Focal segmental glomerulosclerosis is caused by what?

(A) causes
The FSGS There are many risk factors. Injury such as poisoning, humoral and hemodynamic changes can lead to the damage of the capillary wall, so that the macromolecular protein and retention, and immunoglobulin deposition and then combined with C1q and C3, causing the degeneration of the podocytes and the basemembrane detachment. The study found that the phenotype of podocytes in primary FSGS has changed. Damage of the epithelial cells is unclear capillary loop collapse and sclerosis of FSGS may be a manifestation of epithelial cell lesions increased tissue repair. Focal sclerosis lesions rapid recurrence after renal transplantation, indicating that systemic factors in the pathogenesis of FSGS.
Residual nephron hemodynamic changes, cause the compensatory glomerular capillary hypertension, hyperperfusion and hyperfiltration, resulting in damage epithelial cells and endothelial cells, mesangial cell dysfunction, leading to progressive focal sectionsegmental sclerosis. This pathological process is aggravated by ingestion of a large number of proteins, limit protein intake and blood pressure lowering treatment and reduce the Endothelial cell damage caused by platelet aggregation and microthrombosis, and increase the development of lesions; occurrence and the pathogenesis of many of FSGS, such as chronic streptococcal infection, glomerulonephritis, chronic renal allograft rejection, reflux nephropathy and analgesic nephropathy. In addition, it is also observed near marrow glomerular glomerular filtration rate than the cortex glomerulus, but also support the hemodynamic changes of FSGS risk factors.
Drug abuse and AIDS can cause typical FSGS nephrotic syndrome and progressive renal failure, it can be the final outcome of most of the proliferative glomerulonephritis.However, the majority of cases are idiopathic, pathological type was of FSGS is found when the first renal biopsy.
Segmental glomerular sclerosis in addition to be found in FSGS, also can be the final result of the proliferative glomerulonephritis (eg, glomerulonephritis) or related with hyperfiltration in nephrotic syndrome, some patients go through a Bureau stove segmental proliferative phase, the formation of segmental necrosis and scarring, this situation is common in secondary glomerulonephritis.
(B) in the pathogenesis
The pathogenesis of this disease is inconclusive, only a series of observations and inferences:
A mesangial uptake of macromolecules excessive study found that to test the animal intravenous injection of exogenous protein, can cause changes similar to the disease, suggesting that long-term heavy proteinuria can lead to damage of the epithelial cells, glomerular mesangial cells over- load to the development of glomerular focal segmental sclerosis.
Glomerular hemodynamic changes in glomerular capillary loop Benbingfasheng in high-pressure role is very important. Studies have shown: the animal model of part or most of nephrectomy, the remaining renal tissue of six months or so that the focal segmental sclerosis. Prompted the disease to occur may be related to hemodynamic changes. The mechanism may be compensatory capillary hypertension in the remaining kidney tissue, as well as the goals, the expansion of the efferent arteriole, glomerular capillary loop completely open to the systemic circulation, resulting in glomerular hyperperfusion, high transmembrane pressure, filtration The increase in protein and other soluble molecules, causing capillary loop epithelial and endothelial cell injury and mesangial cell dysfunction.Given, such as diet control or angiotensin-converting enzyme inhibitor therapy, so that high pressure in the glomerular capillary to reduce the development of focal segmental sclerosis moderated, this is better able to explain the glomerular capillary loop HV role.
3 hyperlipidemia disease, development, and hyperlipidemia was positively correlated.The study found: (1) increase in food fat can test animals glomerular sclerosis, glomerular lesions and elevated blood lipids to the same extent. ② congenital growth process of obese rats natural occurrence of focal segmental glomerulosclerosis. ③ to lipid-lowering drug therapy, with the decline in blood lipids, glomerular damage also reduced. (4) human obesity associated with blood cholesterol, triglycerides increased and cardiac hypertrophy, and kidney, there may be similar to the primary focal segmental glomerulosclerosis lesions. Such cases, the control diet, weight loss weight loss, followed by reducing urinary protein nephrotic syndrome can be eased.
