Focal Segmental Glomerulosclerosis
Disease Details
Family Health Simplified
- Description
- Focal segmental glomerulosclerosis (FSGS) is a kidney disorder characterized by scarring in scattered regions of individual glomeruli, the filtering units within the kidneys.
- Type
- Focal Segmental Glomerulosclerosis (FSGS) can be classified into primary (idiopathic) and secondary types based on its cause. Regarding genetic transmission, FSGS can inherit in an autosomal dominant or autosomal recessive pattern, although it can also occur sporadically without a clear genetic link.
- Signs And Symptoms
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The most common symptoms are a result of abnormal loss of protein from the glomerulus of the kidney, and include:
Frothy urine (due to excess protein)
Excess water retention (pitting edema, due to loss of serum albumin)
Susceptibility to infection (due to loss of serum antibodies)Common signs are also due to loss of blood proteins by the glomerulus of the kidney, including:
Protein in the urine (often in the nephrotic syndrome-range of >3.5 g/day)
Low serum albumin (<3.5 g/dl)
Low serum antibodies
High serum cholesterol (compensatory by the liver to compensate for low serum oncotic pressure)
Fatty casts in the urine (secondary to hypercholesterolemia) - Prognosis
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The majority of untreated cases of FSGS will progress to end-stage kidney disease. Important prognostic factors include the degree of proteinuria and initial response to therapy.
Patients with nephrotic-range (>3.5 g/day) proteinuria have over a 50% rate of progression to end-stage kidney disease at 10 years. Only 15% of patients with sub-nephrotic ranges of proteinuria progress to end-stage renal failure at 10 years.Initial response to therapy also dictates long-term outcomes. Those defined as having a "complete response" typically manifest a proteinuria of <300 mg/day; those with a "partial response" manifest a sub-nephrotic range of proteinuria, <3.5 g/day. Either complete or partial response is associated with 80% kidney survival at 10 years, compared with about 50% among non-responsive patients. - Onset
- Focal segmental glomerulosclerosis (FSGS) can present at any age, although it most commonly affects adolescents and young adults.
- Prevalence
- The prevalence of focal segmental glomerulosclerosis (FSGS) varies, but it is estimated to affect approximately 7 per million people annually. It is a significant cause of nephrotic syndrome, particularly in adults.
- Epidemiology
- FSGS accounts for 35% of all cases of nephrotic syndrome, making it one of the most common causes of nephrotic syndrome in the United States. FSGS accounts for 2% of all cases of kidney failure. African American patients have four times the likelihood of developing FSGS. Men are about two times as likely to develop FSGS compared to women.
- Intractability
- Focal Segmental Glomerulosclerosis (FSGS) can be challenging to treat and is often considered difficult to manage. It is a type of nephrotic syndrome characterized by scarring (sclerosis) in parts of the glomeruli in the kidney. Treatment options include corticosteroids, immunosuppressive drugs, and other medications to manage symptoms and slow disease progression, but responses can vary. Some patients may progress to end-stage kidney disease, requiring dialysis or a kidney transplant. Therefore, FSGS can be considered intractable, especially in cases where conventional treatments are ineffective.
- Disease Severity
- Focal segmental glomerulosclerosis (FSGS) is a kidney disorder characterized by scarring (sclerosis) in some of the glomeruli, which are tiny structures within the kidneys that filter waste from the blood. The severity of FSGS can vary widely among individuals. In some cases, it leads to progressive kidney damage and eventually chronic kidney disease or kidney failure. Patients may experience symptoms like proteinuria (high protein levels in the urine), edema (swelling), and hypertension (high blood pressure). Early diagnosis and treatment are crucial in managing the disease and slowing its progression.
- Healthcare Professionals
- Disease Ontology ID - DOID:1312
- Pathophysiology
- FSGS is primarily a disease of the renal glomerulus, the site of filtration of ions and solutes. Podocytes are specialized cells lining the Bowman's capsule that contribute to the filtration barrier, preventing molecules larger than 5 nm from being filtered. FSGS involves damage to the renal podocytes such that larger molecules, most notably proteins, are filtered and lost through the kidney. Thus, many of the signs and symptoms of FSGS are related to protein loss.On histology, FSGS manifests as scarring (sclerosis) to segments of glomeruli; moreover, only a portion of glomeruli are affected. The focal and segmental nature of disease seen on histology help to distinguish FSGS from other types of glomerular sclerosis.FSGS can be classified by the putative cause of damage to podocytes. Primary FSGS involves cases in which no cause is readily identifiable. It is presumed that a set of unidentified circulating factors in the blood contribute to podocyte damage in these cases.Secondary FSGS is caused by an identifiable stress or toxin that injures podocytes. Many causes of secondary FSGS contribute to podocyte injury through hyperfiltration, which is a scenario of excess filtration by renal glomeruli. Hyperfiltration can be caused by obesity, diabetes or loss of the contralateral kidney, among other causes.Secondary FSGS can also be caused by toxins, including anabolic steroids and heroin.A number of genes have been implicated in FSGS. These include: NPHS1, which encodes the protein nephrin that contributes to the filtration barrier; NPHS2, which encodes the protein podocin found in podocytes; and INF2, which encodes the actin-binding protein formin.The pathogenesis of HIV-associated FSGS is unclear, but may be primarily due to the presence of the G1/G2 risk alleles for APOL1. There is some data to suggest that HIV can infect tubular epithelial cells and podocytes, but much remains to be known.
