What Is Focal Segmental Glomerulosclerosis?

Introduction

Focal Segmental Glomerulosclerosis (FSGS) may sound like a very complex term, but it is essentially a condition that affects the filtration of the blood that the kidney is responsible for.¹ Kidneys are very important in keeping our bodies clean by filtering out toxins, which pass out of the body in the form of urine. 

For patients, an understanding of FSGS empowers informed decision-making about their treatment options, lifestyle adjustments, and the importance of regular checkups. For healthcare professionals, a grasp of FSGS allows for accurate diagnosis, proper management, and the ability to provide comprehensive guidance to patients affected by the condition.

The basics of FSGS 

Definition and explanation of glomerulosclerosis 

To understand FSGS, we need to start by understanding how the kidney functions.

The kidney is made up of many tiny structures called glomeruli, which act as a sieve to filter out harmful waste and excess fluids and keep in important molecules such as protein that our body needs. 

‘Sclerosis’ means hardening or scarring, and so ‘glomerulosclerosis’ refers to the gradual scarring of the glomeruli specifically. 

When glomerulosclerosis occurs, these filters become damaged, causing them to lose their efficiency. Over time, these glomeruli develop scar tissue, which disrupts their normal function. This scarring can limit the kidney's ability to filter waste and can lead to more serious health conditions.  

Description of focal segmental glomerulosclerosis 

“Focal” means that the scarring doesn’t happen in every glomerulus; it's only in some of them. "Segmental" indicates that only parts of these affected glomeruli are scarred, not the entire structure. In FSGS, the scarring occurs in patches (i.e. segments) within the glomeruli. This specific pattern of scarring can be quite distinctive when seen under a microscope, which helps doctors diagnose the condition accurately.

Impact on kidney function and filtration 

The kidneys work as an intricate network of filters responsible for cleaning your blood. In FSGS, those glomeruli get scarred and aren’t able to be as selective in what they filter in or out.² This can result in larger molecules, particularly proteins, leaking through the filter and, therefore, into the urine. The medical term for this is proteinuria, and when this happens, it shows that there has been significant damage to the kidneys.  

As the scarring progresses and more protein leaves the body in the urine, the kidneys might struggle to regulate the balance of fluids and electrolytes in the body. This excess fluid can lead to swelling (oedema), usually around the ankles and eyes, as well as increased blood pressure. 

Causes and risk factors

Causes of FSGS broadly fall into two categories: primary and secondary.  

Primary generally means that the scarring to the kidney happens for an unknown reason (idiopathic). Secondary refers to the fact that there is some form of underlying condition or medication that has led to kidney scarring in FSGS. The most common secondary causes are: 

• Genetic predisposition: certain genetic variations can make individuals more susceptible to kidney damage.
• Hypertension: high blood pressure puts a lot of stress on the cells of the glomerulus (podocytes) and, therefore, increases the chances of scarring.³ 
• Obesity: being obese increases the pressure of blood flowing through the kidneys (i.e. causing kidney hypertension), which damages the kidneys.⁴ 
• HIV/AIDS: the virus that causes HIV can spread to the kidney and directly attacks podocytes, further causing scarring and damaging the filtration system. 
• Drug-related: these include drug toxicity of medications (such as NSAIDs like ibuprofen or even the medications needed to manage HIV) or illicit drugs (such as heroin). 

Clinical presentation 

FSGS has a range of clinical symptoms, but the most common ones are as follows:  

• Frothy urine as a result of protein in the urine 
• Swelling around ankles and feet (oedema) due to accumulation of fluid 
• High blood pressure (hypertension) due to increased fluid in the body from the build-up of salts that would usually be filtered out 
• Weight gain as a result of the extra fluid in the body 
• Decreased urine output as kidneys are not working as well

Variability in symptom severity  

While these symptoms are characteristic of FSGS, the severity of their presentation can vary widely among individuals. Some patients might experience mild discomfort, while others may endure severe complications. This emphasises the importance of regular monitoring and follow-up with kidney specialists. 

