With the advances in experimental diagnosis, we have numerous methods to assess early kidney injury, the extent of injury, the nature of injury, and the site of injury. Clinicians should first clarify the design principles and uses of these diagnostic tools, understand the specificity, sensitivity and value of the use of the method, as well as its limitations and possible influencing factors, etc., and reasonably select effective and economical diagnostic items, taking into account the characteristics of the disease, cultural background, acceptance level and even economic status. For various clinical conditions where kidney damage may occur, such as: infection, drug or chemical toxicity, diabetes, hypertension, etc., relevant early damage markers should be selected for monitoring in time for their early detection and early treatment, which is of great importance to the prognosis of patients.
Urine analysis
Urine is a window to reflect the pathology of the urinary system. As a non-invasive means, urinalysis plays an important role in the diagnosis and treatment of many kidney diseases; and with the development of biological techniques and immunochemistry, urinalysis has entered a new era. Therefore, nephrologists should focus on and improve their understanding of routine urine microscopy and pay attention to new methods and clinical applications of urinalysis, so as to provide more accurate information for the diagnosis and treatment of diseases.
Urinalysis usually includes routine urine examination and special component examination: general trait examination, biochemistry, bacteriology, protein electrophoresis, microprotein determination, special enzymatic examination, immunological testing, cytopathological testing and many other items.
I. Routine urinalysis.
1.General trait examination: urine volume, urine color, urine odor, urine specific gravity and PH, etc.
2, urine biochemical examination; protein, sugar, ketone body, urinary bilirubin, urinary bilirubin, nitrite, etc.
3.Microscopic examination of urine sediment.
l Specimen preparation: extremely critical. Take 10 ml of fresh urine (preferably fresh morning urine) and centrifuge (1,500 rpm/min, 5 min), discard the supernatant, mix 0.5 ml of sediment, smear and observe under the microscope.
l Content of urine sediment examination.
(1) Cellular composition (RBC, WBC, phagocytes, epithelial cells, etc.).
(2) Tubular type: transparent tubular type, cellular tubular type, granular tubular type, wax-like tubular type, crystalline tubular type, fatty tubular type, etc.
(3) Crystals: amorphous crystals, phosphate crystals, calcium oxalate crystals, uric acid crystals, etc.
(4) Bacteria, parasites, yeast, mucus filaments, and special examination contents according to clinical needs, etc.
l Current commonly used methods.
(1) Standard microscopy method: slow, recognition is affected by subjective factors, not suitable for hospitals with a large workload can not complete a large number of urine sediment detection within 2h.
(2) automated urine sediment analysis (such as Japan’s Toa UF-100/50): simple to use, fast, without centrifugation, good repeatability. At present, it is still a screening instrument and cannot completely replace the urine sediment microscopy method.
Second, increased urine protein.
Normal urine can excrete trace amounts of protein (generally 30-100mg/d), random urine 0-80mg/L, protein qualitative negative. Source: Part from the plasma (glomerular filtration), this is because under normal circumstances < 50,000 KD of plasma protein can be passed through the glomerular filtration membrane, so that the original urine contains a small amount of protein, but the vast majority of these proteins are reabsorbed by the renal tubules, only a very small amount of leakage from the urine; while the other part is secreted by the renal tubules. According to the molecular weight of the urine protein can be divided into the following three categories: (1) high molecular weight: > 90,000 KD, very small amounts, mainly SIgA, THP secreted by the renal tubules.(2) Medium molecular weight: 4-9 KD, mainly from plasma proteins, but albumin accounts for about 1/2-2/3 as much. (3) Low molecular weight: <40,000 KD, mostly reabsorbed by renal tubules at normal glomerular function with minimal content. Including: a1-MG, b2-MG, lysozyme, etc.
Urinary protein >150mg/d or >100mg/m2.d (4mg/m2.h) is considered proteinuria. If proteinuria is present, the clinician must first address the following questions: whether it is true proteinuria, the degree of proteinuria, and the nature of the proteinuria.
1, urine protein test to determine whether it is true proteinuria: (1) urine protein qualitative – test paper method: simple, many factors affecting, specificity and sensitivity are poor. It is only used as a primary screening test. (2) Semi-quantitative – urine protein/urine creatinine (P/Cr): morning urine or random urine. Simple and easy to perform, it is the current recommended method for detecting urinary protein by NKF-K/DOQI in the US. Normal value <0.2mg/gCr.(3) 24h urine protein quantification: The most accurate method for measuring urine protein. Pay attention to the issue of accuracy of retained urine volume.
