Definition of proteinuria
Due to the filtration of the glomerular filtration membrane and the reabsorption of the renal tubules, the amount of protein (mostly proteins of small molecular weight) in the urine of a healthy person is very small (less than 150 mg excreted daily), and the qualitative protein examination is negative. When the amount of protein in the urine increases, it can be detected by ordinary routine urinalysis and is called proteinuria. If the urine protein level is ≥3.5g/24h, it is called massive proteinuria.
How proteinuria in kidney disease is formed
Proteinuria is a typical symptom of chronic kidney disease, and the cause of proteinuria is inextricably linked to the barrier function of the glomerulus.
Glomerular capillaries are composed of three layers, from the inside to the outside: the endothelial cell layer, the basement membrane layer and the epithelial cell layer. Since these three layers of cells are distributed with filter pores of different sizes and negative charges, the barrier function of glomerular capillaries can be divided into two types, namely, mechanical barrier filter pores and charge barrier negative charges.
1.Mechanical barrier filter pore
The glomerular filtration barrier is composed of three layers from the inside out.
① The inner layer is the endothelial cells of capillaries. There are many small pores of 50-100 nm in diameter on the endothelial cells, called window pores (fenestration). Water, various solutes and large molecules of protein can pass freely through the window pores; however, they can prevent blood cells from passing through and act as a blood cell barrier.
The middle layer is a non-cellular basement membrane with a microfibrillar meshwork structure. Larger molecules in plasma, such as proteins, cannot pass through the basement membrane. The basement membrane is the main barrier of the glomerulus to prevent the filtration of large molecules of protein.
(iii) The outer layer is the epithelial cells of the glomerulus. The epithelial cells have pedicles, and the interlocking pedicles form a cleft between them. There is a filtration slitmembrane with 4-14 nm diameter pores, which prevents the passage of macromolecular proteins filtered from the inner and middle layers and is the last barrier to filtration. Endothelial cells, basement membrane and epithelial cells together form the glomerular filtration membrane. The different sized filtration pores on the filtration membrane only allow small molecules to pass easily, while substances with a larger effective radius can only pass through the larger pores, and in general, substances with an effective radius of less than 1.8 nm can be completely filtered. In general, substances with an effective radius of less than 1.8 nm can be completely filtered. Large molecules with an effective radius of more than 3.6 nm, such as plasma albumin (molecular weight of about 69,000), are almost completely unfilterable.
2, charge barrier negative charge
Each layer of the filter membrane contains many negatively charged substances, so the permeability of the filter membrane is also determined by the charge of the filtered material. These negatively charged substances repel negatively charged plasma proteins, limiting their filtration. Although plasma albumin has an effective radius of 3.5 nm, it has difficulty passing through the filtration membrane because of its negative charge. When various pathological injuries (including primary and secondary injuries) act on the kidney, they lead to local microcirculatory disorders in the damaged kidney, prompting ischemia and hypoxia in the kidney tissues (functional kidney units). As a result of ischemia and hypoxia, glomerular capillary endothelial cells are damaged. Once the glomerular capillary endothelial cells are damaged, they attract inflammatory cell infiltration in the blood circulation and release pathogenic inflammatory mediators (IL-1, TNF–α, etc.), and the pathological injury at this time causes an inflammatory response in the damaged kidney. When the kidney is in a pathological state, the glomerular basement membrane (GBM) undergoes a series of changes: its filtration pores are enlarged or occluded, the GBM is broken, the charge barrier is damaged, renal permeability is enhanced, and the negatively charged glycoproteins on the filtration membrane are reduced or lost, all leading to a significant increase in the filtration of negatively charged plasma proteins compared to normal. Therefore, proteinuria is formed clinically in this period.
Several possible conditions of pseudoproteinuria
Pseudoproteinuria? Pseudoproteinuria, as the name implies, is not true proteinuria. For some reason, a routine urine test is positive for protein.
Pseudoproteinuria is usually seen in the following conditions, and if any of these conditions cause proteinuria, an in-depth examination is recommended.
Pseudoproteinuria is seen in the following cases.
① Blood, pus, inflammatory or tumor secretions, as well as menstrual blood and leukorrhea are mixed in the urine, and routine qualitative proteinuria tests can be positive. After the urine is centrifuged and precipitated or filtered, the qualitative protein test will be significantly reduced or even turn negative;
②After the urine is left for a long time or cooled, salt crystals can be precipitated, making the urine white and cloudy, which can be easily mistaken for protein urine, but warming or adding a little acetic acid can make the cloudy urine clear to help distinguish;
(3) urine mixed with semen or prostate fluid, or lower urinary tract inflammatory secretions, etc., urine protein reaction can be positive. In this case, the patient has manifestations of lower urinary tract or prostate disease, and the urine sediment can find spermatozoa, more flattened epithelial cells, etc., which can be distinguished;
④Lymphatic urine, which contains less protein, is not necessarily chylomicronous;
⑤ Some drugs such as rifampicin and Sandozanin, when excreted from the urine, can make the urine cloudy similar to proteinuria, but the protein qualitative reaction is negative.
