Focal segmental glomerulosclerosis (FSGS) is the leading cause of kidney disease worldwide. The putative etiology of primary FSGS is plasma factor with reactivity to immunosuppressive therapy and risk of recurrence after kidney transplantation. Adaptive FSGS is associated with excessive nephron loading due to increased body size, decreased nephron capacity, or solitary glomerular hyperfiltration associated with certain diseases.
Introduction
Focal segmental glomerulosclerosis is the leading glomerular cause of renal failure. He refers to a histological picture that characterizes 6 possible underlying etiologies, sharing the common theme of contusion and podocyte depletion.
Diagnosis of focal segmental glomerulosclerosis relies on clinical history integration(family diseases, history of birth, peak weight and body weight, drug use), laboratory clinical findings (serum albumin, urine protein, and viral serologies) and renal histopathology. Proteinuria may be in the nephrotic or subnephrotic range. The elimination of other systemic diseases or primary kidney pathologies that can lead to a similar presentation is critical.
Epidemiology and global burden
The prevalence of focal segmental glomerulosclerosis, compared with other diagnoses of similar diseases, is increasing worldwide. However, absolute incidence and prevalence are difficult to ascertain given the large global variation in indications, availability, and pathologic support for renal biopsy.
A review of the published literature around the world has been carried out, which shows that the annual incidence rates are between 0.2 and 1.8 per 100,000 population per year. The median incidence rate was 2.7 patients per million. There is a significant racial and ethnic predisposition. In addition, the symptoms of kidney failure in women are milder than in men.
Typology
Classification of focal segmental glomerulosclerosis is multifaceted. It includes pathophysiological, histological and genetic aspects. Initially, FSGS was divided into primary (idiopathic) and secondary forms. The latter include family (genetic), virus-associated, drug-relatedinduced forms.
Clinical guidelines for focal segmental glomerulosclerosis may refer to the histological variant, primarily the glucocorticoid reactivity of the tip lesion and the aggressive, inexorable nature of the collapsing variants.
6 clinical forms
Combining genetic susceptibility, pathophysiological factors, clinical history, and response to therapy, it is reasonable to group FSGS into six clinical forms. They include:
- primary;
- adaptive;
- highly genetic;
- viral-mediated;
- drug-related;
- APOL1-related.
Histopathology of the disease
Minimal symptoms of glomerulonephritis in adults are manifested by the absence of tubulointersittal scarring. The tip lesion is a focal adhesion of the glomerular fascicle to the Bowman's capsule near the proximal tubule take-off.
The most typical variant is collapsing. A specific example can be evaluated in the setting of endothelial tubulo-reticular inclusions observed on ultrastructural analysis. They can be observed in high states of interferons, including viral infection. Minimal disease change and tip involvement are the most responsive and least progressive, and collapsing glomerulopathies that are resistant to therapy and rapidly progressive.
Signs indicating illness
Signs and symptomsglomerulonephritis in adults depend on the presence of an acute or chronic form. They include:
- Pink or brown-colored urine due to an increased number of red blood cells (hematuria).
- Frothy urine due to excess protein (proteinuria).
- High blood pressure (hypertension).
- Fluid retention (edema). Appears on the face, arms, legs and abdomen.
Separate symptoms of kidney failure in women:
- Reduced urine output.
- Fluid retention causing leg swelling.
- Shortness of breath.
- Fatigue.
- Confused mind.
- Nausea.
- Weakness.
- Irregular heartbeat.
- Pain in the kidney area.
- Fooning or coma in severe cases.
The surest way to detect FSGS
The first thing to do is a urine test for the kidneys. It includes two tests:
- Ratio of albumin to creatinine. Too much albumin in the urine is an early sign of kidney damage. Three positive results within three months or more is a sign of illness.
- Globular filtration rate. The blood is tested for a waste product called creatinine. It comes from muscle tissue. When the kidneys are damaged, there are problems removing creatinine from the blood. The test result is used in a mathematical formula with age, race and gender to find out the glomerular filtration rate.
Main reasons
Conditions that can lead to inflammationkidney glomerulus are:
- Infectious diseases. Glomerulonephritis can develop 7-14 days after skin infections (impetigo) or streptococcal infections of the throat. To fight them, the body is forced to produce many additional antibodies that can eventually settle in the glomeruli, causing inflammation.
