How To Diagnose Proteinuria That Is Difficult To Detect And Has A Poor Prognosis?

Mar 14, 2024

Kidney disease is a type of disease in which most symptoms are atypical and very hidden. Its early detection is often diagnosed by detecting proteinuria after a urine routine. Proteinuria is of great significance for the diagnosis, evaluation of treatment effects, and prognosis of kidney disease.

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1. Definition of proteinuria

Due to the filtration effect of the glomerular filtration membrane and the reabsorption effect of the renal tubules, the daily urinary protein excretion of healthy people is <150 mg. When the protein content in urine exceeds the normal range, that is, the qualitative urine test is positive; if the 24-hour urine protein quantification (24h-UTP) is >150 mg, proteinuria can be diagnosed.

2. Four methods to diagnose proteinuria

Drawing on the diagnostic ideas of hematuria, clinical practice usually follows the four-step method of "qualitative, quantitative, localization, and causal factors" to clarify the diagnostic ideas of proteinuria.

Qualification of proteinuria

This step is the most basic and important, which is to determine whether the proteinuria is true proteinuria or pseudoproteinuria, otherwise, the next steps will be impossible to discuss.


Any urine routine that is positive for protein, except for (urates, penicillin, sulfonate contrast agents, alkaline urine, overly concentrated urine, etc.) and contamination (urethral orifice or local secretions from the vulva, female menstrual blood, leucorrhea, etc.) Except for false positives, it is defined as urine protein positive; otherwise, urine protein is negative, and false negatives (such as excessive urine dilution, etc.) need to be excluded.


It is particularly emphasized here that the qualitative results of urine protein must be combined with urine-specific gravity. Generally speaking, there is a direct relationship between the two, that is, the more protein in the urine, the higher the specific gravity of the urine. If proteinuria is suspected but multiple urine tests are qualitatively negative, the possibility of urine dilution should be considered.


I once encountered a patient with a recurrence of nephrotic syndrome in clinical practice. The patient's blood albumin had dropped significantly, but multiple routine urine tests were negative. Later, the patient's multiple routine urine tests found that the specific gravity was between 1.000 and 1.005.


After careful questioning, it was revealed that the patient had drunk a large amount of water during the examination, causing the urine sample to be diluted. In clinical practice, patients must be reminded to drink an appropriate amount of water during urine testing to avoid false negatives for urine protein due to sample dilution.

Quantification of proteinuria

After confirming true proteinuria, a quantitative urine protein test is required to determine whether it is nephrotic level (i.e., 24h-UTP>3.5g, also known as massive proteinuria) or non-nephropathic level proteinuria.


For those who cannot collect urine for 24 hours, such as infants and young children, when the urine protein/creatinine ratio is >0.2, it can be considered elevated.


It should be noted that in patients with obvious gross hematuria in clinical practice, such as patients with IgA nephropathy, purpura nephritis, acute post-streptococcal glomerulonephritis, and other diseases, the presence of a large number of red blood cells in the urine can make the total urinary protein quantitatively obvious. The urinary total protein/creatinine level also increases significantly, which will affect the clinical assessment of the condition.


Compared with indicators of urinary albumin quantification and urinary albumin/creatinine ratio, urinary microalbumin (MA) levels are not affected by gross hematuria.

Therefore, it is recommended to check urinary total protein quantification, urinary albumin quantification, urinary total protein/creatinine, urinary albumin/creatinine, and other indicators at the same time to reduce possible errors in a single indicator, especially when the patient has obvious hematuria.

Location of proteinuria

Clinical routine uses urine protein electrophoresis (mostly sodium dodecyl sulfate-agarose gel electrophoresis). Using albumin, which is the most abundant protein component in urine, as the boundary, urinary protein can be divided into large, medium, and small molecules. , among which large and medium molecule proteins are mainly seen in glomerular diseases, while small molecule proteins (>50%) are mainly found in renal tubular and interstitial diseases.


