Symptoms and Diagnosis 
of Focal Segmental 
Glomerulosclerosis (FSGS)

Recognizing FSGS: From symptom onset to diagnosis

FSGS may come to clinical attention through a range of symptoms and laboratory abnormalities.^1,2 Because signs of disease can vary, timely recognition of symptoms, assessment of kidney involvement, and confirmatory kidney biopsy are important for accurate diagnosis and appropriate management.^1,2

Understanding the clinical presentation of FSGS

Proteinuria is a central clinical feature of FSGS, reflecting podocyte injury and disruption of the glomerular filtration barrier, key drivers of symptoms in FSGS.^1-3 Proteinuria is both a core manifestation of disease and an important marker of progression.^2,4

Yet, clinical presentation can vary.¹ Some patients seek care because they notice swelling, fatigue, or urinary changes, while others are identified only after abnormal laboratory findings suggest glomerular disease.^1,2,5 Often, patients will already present with nephrotic syndrome, characterized by heavy proteinuria (≥3.5 g/day), hypoalbuminemia, edema, and often hyperlipidemia.^1,2,5

• In primary FSGS, heavy proteinuria, a key indicator of nephrotic syndrome, may occur relatively abruptly^2,5 and prompt urgent referral for further evaluation

This variability in presentation is reflected in the symptoms that patients experience and commonly includes¹:

Edema (swelling)¹

Swelling, often involving the face, eyelids, lower extremities, or abdomen, is one of the most common symptoms that prompts patients to seek medical evaluation. Patients may notice tightness of the skin, weight gain, or discomfort due to fluid accumulation

Fatigue¹

Many patients report persistent fatigue, which can affect daily functioning, work productivity, and physical activity

Urinary changes^1,5

Foamy or frothy urine may occur when proteinuria becomes substantial. However, some patients have significant proteinuria without overt symptoms, meaning abnormalities may only be detected through laboratory testing

Other systemic symptoms¹

Patients may also report shortness of breath, sleep disturbances, gastrointestinal symptoms such as nausea, or generalized pain and discomfort associated with edema or treatment effects

Recognizing FSGS early is important as persistent proteinuria may precede full clinical characterization, and delayed recognition can allow progression to substantial kidney impairment and, over time, kidney failure.^4,5

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Long-Term Outcomes in Nephrotic Syndrome by Kidney Biopsy Diagnosis and Proteinuria

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Diagnostic evaluation of FSGS

Diagnosing FSGS requires integration of clinical findings, laboratory testing, and kidney biopsy.^1,2

When patients seek medical care, an initial evaluation may reveal clinical features of nephrotic syndrome, such as edema, as well as laboratory abnormalities, including proteinuria on urinalysis and evidence of impaired kidney function.^2,6

Because proteinuria is central to suspected glomerular disease and helps identify patients who may have nephrotic syndrome (>3.5 g/day), it is quantified using^2,6,7:

Laboratory abnormalities reflecting disease severity and complications of nephrotic syndrome may also be evaluated. Common assessments include^2,6,8:

Serum albumin

Hypoalbuminemia (<3.5 g/dL) commonly occurs in nephrotic syndrome due to urinary protein loss

Lipid profile

Hyperlipidemia, including elevated total cholesterol and low-density lipoprotein (LDL) cholesterol, is frequently observed in patients with nephrotic-range proteinuria

Serum creatinine and estimated glomerular filtration rate (eGFR) may also be used to assess kidney function.^2,8 Patients may present with reduced eGFR, indicating chronic kidney disease.^2,4

Collectively, these findings help characterize kidney function and identify features of nephrotic syndrome.^2,6,8

Kidney biopsy: Confirming the diagnosis

Despite the availability of multiple clinical and laboratory assessments, definitive diagnosis of FSGS requires kidney biopsy to determine clinical classification and guide management.²

A biopsy evaluation²:

Because FSGS represents a pattern of glomerular injury with multiple potential causes, biopsy findings must be interpreted alongside clinical features to determine the underlying mechanism of disease and classification of FSGS.^2,6 This is important for determining appropriate treatment and management strategies.^2,6

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Managing FSGS

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Why early recognition matters

Many patients with FSGS enter the healthcare system after symptoms have appeared or kidney function has already declined.¹ Earlier recognition of symptoms and evaluation of persistent proteinuria may help identify patients sooner in the course of disease and lead to better long-term outcomes.^1,4

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Learn about FSGS pathophysiology, long-term outcomes, and the humanistic burden experienced by patients and their care providers

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