Focal segmental glomerulosclerosis (FSGS) is characterized by partial scarring of individual renal corpuscles. It is a group of different diseases that can lead to nephrotic syndrome in the majority of cases. Treatment depends on the underlying cause.
What is focal segmental glomerulosclerosis?
Focal segmental glomerulosclerosis represents a collective term for several different diseases that lead to partial scarring (sclerosis) in kidney tissue. It is also synonymously referred to as focal sclerosing glomerulonephritis. The addition of “focal segmental” already indicates that glomerulonephritis does not affect the entire kidney, but only certain renal corpuscles. Furthermore, the entire vascular tangle is not affected in the renal corpuscles. Again, individual vascular lobules are left out of the changes. Filtration processes of the primary urine take place in the renal corpuscles. However, the sclerosis of the renal tissue in the renal corpuscles leads to a restriction of the filtering function. Thus, proteins from the blood that have not been filtered out can enter the urine. About 75 percent of FSGS patients then develop the so-called nephrotic syndrome, which is characterized by massive proteinuria, hypoproteinemia, hyperlipoproteinemia and edema. The remaining 25 percent of patients show only increased excretion of proteins in the urine (proteinuria) as their only symptom. Approximately 10 to 20 percent of all cases of nephrotic syndrome are due to focal segmental glomerulosclerosis. The disease affects males in the majority. In most cases, FSGS begins at an age younger than 50 years.
Causes
The causes of focal segmental glomerulosclerosis can be varied. Thus, there are primary and secondary forms of this disease. In the primary forms of FSGS, genetic factors appear to play a role in some cases. In these cases, proteins of the so-called podocytes (covering cells of the renal corpuscles) are affected by mutations. However, many cases are idiopathic. Here, a specific cause cannot be found. Among other things, a malfunction of T cells is suspected. This results in autoimmune reactions that lead to the deposition of immune complexes in the area of the renal corpuscles. As a consequence, vitreous (hyaline) deposits with additional fusions of podocytes develop. According to recent findings, at least in some cases the urokinase receptor (uPAR) is involved in the pathogenesis of the disease. Normally, this receptor is anchored in the membrane. However, in its soluble form, it can lead to changes in renal tissue. The soluble urokinase receptor represents a so-called permeability factor, which influences the filtering function of the renal corpuscles. This would also explain the fact that in kidney transplanted patients sclerosis of renal corpuscles can also occur again within a short time. The secondary form of FSGS can be triggered by various diseases such as IgA nephritis, lupus nephritis, other renal diseases, hepatitis C, HIV, heroin abuse, severe obesity, or hypertension.
Symptoms, complaints, and signs
The main symptom of focal segmental glomerulosclerosis is increased excretion of proteins in the urine (proteinuria). Sometimes it is the only symptom. However, in the majority of cases, a nephrotic syndrome develops with massive proteinuria, hypoproteinemia, hyperlipoproteinemia, and edema. Hypoproteinemia is characterized by decreased protein content in the blood. This results in altered permeability, leading to water retention (edema) in the tissues. At the same time, the metabolism of blood lipids is disturbed (hyperlipoproteinemia). In the long term, kidney function deteriorates to the point where dialysis is required. The disease is chronically progressive and can lead to complete kidney failure. Depending on the form of the disease, there are cases with favorable or poor prognosis.
Diagnosis
For the treatment of FSGS, it is critical to know what type of disease is present. For example, primary FSGS often responds to treatment with immunosuppressants. In the secondary form of the disease, the pressure in the glomeruli must be lowered with medication. Therefore, a differential diagnosis is absolutely necessary.A comprehensive medical history is taken to determine any underlying diseases. The level of protein excretion in the urine, the course of the disease, and electron microscopic findings are also important for diagnosis.
Complications
Focal segmental glomerulosclerosis belongs to a group of different diseases that affect the kidneys. In this case, partial scarring occurs on individual renal corpuscles that are responsible for the filtration process of the primary urine. The renal corpuscles themselves, however, never cover the complete vascular tangle of scarring. Scarring threatens the renal tissue with sclerosis. Focal segmental glomerulosclerosis carries significant risks of complications and requires close medical attention. If medical therapy is initiated too late, kidney failure may result. The syndrome usually affects men from the age of about 45. The disease may be genetic, due to an autoimmune reaction or a defective renal corpuscle filter function. A thorough differential diagnosis provides information as to which type the syndrome belongs to. In far more than half of all patients, the findings progress to nephrotic syndrome with massive protein excretion. Edema in the tissues and disturbed blood fat metabolism are the consequences. The kidneys begin to severely restrict their function and the affected person becomes a dialysis patient. If the syndrome develops chronically, total kidney failure can occur. In such a case, only a kidney transplant can help. If medical measures are taken at an early stage, as well as regular electron microscopic findings of the urine, the therapy usually includes only various preparations, the tolerability of which is adjusted to the patient.
When should one go to the doctor?
