In the United States, a kidney disease is considered rare if it affects fewer than 200,000 people. There are about 150 types and subtypes of rare kidney diseases. Since these diseases are so uncommon and there are so many, they can be difficult to diagnose. Many of the symptoms overlap with those of other kidney problems, complicating the issue even more. If you notice changes in your urine, new swelling, or increased fatigue, it’s time to talk to your healthcare provider.

This article discusses the tests used to diagnose rare kidney disease. Some check kidney function, and others take a close look at kidney tissues. Reaching an accurate diagnosis is key to choosing the right treatment option for your rare kidney disease.

Physical Exam and Medical History

Diagnosing rare kidney diseases usually begins with a physical exam. Your doctor will take your medical history and ask about your symptoms. Be sure to describe symptoms that recently started as well as those that have become worse over time.

Your doctor will also ask about your family history of kidney disease. Some rare kidney diseases are passed down from parents to their children. Knowing your personal and family medical history can help point your healthcare provider to the right diagnosis.

During the physical exam, your doctor will weigh you and take your blood pressure. Hypertension (high blood pressure) can be a sign of rare kidney diseases, but it can also occur on its own or as part of other chronic health conditions. Your doctor will look for signs of edema (swelling) in your legs, feet, and hands.

If your primary care doctor thinks you may have kidney disease, they’ll refer you to a nephrologist (kidney specialist). A nephrologist will be more familiar with rare kidney diseases.

Blood and Urine Tests

The next step in diagnosing a rare kidney disease involves blood and urine tests. Blood tests measure levels of different substances to check kidney function. For example, your nephrologist will check how well your kidneys filter waste.

Estimated Glomerular Filtration Rate

Your estimated glomerular filtration rate (eGFR) indicates your kidneys’ filtering abilities. Your nephrologist will first run a blood test to measure your creatinine levels. Creatinine is a waste product made by your muscles. Healthy kidneys filter creatinine out of the blood and get rid of it in urine. People with kidney damage can’t properly filter waste, so creatinine builds up in their bloodstream.

According to the American Kidney Fund, a normal serum creatinine level is 0.7 to 1.3 milligrams per deciliter for males and 0.6 to 1.1 milligrams per deciliter for females. Age and muscle mass are also taken into account.

The higher your creatinine levels are, the lower your eGFR will be. A healthy eGFR is 90 or higher. Anything from 60 to 89 may indicate early kidney disease, and an eGFR below 60 that lasts at least three months is a sign of mild to moderate kidney disease. An eGFR below 15 indicates kidney failure.

Catching an abnormal eGFR early is key to preserving your kidney function. Lifestyle changes such as a kidney-friendly diet and regular exercise may help slow your disease progression.

Urine Tests

Urine tests check your urine (pee) for abnormalities. Kidney diseases damage the glomeruli, the kidneys’ tiny filtering units. These units usually prevent larger substances from leaving the body. Damaged glomeruli let out protein and blood, which are measured in urine to diagnose kidney disease.

Proteinuria — or protein in urine — is one of the earliest signs of kidney disease. Nephrologists look at a measurement called the urine albumin to creatinine ratio (uACR). Albumin is your blood’s main protein source. The test compares the level of albumin to creatinine to see how well your kidneys are working. A high uACR may be a sign of kidney disease.

Electrolyte Panel

Your doctor may run blood tests to measure your levels of electrolytes, electrically charged molecules that help your body perform essential functions. Your kidneys help control your electrolyte levels to keep processes like these running smoothly:

• Controlling fluid balance
• Maintaining healthy blood pressure
• Keeping a steady heart rate and rhythm

• Moving nutrients and waste in and out of cells

Kidney disease can cause abnormal electrolyte levels. Healthy kidneys reabsorb electrolytes, whereas damaged kidneys release them into the urine. Your nephrologist may check your sodium and potassium levels. Electrolyte levels that are out of balance can lead to other health problems.

Tests for Specific Rare Kidney Diseases

Depending on the type of rare kidney disease you have, you might need special tests. For example, people with Fabry disease have an enzyme (protein) called alpha-galactosidase A (alpha-GAL) that doesn’t work properly. Enzyme tests can check alpha-GAL’s activity. DNA sequence analysis — a test that looks at your genetic code — can also help doctors make an accurate diagnosis.

A rare liver disease called primary hyperoxaluria also affects the kidneys. This condition occurs when oxalate, a chemical, builds up in the kidneys, leading to kidney stones. Doctors use blood tests to measure oxalate levels and diagnose primary hyperoxaluria.

Imaging Tests

Imaging tests let nephrologists take a closer look at the kidneys to pinpoint a problem. The American Kidney Fund notes that these tests can help diagnose:

• Kidney stones
• Tumors
• Fluid-filled sacs called cysts
• Problems with blood flow to the kidneys
• Kidney injuries

Doctors select imaging tests based on the information they need. Ultrasound uses sound waves to create pictures. MRI uses strong magnets to make detailed three-dimensional images. CT scans take X-rays from different angles to produce detailed pictures.

Kidney Biopsy

Some rare kidney diseases can be diagnosed only with a biopsy. This test involves removing a small piece of kidney tissue to be examined under a microscope. The most common type of kidney biopsy is a percutaneous biopsy. Your nephrologist or a radiologist takes the tissue sample using a thin needle inserted into your skin.

The tissue sample is sent to a lab for analysis and diagnosis. This is the best way to tell the difference between rare kidney diseases and other conditions. For example, finding extra complement 3 (C3) protein in the tissue confirms a complement 3 glomerulopathy diagnosis. Sometimes, doctors use specialized microscopes to diagnose dense deposit disease or C3 glomerulonephritis, which are subtypes of C3 glomerulopathy.

Genetic Testing

Some rare kidney diseases are genetic, meaning they’re passed down in your DNA. If you have a family history of rare kidney disease, your doctor may recommend genetic testing. They’ll take a small blood or saliva sample and send it to a lab for analysis. The goal is to find genetic mutations (changes or variants) known to cause kidney disease.

Types of rare kidney diseases caused by genetic mutations include:

• Polycystic kidney disease (PKD) — Mutations in the PKD1 or PKD2 gene cause cysts in the kidneys.
• Cystinosis — Changes in the CTNS gene cause cysteine (a protein component) to build up inside cells.
• APOL1-mediated kidney disease — Variants in the APOL1 gene increase the risk of certain kidney diseases.
• Hemolytic uremic syndrome — Gene mutations or bacterial infections can cause red blood cells to clog the kidneys’ filters.
• Fabry disease — Changes in the GLA gene cause a shortage of alpha-GAL, leading to a harmful buildup of fatty substances in cells.

Understanding the genetic cause of kidney disease can help guide treatment, inform family members, and provide a clearer picture of what to expect in the future.

Talk With Others Who Understand

On MyKidneyDiseaseTeam, people with kidney disease and their loved ones come together to ask questions, give advice, and share their stories with others who understand life with kidney disease.

Are you living with a rare kidney disease? What tests led to your diagnosis? Share your story in the comments below, or start a conversation by posting on your Activities page.