Hyperlipidemia cause glomerular focal segmental sclerosis may be mesangial cells have the ability to intake of low-density lipoprotein (LDL), oxidized LDL receptor on mesangial cells, and therefore glomerular uptake of oxidized LDL and oxidized LDL is a lipoprotein lead to hardening of the arteries of the most toxic. LDL stimulates mesangial cell proliferation and cell death, leading to glomerulosclerosis. Such as the aforementioned glomerular hemodynamic changes, and high filtration state can lead to glomerular focal segmental sclerosis, and proteinuria. In addition, glomerular lipid deposition is also a focal segmental sclerosis CAUSE. Monocyte-macrophage cells or glomerular mesangial cells engulfed the deposition of LDL, the formation of foam cells (foam cells) and foam cells play an important role in the development of atherosclerosis, so the more support for glomerular focal segmental sclerosis and atherosclerosis, there is a common pathogenesis. Minimal change disease or membranous nephropathy lipids than the disease is higher, but the glomerular foam cell infiltration are not severe and the disease.Glomerular fat calm can also cause glomerular capillary endothelial cell injury, as well as platelets, macrophages, monocytes, aggregation, stimulate the production of cytokines such as IL-1, of TGFβ, these make the mesangial cell proliferation, extracellular matrix components increased and the glomerular capillary lumen clotting.
(4) single-macrophages within the glomerular infiltration of mononuclear macrophages can produce a variety of cytokines, such substances to stimulate mesangial cell proliferation leading to glomerulosclerosis. Of the disease, monocyte-macrophage cells and histocompatibility antigens (MHC) of the number of positive 1a cells increased the number of these cells with focal segmental sclerosis lesions consistent. The cells and the cell adhesion molecule (ICAM) can activate macrophages, and glomerular macrophage activity. The same time, the monocyte-macrophage cells of the renal interstitial apparent infiltration, infiltration and proteinuria and renal function consistent with the extent of damage. In addition, the glomeruli of the above-mentioned lesions and cholesterol levels and obesity development process is also relevant. Interstitial mononuclear macrophage infiltration reduce the prednisone treatment, along with improved renal function, but glomerular cell infiltration and sclerosis is difficult to reduce the proteinuria will not improve.
Segmental glomerular capillary loop coagulation allows activation of the platelet release of platelet-activating factor (PAF), platelet-derived growth factor (PDGF), these factors effect caused in the mesangial lesions. Experiments show that the anticoagulant such as heparin, warfarin, or thromboxane inhibitors, can reduce the glomerular focal segmental sclerosis lesions, reduce proteinuria, without affecting renal blood flow and glomerular filtration rate.
Plasma factor effect of the disease after renal transplantation can rapidly recurrence, the recurrence rate of up to 35% ~ 50%. Therefore, considering that there may be some plasma factors cause the disease. Some people have in recent years immunoadsorption treatment for the patients and allows urine protein to reduce urinary protein complex l stop adsorption, re-adsorption can still make urine protein decreased, suggesting that the blood of patients with a glomerular capillary loop permeability The increase of material.
Visceral epithelial cell lesions occur in the disease development, not only the mesangial matrix plays an important role, and epithelial cells in lesions of the disease starting stove.Pathological observation noted that the onset of the disease both the visceral epithelial cell hypertrophy (hyperplasia), cytoplasm diluted with capillary loop mast, while the filtrate leakage of poor filtration area increases, the formation of false cells. With hypertrophy and dilatation of the capillary loop with fake cell adhesion in the glomerular capsule, forming the start of segmental sclerosis stove On this basis, the development of sclerosis.
Genetic factors compatriots, relatives of the disease report few, but there are all the same report of the disease in MHC antigen donor kidney transplant recurrence rate was 82% recurrence rate of 53%, not identical related kidney other allogeneic donor kidney recurrence rate of 35% is highly suggestive of genetic factors. In laboratory animals also has the obvious tendency of the germ line.