Nephrotic syndrome is a kidney condition where damaged filters in the kidneys leak large amounts of protein into the urine, typically more than 3.5 grams per day in adults. This protein loss triggers a cascade of problems: the blood’s protein levels drop, cholesterol rises, and fluid accumulates in the body’s tissues, causing visible swelling. It’s not a single disease but rather a pattern of symptoms that can result from several different underlying conditions.
How the Kidney’s Filters Break Down
Your kidneys contain roughly one million tiny filtering units, each with a cluster of blood vessels called a glomerulus. These filters are lined with specialized cells called podocytes, which extend finger-like projections that interlock with one another. The gaps between these projections are bridged by a thin membrane that acts as the kidney’s final checkpoint, deciding which molecules pass through and which stay in the blood. Proteins like albumin are normally too large and too negatively charged to slip through.
In nephrotic syndrome, this membrane is damaged or missing entirely. When the projections flatten out (a change visible under an electron microscope), the checkpoint fails and proteins pour into the urine. This can happen because of genetic mutations that weaken the membrane’s structure, immune system attacks on the filtering cells, or damage from chronic diseases like diabetes. Regardless of the trigger, the end result is the same: the kidney can no longer hold onto the proteins your blood needs to function properly.
What Causes It
About 70% of cases stem from diseases that originate in the kidney itself. The most common of these is minimal change disease, which accounts for 85 to 95% of nephrotic syndrome in children under 10 but only 10 to 15% in adults. Under a standard microscope, the kidney tissue looks completely normal, which is how the condition got its name. Only electron microscopy reveals the flattened podocyte projections. Most children with minimal change disease respond well to steroid treatment.
In adults, the primary kidney diseases behind nephrotic syndrome shift. Focal segmental glomerulosclerosis, where patches of scar tissue form in the filters, and membranous nephropathy, where immune deposits thicken the filtering membrane, become more common causes. These tend to be harder to treat and carry a higher risk of progressing to permanent kidney damage.
The remaining 30% of cases are secondary, meaning another systemic illness is driving the kidney damage. Diabetes is the most common culprit. Diabetic kidney disease affects roughly 40% of people with diabetes and can eventually produce nephrotic-range protein loss. Lupus is another frequent cause: kidney inflammation develops in 35 to 75% of lupus patients, and of those, 30 to 70% will have nephrotic syndrome at some point. Other triggers include HIV, hepatitis B and C, certain medications (particularly some anti-inflammatory drugs), and some cancers.
Symptoms and How They Develop
Swelling is usually the first thing people notice. It often starts around the eyes in the morning and shifts to the ankles and feet later in the day. In severe cases, fluid can accumulate in the abdomen or around the lungs, making it hard to breathe. The swelling can be dramatic enough that people gain several pounds of water weight in a matter of days.
Two competing theories explain why this swelling happens. In one model, the loss of albumin from the blood reduces the blood’s ability to hold onto water. Fluid leaks out of blood vessels and into surrounding tissues, and the body responds by retaining salt and water to compensate, which only makes the swelling worse. In the other model, the damaged kidneys directly retain too much sodium, expanding blood volume until excess fluid is pushed into the tissues. In practice, both mechanisms likely contribute to different degrees in different patients.
Other noticeable symptoms include foamy or frothy urine (from the excess protein), fatigue, loss of appetite, and weight gain from fluid retention. Because cholesterol levels rise as the liver tries to compensate for lost proteins, people with nephrotic syndrome also face increased cardiovascular risk over time.
Serious Complications
Blood clots are one of the most dangerous complications. The risk of venous clots ranges from 2% to 37% across studies, and arterial clots occur at roughly eight times the rate seen in the general population. This happens for several interconnected reasons. The kidneys leak out natural anticoagulant proteins (like antithrombin) along with albumin. Meanwhile, the liver ramps up production of clotting factors like fibrinogen. Platelets also become stickier because albumin loss frees up a fatty acid that promotes clot-friendly signaling. The renal veins are particularly vulnerable because blood flowing out of the damaged kidneys is already concentrated and depleted of clot-preventing proteins.
Infection risk also increases significantly. The kidneys leak out antibodies, particularly a type called immunoglobulin G, leaving the immune system weakened. This is compounded by the immune-suppressing medications used to treat many forms of nephrotic syndrome. Children are especially vulnerable to bacterial infections of the abdominal lining and bloodstream.
How It’s Diagnosed
Diagnosis requires three findings: protein in the urine above 3.5 grams per 24 hours, low blood albumin below 3.0 g/dL, and visible swelling. A urine dipstick can flag heavy protein loss, but a full 24-hour urine collection or a spot urine protein-to-creatinine ratio gives a more precise measurement. Blood tests confirm low albumin and typically show elevated cholesterol and triglycerides.
Identifying the underlying cause often requires a kidney biopsy, where a small sample of tissue is examined under regular and electron microscopes. In young children presenting with a classic first episode, biopsy is often skipped because minimal change disease is overwhelmingly likely, and doctors will try steroid treatment first. In adults, biopsy is more important because the range of possible causes is wider and treatment decisions depend heavily on the specific diagnosis.
Treatment Approaches
Treatment targets both the symptoms and the underlying cause. For symptom management, diuretics help the body shed excess fluid and reduce swelling. Blood pressure medications that block the renin-angiotensin system, such as ACE inhibitors, serve double duty: they lower blood pressure and independently reduce the amount of protein leaking through the kidneys. Newer medications called SGLT2 inhibitors, originally developed for diabetes, are also being used to reduce proteinuria and protect kidney function. The goal is to bring protein loss below 0.5 grams per day when possible.
For the underlying disease, corticosteroids remain the first-line treatment, particularly for minimal change disease. A typical course runs 12 to 20 weeks. Most children with minimal change disease respond well, though relapses are common. When steroids don’t work or cause intolerable side effects, other immune-suppressing medications are used as alternatives. For secondary causes like diabetes or lupus, treating the underlying disease is essential to controlling the kidney damage.
Dietary changes play a supporting role. Limiting salt intake helps control fluid retention, and moderate protein intake is generally recommended, since eating excessive protein doesn’t replace what’s being lost and may actually accelerate kidney damage. Statin medications are often prescribed to manage the elevated cholesterol that accompanies nephrotic syndrome, and blood thinners may be necessary for patients at high clot risk.
Long-Term Outlook
Prognosis varies enormously depending on the underlying cause. Children with minimal change disease have an excellent long-term outlook. The vast majority respond to steroids, and most eventually outgrow the condition, though relapses during childhood are common. Adults with minimal change disease also tend to respond well, though they may take longer to achieve remission.
Focal segmental glomerulosclerosis carries a less favorable prognosis. A significant proportion of patients don’t respond fully to treatment, and the condition can progress to kidney failure requiring dialysis or transplantation over years to decades. Membranous nephropathy falls somewhere in between: about a third of patients improve spontaneously, a third remain stable, and a third progress. For secondary nephrotic syndrome, the kidney outcome depends largely on how well the underlying disease can be controlled.