According to the Cleveland Clinic, “Proteinuria is due to increased levels of protein in the urine.” Your kidneys filter waste products from your blood while retaining what your body needs — including proteins. However, some diseases and conditions allow proteins to pass through the filters of your kidneys, causing protein in the urine.

 

HOW DOES PROTEIN GET INTO URINE? ⁽¹⁾

Protein gets into the urine if the kidneys aren’t working properly. Normally, glomeruli, which are tiny loops of capillaries (blood vessels) in the kidneys, filter waste products and excess water from the blood.

Glomeruli pass these substances, but not larger proteins and blood cells, into the urine. If smaller proteins sneak through the glomeruli, tubules (long, thin, hollow tubes in the kidneys) recapture those proteins and keep them in the body.

However, if the glomeruli or tubules are damaged, if there is a problem with the reabsorption process of the proteins, or if there is an excessive protein load, the proteins will flow into the urine.

 

WHAT ARE THE SYMPTOMS OF PROTEINURIA? ⁽²⁾

Often, someone with proteinuria doesn’t experience symptoms, especially if kidneys are just beginning to have problems. However, if proteinuria is advanced, symptoms can include:

• More frequent urination
• Shortness of breath
• Tiredness
• Nausea and vomiting
• Swelling in the face, belly, feet or ankles
• Lack of appetite
• Muscle cramping at night
• Puffiness around the eyes, especially in the morning
• Foamy or bubbly urine

Conditions that can cause a temporary rise in the levels of protein in urine, but don’t necessarily indicate kidney damage, include:

• Dehydration
• Emotional stress
• Exposure to extreme cold
• Fever
• Strenuous exercise

However, according to the Mayo Clinic ⁽²⁾, there are diseases and conditions that can cause persistently elevated levels of protein in urine, which might indicate kidney disease, such as:

• Amyloidosis (buildup of abnormal proteins in your organs)
• Certain drugs, such as nonsteroidal anti-inflammatory drugs
• Chronic kidney disease
• Diabetes
• Endocarditis (an infection of the inner lining of the heart)
• Focal segmental glomerulosclerosis (FSGS)
• Glomerulonephritis (inflammation in the kidney cells that filter waste from the blood)
• Heart disease
• Heart failure
• High blood pressure (hypertension)
• Hodgkin’s lymphoma (Hodgkin’s disease)
• IgA nephropathy (Berger’s disease) (kidney inflammation resulting from a buildup of the antibody immunoglobulin A)
• Kidney infection (pyelonephritis)
• Lupus
• Malaria
• Multiple myeloma
• Nephrotic syndrome (damage to small filtering blood vessels in the kidneys)
• Orthostatic proteinuria (urine protein level rises when in an upright position)
• Preeclampsia
• Pregnancy
• Rheumatoid arthritis (inflammatory joint disease)
• Sarcoidosis (collections of inflammatory cells in the body)
• Sickle cell anemia

TESTING FOR PROTEINURIA

The only way to know if you have protein in your urine, an established marker for chronic kidney disease, is to have a urine test.

“Integral to the process of evaluating for proteinuria is quantification of the total amount of protein spilling into the urine. The various methods to detect proteinuria include urine dipstick and sulfosalicyclic acid test (SSA); quantification methods include the ratio of albumin or protein to creatinine (UACR or UPCR) and the 24-hour urine protein collection.

The gold standard for quantification of proteinuria is the 24-hour urine collection. The test is performed by voiding upon waking and then collecting all urine on subsequent voids until the first void of the next day.“ ⁽¹¹⁾

In a retrospective study ⁽⁵⁾, researchers evaluated data from 265 patients with systemic AL amyloidosis who visited the Amyloidosis Center at Boston University Medical Center between July 1, 2018, and Jan. 1, 2020. This study examined the correlation between 24-hour urine testing and [urine protein-to-creatinine ratio] UPCR at various proteinuria levels in patients with AL amyloidosis. All patients underwent proteinuria measurement by 24-hour collection and UPCR in the same day. According to Andrea Havasi, MD, “In summary, although 24-hour urine collection is cumbersome, we continue to recommend it in patients with AL amyloidosis and kidney involvement.

 

CONCLUSION ⁽¹²⁾

Amyloidosis can be a life-threatening disease because it can cause progressive organ damage and irreversible failure. Although it may affect any organ, one of the most frequently involved organs is the kidney, and clinically evident renal disease occurs in about 50-80% of cases. Typical manifestations of renal involvement are proteinuria, nephrotic syndrome (i.e., concomitant proteinuria, hypoalbuminemia, and peripheral edema), renal insufficiency, and end-stage renal disease (ESRD) requiring hemodialysis. All forms of systemic amyloidosis can lead to renal involvement. AL amyloidosis induces proteinuria and renal insufficiency in up to 73% and 50% of cases, respectively. ATTR amyloidosis typically does not involve the kidneys, but it can induce proteinuria and ESRD in some patients.

 

Therefore, when you have a patient with proteinuria, investigate why and don’t assume a benign origin. There are many serious causes, one of which may be amyloidosis.

 

Stay curious.

 

 

 

======== References  =========

1. https://my.clevelandclinic.org/health/diseases/16428-proteinuria
2. https://my.clevelandclinic.org/health/diseases/16428-proteinuria
3. https://www.mayoclinic.org/symptoms/protein-in-urine/basics/causes/sym-20050656
4. https://www.kidneyfund.org/kidney-disease/kidney-problems/protein-in-urine.html
5. https://www.kidney.org/atoz/content/proteinuriawyska
6. https://www.healio.com/news/nephrology/20220209/researchers-regard-24hour-proteinuria-collection-best-for-amyloid-light-chain-amyloidosis
7. https://medlineplus.gov/lab-tests/albumin-blood-test/#:~:text=Albumin%20is%20a%20protein%20made,and%20enzymes%20throughout%20your%20body.
8. https://www.kidney.org/content/kidney-failure-risk-factor-urine-albumin-to-creatinine-ration-uacr
9. https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/24hour-urine-collection#:~:text=A%2024%2Dhour%20urine%20collection%20is%20a%20simple%20lab%20test,is%20returned%20to%20the%20lab
10. https://www.kidneyfund.org/all-about-kidneys/tests-for-kidney-disease/urine-tests
11. https://www.mdedge.com/clinicianreviews/article/210146/nephrology/proteinuria-and-albuminuria-whats-difference
12. https://emedicine.medscape.com/article/238158-workup
13. Talamo G, Mir Muhammad A, Pandey MK, Zhu J, Creer MH, Malysz J. Estimation of Daily Proteinuria in Patients with Amyloidosis by Using the Protein-To-Creatinine ratio in Random Urine Samples. Rare Tumors. 2015 Feb 18;7(1):5686. doi: 10.4081/rt.2015.5686. PMID: 25918613; PMCID: PMC4387359.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387359/#:~:text=AL%20amyloidosis%20induces%20proteinuria%20and,50%25%20of%20cases%2C%20respectively.&text=ATTR%20amyloidosis%20typically%20does%20not,and%20ESRD%20in%20some%20patients