How Proteinuria Is Diagnosed

Kidney disease is a type of disease with atypical symptoms and strong concealment in most diseases. Its early detection is often diagnosed after proteinuria is detected after a urine routine. Proteinuria is of great significance for the diagnosis, evaluation of treatment effects, and prognosis of nephropathy.

Definition of proteinuria

Due to the filtration of the glomerular filtration membrane and the reabsorption of the renal tubules in healthy people, the daily excretion of protein in urine is less than 150 mg. When the protein content in urine exceeds the normal range, that is, the routine urine test is positive; the 24-hour urine protein quantification (424h-UTP) > 150mg can be diagnosed as proteinuria.

Diagnosis of proteinuria

Drawing lessons from the diagnostic ideas of hematuria, the clinic usually clarifies the diagnostic ideas of proteinuria according to the four determination methods of "qualitative, quantitative, localization, and cause determination".

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 Qualitative proteinuria

This step is the most basic and important, that is, to determine whether the proteinuria is true proteinuria or pseudo proteinuria, otherwise, the next steps will be impossible to talk about.

Where routine urine protein is positive, except for (urate, penicillin, sulfur contrast agent, alkaline urine, and excessively concentrated urine, etc.) Except for false positives, it is defined as positive urine protein; otherwise, it is negative urine protein, and false negatives (such as excessive dilution of urine, 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 directly proportional 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 routines are negative, the possibility of urine dilution should be considered.

I once encountered a patient with recurrent nephrotic syndrome in the clinic. The albumin in the blood of the patient had dropped significantly, but the urine routine examinations were negative many times. Later, the urine routine examination of the patient found that the specific gravity was 1.000-1.005. After careful questioning, it was learned that the patient drank a lot of water during the examination, which resulted in the dilution of the urine sample. In clinical practice, patients must be reminded to drink an appropriate amount of water during the urine test to avoid false negatives for urine protein due to sample dilution.

Quantification of proteinuria

After confirming true proteinuria, urine protein quantitative examination is required to confirm that it is proteinuria at nephropathy level (ie 24h-UTP>3.5g, also known as massive proteinuria) or non-nephropathic level proteinuria.

For those who cannot keep 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 IgA nephropathy, purpura nephritis, glomerulonephritis after acute streptococcal infection, and other diseases, there are a large number of red blood cells in the urine, which can make the total urine protein quantitatively obvious. Elevated urine total protein/creatinine level will also significantly increase, which will affect the clinical assessment of the disease. Compared with indicators of urinary albumin quantification and urinary albumin/creatinine ratio, urinary microalbumin (MA) level was not affected by gross hematuria. Therefore, it is recommended to check the total urinary protein quantification, urinary albumin quantification, urinary total protein/creatinine, urinary albumin/creatinine, and other indicators at the same time to reduce the possible error of a single indicator, especially when the patient has obvious hematuria.

Localization of proteinuria

Urine protein electrophoresis (mostly sodium dodecyl sulfate-agarose gel electrophoresis) is routinely used in clinical practice. Urinary protein can be divided into large, medium, and small molecules based on albumin, which is the most abundant protein component in urine. Among them, those with large and medium molecular proteins are mainly seen in glomerular diseases, and those with small molecular proteins (>50%) are seen 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 macromolecular protein Protein, the patient in the picture mainly has small and medium molecular proteinuria, which is considered as a renal tubulointerstitial disease. The final renal biopsy pathology also confirmed this, and the patient was chronic interstitial nephropathy caused by analgesic overdose. However, clinically, urine protein electrophoresis has not been carried out in some primary hospitals, and other indicators can be used to replace it at this time.

α1-MG is relatively stable in clinical routine testing and is less affected by the 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. Judgment criteria are conducive to early screening, discovery, and diagnosis of renal tubular and interstitial diseases.

The molecular weight of urine protein can be used as a preliminary judgment of glomerular and tubulointerstitial diseases, but it is not absolute. The accurate diagnosis of kidney diseases still requires renal biopsy.

Causes of proteinuria

For true proteinuria, in addition to clarifying the quantification and location, the most important thing is to combine clinical symptoms (such as rash, joint swelling, pain, fever, abdominal pain, hematuria, edema, hypertension, extrarenal manifestations, etc.), antecedent infection history, family history, etc. History, relevant laboratory tests, kidney biopsy, or related gene mutation analysis when necessary, for etiological diagnosis. If proteinuria is accompanied by hematuria, it often indicates glomerular diseases such as glomerulonephritis; in rare cases, it can also be seen in vascular diseases of the urinary system, such as hemangioma and telangiectasia, but those with hematuria and proteinuria caused by vascular diseases Blood clots are often seen in the urine.

In the diagnosis process of proteinuria, qualitative and definite cause, quantitative and localization are parallel to each other, rather than a fixed sequential relationship. Diagnosis of kidney disease often does not require all four of them to be identified. It may be possible that some of them are identified, and the disease is diagnosed. This requires physicians to use clinical experience flexibly. Accurate diagnosis still requires renal biopsy pathology. However, for patients with contraindications who cannot undergo renal puncture, the qualitative, and quantitative, localization, and determination of proteinuria are very important for customizing an effective treatment plan.

The important impact 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 a large amount of proteinuria is not controlled for a long time, and then complicated by infection, it is easy to develop into end-stage renal disease (ESRD), and the prognosis is very poor [2].

I once received a patient with stage II membranous nephropathy. At that time, the pathological results of the renal biopsy showed that the condition was not very serious. The patient has used tripterygium wilfordii combined with hormones, cyclophosphamide combined with hormones, and tacrolimus combined with hormones in many hospitals, but the 24h-UTP is always greater than 3.5g, and the nephrotic syndrome has never been relieved. When the patient was first diagnosed, the serum creatinine level was still normal, but because the proteinuria level could not be controlled, it was considered refractory membranous nephropathy. From the second year, the patient's serum creatinine began to gradually increase. By the third year, the patient's serum creatinine had reached the level of uremia, and finally, he had to undergo hemodialysis treatment, which shows the importance of the degree of control of proteinuria to the prognosis of patients with renal disease.

for more information:Ali.ma@wecistanche.com