factors that impact GFR. Independent from age, sex, race, muscle mass | [22,55] |
| Markers of structural damage | |||||||
| Glomerular damage | |||||||
| Podocin | Podocyte associated molecule | 450 kDa | Present exclusively in podocytes (specialized glomerular epithelial cells), especially near the slit diaphragms | Podocin is one of the proteins that constitute the slit-diaphragms of the glomerulus (modified tight junction that facilitates size and charge dependent permselectivity) | Released in urine following podocyte damage | Physiological podocyturia, more in concentrated urine | [27,56] |
| Tubular damage | |||||||
| NGAL | Lipocalin protein | 25 kDa | Activated neutrophils, and various epithelial cells, kidney tubular cells | Plays a role in iron metabolism and innate immunity to bacteria, kidney development, growth factor for stimulated epithelia (inflammation, bacterial infection or neoplasia), tubular regeneration after injury, protective effect for kidney ischaemia-reperfusion injury | Highly expressed in response to tubular injury | Inflammation | [39,57] |
| MMP | Metalloproteinases | Pro-MMP 72 kDa; MMP-2 59–62 kDa; proMMP-9 68–92 kDa (dependent on activation status) | All cells | Degradation of extracellular matrix proteins, role in apoptosis | Small molecules pass through glomerular filtration, but in most healthy animals are reabsorbed in the proximal tubules. Excretion in urine increases with tubular or glomerular damage | Endotoxemia influences plasma levels | [24] |
| NAG | Enzyme | 130–140 kDa | Lysosomal enzyme in proximal tubular epithelium | Lysosomal enzyme | Released in case of tubular damage | Physiologic exostosis into the tubular lumen. Urine concentration -> NAG: creatinine ratio Instability in alkaline urine |
[50,58] |
Legend: SDMA—symmetric dimethylarginine; NGAL—neutrophilgelatinase-associated lipocalin; MMP—matrix metalloproteinases; NAG—N-acetyl-β-D-glucosaminidase; GFR—glomerular filtration rate.