- Bacterial endocarditis. The bacteria can spread through the bloodstream and take up residence in the heart, causing infection of one or more heart valves. Bacterial endocarditis is associated with glomerular disease, but the relationship between the two is unclear.
- Viral infection. Human immunodeficiency virus (HIV), hepatitis B and C can cause disease.
- Lupus. May affect many organs and parts of the body, including blood cells, skin, kidneys, heart, joints, and lungs.
- Goodpasture's syndrome. This is a rare lung disease that mimics pneumonia. It can cause glomerulonephritis and bleeding in the lungs.
- Nephropathy. This primary glomerular disease results from deposits of immunoglobulin in the glomeruli. May progress for years without noticeable symptoms.
Additional reasons
Additional causes of the disease include:
- Polyarteritis. This form of vasculitis affects small to medium sized blood vessels. Known as Wegener's granulomatosis.
- High blood pressure. Kidney function is reduced. They process sodium worse.
- Focal segmental glomerulosclerosis. It is characterized by diffuse scarring of some glomeruli. This condition may be the result of another disease or may occur for an unknown reason.
- Diabetic kidney disease (diabetic nephropathy).
- Alport Syndrome. hereditary form. It may also impair hearing or vision.
- Multiple myeloma, lung cancer and chronic lymphocytic leukemia.
Mechanism of disease
Focal segmental glomerulosclerosis is a diverse syndrome that occurs after podocyte injury for a variety of reasons. Sources of damage vary:
- circulating factors;
- genetic anomalies;
- viral infection;
- drug treatment.
For the most part, the interaction between these drivers is unclear and complex. For example, adaptive FSGS includes both podocyte stress (mismatch between glomerular load and glomerular capacity) and genetic susceptibility.
Podocyte damage from any form of FSGS (or from other glomerular diseases) initiates the process leading to acute nephritic syndrome. There is a progressive loss of damaged podocytes into the urinary space. To balance the deficit, these cells compensate by hypertrophy by coating the surfaces of the glomerular capillaries.
In adaptive FSGS, glomerular hypertrophy occurs early in the disease process. In other forms, glomerular hypertrophy occurs with progressive loss of a nephron. This leads to increased pressureand currents in the remaining glomeruli of the patent.
The following sections discuss the pathological mechanisms, therapy and treatment of focal segmental glomerulosclerosis.
Primary FSGS
Includes genetic, viral and drug-related FSGS. The mechanism of podocyte injury involves a circulating factor, possibly a cytokine, that renders particular patients susceptible. This is the most common form in teenagers and young adults. It is commonly associated with nephrotic-series proteinuria (sometimes massive), decreased plasma albumin levels, and hyperlipidemia.
Currently, primary FSGS is treated with immunosuppressive agents. These are glucocorticoids and calcineurin inhibitors that directly modulate the podocyte phenotype. Recurrent FSGS remains a clinical problem. Only one of 77 initial kidney biopsies in patients who subsequently relapsed showed a perihilar variant. Plasma exchange therapy may induce temporary remission.
Adaptive FSGS
Occurs after a period of glomerular hyperfiltration at the nephron level and post-pathophysiology hypertension. Conditions that are associated with its development include:
- congenital cyanotic heart disease;
- sickle cell anemia;
- obesity;
- androgen abuse;
- sleep apnea;
- high protein diet.
Duration of single-nephron glomerularhyperfiltration is usually measured decades before glomerulosclerosis progresses. Adaptive FSGS leads to progressive cycles of glomerular hypertrophy, stress and exhaustion, and excessive deposition of extracellular matrix in the glomerulus. Renal biopsy features supporting the diagnosis include large glomeruli, predominance of perigillar scars showing sclerotic changes. Clinical features include normal serum albumin, which is uncommon in primary FSGS.
Genetic FSGS
Takes two forms. Some patients with a certain genetic predisposition will develop the disease while others will not. The number of genes associated with FSGS is increasing every year, in large part due to the proliferation of whole exome sequencing. At least 38 have been identified to date.
Some genes are associated with a syndrome that includes extrarenal manifestations. This may provide a clinical clue that a patient may have a mutation in a particular gene. Others are associated with characteristic changes in basement membrane morphology or mitochondrial morphology.
If the family has not previously been genetically tested, the most effective approach is to use panels focused on early FSGS (infant and childhood). Genetic test resources worldwide are available from the National Center for Biotechnology Information and the National Institutes of He alth.
