What Is Focal Segmental Glomerulosclerosis?

Focal segmental glomerulosclerosis (FSGS) is a primary glomerular disease common in children and adults with nephrotic syndrome (NS). The histopathological feature is segmental glomerular scarring with or without Without the formation and adhesion of foam cells in the glomerular capillaries. Focal means that only part of the glomerulus is involved (involved glomeruli <50%); segmental means that some of the leaflets of the glomerulus are involved; globular sclerosis means the entire glomerular phase Changes or scarring.

Basic Information

English name

focal segmental glomerulosclerosis

Visiting department

Nephrology

Multiple groups

Children, adolescents

Common locations

kidney

Common causes

Poisoning damage, humoral immunity and hemodynamic changes, etc.

Common symptoms

Proteinuria, edema, hematuria, etc.

Causes of focal segmental glomerulosclerosis

FSGS has many causes. For example, poisoning damage, humoral immunity, and hemodynamic changes can cause capillary wall damage, resulting in the production and retention of macromolecular proteins. After deposition of immunoglobulins, C1q and C3 can be combined to cause degeneration of the foot cells and cause The base film phase is detached.

Residual nephron hemodynamic changes, causing compensatory hypertension, high perfusion and high filtration of glomerular capillaries, causing damage to epithelial cells and endothelial cells, and abnormal mesangial cell function, leading to progressive focal Segmental sclerosis. This pathological process can be exacerbated by a large amount of protein intake, limiting protein intake and reducing blood pressure treatment. Endothelial cell damage causes platelet aggregation and microthrombosis, which aggravates the development of the disease; many FSGS occur in connection with this pathogenesis, such as chronic streptococcal nephritis, chronic allograft rejection, reflux nephropathy, and analgesics Kidney disease, etc.

Clinical manifestations of focal segmental glomerulosclerosis

The disease mostly occurs in children and adolescents, with slightly more men than women. A few patients have upper respiratory infections or allergic reactions before onset. The most common clinical symptoms are nephrotic syndrome. About 2/3 of the patients have a large amount of proteinuria and severe edema. The amount of urinary protein can range from 1 to 30 g / day. About 50% of patients have hematuria, and microscopic hematuria is common. See, occasionally gross hematuria. 30% to 50% of adults have mild persistent hypertension or chronic nephritis syndrome. Patients have 24-hour urine protein <3.5 g / day, edema is not obvious, and hematuria, hypertension, and renal insufficiency are common. More than 50% of them can present nephrotic syndrome with obvious clinical manifestations of "three highs and one low". A few patients have no obvious symptoms, and proteinuria is occasionally found during routine urine tests.

The clinical manifestations of pediatric patients are similar to those of adults, mostly with nephrotic syndrome, and the incidence of hypertension and renal insufficiency is lower than that of adults. Most FSGS showed chronic progressive progression, eventually leading to renal failure, and a small number of patients progressed more quickly, with renal failure appearing earlier.

Focal segmental glomerulosclerosis

Routine urine test

Microscopic hematuria and proteinuria; often with sterile leukocyte urine and glucosuria; those with impaired renal tubular function have amino acid urine and phosphate urine, and the incidence is higher than other types of NS.

Blood test

Have obvious hypoalbuminemia, plasma albumin is usually lower than 25g / L, a few can be below 10g / L; glomerular filtration rate (GFR) decreases, blood urea nitrogen, creatinine increases; most patients have high lipids Bloodemia, serum C3 is usually normal, IgG levels are reduced, C1q is mostly normal, and 10% to 30% of patients have positive circulating immune complexes; when blood volume is reduced, hematocrit can increase, white blood cells and classification are normal, and platelets are slightly increased ; Water retention will cause lower blood sodium concentration, long-term sodium or acquired adrenal insufficiency will also lead to lower blood sodium concentration; hyperlipidemia will cause pseudo hyponatremia, because platelets can release potassium ions in vitro. Therefore, thrombocytosis can also cause pseudohyperkalemia.

3. Renal biopsy light microscopy

Typical FSGS lesions are characterized by focal segmental glomerular damage. The lesions involve a small number of glomeruli and vitreous sclerosis in some segments of the glomerulus. The lesions usually begin in the deep layer of the cortex or near the medullary glomerulus, gradually Expanded into the renal cortex, the diseased glomeruli showed segmental sclerosis, unaffected glomeruli were normal or the mesangial matrix increased, hyaline-like substances were deposited under the endothelial cells of the damaged capillaries, and foam cells were occasionally formed in the sclerotic area , Common localized epithelial cell proliferation.

4. Electron microscopy

There are a large number of cases of proteinuria, most or all of the glomeruli show diffuse or segmental foot process changes, foam cells can be seen in the capillary wall and / or mesangial area early, mesangial matrix increased and some capillaries collapsed. Under the endothelial cells and mesangial area, there are electron dense deposits, mesangial cells proliferate, bulk electronic denses correspond to glassy changes under light microscope and immunofluorescence IgM and C3 deposition. Fine-grained electron dense deposits can also be seen under the cells.

5.Immunofluorescence

C3 or IgM and C1q were found to be irregular, granular or nodular in the hardened or necrotic area. The disease-free glomeruli were negative. Occasionally, IgM and C3 were distributed in the mesangial area. IgG and IgA were rare.

Diagnosis of focal segmental glomerulosclerosis

In the diagnosis of FSGS, renal biopsy should be relied on and all possible secondary factors such as HIV infection and drug use should be ruled out. Careful interrogation of medical history, physical examination, and laboratory tests can help differentiate the diagnosis.

Focal segmental glomerulosclerosis

Glucocorticoid

Prednisone (prednisone) should be treated in time before hormone resistance appears. The average time to complete remission is usually 3 to 4 months. Therefore, the NS caused by FSCS in adults has not been resolved after 6 months of prednisone treatment, which is called hormone resistance. For the elderly, most scholars advocate prednisone treatment every other day for 3 to 5 months. For those with hormone dependence, resistance and relapse, prednisone plus intermittent cyclophosphamide shock treatment can increase the remission rate, and the total amount of cyclophosphamide should not exceed 12 grams.

2. Cyclosporine (CsA) and Colapril (FK506)

Cyclosporine commonly used doses can reduce urinary protein and induce remission after 6 months of treatment, but often relapse when the dose is reduced or discontinued. Therefore, maintenance mitigation should be applied for a long time. Due to its nephrotoxicity, blood creatinine should be monitored during use and the dose adjusted according to the situation. Colapril has a similar mechanism to cyclosporine and can be used with hormones. Commonly used for those who are ineffective or dependent on cyclosporine treatment.

3. Cytotoxic drugs (cyclophosphamide and phenylbutyric acid mustard)

Can be used as a secondary therapy, but its clinical effect remains to be confirmed.

4. Plasma exchange and protein adsorption therapy

Can be used in patients with recurrent FSGS kidney transplantation. Plasma exchange or protein adsorption can reduce circulating immune factors and temporarily reduce urine protein.

5. Non-steroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme inhibitors (ACEI)

Can reduce proteinuria and hyperlipoproteinemia by reducing GFR.

6. Other drugs

Other drugs such as azathioprine, mycophenolate mofetil (MMF), and angiotensin II receptor blockers (ACEI and ARB) can also be selected.