- Carrier Status
- Carrier status is not typically applicable to Focal Segmental Glomerulosclerosis (FSGS) as it is not an inherited disorder in a simple Mendelian fashion. Instead, FSGS can be associated with both genetic mutations and various environmental factors, making it more complex than a single-gene inheritance pattern.
- Mechanism
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Focal segmental glomerulosclerosis (FSGS) is a disease characterized by scarring (sclerosis) in some of the glomeruli (focal) and only in certain segments (segmental) of each affected glomerulus. The underlying mechanisms include:
**Mechanism:**
- **Podocyte Injury**: Podocytes are specialized cells in the kidney that play a crucial role in filtration. Injury to these cells is central to the development of FSGS. The damage results in the detachment of podocytes from the glomerular basement membrane and subsequent scarring.
- **Proteinuria**: Damage to the filtration barrier leads to leakage of proteins into the urine (proteinuria), which is a hallmark of FSGS.
- **Progressive Scarring**: Over time, repeated cycles of injury and repair result in chronic scarring and loss of kidney function.
**Molecular Mechanisms:**
- **Genetic Mutations**: Mutations in genes encoding podocyte proteins (e.g., NPHS1, NPHS2) can lead to dysfunction and FSGS.
- **Circulating Permeability Factors**: Some forms of FSGS are associated with unidentified circulating factors that increase glomerular permeability, contributing to proteinuria and glomerulosclerosis.
- **Cell Signaling Pathways**: Dysregulation in pathways such as the slit diaphragm signaling, actin cytoskeleton dynamics, and podocyte adhesion contribute to podocyte injury.
- **Endothelial Dysfunction**: Damage to the endothelial cells lining the glomerular capillaries can exacerbate podocyte injury and contribute to sclerosis.
- **Immune System Activation**: Inflammatory cytokines and chemokines released by immune cells can mediate podocyte injury and glomerular scarring.
Understanding these mechanisms is crucial for developing targeted therapies to treat and manage FSGS. - Treatment
- First-line treatment for primary FSGS consists of anti-inflammatory drugs. Specifically, glucocorticoids are begun in patients manifesting with nephrotic-range proteinuria (>3.5 g/day). For patients who maintain nephrotic-range proteinuria despite glucocorticoids, or for patients who demonstrate glucocorticoid intolerance, calcineurin inhibitors (e.g., tacrolimus) are initiated. Successful treatment is defined as a drop in proteinuria to sub-nephrotic ranges.The treatment of secondary FSGS involves addressing the particular toxic or stress agent.
- Compassionate Use Treatment
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Focal segmental glomerulosclerosis (FSGS) is a serious condition where scar tissue forms in parts of the kidneys' filtering units. When standard treatments fail, compassionate use, off-label, or experimental approaches may be considered:
1. **Compassionate Use Treatment**:
- Compassionate use allows patients with serious or life-threatening conditions to access investigational drugs or therapies outside of clinical trials. In the context of FSGS, this might include experimental immunosuppressants or antiproteinuric agents being tested for efficacy in clinical trials.
2. **Off-label Treatments**:
- **Rituximab**: Originally approved for lymphoma and rheumatoid arthritis, it’s used off-label for FSGS due to its immunomodulatory properties.
- **Adalimumab (Humira)** and **Etanercept (Enbrel)**: TNF inhibitors studied for their potential in reducing proteinuria in FSGS patients.
- **Plasmapheresis (Plasma Exchange)**: Sometimes used off-label to remove harmful antibodies from the bloodstream in severe cases.
3. **Experimental Treatments**:
- **Sparsentan**: A dual endothelin receptor antagonist/angiotensin II receptor blocker currently under investigation.
- **VX-147**: A novel experimental treatment targeting APOL1-mediated kidney disease, currently in clinical trials for high-risk FSGS patients.
- **Stem Cell Therapy**: Considered experimental, aimed at repairing damaged kidney tissue.
Patients with FSGS should consult their specialist to explore these options and determine eligibility for such treatments. - Lifestyle Recommendations
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Focal segmental glomerulosclerosis (FSGS) is a disease that affects the kidneys' filtering units, leading to scarring and kidney damage. Lifestyle recommendations for managing FSGS include:
1. **Dietary Changes:**
- Reduce salt intake to manage blood pressure.
- Limit protein intake to decrease kidney workload.
