Proteinuria
Proteinuria is the presence of an abnormal amount of protein in the urine, which can signal kidney damage or other health conditions. While healthy kidneys normally keep proteins in the blood and out of urine, damaged kidneys may allow protein to leak through, making proteinuria an important early warning sign of potential kidney problems.
Table of contents
- What is proteinuria?
- What causes proteinuria?
- Signs and symptoms
- How is proteinuria diagnosed?
- Treatment and management
- Who is at risk?
What is proteinuria?
Proteinuria is a broad term used to describe protein in the urine. It is a general term for the presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine[1]. Normally, your urine contains very little protein. A large amount of protein in urine may mean you have a kidney problem[5].
Your kidneys are organs that filter extra water and waste out of your blood to make urine. Proteins are large molecules that are essential for your body to work properly. They have many important functions, including giving your body energy, rebuilding muscles, and helping your immune system. Protein is found in all parts of your body, including your blood[5].
When your kidneys clean waste from your blood, tiny filters called glomeruli (groups of tiny blood vessels in your kidneys) prevent the large protein molecules from leaving your body through your urine[5]. If there is a problem with your kidneys, protein can leak into your urine. Healthy glomeruli contain about 1 million of these filtering units, which keep the nutrients you need, such as protein, in your body, and remove waste products that you don’t need through urine[24].
Almost half of the protein lost in normal urine is derived from the distal tubule, known as Tamm-Horsfall glycoprotein[1]. Persistent proteinuria is a marker of kidney damage. It also helps with the diagnosis, prognosis, and therapy[1].
What causes proteinuria?
Proteinuria can be classified as transient and persistent[1].
Transient proteinuria
Transient proteinuria is temporary and can be caused by conditions that usually don’t require treatment[1]. Common things that can cause temporary proteinuria include:
- Dehydration — when the body doesn’t have enough water and other fluids to work as it should[2]
- Urinary tract infection[1]
- Fever[1]
- Heavy exercise or strenuous physical activity[1]
- Exposure to extreme cold[2]
- High stress[3]
- Inflammation[3]
- Low blood pressure[3]
- Pregnancy[1]
- Taking aspirin every day[9]
Transient proteinuria does not involve underlying kidney disease and requires no treatment[8].
Orthostatic proteinuria
Orthostatic proteinuria occurs after the patient has been upright for a prolonged period and is absent in early morning urine. This is rare in patients more than 30 years of age[1]. It is most often found in tall, thin adolescents and young adults less than 30 years of age. The kidneys are usually healthy. Orthostatic proteinuria is not harmful and usually goes away with age[3].
Persistent proteinuria
Persistent proteinuria is more serious and happens in people with kidney disease or conditions that affect the kidneys[3]. Conditions that can cause persistent proteinuria include:
- Primary renal disease
- Secondary renal disease
- Other conditions
- Chronic kidney disease[1]
- Diabetic nephropathy (kidney disease)[2]
- Focal segmental glomerulosclerosis (FSGS)[2]
- IgA nephropathy (Berger disease)[2]
- Membranous nephropathy[2]
- Multiple myeloma[2]
- Nephrotic syndrome[2]
- Preeclampsia[2]
- Amyloidosis[2]
- Certain drugs, such as nonsteroidal anti-inflammatory drugs[2]
- Heart disease and heart failure[2]
- Kidney stones[3]
- Kidney cancer[3]
- Poisoning[3]
Proteinuria can be caused by diseases not involving the kidneys, such as multiple myeloma, a cancer of the plasma cells in the bone marrow. In this case, the blood is flooded with too many proteins that are then filtered into the urine. The condition is known as overflow proteinuria[8].
Signs and symptoms
Most people who have proteinuria won’t notice any signs, especially in early or mild cases[3]. You may not have any symptoms in the early stages of proteinuria[9]. In most cases, proteinuria has no symptoms and is detected during a routine screening in people with high blood pressure or diabetes[8].
Over time, as it gets worse, you might have symptoms including[3]:
- Foamy or bubbly urine[3]
- Swelling (edema) in your hands, feet, belly, and face[3]
- Swelling around your eyes, especially in the morning[9]
- Urinating more often[3]
- Shortness of breath[3]
- Fatigue or tiredness[3]
- Loss of appetite[3]
- Upset stomach and vomiting[3]
- Muscle cramps at night[3]
- Weight gain caused by fluid retention[8]
If protein loss is severe, swelling or edema can occur. Edema can be present in the face and around the eyes, arms, hands, legs, ankles and feet, or abdomen[8].
How is proteinuria diagnosed?
A urine test called a urinalysis can tell whether you have too much protein in your urine[3]. First, you’ll urinate into a cup. A lab technician will dip in a stick with chemicals on the end. If the stick changes color, it’s a sign of too much protein. You might need to have this test more than once to find out how long the protein is there. The technician will also look at the urine under a microscope[3].
Your healthcare provider may give you a cleansing wipe, a small container, and instructions for how to use the “clean catch” method to collect your urine sample. It’s important to follow these instructions so that germs from your skin don’t get into the sample[5].
You may also need to collect all of your urine for 24 hours. Either test can tell if there is protein in your urine[4].