In case of swelling, edema and water retention on the body, a doctor should be consulted. If the changes increase in extent and intensity, a visit to the doctor is necessary as soon as possible. Thickening of the fingers and feet is considered unusual and should be examined. If the affected person has a diffuse feeling of illness or experiences inner restlessness, he or she should consult a doctor. If changes in kidney activity occur, there is reason for concern. Pain, disturbances in urination or an abnormality in the amount of urine should be examined and treated. A general weakness, a gradual decrease in performance and fatigue are considered indications that should be discussed with a physician. This is especially true if they increase or lead to impairment in coping with everyday life. If noticeable changes in weight occur for no apparent reason, it is advisable to consult a physician. If there is blood in the urine, action is required. As soon as blood loss is noticed again when going to the toilet, a doctor must be consulted, as there is a risk of permanent kidney dysfunction. If you feel generally unwell, have an elevated body temperature, sleep disturbances, irritability or nervousness, you should consult a doctor. If the complaints persist unabated for several weeks, there are health impairments that need to be clarified.
Treatment and therapy
Primary focal segmental glomerulosclerosis with nephrotic syndrome requires urgent treatment because it would otherwise lead to renal dysfunction requiring dialysis. Thus, immunosuppressive treatment has been shown to reduce proteinuria or, in some cases, even lead to its complete remission in the majority of patients. Prednisone is administered as a priority. In case of intolerance to prednisone, the patient is treated with cyclosporine. If relapses occur frequently, a combination treatment of prednisone with cyclosporine is usually considered. This also applies to patients who do not respond to prednisone alone. In case of nonresponse to both drugs or intolerance to both, therapy with mycophenolate mofetil can also be given. FSGS without nephrotic syndrome does not need to be treated with immunosuppressants. In all patients who cannot be or do not need treatment with immunosuppressants, therapy with ACE inhibitors or AT1 antagonists should be given. The same applies to patients with secondary FSGS who are given these drugs in addition to treatment of the underlying disease.
Outlook and prognosis
If medical care is very late or is not sought, focal segmental glomerulosclerosis shows an unfavorable disease course. The patient is at risk of renal failure in addition to various medical conditions. Without immediate intensive medical care, the affected person will die prematurely. The prognosis is also unfavorable in the case of a chronic course of the disease. Here, too, the patient is at risk of organ failure with potentially fatal consequences. Dialysis treatment is carried out beforehand, which is associated with severe impairments to the quality of life and limitations in coping with everyday life. If the disease is diagnosed at an early stage and then treated optimally, the prognosis improves considerably. Nevertheless, despite all efforts, no cure can be expected. The administration of medication can alleviate the symptoms. If there are hardly any side effects and the active substances are well accepted by the organism, the increased excretion of proteins can be avoided or at least significantly reduced. The patient must undergo long-term therapy, since discontinuation of the drugs will result in an immediate relapse of the symptoms. The difficulty of treatment also lies in the tolerance of the drugs. In many cases, the organism does not respond sufficiently to the active ingredients of the drugs. Therefore, it often becomes necessary to change the medication.
Prevention
Because of the many causes of FSGS, a universal recommendation for prevention cannot be given. Because some kidney diseases are a consequence of obesity, diabetes, and other metabolic syndrome disorders, a healthy lifestyle with a balanced diet, plenty of exercise, and avoidance of alcohol and smoking are recommended to reduce the risk of FSGS.
Follow-up
There are no special or direct measures and options of aftercare available to the affected person for this disease. The patient is primarily dependent on a quick diagnosis with the subsequent treatment, so that there are no further compilations and complaints with this disease. The earlier the disease is diagnosed and treated, the better the further course of the disease usually is, since self-healing is not possible. Therefore, early diagnosis and subsequent treatment are always in the foreground with this disease. In the case of this disease, the affected person should have his kidneys checked regularly. Only in this way can further damage to the kidneys be detected early and then treated. As a rule, the disease is treated with the help of medication. Those affected are dependent on the correct dosage and also on taking the medication regularly. If there are any uncertainties or questions, a doctor must be contacted. A doctor must also be consulted in the event of unexpected side effects. The disease does not usually reduce the life expectancy of the person affected if it is treated properly. Further measures of aftercare are not necessary in this case.
What you can do yourself
Focal segmental glomerulosclerosis requires medical care because the affected person is at risk of kidney failure as the disease progresses without help. Patients are unable to achieve symptom relief with alternative healing methods or through the body’s natural healing powers. Therefore, at the first signs of the disease, consultation with a doctor should be made and his advice followed. In everyday life, the patient can make sure that he keeps his own weight within the normal range. With the BMI calculator, it is possible at any time to find out in which range the affected person is by entering age, current weight and height. If the person is overweight, a diet plan should be worked out that contributes to weight reduction without side effects, stress or a strong feeling of deficiency. Basically, attention should be paid to a healthy and balanced diet. A diet rich in vitamins with plenty of fresh fruits and vegetables strengthens the immune system and promotes well-being. The consumption of sugar should be reduced. At the same time, alcohol and nicotine should be avoided.Additionally, adequate exercise and regular oxygen intake are important to support health and reduce overall susceptibility to disease as well as infection.