2, determine the nature of urine protein: glomerular, tubular, mixed, overflow? The general characteristics of various types of proteinuria: (1) Glomerular: increased Alb is predominant, and the quantification is often >1-2g/24h urine. It is seen in various glomerular diseases. According to the degree of damage to the filtration membrane and the components of proteinuria, there are 2 types of proteinuria: selective and non-selective. (2) tubular: mainly increased small molecule proteins (such as a1-MG, b2-MG, lysozyme, etc.), while Alb is normal or increased; the quantification is often <1g/24h urine.
3, examination methods: special protein determination (currently often used to determine the urine microprotein series), urine protein electrophoresis.
3, urine microprotein series determination.
A sensitive and reliable means of detecting kidney damage and other subclinical early kidney damage such as glomerular filtration and tubular function. Currently, urinary microalbumin (mAlb), transferrin (uTf), a1-microglobulin (a1-MG), urinary b2-microglobulin (b2-MG) and urinary retinol-binding protein (RBP), immunoglobulin (IgG), etc. are commonly used.
1, urinary microalbumin (mAlb): refers to the urinary albumin content more than normal, but below the range of conventional test strip method can be detected, is a sensitive indicator of early glomerular damage. 69,000 KD medium molecular protein, negatively charged, 3.6 nm in diameter, isoelectric point 4.7. Under normal circumstances, most mAlb can not pass the glomerular filtration membrane. When the GBM barrier function is impaired, the permeability increases and albumin filtration increases, but 99% is reabsorbed by the proximal tubule. Therefore, elevated mAlb reflects not only the impairment of glomerular filtration but also the impairment of renal tubular reabsorption. Urinary mAlb, as the earliest objective indicator of glomerular microangiopathy, is important for the early diagnosis of glomerular diseases (especially diabetic nephropathy). The normal reference range is 0-30mg/L. In addition, hypertension, obesity, hyperlipidemia and strenuous exercise may also increase urinary mAlb.
2, urinary transferrin (uTf): a single-chain sugar medium molecular protein, molecular weight 77,000 KD, diameter 3.8 nm, molecular diameter size and albumin close to the isoelectric point 5.5, with a negative charge. uTf and mAlb are medium molecular protein, molecular weight is similar, but its negative charge is less than Alb, more easily through the negatively charged glomerular filtration barrier. Because of the electrostatic homogeneous rejection of the charge-selective barrier of the filtration membrane, most of uTf cannot pass the glomerular filtration membrane and is more likely to leak out than albumin when the charge barrier is damaged at an early stage, so uTf is a more sensitive indicator of glomerular filtration membrane damage than Alb. The normal reference range by scattering turbidimetry is <2.0 mg/L. uTf appears earlier than urinary mAlb, and uTf/Cr is more sensitive than changes in the urinary mAlb/Cr ratio. In addition, increased uTf often indicates the possible presence of early lesions of small vessel disorders.
3. Urinary immunoglobulins: urinary IgG and IgA are increased when the glomerulus is further damaged; urinary IgM is increased when the glomerulus is severely diseased. The presence of urinary Alb and IgG indicates the transition to chronic lesions. Urinary IgG is a macromolecular protein with a molecular weight of 150,000-170,000 KD, and its content directly reflects the degree of glomerular damage, and the presence of IgG in the urine indicates serious glomerular lesions. Therefore, the combined test of urinary mAlb can systematically determine the damage of each part of the kidney. Normal reference range urinary IgG: 0.1-0.5mg/L. urinary IgA: 0.4-1.0mg/L, urinary IgM: 0.02-0.04mg/L.
4. a1-microglobulin (a1-MG): a glycoprotein with a molecular weight of 27,000 KD, which exists in the blood in two forms: free state or combined with macromolecular protein. Under normal conditions, a1-MG bound with IgA cannot pass the glomerular filtration membrane, while free a1-MG can freely pass the glomerular filtration membrane, but is reabsorbed and metabolized in the renal proximal tubule, and only a small amount is excreted from the urine. When the proximal tubule is damaged, its excretion increases, so a1-MG can sensitively reflect the renal tubular reabsorption function. The concentration of urinary a1-MG in urine is much higher than other low molecular weight protein fractions, and is the preferred indicator for the detection of low molecular weight protein in urine, which can replace the long-used urinary b2-MG. Continuous measurement of a1-MG can help observe changes in renal tubular disease and assess the prognosis of renal disease.