Normal values with a random urine sample range from 0 to 14 mg/dL, and for a 24-hour urine collection values less than 80 mg are considered normal[3].
According to the UK chronic kidney disease guidelines, proteinuria is defined as a urine protein creatinine ratio (UPCR) of more than 45 mg/mmol, but this does not warrant further evaluation in the absence of hematuria unless the UPCR is more than 100 mg/mmol[1]. According to the NICE guidelines, proteinuria is defined as a UPCR of more than 50 mg/mmol or a urine albumin creatinine ratio (UACR) of more than 30 mg/mmol[1].
Your doctor may do more tests to find out what is causing the protein to get into your urine. You may need regular urine tests in the future[21]. Your doctor may also test your kidney function with the glomerular filtration rate (GFR) or with an ultrasound exam of your kidneys[17].
Treatment and management
Medical management of proteinuria has two components: nonspecific treatment that is applicable irrespective of the underlying cause, and specific treatment that depends on the underlying renal or nonrenal cause[10].
Medications
Medications play a crucial role in managing proteinuria. Nonspecific treatment includes renin-angiotensin-system inhibitors such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). These agents are indicated in patients with proteinuria, even those without diabetes[10].
ACE inhibitors and ARBs reduce intraglomerular pressure by inhibiting angiotensin II–mediated efferent arteriolar vasoconstriction. Multiple trials have reported that ACE inhibitors are effective at reducing proteinuria in both diabetic and non-diabetic populations. ACE inhibitors also reduce the rate of progression of kidney disease, and the risk of dialysis or transplantation by up to 50% in patients with proteinuria[15].
The angiotensin receptor antagonists are effective for reducing proteinuria in diabetic and non-diabetic populations. Major trials have also reported that they slow the progression of kidney disease. During the first 6–12 months of treatment, a 50% reduction in proteinuria is associated with a 40–50% reduction in the risk for progression of kidney disease[15].
Diuretics are also nonspecific treatments that target edema[10]. Taking medications as prescribed by your doctor is the best way to help reduce the protein in your urine[11].
Blood pressure control
Keeping blood pressure in check is crucial to slowing kidney damage. Most guidelines recommend a blood pressure below 130/80 mm Hg for individuals with kidney disease[11]. Normalization of systemic blood pressure in a patient with hypertension should result in a reduction in intraglomerular pressure and a fall in albuminuria[15].
Diet modifications
Diet plays a significant role in managing proteinuria. Work with your doctor and dietitian to set up a diet that will be healthy for you[21]. You may need to:
- Eat a heart-healthy diet to keep the fat (cholesterol) in your blood under control[21]
- Reduce sodium (salt) intake. Excessive salt can worsen blood pressure and fluid retention. Aim for a low-sodium diet (less than 2,300 mg per day)[11]
- Limit protein intake. Too much dietary protein can strain the kidneys and increase protein leakage into the urine. The source of protein also matters — plant proteins have been shown to be easier on the kidneys than animal protein sources[11]
- Limit the amount of fluids you drink[21]
Lifestyle modifications
Additional lifestyle changes can help manage proteinuria:
- If your doctor recommends it, get more exercise. Walking is a good choice. Bit by bit, increase the amount you walk every day. Try for at least 2½ hours a week[21]
- Do not smoke. Smoking raises your risk of many health problems, including kidney damage[21]
- If you have diabetes, try to keep your blood sugar at normal or near-normal levels. Follow your diet and check your blood sugar as often as your doctor recommends[21]
- Managing your weight[23]
Medication precautions
Do not take ibuprofen, naproxen, acetaminophen (Tylenol), or similar medicines, unless your doctor tells you to. These medicines may make kidney problems worse. Check with your doctor before taking any natural health products or over-the-counter medicines[21].
Can proteinuria be reversed?
You can reverse mild or temporary forms of proteinuria, but not all types are as easy to treat. Mild or temporary proteinuria usually doesn’t require treatment and often clears up independently. For example, temporary dehydration causes proteinuria but disappears once your body rehydrates. You can also reverse proteinuria after you eliminate a fever or reduce significant stress[23].
Unfortunately, reversing proteinuria from chronic conditions or kidney disease is not as easy. Treating the underlying issue is the only way to address protein in the urine to prevent dangerous health problems[23].
Who is at risk?
Anyone can get proteinuria. However, you may be more likely to get proteinuria if you[9]:
- Are 65 years old or older[9]
- Have a family member who has or had kidney disease[9]
- Have diabetes or another condition that affects your kidneys[9]
- Have high blood pressure[3]
- Are Black, Hispanic, Native American or Pacific Islander[9]
- Are obese[3]
Proteinuria is relatively common. About 6.7% of the United States population has proteinuria[9].
High protein levels in your urine over a period of time may be the first sign that kidney disease or another condition has damaged the filters in your kidneys. A protein in urine test can help you find kidney damage early. This may help your healthcare provider determine the best treatment. You can also start making changes to protect your kidneys[5].
Proteinuria can serve as an indicator of early renal disease. It marks an increased risk of renal damage secondary to hypertension and cardiovascular disease. The degree of proteinuria correlates with disease progression[1]. Protein in your urine is serious. Proteinuria may increase your risk of death from heart disease and cardiovascular disease[9].
