Yes, identifying the underlying cause is a critical part of the diagnostic and treatment process for nephrotic syndrome. In the UK, medical professionals categorise the condition into two groups: primary (starting in the kidney) and secondary (caused by another disease). Because the treatment for a protein leak caused by diabetes is entirely different from one caused by an autoimmune disorder, specialists must perform a series of “screening” tests to find the root cause.
In the NHS, this “detective work” usually happens alongside your initial treatment for swelling and protein loss. While the immediate goal is to stabilise your symptoms, the long-term goal is to treat the “parent” condition to prevent the syndrome from returning. Whether you are an adult with a new diagnosis or the parent of a child who isn’t responding to steroids, understanding these underlying tests is vital for navigating your care plan.
What We’ll Discuss in This Article
- The difference between primary and secondary nephrotic syndrome.
- Common systemic diseases that specialists screen for in the UK.
- The role of blood tests in identifying autoimmune and infectious triggers.
- Why age plays a significant role in which tests are ordered.
- Screening for rare conditions like amyloidosis or certain cancers.
- How finding the underlying cause changes your long-term treatment.
Primary vs. Secondary: Why it matters
The “underlying cause” determines whether your kidney filters are the source of the problem or simply the victims of a wider disease.
- Primary Nephrotic Syndrome: This is when the disease is limited to the kidneys (e.g., Minimal Change Disease or FSGS). Treatment usually focuses on the immune system using steroids.
- Secondary Nephrotic Syndrome: This is when a condition elsewhere in the body such as high blood sugar or an overactive immune system damages the filters. In these cases, the protein leak will only stop if the secondary disease is brought under control.
[Image showing the kidneys being affected by systemic conditions like diabetes or lupus]
Common underlying causes tested in the UK
When you are referred to a renal clinic, the specialist will order a “screening panel” of blood and urine tests. The most common conditions they look for include:
1. Diabetes (Diabetic Nephropathy)
Diabetes is the most common secondary cause of nephrotic syndrome in UK adults. High blood sugar levels physically damage the filters over many years. A simple HbA1c blood test is used to check for this.
2. Autoimmune Diseases
Conditions like Systemic Lupus Erythematosus (SLE) can cause the immune system to attack the kidneys (Lupus Nephritis). Specialists use an “Autoantibody Screen” (ANA, dsDNA) to look for these markers.
3. Viral Infections
Certain viruses can trigger an immune response that leads to a protein leak. In the UK, it is standard to screen for:
- Hepatitis B and C
- HIV
4. Rare Protein Disorders
In older adults, specialists may check for Amyloidosis or Multiple Myeloma, where abnormal proteins produced elsewhere in the body get “stuck” in the kidney filters.
| Underlying Category | Specific Condition | Key Diagnostic Test |
| Metabolic | Diabetes | HbA1c Blood Test |
| Autoimmune | Lupus (SLE) | ANA / dsDNA Antibodies |
| Infectious | Hepatitis / HIV | Viral Serology Screen |
| Inflammatory | Vasculitis | ANCA Blood Test |
| Malignancy | Lymphoma / Myeloma | Protein Electrophoresis |
How age affects the testing process
The “testing list” changes depending on the patient’s age, as different causes are more likely at different life stages.
- Children: Most cases are primary (Minimal Change Disease). Specialists rarely do extensive secondary screening unless the child has other symptoms like joint pain or a rash. Genetic testing may be used if the child is a baby or doesn’t respond to steroids.
- Adults: Almost all adults will undergo a full secondary screen because the likelihood of a systemic cause (like diabetes or lupus) is much higher. A kidney biopsy is also more common in adults to find the specific “pattern” of the damage.
Nephrotic vs. Nephritic Underlying Triggers
Sometimes, the underlying cause determines whether a patient presents with a nephrotic or nephritic “pattern” of disease.
| Feature | Nephrotic Trigger Focus | Nephritic Trigger Focus |
| Common Trigger | Chronic Diabetes | Recent Strep Infection |
| Screening Goal | Find the cause of “leakiness” | Find the cause of “inflammation” |
| Key Blood Test | Glucose and Autoantibodies | Anti-GBM or Complement levels |
| Typical Finding | Metabolic or chronic damage | Acute immune flare-up |
To Summarise
Testing for underlying causes is a standard and essential part of your treatment. By ruling out conditions like diabetes, lupus, or infections, your UK specialist can ensure you are on the most effective medication for your specific type of kidney damage. While some tests are simple blood draws, others, like a biopsy, provide a deeper look at the filters. Identifying the “why” behind the protein leak is the best way to protect your kidneys for the long term.
If you experience severe, sudden, or worsening symptoms, such as difficulty breathing or extreme facial swelling, call 999 immediately.
Do I need these tests if I’m already on steroids?
Yes. If the underlying cause is something like an infection, steroids might not be the right treatment or could even make the infection worse.
Will my GP do these tests?
A GP may start basic tests like HbA1c (for diabetes), but most of the “specialist” screening for lupus or rare proteins is handled by the hospital renal team.
Can a medication be an underlying cause?
Yes. Certain drugs, like NSAIDs (ibuprofen/naproxen), can trigger nephrotic syndrome. Your doctor will review all your current medications as part of the screening.
How long do the “secondary screen” results take?
Most blood results return within 48 hours, but complex immunology or viral tests can take up to a week.
What if no underlying cause is found?
This is common and is called “idiopathic” (primary) nephrotic syndrome. It means the issue started within the kidney filters themselves.
Is genetic testing common?
In adults, it is rare. It is mostly used for infants (congenital cases) or children who do not respond to any standard medical treatments.
Authority Snapshot
This article was reviewed by Dr. Stefan Petrov, a UK-trained physician with experience in general medicine and renal diagnostics. The information follows NHS and NICE clinical knowledge summaries for the investigation of glomerular diseases. Our goal is to help patients understand the “detective work” involved in their diagnosis and how it leads to more personalised, effective care.
