Table 1.
Coagulation regulators with known functions in renal physiology and pathophysiology
| Coagulation regulator (alternative name(s)) | Function | Expression | Effects in renal physiology and pathophysiology | Refs |
|---|---|---|---|---|
| Procoagulant | ||||
| Tissue factor (thromboplastin, CD142, factor III) | Initiator; cofactor for factor VIIa in factor IX and factor X activation | Subendothelium | Induced in CGN, TMA, DN and endotoxaemia Inhibition protects against CGN and TMA |
33–38,40,41, 43–45,98, 102, 190 |
| Factor Xa | Enzyme | Plasma | Inhibition is protective in DN, endotoxaemia, MsPGN and IR | 49–51,97,136 |
| Factor VIII (antihaemophilic factor) | Cofactor for activated factor IX in factor X activation | Plasma | Links impaired kidney function with risk of venous thrombosis | 75 |
| Factor V (labile factor) | Cofactor for factor Xa in prothrombin activation | Platelets and plasma | Factor V-dependent initiation of coagulation in human mesangial cells in vitro FV Leiden mutation conveys protective effects in DN |
42,112 |
| Prothrombin/thrombin (factor IIa) | Zymogen and protease | Plasma | Elevated in AKI, nephrotic syndrome, CKD, CGN and other renal diseases Inhibition protects against tubular atrophy, AKI and proinflammatory and proliferative responses in proximal tubular cells and mesangial cells |
55,56,90,106, 108,135, 54, 165 |
| Fibrinogen (factor I) | Fibrin precursor | Plasma, platelets | Plasma levels are elevated in diabetic patients and after renal IR Heterozygous but not homozygous depletion is protective in AKI, CGN and IR Bβ 15–42 peptide protects against renal IR injury |
48,119,147, 149–151 |
| Anticoagulant | ||||
| Thrombomodulin | Cofactor for thrombin in protein C activation | Endothelial surface | Shedding of thrombomodulin and elevated plasma levels of soluble thrombomodulin in diabetes and CKD Soluble thrombomodulin is protective in experimental glomerulonephritis and IR Thrombomodulin lectin-like domain deficiency exacerbates HUS and DN |
81,86,101, 103–105,131, 133,181 |
| Protein C | Zymogen and protease | Plasma | Renal-specific expression is reduced in various kidney diseases Activation is impaired in animals and patients with diabetes and in renal insufficiency Treatment with activated protein C is protective in experimental DN, IR and endotoxaemia |
25,28,29,46, 82,100,167, 168,172 |
| Antithrombin (heparin cofactor) | Protease inhibitor | Plasma | Deficient in experimental nephrotic syndrome Protects against tubular atrophy, AKI and PAN-induced nephrosis |
145,191 |
| Tissue factor pathway inhibitor (extrinsic pathway inhibitor) | Protease inhibitor | Endothelial surface via GPI, platelets, plasma | Induced in CGN Elevated levels partially compensate coagulation activation in diabetes Deficiency inhibits experimental glomerulonephritis Inhibition is protective in experimental kidney fibrosis |
125,182, 184,185 |
AKI, acute kidney injury; CGN, chronic glomerulonephritis; CKD, chronic kidney disease; DN, diabetic nephropathy; GPI, glycosylphosphatidyl inositol; HUS, haemolytic uraemic syndrome; IR, ischaemia–reperfusion; MsPGN, mesangioproliferative glomerulonephritis; PAN, puromycin aminonucleoside; TMA, thrombotic microangiopathy.