How To Measure Protein In Urine: A Guide For Kidney Disease Patients

When it comes to kidney disease, the presence of protein in the urine, known as proteinuria, is of utmost importance. In fact, I often emphasize that among all the critical aspects of kidney disease, managing proteinuria is at the top of the list. I've already created four videos on the topic of proteinuria—videos 40, 72, 77, and 91—where I've discussed it from different angles. However, despite these detailed discussions, several questions remain unanswered, and many more will arise in the future. Today, we will address one of the most significant questions: How is proteinuria measured, and why is there so much confusion regarding its units?

Introduction to Proteinuria Measurement

Hello, I'm Dr. Owais Zakar from Expert Quansar Clinic of Lahore. Historically, humans have been aware of the presence of protein in urine for centuries, if not millennia. However, a major breakthrough occurred in the past 100-200 years when we learned how to measure protein in urine precisely. With this advancement came a new confusion: the discovery of albumin and the ability to measure it separately from total protein.

Before the measurement of albumin became common, all measurements were of total protein. But why is it so crucial to measure albuminuria or proteinuria in kidney disease? The reason is that the presence of albumin in urine, or proteinuria, indicates significant kidney damage. Moreover, albuminuria is a major cardiovascular risk factor, meaning that patients with albuminuria are at a much higher risk of developing heart problems or brain conditions, such as heart attacks, heart failure, edema, strokes, or paralysis.

Proteinuria is also associated with widespread inflammation throughout the body and the process of atherosclerosis, which increases the likelihood of damage to blood vessels and the organs they supply. This is why when you look at international kidney disease guidelines, such as KDIGO (Kidney Disease: Improving Global Outcomes), you see that kidney function stages are aligned with proteinuria stages. As you move down the chart, kidney function worsens, and as you move from left to right, proteinuria worsens. When both are in their worst stages, the areas on the chart are marked red, indicating high risk and the need for immediate action.

Albumin vs. Total Protein in Urine

Understanding the significance of proteinuria or albuminuria leads us to the next step: distinguishing between albumin and total protein in urine. From a practical standpoint, it's important to know that there are two primary types of protein in urine: albumin, which constitutes the majority, and other proteins present in much smaller amounts. For most practical purposes, whether you measure albumin or total protein, the result is almost always representative of albumin.

However, there are a few rare situations where albumin in the urine might be low or normal, while another protein is elevated. The most notable example of this is multiple myeloma, a type of cancer affecting the bones. In multiple myeloma, plasma cells (a type of immune cell) produce excessive amounts of protein, which then enters the bloodstream and is excreted through the kidneys into the urine. In such cases, total protein levels in urine are high, but albumin levels may be low.

Methods of Measuring Proteinuria

Now, let's discuss the steps involved in measuring protein in urine. Typically, the process begins with a simple urinalysis, which provides a preliminary indication of protein levels, often reported as trace, 1+, 2+, etc. This test usually involves dipping a strip into the urine sample. The strip is then compared to a specific color chart, which gives a rough estimate of protein levels.

Some labs may use reagents to perform this test, but most rely on the strip method. These strips can be specific to albumin or detect other proteins. It’s always a good idea to ask your lab which type of protein the strip is designed to detect, although most available strips are specific to albumin.

If the strip test shows a positive result for protein, it’s likely that the urine contains albumin. This dipstick or strip test is known as a screening test and doesn't provide the total amount of protein in the urine. For a more accurate understanding of kidney disease progression and to monitor the effectiveness of treatment, we need a specific numerical value, which leads us to the next level of testing.

Advanced Testing: Protein-to-Creatinine Ratio

Traditionally, a 24-hour urine protein test was used to measure the total protein in urine. I’ve explained how to collect a 24-hour urine sample in detail in Episode 40, which you can refer to. However, collecting urine over 24 hours is impractical and often inaccurate. It requires carrying a gallon container throughout the day, storing it at a specific temperature (usually in an icebox), which is inconvenient and prone to error. As a result, the measurements were often inaccurate, despite the effort involved.

To address these challenges, scientists developed a new test called the Protein-to-Creatinine Ratio (PCR) or Albumin-to-Creatinine Ratio (ACR). For patients, it's important to understand that albumin and total protein are almost the same, with only minor differences, so there’s no need to worry about the terminology.

During research, it was found that the amount of creatinine in urine varies throughout the day, depending on factors like diet and physical activity. Similarly, albumin levels in urine can also vary. However, when you calculate the ratio of albumin to creatinine, this ratio remains consistent throughout the day. After extensive research and numerous measurements across different patient groups, scientists concluded that the Albumin-to-Creatinine Ratio (ACR) is a highly specific and accurate test. It eliminates the inconvenience of the 24-hour urine collection and provides more reliable results.

Conclusion: The Shift from 24-Hour Urine Collection to ACR

As a result, the 24-hour urine protein test has gradually become obsolete. In Pakistan, some people may still undergo this test, but it’s essential to understand that it has very limited indications today. In 98% of cases in the Western world, the primary tests used are the Urine Protein-to-Creatinine Ratio or the Urine Albumin-to-Creatinine Ratio. I rarely recommend a 24-hour urine protein test unless the patient is experiencing acute kidney injury, where it might still have some relevance.

In summary, measuring protein or albumin in urine is crucial for understanding and managing kidney disease. The transition from older methods like the 24-hour urine collection to more accurate and convenient tests like the ACR represents significant progress in the field. By understanding these tests, patients can better monitor their condition and reduce the risks associated with kidney disease and its complications.