Does Proteinuria Necessarily Mean Kidney Disease?

‍Due to the filtration of the glomerular filtration membrane and the reabsorption of the renal tubules, the content of protein in the urine of healthy people (mostly refers to proteins with smaller molecular weights) is very small, no more than 150mg per day. However, recent studies have found that proteinuria is not uncommon, on the contrary, it is more common in the Chinese population. However, the general public does not have a deep understanding of it. Some people are extremely panicked, thinking that as long as proteinuria occurs, it means kidney disease or even kidney failure, while some people don't think so. So, how to correctly understand proteinuria?

 

 

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This article involves the prevalence and causes of proteinuria, hoping to help everyone understand proteinuria correctly and actively deal with it.

The prevalence of proteinuria

At the annual meeting of the European Society of Nephrology in 2022, important data was announced, that is, after examining 15,000 Dutch participants, about 3% of them were diagnosed with proteinuria. Of note, approximately two-thirds of this 3 percent had never had kidney disease diagnosed¹. Tips, the prevalence of proteinuria is far more than people imagine. So, what is the prevalence of proteinuria in China?

In a Chinese study published in 2021, the subjects were people aged 18-75 from 6 provinces in China. A total of 2693 subjects were randomly selected from 12 counties in 6 provinces for physical examination and 24-hour urine collection. The study finally included 2607 participants, and detected 234 patients with microalbuminuria, with a detection rate of 8.98% (95% CI, 7.91%-10.14%). The detection rates of microalbuminuria in males, 50 years old and above, smoking, obesity, hypertension, and diabetes were 10.48%, 11.91%, 10.94%, 14.82%, 16.85%, and 23.21%, which were higher than the corresponding groups. The difference was statistically significant (P<0.05).

The results of the multivariate Logistic regression analysis model showed that compared with those without hypertension, without diabetes, and normal-weight people, patients with hypertension (OR=2.843, 95% CI, 2.093~3.862), patients with diabetes (OR=2.453, 95% CI, 1.626~3.702) and obese people (OR=1.941, 95%CI: 1.338~2.815) had a higher risk of MAU (all P<0.001)².

 

The above data show that the actual prevalence of proteinuria in China may be relatively high, which requires physicians to pay attention to it.

The cause of proteinuria

In addition to being related to abnormal kidney function, proteinuria is also related to diet, drugs, and even false positive proteinuria.

01 Proteinuria and abnormal kidney function

A large number of studies have proved that proteinuria is a typical symptom of chronic kidney disease (CKD), which is inseparable from glomerular barrier dysfunction. In addition, some studies have shown that the reabsorption disorder of the proximal tubule is also related to the formation of proteinuria. In addition to renal causes, abnormal plasma proteins and tissue breakdown may lead to abnormal proteinuria in patients³.

In addition, proteinuria and microalbuminuria are often associated with type 1 or type 2 diabetes and hypertension. This also suggests that proteinuria is an important indicator of certain diseases that have adverse effects on the kidneys⁴. In general, proteinuria is closely related to abnormal renal function and is an important indicator for evaluating CKD and renal function.

02 Proteinuria and Diet

Of note, a low-quality diet may also contribute to proteinuria. For example, a prospective study from the United States showed that a high-quality plant-based diet can reduce the risk of proteinuria and decrease the estimated glomerular filtration rate (eGFR) in patients. The study included 2869 patients with a mean age of 45.3 (±3.6) years.

 

After adjusting for demographics, behavior, and eating patterns, lower diet scores (APDQS) were associated with worse CKD indicators. Proteinuria levels were reduced in the highest APDQS population compared with the lowest APDQS quintile (-0.25 mg/g; 95% CI, -0.37 to -0.13 mg/g, P<0.001). And after adjusting traditional CKD risk factors such as diabetes and hypertension, this trend is still obvious⁵.

03 False positive proteinuria

It should be noted that proteinuria, especially microalbuminuria, may not be due to the deterioration of the patient's renal function, so the patient must undergo multiple proteinuria tests to know how the condition is. The current study identified the following causes as possible causes of proteinuria or microalbuminuria, leading to false-positive proteinuria:

• Fever, strenuous exercise, physical labor, etc. may cause a transient increase in proteinuria, which is usually harmless to the human body.
• Whether the spine is normal: Some patients with deformed/abnormal spine are prone to proteinuria <1g/24h, but their kidney function is normal. This condition is common in lanky teenagers.
• Patients with severe heart failure and sleep apnea syndrome may also have proteinuria <1g/24h and have normal renal function.
• Discoloration of the urine, such as red/smoky, may be associated with a respiratory infection.
• HIV and hepatitis infection may also be associated with proteinuria or microalbuminuria⁴.
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Also, look for bacteria in the urine sample, as inflammation of the urethra can lead to proteinuria. At the same time, the urine sediment test should also be checked for the presence of blood cells, and sperm, because menstruation, and semen can also cause false positive proteinuria⁶.

04 Proteinuria and drugs

In addition to pathological proteinuria and transient proteinuria, drug-induced proteinuria is often seen in clinical practice. Nephrotoxic drugs such as penicillin and azithromycin may worsen renal function and lead to proteinuria⁷.

In addition, some elderly people do not take their medicines regularly, which may lead to excessive drug use and proteinuria⁸. These circumstances indicate that for patients with proteinuria and microalbuminuria, physicians should review the patient's prescription and medication history.

 

In short, the occurrence of proteinuria does not mean that there is a problem with renal function, and everything from infection to excessive exercise may lead to proteinuria or microalbuminuria. In fact, according to the definition of CKD according to the KDIGO clinical guidelines, the staging of kidney disease also needs to estimate the glomerular filtration rate (eGFR)⁹. From the side, it reflects that the diagnosis of kidney disease is not just an indicator of proteinuria. However, the current prevalence of proteinuria is indeed not optimistic, indicating that there are many high-risk groups of CKD.

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