Protein in Urine and Its Relationship to Cancer

Nicole Valentine
Nicole Valentine
November 3, 2023
6
min read
Medically reviewed by:
Joseph Bannon, D.O.
Protein in Urine and Its Relationship to Cancer
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Protein in urine, known as proteinuria, is not always a cause for concern. However, if urine test strips are positive for protein, it's always worth looking into because, in some cases, proteinuria can be related to certain types of cancers. Read on to learn about the relationship between protein in the urine and cancer, including which types of cancer may be indicated by proteinuria, some reasons why proteinuria increases your risk of cancer, and what further testing your doctor might order if you have a positive urine protein test.

Chronic Proteinuria and Cancer

Something as simple as overexercising can cause elevated protein levels in urine, but this is generally a temporary condition that goes away quickly without causing major damage to your body [1]. Chronic proteinuria, on the other hand, can sometimes signify a serious problem, such as a Chronic Kidney Disease or CKD, which results in a gradual loss of kidney function. One of the common reasons for CKD is nephrotic syndrome, a kidney disorder where small clusters of blood vessels in the organ become inflamed and allow protein to leak into the urine.

Nephrotic syndrome and proteinuria frequently occur without any relation to cancer. However, having nephrotic syndrome increases your risk of having or developing cancer enough to be a cause for concern.

Although elevated protein in the urine can have many potential causes, proteinuria is frequently associated with certain site-specific cancers, including cancer of the:

  • Kidneys [3]
  • Rectum
  • Ovaries
  • Lung
  • Liver [4]
  • Urethra, bladder, and ureters [5]
  • Stomach [6]
  • Immune system cells
  • Blood-forming tissue like bone marrow [7]
Chronic Kidney Disease (CKD) can result from conditions like nephrotic syndrome, which may cause elevated protein levels in urine and increase the risk of developing cancer.

Proteinuria as a Risk Factor for Cancer

Proteinuria can be both a symptom of cancer and a risk factor for developing it. Three main mechanisms of action—inflammation, renin-angiotensin system activation, and endothelial dysfunction—are frequently proposed as ways that proteinuria may indicate an increased risk of both both cancer development and mortality. Here's a look at how each of these actions can contribute to cancer formation and spread in the body.

1. Inflammation

Proteinuria is a common symptom of kidney dysfunction, which is known to induce chronic inflammation in the body [8]. Researchers believe that inflammatory cells and mediators in tumors can cause cancerous cells to reproduce rapidly, potentially accelerating tumor growth [4]. Chronic inflammation is linked to other stages of tumor growth as well, including cell mutation, formation of a tumor's blood supply, and metastasis, the spread of cancerous growths in the body [9]. A person with proteinuria is likely to have kidney dysfunction and accompanying chronic inflammation, which puts them at a higher risk for developing cancerous tumors.

2. Renin-angiotensin system activation

The renin-angiotensin system, composed of powerful enzymes and hormones, regulates blood pressure and cardiovascular health within the body. Components of this system are found locally in organs such as the liver, kidneys, pancreas, brain, and reproductive organs. When the renin-angiotensin system is activated locally within one of these organs, it may influence tumor development [10]. It can also lead to proteinuria. This is another potential reason that elevated urine protein can indicate an increased risk of developing cancer [4].

3. Endothelial dysfunction

Endothelial dysfunction is a type of coronary artery disease in which the large blood vessels on the heart's surface constrict instead of dilating, often causing chronic chest pain [11]. The condition can increase the invasiveness of cancerous cells, allowing them to spread quickly and aggressively [4]. Because endothelial dysfunction is associated with proteinuria, a positive urine protein test may indicate the potential for endothelial dysfunction and a higher incidence of metastatic spread of cancer cells [7].

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Proteinuria as a Symptom of Cancer

In some cases, proteinuria may be caused by cancer already present within the body. Tumors that invade the kidneys can lead to proteinuria. Whether the cancer originates in the kidneys or spreads there from another location, tumors can cause damage or swelling in the kidneys. They may also cause blood clots in the renal vein. Damage to the kidneys often causes them to malfunction and allows protein to escape into the urine [2].

Urothelial carcinoma, cancer of the urothelial cells that line the bladder, urethra, ureters, and renal pelvis, can lead to elevated urine protein. It's believed that the urothelial carcinoma may leak protein into the urine [5].

Multiple myeloma, a cancer that attacks the plasma cells of the blood, can cause the body to secrete Bence-Jones protein in the urine.  Bence-Jones protein can damage the kidneys, but unlike other proteins, they don't show up in urine test strips. Your doctor must order a lab urine test to detect this type of urine protein [12].

With certain types of lung cancer, the first manifestation in the body can be nephrotic syndrome with accompanying protein in the urine. Although this is rare and the reasons it occurs aren't well understood, it's important to be aware of the possibility that nephrotic syndrome could be the first presenting symptom of lung cancer [13].

Proteinuria as a Predictor of Mortality

The relationship between proteinuria and cancer isn't entirely understood, and the research is ongoing. However, it's clear that elevated urine protein is associated with a higher incidence of cancer and a higher risk of mortality. Multiple studies across different populations have demonstrated that even trace amounts of protein in the urine are related to an increased risk of death from cancer. Generally, the more protein in the urine, the greater the risk of death [4], [7], [14].