5, urinary retinol binding protein (RBP): low molecular weight protein with a molecular weight of 2.1 KD, which can freely pass through the glomerular filtration membrane, but 99.9% is reabsorbed in the proximal tubule. Under normal conditions, urinary excretion is minimal (100ug/d). When renal tubular injury is disrupted, the reabsorption is disrupted and more is excreted, therefore, elevated RBP is one of the sensitive indicators of proximal tubular injury. Urinary RBP remains stable at PH=4.5, which is different from urinary b2-MG and has more practical value than urinary b2-MG in the diagnosis of proximal tubular injury, and is a sensitive indicator for the diagnosis of renal tubular damage.
6, urinary N-acetyl-glucosaminidase (NAG): molecular weight 13-14 million KD, is an acidic hydrolase present in the lysosome, mainly in the proximal tubular brush border. Its elevation is the earliest indicator of proximal tubular injury. Chemical colorimetric detection of NAG, the normal reference range <18.5 U/L. NAG is commonly used in early kidney injury in kidney disease, monitoring of kidney transplant rejection and early diagnosis of drug nephrotoxicity, early diagnosis of diabetic nephropathy, etc.
IV. Special urine tests.
1. Immunohistochemical methods: cell composition, cell typing, etc. Such as the type of lymphocytes: CD classification (CD3+, CD4+, CD8+, CD14, etc.); glomerular foot cells (Podocalyxin as marker), etc.
2. Detection of cytokine genes and protein levels: e.g. TGF-b, MCP-1, ILs, etc.
Renal function tests
I. Glomerular function tests
(i) Glomerular filtration rate (GFR): The commonly used markers for measuring the gold standard of GFR are inulin, 99mTc-DTPA, 51Cr-EDTA, 125I-iodohexol, 125I-iodopeptidate.
1.Inulin clearance: Cin can accurately reflect glomerular filtration function and is the gold standard for measuring GFR. However, the operation of Cin determination is complicated, takes a long time, and requires intravenous drip and multiple blood collection, so it has little clinical application and is mainly used in scientific research.
2.Radionuclide GFR measurement: The commonly used radionuclides are 99mTc-DTPA, 51Cr-DTPA and so on. It can accurately reflect GFR, and the method is simple and sensitive, without collecting urine volume, multiple blood collection and continuous intravenous drip; the disadvantage is that it requires the use of radioisotopes and is expensive.
3.Methods commonly used in clinical practice for estimating GFR:
(1) Blood creatinine (Scr) and blood urea nitrogen (BUN) concentrations: Scr and BUN are mainly cleared by the kidneys, and their concentration determination is a common clinical index for glomerular function examination. BUN increases only when GFR decreases to 1/2 of normal, and Scr increases significantly when GFR decreases to 1/3 of normal. Therefore, BUN and Scr are not early and sensitive indicators of GFR. there are many factors affecting BUN and Scr. Such as age, muscle tissue volume and metabolic status, diet, disease status (fever) and many other factors influence. Therefore, elevated BUN and Scr do not necessarily indicate impaired glomerular function and should be used in conjunction with the clinical situation when evaluating GFR.
BUN/Scr can be used to differentiate prenephrogenic from nephrogenic azotemia. when BUN is elevated and the ratio is increased, it indicates prenephrogenic azotemia; on the contrary, it indicates the result of substantial renal disease.
(2) Cystatin C (CysC), also known as cystatin C. Low molecular weight basic non-glycosylated protein with a molecular weight of 13 kD; secreted by all nucleated cells and produced at a constant rate. It is not affected by inflammation or tumor, nor by muscle volume. Kidney is the only organ that removes circulating CysC; glomerulus is freely filtered and not excreted by renal tubules; it is reabsorbed and degraded in the proximal tubule; its clinical significance is the same as Scr and BUN, but it is more sensitive than Ccr. It correlates better with GFR and has the tendency to replace the traditional Scr and BUN tests. The normal reference range of blood CysC is 0.6-2.5mg/L.