As shown in Figure 2, albumin and transferrin are medium molecular proteins, α1-microglobulin (α1-MG) and β2-microglobulin are small molecular proteins, and immunoglobulin G is a large molecule protein. Protein, the patient in the picture mainly has small and medium molecule proteinuria and is considered to have renal tubulo-interstitial disease.


The final renal biopsy pathology also confirmed that the patient had chronic interstitial nephropathy caused by an overdose of analgesics. However, clinically, some primary hospitals have not yet carried out urine protein electrophoresis examination, and other indicators can be used instead.


α1-MG is relatively stable in routine clinical testing and is less affected by pH value. At this time, the ratio of α1-MG to urinary MA, that is, α1-MG/MA, which is close to or >1 can be used as an indicator of small molecule proteinuria. The judgment standard is conducive to early screening, detection, and diagnosis of renal tubular and interstitial diseases.


Based on the molecular weight of urinary protein, it can be used as a preliminary judgment of glomerular and tubulointerstitial diseases, but it is not absolute. Accurate diagnosis of kidney disease still requires renal puncture biopsy.

Causes of proteinuria

For true proteinuria, in addition to clarifying the quantification and localization, the most important thing is to combine the clinical symptoms (such as rash, joint swelling, pain, fever, abdominal pain, hematuria, edema, hypertension, extrarenal manifestations, etc.), previous infection history, family Medical history, relevant laboratory tests, kidney biopsy or related gene mutation analysis if necessary, to diagnose the cause.


If proteinuria is accompanied by hematuria, it usually indicates glomerular diseases such as glomerulonephritis; in rare cases, it can also be seen in urinary system vascular diseases, such as hemangiomas and telangiectasia, but hematuria and proteinuria are caused by vascular diseases. Blood clots are often seen in urine.


In the process of diagnosing proteinuria, qualitative and causal, quantitative and localization relationships are parallel to each other, rather than a fixed sequential relationship.


The diagnosis of kidney disease often does not require all four factors to be clearly determined. If some of them are determined, the disease will be confirmed. This requires doctors to use clinical experience flexibly. Accurate diagnosis still requires the use of renal biopsy pathology.

However, for patients who have contraindications and cannot undergo renal puncture, the qualitative, quantitative, localized, and determined causes of proteinuria are very important for customizing effective treatment plans.


In clinical practice, it is indeed common to encounter patients with positive urine protein.


No, a 30-year-old man came to the outpatient clinic the day before yesterday. He complained of "recurrent double eyelid edema with increased nocturia for 2 years." The blood pressure was 160/100mmHg, urine protein (+), red blood cells 5 to 10/HP, and granular casts. 1~2/HP, serum creatinine 145μmol/L, hemoglobin 85g/L, serum albumin 32g/L.


Astute readers, what do you think is the most likely diagnosis for this patient?


I believe that through learning about the diagnosis of proteinuria, most readers can quickly get the answer. You can also click to read the original text and download the answers from the Doctor Station APP.

3. Be alert to the adverse effects of proteinuria on the prognosis of kidney disease

Persistent proteinuria is not only one of the most common clinical manifestations of chronic kidney disease but also one of the important factors that aggravate the degree of chronic renal failure and vascular aging. If long-term massive proteinuria is not controlled and is complicated by infection, it is easy to develop end-stage renal disease (ESRD), and the prognosis is often poor [2].


The author once treated a patient with stage 2 membranous nephropathy. The patient's renal puncture pathology results at that time showed that the condition was not very serious. The patient has used tripterygium wilfordii combined with hormones, cyclophosphamide combined with hormones, tacrolimus combined with hormones, and other regimens in many hospitals, but the 24h-UTP has always been greater than 3.5g, and the nephrotic syndrome has never been relieved.


The patient's serum creatinine level was still normal when he was first diagnosed, but because the proteinuria level could not be controlled, he was considered to have refractory membranous nephropathy. Beginning in the second year, the patient's serum creatinine began to gradually increase. By the third year, the patient's serum creatinine had reached the uremic level, and he finally had to undergo hemodialysis treatment, which shows the importance of proteinuria control to the patient's renal prognosis.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.

 

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

 

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

 

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

 

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

 

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

 

Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

 

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

 

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.

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