One study researching the association between nephrotic syndrome and cancer found a 73% increased risk of cancer in patients with nephrotic syndrome in the five-year follow-up period following diagnosis. The site-specific cancers most prevalent in these patients were lung cancer, kidney cancer, lymphoma, and multiple myeloma. The patients with nephrotic syndrome also had a higher mortality rate than those without [15]. Another study found that the median survival time of cancer patients with accompanying proteinuria was only half as long as that of patients without protein in their urine [16].

Other Cancer Symptoms

Proteinuria is one potential sign of cancer. Although symptoms can vary between people and depending on the type of cancer, some general symptoms frequently occur in cancer patients. These include

  • Fatigue
  • Unexplained weight change
  • Lack of appetite or trouble swallowing
  • Nausea or vomiting
  • Swelling or lumps
  • Unusual bleeding or bruising
  • Bladder or bowel changes
  • Fever or night sweats
  • Headache
  • Vision or hearing changes [17]

If you have one or more of these symptoms, talk to your doctor. You can also use a urine test strip to check for protein, as this will give you more information to pass on to your healthcare provider.

What if You Have a Positive Urine Protein Test?

Urinalysis test strips can help you monitor your health and catch problems early on. If a urine test strip shows protein in your urine, don't panic. Cancer is only one of many potential causes of kidney disease and proteinuria. However, it's critical to follow up with your healthcare provider. Even if the protein in urine isn't related to cancer, kidney disease is a significant health concern that needs treatment and follow-up. If it is related to cancer, prompt treatment is essential for the best prognosis.

Your doctor is likely to order further testing to help pinpoint the cause of the proteinuria and determine if cancer is present. They might request a 24-hour urine protein test or a urinalysis conducted by a lab. These urinalyses help your doctor better understand the amount and type of protein in the urine, giving them further insight into its cause. They might do a kidney biopsy, where they take a small sample of tissue from your kidney to test it for damage. They might also order bloodwork or imaging tests. Complete all follow-up testing to ensure an early and accurate diagnosis.

References

[1] W. Wolyniec et al., “Factors influencing post-exercise proteinuria after marathon and ultramarathon races," Biol Sport 37(1), 2020. [Accessed October 29, 2023].

[2] B. S. Kaplan et al., “Glomerular Injury in Patients with Neoplasia," Annual Review of Medicine, 27, 1976. [Accessed October 29, 2023].

[3] J. Dryden, “Kidney cancer detected early with urine test,” Washington University in St. Louis, 2015. [Accessed October 29, 2023].

[4] Y. Mok et al., “Kidney Function, Proteinuria, and Cancer Incidence: The Korean Heart Study,” American Journal of Kidney Disease, 70(4), 2017. [Accessed October 29, 2023].

[5] M. Sakakima et al., “A Case with Significant Proteinuria Caused by Secreted Protein from Urothelial Carcinoma,” Case Reports in Nephrology, 2011. [Accessed October 29, 2023].

[6] M. Wakashin et al., “Association of gastric cancer and nephrotic syndrome: An immunologic study in three patients,” Gastroenterology, 78(4), 1980. [Accessed October 29, 2023].

[7] M. Matsui et al., “Trace proteinuria as a risk factor for cancer death in a general population,” Scientific Reports, 11, 2021. [Accessed October 29, 2023].

[8] J. Park et al., “Associations Between Kidney Function, Proteinuria, and the Risk of Kidney Cancer: A Nationwide Cohort Study Involving 10 Million Participants,” American Journal of Epidemiology, 190(10), 2021. [Accessed October 29, 2023].

[9] N. Singh et al., “Inflammation and Cancer,” Annals of African Medicine, 18(3), 2019. [Accessed October 29, 2023].

[10] E. Ager et al., “The renin-angiotensin system and malignancy,” Carcinogenesis, 29(9), 2008. [Accessed October 29, 2023].

[11] Stanford Medicine staff, “Endothelial dysfunction,” Stanford Medicine Health Care. [Accessed October 28, 2023]

[12] Medical News Today staff, “What causes Bence Jones protein in urine,” Healthline Media. [Accessed October 28, 2023].

113] D. Gu et al., “Primary lung cancer firstly presents as nephrotic syndrome: one case report and literature review,” Translational Cancer Research, 8(8), 2019. [Accessed October 29, 2023].

[14] M. J. Ki et al., “Proteinuria as a Risk Factor for Mortality in Patients with Colorectal Cancer,” Yonsei Medical Journal, 54(5), 2013. [Accessed October 29, 2023].

[15] C. Christiansen et al., “Risk and Prognosis of Cancer in Patients with Nephrotic Syndrome,” Clinical Research Study, 127(9), 2014. [Accessed October 29, 2023].

[16] N. Sawyer et al., “Prevalence, concentration, and prognostic importance of proteinuria in patients with malignancies,” British Medical Journal, 296(6632), 1988. [Accessed October 29, 2023].

[17] American Cancer Society staff, “Signs and Symptoms of Cancer,” American Cancer Society. [Accessed October 29, 2023].

About the Author
Nicole Valentine

Nicole Valentine is a blog and article writer with experience writing about a huge array of topics. She is passionate about sustainability, healthy living, and mindful parenting.

About the Reviewer
This blog was
Medically reviewed by:
Joseph Bannon, D.O.

Dr. Bannon is a US-trained physician in the Midwestern United States with board certification in Family Medicine through the American Board of Osteopathic Family Physicians. He has experience in both inpatient and outpatient settings, with a focus on preventative medicine and primary prevention. A passion for delivering evidence based medicine to rural/underserved areas has been a driving force in his desire to contribute to the medical literature community.

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