(3) GFR prediction formula based on Scr: endogenous creatinine clearance (Ccr), Schwartz formula, Cockcroft-Gault formula, MDRD series formula, etc.
l Endogenous creatinine clearance (Ccr): 3 days of continuous low protein diet, accurate retention of 24h urine on the fourth day, blood collection at the end of urine collection, and determination of blood and urine creatinine concentrations respectively, calculated according to the following formula.
Ccr (ml/min)=UV/P.
U=urinary creatinine concentration (umol/L); V=urine volume per minute (ml/min); P=Scr (umol/L). Corrected Ccr=Ccr×1.73 (m2)/pediatric measured body surface area (m2).Ccr is usually higher than Cin, but the sensitivity of Ccr is close to that of Cin. Ccr can reflect impaired glomerular function earlier and is a sensitive indicator for determining glomerular damage.
l Schwartz formula: Ccr (ml/min) = K × length (cm)/Scr (umol/L).
The K constants for different ages and genders are shown in the following table.
Group
K value
Low weight infants <2,500g
29
0-18 months
40
2-16 years old girl
49
Boys
2-13 years
49
13-16 years old
62
(4) Blood b2-microglobulin (b2-MG) concentration: a small molecular protein (11780 KD) produced by nucleated cells in vivo and present in almost all nucleated cells. It can freely pass through the glomerular filtration membrane and is almost completely reabsorbed (99.9%) in the proximal tubule. As with Scr and BUN, elevated blood b2-MG suggests reduced GFR and impaired glomerular filtration. Blood b2-MG levels are not affected by age, sex, amount of muscle tissue, or amount of dietary protein; however, blood b2-MG is increased in inflammation and tumors. Attention should be paid to the differentiation. The normal reference value of blood b2-MG is 1.5 mg/L.
Second, renal tubular function: reabsorption, secretion and excretion function; concentration and dilution function, etc.
Tubular function is an important part of the overall kidney function, but because the clinical manifestations of tubular function abnormalities are not as significant as the impaired glomerular function, so its importance has not been recognized for a long time by everyone. In recent years, as people’s knowledge of renal physiology, biochemistry and pathology has gradually improved, many diseases with tubular damage as the main manifestation have become more and more clinically important, and various tests of tubular function have been developed. Renal tubular function includes the respective reabsorption and secretion functions of the proximal and distal tubules, which are described below.
1, proximal tubule function test: proximal tubule is an important part of the renal tubule in the role of reabsorption, its main function is to reabsorb water, sodium, potassium, calcium, chloride, bicarbonate, phosphate, salt and glucose, amino acids and other organic substances in the original urine. It can be reflected by measuring urinary sugar, urinary amino acids, urinary b2-MG, urinary a2-MG, NAG, etc.
(1) Phenol red excretion test.
(2) Determination of maximum renal tubular reabsorption: the maximum renal tubular glucose reabsorption (TmG) is commonly used to express.
(3) Determination of maximum renal tubular secretion: expressed by the maximum renal tubular secretion of para-aminomaluronic acid (TmPAH).
The above three methods are more cumbersome and not easy to implement clinically, so they are mostly used in experimental research and less used clinically.
(4) Urinary lysozyme and b2-MG assay: both are small molecule proteins, which can be freely filtered by the glomerulus. The vast majority are reabsorbed in the renal tubules, and the amount detected in the urine is extremely small. When the blood level is normal, urinary lysozyme is <3ug/m1 and urinary b2-MG is <0.2ug/ml, if it exceeds this value, the proximal tubular reabsorption function is impaired. These two indicators are clinically convenient to measure and are relatively sensitive.
2, distal tubule function measurement: the main function of the distal tubule is the metabolism of potassium, sodium and chloride and the regulation of acid-base balance. Under the regulation of various neurological and endocrine factors, it determines the final quality and quantity of urine. It can be reflected by monitoring urine specific gravity, urine osmolality, concentration and dilution function, urine acidification function, etc.
(1) Urine specific gravity: It is a convenient and rapid indicator to reflect urine permeability. However, there are many factors affecting it. It mainly includes urine pH, albumin, glucose, urea, etc. For newborns, the values measured by spectrophotometer method and test paper method are inaccurate. The variable range of 24-hour urine specific gravity in normal human is 1.003-1.030, generally between 1.010-1.020. The difference between the highest and lowest specific gravity of a single urine should be >0.009.
