Renal Failure, Proteinuria, and Lupus Nephritis

Up to 1/3 of people with lupus will experience kidney involvement as inflammation damages the kidneys. The damage can be so severe the kidneys can no longer function, known as renal failure.

The kidneys are responsible for filtering toxins and waste out of the blood. Damaged kidneys are no longer able to perform this cleaning. This is known as renal failure.

According to a 2020 study in the Journal of Rheumatology, the overall incidence of renal failure in people with lupus was 8.5%. The Hopkins Lupus Cohort was used for this study.

The Hopkins Lupus Cohort is a group of 2,528 people with lupus who are being followed over 25 years by researchers. They are tested every 3 months, in the hope that they can increase our knowledge of lupus diagnosis and treatment. 151 people out of this group have experienced renal failure at the time of this study.

In renal failure, one or both kidneys may be damaged. Even if only one kidney is failing, the other kidney may not be able to take up the slack. Common therapies include:

• Dialysis
  • The regular use of a machine to filter the blood
• Kidney Transplants
  • The use of someone else’s donated kidney to replace one or both damaged
    kidneys

You can read more about both options here.

Testing can help determine treatment options

Each therapy comes with benefits and risks. But, both have good rates of success. But, testing can help identify kidney involvement before the need for drastic treatments.

Urine tests are the best way to measure how well the kidneys are functioning. These tests look at the chemicals and materials present in urine.

Proteinuria is a key (though not definitive) indicator of kidney damage that is measured in urine tests. While blood tests can also determine kidney damage and failure, urine tests are both non-invasive and give a lot of information about the health of a person’s kidneys. This means that these urine tests can be done even at times when blood collection may not be possible.

What is Proteinuria?

Proteinuria is the medical term for greater amounts of protein in urine. Proteins are a general term for chains of amino acids that are important to the body’s function. Many different types of proteins can be found in blood plasma (the clear liquid portion) and they they perform many roles in the bloodstream and throughout the body.

Usually, blood proteins stay in the blood; the kidneys only filter them out if they are waste. They are considered “waste” if their structure is damaged or they are specifically ‘marked’ for removal. Otherwise, the body reabsorbs the proteins into the bloodstream.

Proteinuria can happen to anyone, not just people with lupus. Causes include:

• high levels of stress
• heavy exercise
• recent fevers
• aspirin use
• exposure to the cold

The kidneys remove proteins in order to return to homeostasis, a balance of blood chemistry important for health.

Proteinuria and the Kidneys

When the kidneys are inflamed, the part of the kidneys that handle the filtering and the returning of blood proteins to the bloodstream – a network of organ folds and blood vessels called glomeruli – become less efficient. Much like with the condition known as “Leaky gut,” inflammation disrupts the seal that forms between the kidneys’ cells.

As blood flows through these damaged regions, bits of blood plasma leak through gaps in the cells to the central chamber of the kidney. From there, this leaked blood flows down into the bladder for excretion in urine. Red blood cells, the oxygen-carrying part of the blood that gives it its red color, can also escape through these gaps.

Most commonly proteinuria is a sign of kidney damage from disease or traumatic injury. Finding proteinuria can either indicate that the medical team needs to test further, or can confirm that there is suspected kidney disease. Either way, proteinuria is a sign that the medical team needs to take action.

Lupus Nephritis and Renal Failure

Lupus nephritis, a form of systemic lupus that attacks the kidneys can lead to kidney damage and renal failure, and result in proteinuria. It affects 30-50% of people with lupus. As the kidneys stop properly filtering water and waste products from the blood, people experience some of the following symptoms:

• Weight Gain
  • As the kidneys improperly regulate water, the body stores excess water and salts in other tissues of the body. This causes water retention and bloating. There may also be metabolism changes that encourage weight gain as the body tries to compensate for the abnormal blood chemistry.
• High Blood Pressure
  • The kidneys help control blood pressure. When the kidneys are working improperly, the viscosity or thickness of the blood changes. This makes the heart work harder to push it through the body and leading to spikes in blood pressure.
• Dark Urine
  • The color of urine depends on the amount of water and other materials in it. Dark yellow urine can be a sign of dehydration. Also, dark brown urine is a sign that unusual materials, such as blood proteins or red blood cells, are being excreted.
• Foamy or Frothy Urine
  • Certain blood proteins, when excreted in urine, react with the other chemicals. Or the change in temperature as the urine leaves the body. They separate out from the mostly-water liquid and, during urination, trap air and become bubbles.
• Gout
  • Intense joint pain caused by an increase in the waste product uric acid. It is also a symptom of lupus nephritis. You can read more about it here.

Classes of lupus nephritis

There are several classes of lupus nephritis, and you can read more about them here. In any case, if left unchecked and untreated, these symptoms become worse over time and can lead to renal failure.

Lupus nephritis needs to be diagnosed as early as possible for the best treatment. Diagnosis, like all forms of lupus, requires a range of tests. This includes (in order from least to most invasive) urine tests, blood tests, and a kidney biopsy. A biopsy is the removal of a sample of kidney tissue to determine how far disease might have progressed. You can read more about blood tests for lupus here.

An Overview of Urine Tests

The test for proteinuria is usually a Urine Protein test. The test measures the ratio of all proteins in the urine. But, it is only one of the possible urine tests.

• A Urinalysis test looks at other substances, including protein, and is part of a general health or annual exam. Because it analyzes the entire sample of urine, it isn’t very specific, but it can catch a wide range of issues (including proteinuria) which can then be tested for more specifically.
• Urine Albumin or microalbumin tests look at the amount of blood albumin in the urine. Albumin is the main protein in blood plasma. When found in unusual amounts, it can indicate that other blood proteins may be leaking through. This kind of blood test is often used to test for diabetes. And, is followed up by further urine tests that screen, more specifically, for other potential signs of disease.

Urine Blood Tests

A few urine tests also include a blood test so that the lab can compare the two samples and more closely assess kidney function:

• A Blood Urea Nitrogen (aka, BUN) and Creatinine test measures urea and creatinine. The primary waste products that the kidneys remove from the bloodstream.
• The eGFR test (estimated glomerular filtration rate) compares the blood creatinine level to the levels found in the urine. It uses an estimation of the typical kidney filtration rate for a person’s age and gender to determine normal and abnormal levels.
• Creatinine Clearance tests measure creatinine in a blood sample and a urine sample. Assessed after a 24 hour period, both give a sense of the daily function of the kidneys.
• Serum Protein Electrophoresis tests determine the type and relative amounts of protein in
  blood serum. Comparing this result to a thorough urinalysis determines if the blood is the source of the protein found in the urine. Typically, this is only done if there is a proteinuria
  issue, in order to pinpoint the source of the issue.

In most cases, you do not need to prepare at all for a urine test aside from eating and drinking normally.

Urine Tests and Measuring Lupus

The various proteins that can be detected through urine tests are very promising indicators, or “biomarkers,” for lupus nephritis. This suggests that tests can help catch the condition early. That means earlier treatments and stemming the progression of kidney damage that leads to renal failure. Early control, in some cases, can prevent reliance on corticosteroids, but that is a case-by-case basis.

In either case, urine tests are one of many tools in the Lupus Warrior’s arsenal to measure lupus disease activity. Kidney damage is easy to overlook (until the damage is too severe for the body to compensate). People with SLE should be vigilant. Whether you are already aware of your SLE, or are in the midst of being diagnosed, you might find this information on other tests for diagnosis of lupus helpful, here.