Nephrotic syndrome is caused by damage to the tiny clusters of blood vessels in your kidneys called glomeruli. These structures act as filters, and when they are damaged, they allow too much protein to leak from the blood into the urine. This damage can be caused by conditions that only affect the kidneys or by systemic diseases that affect the whole body.
In the UK, the causes of nephrotic syndrome are broadly categorised into primary causes (originating in the kidney) and secondary causes (resulting from another illness). The most common primary cause in children is Minimal Change Disease, while in adults, secondary causes such as diabetic nephropathy or autoimmune conditions like lupus are more frequent. Identifying the exact cause is essential for determining the correct treatment plan, which may involve steroids, immunosuppressants, or managing an underlying chronic disease.
What We’ll Discuss in This Article
- The role of the glomeruli and how damage leads to protein leakage.
- Detailed breakdown of primary kidney diseases like Minimal Change Disease and FSGS.
- Common secondary causes, including diabetes, lupus, and infections.
- Triggers that can cause a relapse or worsening of symptoms.
- The clinical differences between nephrotic and nephritic syndrome causes.
- Standard UK diagnostic procedures used to identify the underlying cause.
Primary causes of nephrotic syndrome
Primary causes are conditions where the damage starts directly within the kidneys’ filtering units. These are often autoimmune in nature, where the body’s immune system mistakenly attacks the glomeruli. In many cases, particularly in children, the exact reason why this happens remains unknown.
Common primary causes include:
- Minimal Change Disease (MCD): The most frequent cause in children. Under a standard microscope, the kidney tissue looks normal, but the filters are not working correctly.
- Focal Segmental Glomerulosclerosis (FSGS): Characterised by scarring (sclerosis) in specific sections of the glomeruli. It is a common cause of nephrotic syndrome in adults.
- Membranous Nephropathy: Caused by the buildup of immune complexes that thicken the membranes within the filters.
- Membranoproliferative Glomerulonephritis (MPGN): An uncommon cause involving both inflammation and changes to the structure of the kidney filters.
Clinical Context
According to NICE guidelines, when a child presents with symptoms of nephrotic syndrome, they are often started on steroid treatment immediately because Minimal Change Disease is so likely. In adults, a kidney biopsy is usually necessary to differentiate between these primary causes before starting intensive treatment.
Secondary causes of nephrotic syndrome
Secondary causes occur when a systemic disease or an external factor damages the kidneys over time. These are more common in the adult population and often require managing the main disease to protect kidney function.
The leading secondary causes include:
- Diabetes Mellitus: Long-term high blood sugar levels cause diabetic nephropathy, which is a major cause of kidney protein leak in the UK.
- Lupus (Systemic Lupus Erythematosus): An autoimmune disease that can cause significant inflammation in the kidneys (lupus nephritis).
- Amyloidosis: A rare condition where abnormal proteins called amyloids build up in the kidneys, disrupting their function.
- Infections: Certain viruses and infections, such as HIV, Hepatitis B, and Hepatitis C, can trigger nephrotic syndrome.
- Certain Medications: The use of non-steroidal anti-inflammatory drugs (NSAIDs) or lithium has been linked to kidney filter damage in some patients.
| Cause Type | Disease Example | Mechanism of Damage |
| Primary | Minimal Change Disease | Foot process effacement (microscopic filter changes) |
| Primary | FSGS | Physical scarring of the filtering units |
| Secondary | Diabetes | Thickening and hardening of blood vessels (Sclerosis) |
| Secondary | Lupus | Immune-mediated inflammation of the glomeruli |
Nephrotic vs Nephritic Syndrome
While both involve damage to the glomeruli, the underlying cause and clinical presentation differ. Nephrotic syndrome is primarily a disorder of the ‘barrier’ (leading to protein loss), whereas nephritic syndrome is a disorder of ‘inflammation’ (leading to blood loss).
The following table compares the typical causes and features:
| Feature | Nephrotic Syndrome | Nephritic Syndrome |
| Common Causes | MCD, FSGS, Diabetes | Post-streptococcal GN, IgA Nephropathy |
| Main Clinical Sign | Extreme Swelling (Oedema) | Blood in urine (Haematuria) |
| Pathology | Leaky filtration membrane | Inflamed and ruptured capillaries |
| Proteinuria | Massive (>3.5g/day) | Mild to moderate |
| Blood Pressure | Often normal | Often high (Hypertension) |
Triggers and risk factors for relapses
For many patients, especially those with Minimal Change Disease, the condition can go into remission but may be triggered to return. Identifying these triggers is a key part of long-term management in the UK.
Common triggers include:
- Upper Respiratory Infections: Colds, flu, and sore throats are the most frequent triggers for a relapse.
- Allergic Reactions: Reactions to pollen, dust, or certain foods can sometimes stimulate the immune system enough to cause a flare-up.
- Bee Stings or Insect Bites: In rare clinical cases, these have been documented as sudden triggers for nephrotic symptoms.
- Vaccinations: While generally safe, some patients experience a temporary increase in protein leakage following certain immunisations.
To Summarise
Nephrotic syndrome is caused by damage to the kidney’s filtering units, the glomeruli. Primary causes, like Minimal Change Disease, start in the kidney and are common in children. Secondary causes, such as diabetes or lupus, are more common in adults and result from systemic illness. Understanding the cause is vital for treatment, as it dictates whether steroids, blood pressure management, or treating an underlying infection is the priority.
If you experience severe, sudden, or worsening symptoms, such as shortness of breath or extreme facial swelling, call 999 immediately.
What is the most common cause of nephrotic syndrome in children?
Minimal Change Disease is the most common cause, accounting for about 90% of childhood cases in the UK.
Can diabetes cause nephrotic syndrome?
Yes, diabetic nephropathy is a leading secondary cause of nephrotic syndrome in adults.
Is it always caused by an autoimmune problem?
Not always, but many primary causes are thought to be immune-mediated, where the body’s defences attack the kidney filters.
Can certain medications cause it?
Yes, some drugs like NSAIDs (e.g., ibuprofen) can occasionally trigger kidney issues that lead to nephrotic syndrome.
How do doctors find the exact cause?
In adults, a kidney biopsy is often used to look at the tissue under a microscope. Children are often diagnosed based on their response to steroids.
Does a high-protein diet cause nephrotic syndrome?
No, a high-protein diet does not cause the condition, but it is often managed with specific dietary protein levels once diagnosed.
Authority Snapshot
This article was reviewed by Dr. Stefan Petrov, a UK-trained physician with significant experience in general medicine and emergency care. The information provided aligns with NHS and NICE clinical guidance regarding the pathophysiology and aetiology of nephrotic syndrome. Our focus is to provide clear, evidence-based explanations to help patients understand why their kidneys may be leaking protein.
