Proteinuria (Protein in Urine)

What proteinuria means

Each kidney contains about a million filters called glomeruli. They let water, salts and waste pass into the urine but hold back large molecules such as albumin, the main protein in blood. The tubules then reabsorb most small proteins that do get through. A healthy adult passes less than about 150 mg of protein a day in urine, including less than 30 mg of albumin.

When the glomeruli are damaged, they become leaky and albumin passes through. Protein in urine is also harmful in itself: it irritates kidney tubules and speeds up scarring. That is why lowering proteinuria is a treatment goal.

Albuminuria specifically refers to albumin in urine and is the preferred measure in most adults, especially with diabetes.

Urine protein levels explained

A diagnosis of persistent albuminuria needs at least 2 of 3 abnormal ACR tests over 3 to 6 months, because levels vary from day to day. A first-morning urine sample is the most reliable.

Dipstick results are reported as negative, trace, 1+, 2+, 3+ or 4+. They are a screening tool only, affected by how concentrated your urine is, and should be confirmed with ACR or PCR.

Causes of protein in urine

Temporary (transient) proteinuria

Often harmless and gone on a repeat test:

• fever or acute illness
• intense exercise
• dehydration
• emotional stress, cold exposure
• urinary tract infection

Orthostatic proteinuria

Protein appears only when upright, and the first-morning sample is normal. It is common in teenagers and young adults, and is benign.

Persistent proteinuria from kidney disease

• Diabetes: diabetic nephropathy is the leading cause of chronic kidney disease.
• High blood pressure.
• Glomerulonephritis: IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, lupus nephritis and post-infectious glomerulonephritis.
• Polycystic kidney disease and other inherited conditions.
• Obesity and metabolic syndrome.
• Medicines: long-term NSAIDs, some cancer drugs, lithium.
• Infections: HIV, hepatitis B and C.
• Heart failure.

Overflow proteinuria

Abnormal proteins in the blood exceed what the kidney can handle, as in multiple myeloma (light chains). Standard dipsticks can miss these, so special blood and urine tests are needed.

Proteinuria in pregnancy

New protein in urine after 20 weeks with high blood pressure suggests preeclampsia. A protein-to-creatinine ratio of 0.3 mg/mg or more, or 300 mg or more in a 24-hour collection, meets the threshold. Preeclampsia can also be diagnosed without proteinuria if other warning signs are present.

Symptoms

Low-level proteinuria has no symptoms; it is found only by testing. With heavier loss you may notice:

• foamy or frothy urine that does not settle
• swelling (edema) of the ankles, legs, around the eyes in the morning, or the belly
• weight gain from fluid
• tiredness
• symptoms of the underlying cause, such as thirst in diabetes or headaches with high blood pressure

Occasional bubbles in urine are normal, especially with a strong stream.

Who should be tested

• everyone with diabetes, at least once a year
• people with high blood pressure, heart disease or obesity
• people with a family history of kidney disease
• anyone with swelling or unexplained foamy urine
• in every prenatal visit, blood pressure is checked and urine protein is tested when indicated

How proteinuria is investigated

If proteinuria is confirmed, your doctor will usually check:

• eGFR (kidney function) from a creatinine blood test
• urine microscopy for blood and red cell casts
• blood pressure
• blood sugar or HbA1c, cholesterol and albumin
• kidney ultrasound
• specific tests depending on the picture: autoimmune antibodies, hepatitis and HIV tests, serum protein electrophoresis and free light chains
• kidney biopsy if a glomerular disease is suspected, protein is high without a clear cause, or kidney function is falling

Referral to a nephrologist is usually advised for ACR over about 300 mg/g (30 mg/mmol), proteinuria with blood in the urine, or rapidly declining kidney function.

Treatment

Treatment targets the cause and protects the kidneys.

• ACE inhibitors or ARBs (such as lisinopril or losartan): lower pressure in the glomeruli and reduce proteinuria, even in people with normal blood pressure.
• SGLT2 inhibitors (such as dapagliflozin or empagliflozin): slow kidney decline in chronic kidney disease with albuminuria, with or without diabetes.
• Finerenone: for some people with type 2 diabetes and kidney disease.
• Blood pressure control: typical targets are below about 120 to 130 systolic, individualized by your doctor.
• Blood sugar control in diabetes.
• Glomerulonephritis-specific treatment, such as steroids or immunosuppressants.
• Lifestyle: less salt, stop smoking, healthy weight, avoid regular NSAID use.

Protein restriction is not usually advised for early proteinuria. People with advanced kidney disease may be advised not to eat excessive protein; a dietitian can tailor this.

Outlook

Persistent albuminuria raises the risk of chronic kidney disease progression, heart attack and stroke. The higher the level, the higher the risk. Reducing proteinuria with treatment is linked to slower kidney decline and better heart health. Temporary and orthostatic proteinuria have an excellent outlook.

Frequently asked questions

Is protein in urine serious?

It depends. A single positive result after exercise or fever is often harmless. Protein that persists on repeat tests usually signals kidney damage and raises the risk of kidney failure and heart disease. Early treatment can slow or stop progression.

What are the most common causes of protein in urine?

Diabetes and high blood pressure are the commonest causes of persistent proteinuria in adults. Other causes include glomerular diseases, obesity, some medicines and infections. Temporary causes include fever, intense exercise, dehydration and urinary infections.

Does foamy urine mean protein?

Not necessarily. Foam can appear with a fast stream, concentrated urine or cleaning products in the toilet. Persistent, heavy foam that does not settle, especially with swelling of the legs or eyes, can be a sign of significant proteinuria and should be checked.

What is a normal urine albumin-to-creatinine ratio?

Below 30 mg/g (3 mg/mmol) is normal. Results between 30 and 300 mg/g mean moderately increased albuminuria, and over 300 mg/g means severely increased. Abnormal results should be confirmed on at least two of three tests over 3 to 6 months.

Can proteinuria be reversed?

Sometimes. Temporary proteinuria resolves on its own. In diabetes and high blood pressure, good control plus ACE inhibitors, ARBs and SGLT2 inhibitors can lower protein levels, sometimes back to normal. Some glomerular diseases respond completely to specific treatment.

What does protein in urine mean in pregnancy?

After 20 weeks, protein in urine with high blood pressure can be a sign of preeclampsia, which needs prompt assessment. Protein can also come from a urinary infection or pre-existing kidney disease. Your care team will check blood pressure and a protein-to-creatinine ratio.