- Opt for a balanced diet rich in fruits, vegetables, and whole grains.
2. **Fluid Management:**
- Monitor and possibly restrict fluid intake as advised by a healthcare professional.
3. **Blood Pressure Control:**
- Maintain optimal blood pressure through lifestyle and medication as necessary.
4. **Exercise:**
- Engage in regular, moderate physical activity to promote overall health.
- Avoid strenuous exercise that might stress the kidneys.
5. **Weight Management:**
- Achieve and maintain a healthy weight to reduce strain on the kidneys.
6. **Avoiding Nephrotoxic Substances:**
- Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) and other substances that can harm the kidneys.
7. **Smoking Cessation:**
- Quit smoking to improve overall kidney function and general health.
8. **Stress Management:**
- Incorporate stress-reducing activities such as yoga, meditation, or hobbies.
Always consult with a healthcare provider for personalized advice tailored to individual health needs and conditions. - Medication
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For focal segmental glomerulosclerosis (FSGS), medication options often include:
1. **Corticosteroids**: Prednisone is commonly used to reduce inflammation and suppress the immune system.
2. **Calcineurin inhibitors**: Such as cyclosporine and tacrolimus, which help to suppress the immune system.
3. **ACE inhibitors and ARBs**: Medications like lisinopril or losartan to control high blood pressure and reduce proteinuria.
4. **Immunosuppressive drugs**: Such as mycophenolate mofetil or cyclophosphamide, especially if corticosteroids are not effective or suitable.
5. **Diuretics**: To help manage edema.
Always consult with a healthcare provider for an accurate diagnosis and personalized treatment plan. - Repurposable Drugs
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Focal segmental glomerulosclerosis (FSGS) is a disease that affects the kidney's filtering units, causing serious scarring. Some repurposable drugs that have shown potential in managing FSGS include:
1. **Angiotensin-converting enzyme (ACE) inhibitors** (e.g., lisinopril) - Typically used for hypertension, these can help reduce proteinuria.
2. **Angiotensin II receptor blockers (ARBs)** (e.g., losartan) - Similar to ACE inhibitors, they help in reducing proteinuria and protecting kidney function.
3. **Calcineurin inhibitors** (e.g., cyclosporine, tacrolimus) - These immunosuppressive drugs are traditionally used in organ transplant recipients but can help reduce protein loss in urine.
4. **Glucocorticoids** (e.g., prednisone) - Steroids used for their anti-inflammatory and immunosuppressive effects.
5. **Mycophenolate mofetil (MMF)** - Initially developed for preventing organ transplant rejection, MMF has immunosuppressive properties that may benefit FSGS patients.
It must be noted that these repurposable drugs may not work for all individuals and should be used under the care of a healthcare provider. - Metabolites
- For focal segmental glomerulosclerosis (FSGS), there are no specific characteristic metabolites identified that are consistently associated with the condition. FSGS is identified through clinical features, biopsy of kidney tissue, and other diagnostic evaluations. Metabolic profiling in research may reveal altered levels of various metabolites in affected individuals, but these findings are variable and not yet standardized for clinical use.
- Nutraceuticals
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For focal segmental glomerulosclerosis (FSGS), nutraceuticals refer to dietary supplements or functional foods that may potentially support kidney health. While no specific nutraceuticals have been definitively proven to treat FSGS, some substances under exploration for their potential renal benefits include:
1. Omega-3 fatty acids: May reduce inflammation and proteinuria.
2. Coenzyme Q10: An antioxidant that might improve mitochondrial function in kidney cells.
3. Curcumin: Found in turmeric, it may have anti-inflammatory and antioxidant effects.
4. Resveratrol: A compound in red wine and certain berries, also with anti-inflammatory and antioxidant properties.
It's important to discuss any nutraceuticals with a healthcare provider before use, as they can interact with conventional treatments and other aspects of FSGS management. - Peptides
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Focal segmental glomerulosclerosis (FSGS) is a disease that affects the kidneys' filtering units, known as glomeruli, specifically causing scarring (sclerosis) in sections (segments) of each glomerulus.
1. **Peptides in FSGS**: Research into the role of peptides in FSGS is ongoing. Certain bioactive peptides may contribute to the disease process by promoting inflammation, fibrosis, or aberrant cell signaling within the kidneys. For example, protease-resistant peptides derived from podocyte proteins can damage the glomerular basement membrane.
2. **Nanomedicine in FSGS**: Nanotechnology holds promise for the diagnosis and treatment of FSGS. Nanoparticles can be engineered to deliver drugs directly to the kidneys, minimizing systemic side effects and improving therapeutic efficiency. For example, nanoscale drug delivery systems targeting specific kidney cells or pathways involved in FSGS could potentially halt or reverse disease progression.
In summary, peptides and nanotechnology could play crucial roles in understanding, diagnosing, and treating FSGS, though more research is needed to translate these concepts into clinical practice.