| Leptin |
Hyperleptinemia is observed in patients with CKD and those undergoing dialysis; causing inflammation, glomerulosclerosis, proteinuria, increased sympathetic nervous activity and ROS stimulation.
61
,
65
Elevated serum leptin causes upregulation of type IV collagen and, TGF‐β1 in glomerular endothelial cells, causing these cells to proliferate.
66
In glomerular mesangial cells, hyperleptinemia causes upregulation of the TGF‐β type II receptor, type I collagen synthesis, glucose uptake and mesangial cell hypertrophy. Both endothelial and mesangial cells increase release of extracellular matrix constituents in response to leptin.
67
|
| Resistin |
Serum levels of resistin elevate across mild to advanced CKD and negatively associate with GFR, albumin and hematocrit.
68
,
69
Hyper‐resistinaemia increases release of pro‐inflammatory cytokines including C reactive protein, an acute phase reactant linked to endothelial cell dysfunction, coronary artery disease, adiposity and insulin resistance. A marked increase in TNF, lipoprotein‐associated phospholipase A2 and IL‐6 is also observed in response to raised serum resistin, conferring that resistin may be associated with sub‐clinical inflammation recognized in CKD.
68
,
70
Expression of resistin propagates adhesion molecules in vascular endothelial cells such as anti‐VCAM‐1 and anti‐ICAM‐1, and long pentraxin 3, the latter is also a marker of inflammation. Resistin's induction of VCAM‐1 and ICAM‐1 is directly inhibited by adiponectin. The extent to which this will affect renal function is unclear.
71
Serum resistin has also found to correlate with variability in erythropoietin responsiveness in CKD patients.
72
|
| Visfatin |
Visfatin, an adipocyte derived polypeptide hormone, is expressed preferentially in visceral fat.
73
,
74
Serum visfatin is associated with increased endothelial dysfunction seen in all stages of CKD, which is independent of insulin resistance and inflammation. It associates independently with VCAM‐1; a marker of damage to endothelia.
75
In patients with CKD, higher levels of visfatin are associated with lower GFR, and increased triglyceride and low‐density lipoprotein; it is also proatherogenic in nature.
76
|
| TNF |
TNF is a pro‐inflammatory, proatherogenic compound, released by macrophage cells; it correlates positively with CKD severity and associates with higher cystatin C and UACR.
77
,
78
,
79
,
80
The effects of TNF involve endothelial cell adhesion, ROS activation, increased albumin permeability, cytotoxicity, apoptosis and necrosis.
80
Plays an active role in glomerular inflammation and fibrosis.
79
|
| IL‐6 |
IL‐6 is linked to greater CKD status, higher cystatin‐C, UACR and is implicated in both acute and long‐term inflammation. It is also associated with greater risk of incident CKD and raised in patients with kidney disease.
77
,
81
High levels of IL‐6 contribute to raised serum levels of fibroblast growth factor 23, which is found raised early in CKD and is associated with greater morbidity and mortality, and is linked to inflammatory processes.
82
,
83
|
| MCP‐1 |
MCP‐1 is expressed in great abundance by visceral fat and implicated in CVD; MCP‐1 is released by macrophages and endothelial cells and recruits pro‐inflammatory cells.
84
Plasma levels of MCP‐1 are observed to be raised in CKD and negatively associate with GFR and is independent as a risk factor for death in CKD patients.
85
|
| PAI |
PAI is increased in CKD, and the glycoprotein is found to contribute to the promotion of renal fibrosis.
86
PAI facilitates cell migration of inflammatory compounds such as monocytes and myofibroblasts within the renal interstitium, promoting fibrogenesis. It also induces fibrosis by inhibiting intravascular and tissue fibrinolytic processes.
87
Both PAI‐1 and messenger ribonucleic acid protein are raised in chronic glomerulonephritis, diabetic nephropathy and FSGS. PAI‐1 abundance also correlates with degree of proteinuria.
88
|
| Adiponectin |
Hypoadiponectinemia is observed in increasing visceral obesity and type 2 diabetes mellitus.
60
Adiponectin is insulin sensitizing, anti‐inflammatory, antifibrogenic, anti‐atherogenic and cardioprotective.
89
Circulating adiponectin is raised in CKD, perhaps due to factors such as reduced clearance which is evidenced by normalized levels post kidney transplantation.
60
Adiponectin and albuminuria negatively correlate in patients with CKD.
90
Adiponectin knockout mice exhibited albuminuria and podocyte foot process fusion. Administration of exogenous adiponectin was associated with reduced permeability to albumin by podocytes, seemingly caused by a reduction in oxidative stress.
90
|