Importance of early detection and diagnosis  

Timely identification of FSGS is important, allowing healthcare providers to start the best treatment and limit the damage to the kidneys and the rest of the body. They may also be able to slow the progression of FSGS and potentially preserve kidney function. Early intervention also ensures the best outcomes for people living with FSGS.

Diagnosis 

Focal Segmental Glomerulosclerosis (FSGS) diagnosis involves several parts: 

Medical history and physical examination  

The initial diagnosis of FSGS is usually made through a medical history and physical examination. Insights into a medical background and any underlying conditions can help identify potential risk factors and offer valuable context for interpreting diagnostic results. 

Urinalysis and proteinuria assessment  

Urinalysis is a key initial step, where a sample of urine is analysed, looking at red blood cells, white blood cells, and most importantly, protein. Elevated levels of protein in the urine are a strong indicator of kidney issues. 

Blood tests: serum creatinine  

Blood tests measuring serum creatinine levels are important in assessing kidney function. Creatinine is a substance that the kidneys should filter out, and therefore, increased levels in the blood suggest that there is a filtration problem.  

Renal ultrasound  

Renal ultrasound is a non-invasive imaging technique used to visualise the kidneys' size, shape, and structure. While it may not definitively diagnose FSGS, it can help rule out other kidney conditions and identify any structural abnormalities. 

Kidney biopsy  

A kidney biopsy is often the gold standard for definitively diagnosing FSGS, meaning that it is the best method of identifying if someone has FSGS. This procedure involves getting a small sample of kidney tissue, which can be examined under a microscope. Because of how powerful these microscopes are, the pattern of the kidney tissue can be visualised well. In FSGS, there is a characteristic pattern of scarring and damage in the glomeruli. Seeing how scarred the kidneys are through biopsy also allows assessment of the severity of the condition and, therefore, helps to guide treatment.⁵

Treatment and management 

Conservative management 

A balanced diet with controlled protein, sodium, and potassium intake can help manage symptoms and alleviate the pressure on the kidneys. Lifestyle modifications, such as maintaining a healthy weight and regular exercise, also improve general well-being and health.  

Medications 

• Immunosuppressants: Specific steroids can help calm down the immune system and stop it from attacking the kidneys. 
• ACE inhibitors and angiotensin receptor blockers: these medications can control blood pressure and also reduce proteinuria.
• Diuretics help regulate fluid balance and reduce swelling by promoting increased urine production.

Dialysis and kidney transplantation in severe cases 

In severe cases where kidney function significantly declines, dialysis or kidney transplantation might be necessary.  

Dialysis artificially filters waste products through a machine, effectively doing the work your kidneys should be doing.  

Transplantation involves replacing a damaged kidney with a healthy one through surgery. 

Monitoring disease progression and response to treatment 

Regular monitoring of disease progression and treatment response is crucial. Kidney function, proteinuria levels, blood pressure, and other relevant indicators are closely monitored to assess how well treatment plans are working and the disease progression.  

Prognosis and complications

The prognosis of FSGS depends on the underlying cause of the FSGS and how well someone responds to treatments. Some individuals might experience positive shifts and enhanced well-being, while others might find that they are still struggling with persistent proteinuria and persistent damage to the kidney.  

Potential complications

There are a few potential complications that it is important to monitor and try to avoid as much as possible. One of the major concerns is chronic kidney disease (CKD), which occurs when the kidney has been damaged over a period of time and becomes irreversibly damaged.  

In more serious scenarios, FSGS could progress to end-stage renal disease (ESRD). ESRD is when the kidneys can no longer function well enough to cope with day-to-day life. In these situations, it is likely that a kidney transplant or dialysis (where a machine acts as the kidneys and filters your blood) is needed. 

FSGS and cardiovascular health are closely intertwined, as when the kidney is damaged and filtration is poor, the heart pumps harder to try and compensate for this and to get more blood to the kidneys. This, in turn, puts more stress on the heart and weakens it over time, causing cardiovascular disease. 

Summary

FSGS, a kidney disorder characterised by glomerular damage, exhibits varying symptoms, namely fluid build-up and protein in the urine. Outcomes are based on factors like underlying causes and the response to treatment. Early detection and effective management are of significant importance and can make a huge difference in slowing the progression of kidney disease and avoiding complications.