Classification of proteinuria
Generally speaking, proteinuria is divided into selective proteinuria and non-selective proteinuria. Selective proteinuria refers to protein electrophoresis characterized by proteins with small molecular weight, such as albumin, α1 globulin, transferrin and gamma globulin. Proteins with larger molecular weights, such as α2 globulin, fibrinogen, and β lipoprotein, are less abundant.
In patients with microscopic nephropathy, mild thylakoid proliferative nephritis, partial membranous nephropathy and early lesions of membranous proliferative nephritis and focal segmental sclerosing nephritis, selective proteinuria is mostly present, indicating less damage to the small network (glomerular filtration membrane).
Non-selective proteinuria, in which protein electrophoresis is characterized by the presence of both large and small molecules, indicates that the damage to the small network (glomerular membrane) is more severe.
Is it difficult to recover from a large loss of urine protein?
Proteinuria is a typical symptom of kidney disease, but the amount of urine protein leakage does not reflect the severity of kidney disease. Nephrologists analyze that the amount of protein loss is not proportional to the severity of the disease. Mild chronic kidney disease patients with little urine protein leakage does not necessarily mean that the kidney pathological damage is light; a large amount of proteinuria also does not indicate serious nephropathological damage. For example, in microscopic lesion nephritis and mild thylakoid proliferative nephritis, the kidney lesion is mild, but the daily urine protein amount can be several grams or even a dozen grams. On the contrary, some focal segmental sclerosing nephritis and crescentic nephritis have severe pathological damage, but the daily urine protein amount may only be a few grams. Therefore, the good or bad treatment depends mainly on the type of kidney pathology, the damage and the kidney function.
It also depends on whether the patient can cooperate with the doctor, pay attention to prevent the appearance of recurrence triggers (such as cold, exertion, diarrhea, etc.), adhere to the treatment, and avoid nephrotoxic drugs.
Can protein be supplemented by diet in case of large amount of proteinuria
The view that nephritis patients cannot eat protein-containing foods is wrong and one-sided, even for patients with chronic nephritis that has progressed to an advanced stage – the uremic stage – it is advocated to give a high-quality, low-protein diet.
Daily protein intake should be controlled at 0. 6 to 0. 8 g/kg body weight. Patients with uremia, during dialysis treatment, especially when peritoneal dialysis is performed, the amount of protein eaten daily should be increased to about 1. 2 to 1. 5 g/kg body weight. Patients with nephrotic syndrome, who lose a large amount of protein in urine, such as those with normal renal function, are advocated to eat a high protein diet to correct hypoproteinemia, reduce edema and improve or enhance the body resistance.
If patients with nephritis develop azotemia, or early renal insufficiency, the protein intake should be restricted. Otherwise, it will accelerate the deterioration of renal function. In short, different dietary recipes should be used for different conditions.
When a large amount of proteinuria appears in kidney disease patients, there is no need to be overly panic; when a small amount of proteinuria appears, the severity of the disease should not be overly ignored, and it is better to diagnose the disease in time and develop a corresponding treatment plan for proteinuria. From the perspective of kidney pathological damage to completely restore kidney function and eliminate proteinuria.
The relationship between proteinuria and disease prognosis
The presence of proteinuria can basically be judged as a clinical symptom caused by kidney damage through other ultrasound examinations of the kidney, kidney function tests, and routine urine tests, in addition to excluding other causes such as physiological factors and postural factors.
The clinical significance of proteinuria is very complex. Persistent proteinuria seen clinically often means substantial damage to the kidneys. When proteinuria changes from more to less, it can either reflect an improvement in kidney disease or it can be a sign of worsening kidney function due to the majority of glomerular fibrosis and reduced filtered protein. Therefore, to determine the severity of kidney disease damage, we should not only measure proteinuria, but also consider the amount and duration of urine protein, as well as systemic conditions and renal function tests.
A large number of clinical data show that patients with nephrotic syndrome and persistent proteinuria have a poor prognosis. In focal glomerulosclerosis, membranoproliferative glomerulonephritis, membranous nephropathy, IGA nephropathy, diabetic nephropathy and chronic renal transplant rejection, proteinuria is a significantly unique determinant of progression of renal disease and increased morbidity and mortality. Indeed remission of these diseases and reduction in urinary protein excretion, whether spontaneous or due to aggressive treatment, improves survival. Overview: What is proteinuria?
Causes: What causes proteinuria
(A) Renal proteinuria
1. Glomerular proteinuria
It is seen in acute glomerulonephritis, all types of chronic glomerulonephritis, IgA nephritis, and occult nephritis.
Secondary to autoimmune disorders such as lupus kidney, diabetic nephropathy, purpura nephritis, renal arteriosclerosis, etc. Metabolic disorders are seen in gouty kidneys.
Strenuous exercise, long-distance march, high temperature environment, fever, cold environment, mental stress, congestive heart failure, etc. can also appear proteinuria.
2.Renal tubular proteinuria
The most common causes are interstitial nephritis, renal vein thrombosis, renal artery embolism, heavy metal salt poisoning, etc.
3.Renal tissue proteinuria
Also known as secretory proteinuria. It is caused by the leakage of protein produced by renal tubular metabolism into the urine in the process of urine formation.
(II) Non-nephrogenic proteinuria
1. Humoral proteinuria
Also known as overflow proteinuria, such as multiple myeloma.
2.Tissue proteinuria
Such as protein in the urine of malignant tumors, host proteins produced by viral infections, etc.
3.Protein in the lower urinary tract mixed into the urine causes proteinuria
See in urinary tract infection, urinary tract epithelial cell shedding and urinary tract secretion of mucin.
Diagnosis: What tests should be done for proteinuria?
(A) Medical history
such as history of edema, occurrence of hypertension, history of diabetes mellitus, history of allergic purpura, history of kidney damaging drug use, history of heavy metal salt poisoning.
proteinuria
and history of connective tissue diseases, metabolic diseases and gout attacks.
(B) Physical examination of proteinuria
Pay attention to edema and plasma cavity fluid, skeletal and joint examination, degree of anemia and physical examination of heart, liver and kidney.
Fundus examination, normal or mild vasospasm in the fundus of acute nephritis, arteriosclerosis, hemorrhage and exudation in the fundus of chronic nephritis, and diabetic fundus often appear in diabetic nephropathy.
(C) Laboratory tests for proteinuria
Urine protein examination can be divided into qualitative and quantitative examination and special examination.
1.Qualitative examination
Preferably morning urine, which is the most concentrated and can exclude somatotropic proteinuria. Qualitative examination is only a screening test and is not used as an accurate indicator of urine protein content.
2.Quantitative urine protein test
3.Special urine protein examination
Urine protein electrophoresis examination can distinguish selective proteinuria and non-selective proteinuria. Urine protein electrophoresis examination of multiple myeloma is helpful for staging.
Radioimmunoassay is more helpful in the diagnosis of early renal tubular impairment.
Differential diagnosis: How to differentiate the causes of proteinuria from each other?
(A) Acute glomerulonephritis
Oedema, hypertension, hematuria, proteinuria and tubuluria after streptococcal infection.
(ii) Chronic glomerulonephritis
Edema starts from the lower extremities and spreads from the bottom to the top, with a long course and easy recurrence, often with renal function impairment in the late stage, with the hypertensive type appearing earliest.
(C) pyelonephritis
Systemic infection poisoning symptoms, back pain, bladder irritation symptoms, and laboratory tests for pus urine bacteriuria are its characteristics.
(iv) Systemic lupus erythematosus
It is an autoimmune disease with hair loss, facial butterfly erythema, oral ulcers, wandering arthritis, photosensitivity, Raynaud’s phenomenon, and multi-organ damage, especially heart and kidney, of which kidney damage is the first.
Its proteinuria is generally high, and some patients appear in the form of nephrotic syndrome.
(E) Multiple myeloma
It is more common in elderly men, with heavy anemia and disproportionate renal damage. The disease progresses rapidly and is prone to impairment of renal function, bone destruction, skeletal pain, and pathological fractures.
Its urine protein is overflowing proteinuria.
(F) Other
Trace proteinuria from strenuous exercise, proteinuria from fever, proteinuria from renal stasis in heart failure and proteinuria from drug intoxication are generally not difficult to diagnose because of a clear medical history and corresponding physical examination.
Proteinuria hazards
(1) Thylakoid toxicity of proteinuria.
In the renal failure model, the accumulation of serum proteins in the glomerular thylakoid membrane can be observed, and the aggregation of these macromolecules in the thylakoid region can cause thylakoid cell damage, proliferation of each thylakoid matrix synthesis increase, thus producing glomerulosclerosis. In proteinuric nephropathy models, there are low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) Apo B as well as Apo A deposits in the glomeruli These aggregates can also eventually lead to glomerulosclerosis.
(2) Toxic effects of proteinuria on proximal tubular cells.
When proteinuria occurs, the increased amount of protein entering the tubular epithelium increases lysosomal activity, suggesting that the protein causes lysosomal overflow into the tubular cytoplasm and subsequent cellular damage can stimulate inflammation and scar formation.
(3) Changes in tubular cell biology due to proteinuria.
Many renal diseases presenting with proteinuria have cellular hyperproliferation, representing a nonadaptive response that leads to renal failure. There is increasing evidence that proteins directly modulate tubular cell function, altering their growth characteristics and their cytokine and matrix protein phenotype expression, which can lead to the release of PDGF, FN and MCP-1 from the basal side of tubules and induce the fibrotic process.
(4) Increased tubular interstitial hypoxia due to proteinuria.
Proteinuria reabsorption requires extra energy to digest large amounts of protein, which can cause tubular cell hypoxia, leading to tubular cell injury.