(2) Urine osmolality measurement: reflect the total number of solute molecules and ions in the urine, the unit is mOsm/kg?H2O. urine osmolality fluctuates from 600 to l000mOsm/kg?H2O, the average is 800mOsm/kg?H2O. the ratio of urine osmolality to blood osmolality is 3-4.5:1. the decrease of urine osmolality reflects the diminished concentration function of distal tubule, which is seen in chronic pyelonephritis, nephritis, and blood osmolality. It is seen in chronic pyelonephritis, various chronic interstitial lesions and chronic renal failure.
(3) Urine concentration and dilution test: The concentration and dilution functions of the kidney are mainly carried out in the distal tubules and collecting ducts. Urine concentration test commonly used methods are Mohs test, under normal diet 24h urine daytime to nighttime ratio of 3-4: 1. Method: After eating at 6 pm and limiting water for 12h, the highest specific gravity of the next morning urine should be > 1.020, osmotic pressure > 600mOsm/kg?H2O. dilution test reflects the dilution function of the distal tubule, but requires a large amount of water in a short period of time, for patients with kidney and For patients with renal and cardiovascular diseases can cause adverse reactions, and even cause water intoxication, and there are more factors affecting the test. Therefore, the clinical use has been less.
(4) The ion-free water clearance (cH2O), also known as the free water clearance rate. It refers to the amount of water without solute removed from plasma to urine per unit time. It is now believed that cH2O can more accurately reflect the concentration function of the distal tubules of the kidney. Calculation formula: cH2O=(1-Uosm/Posm)×V. The unit is: ml/min or ml/hr. Uosm is the urinary osmotic molecule concentration, Posm is the plasma osmotic molecule concentration, and V is the urine volume. In acute renal failure, the kidney concentration is almost completely lost and cH2O is close to or equal to 0. When renal tubular function is restored, cH2O can gradually return to normal. cH2O value changes can appear several days before the clinical manifestations and general tests. Therefore, it can be used as a sensitive indicator for early diagnosis of acute renal failure and observation of changes in condition.
(5) Urine electrolyte measurement: urine sodium measurement is often used to identify prenephrosis and tubular necrosis. The former is <20mmol/L, the latter is often >40mmol/L. Urinary Ca/Cr: the initial screening test for idiopathic hypercalciuria, normal <0.18. If >0.21 then measure 24h urinary Ca++, >4mg/d for idiopathic hypercalciuria.
3, other indicators to determine renal tubular function: (1) filtered sodium excretion fraction (FeNa): FeNa (%) = [(urinary sodium/blood sodium)/(urinary creatinine/blood creatinine)] × 100, FeNa < 1 in the absence of tubular injury, and FeNa > 2 in acute tubular necrosis.(2) renal failure index (RFI): RFI = urinary sodium/(urinary creatinine/blood creatinine), its Significance also lies in the identification of acute tubular necrosis and pre-renal azotemia, the former RFI>2, while the latter RFI <1. (3) Urinary enzyme assay (see previous).
(4) Renal tubular acid-base regulatory function: The renal tubular acid-base balance regulatory function is often determined by measuring blood and urine PH, CO2 binding capacity and urinary HCO3-, titratable acid and urinary ammonium, acid and base loading tests to diagnose renal tubular acidosis.
Laboratory diagnosis related to endocrine function of the kidney
Renin-angiotensin-aldosterone, kinin-releasing enzyme, prostaglandin, 1.25-(OH)2-D3, EPO, etc.
Immunological tests for renal diseases
Most renal diseases are immune-mediated, so this type of examination is very important; it is often the main basis for clinical diagnosis, treatment and prognosis. The main tests include: cellular immunity, humoral immunity, and specific antigen antibody testing. Blood and kidney tissue are often used according to the examination site.
(i) Cellular immune examination: such as CD series (CD3+, CD19+, CD4+, CD8+, CD4+/CD8+, NK, etc.)
(ii) Humoral immunity: immunoglobulin (Ig), complement, circulating immune complexes, etc.
(iii) Specific antigen-antibody testing: mainly autoimmune-related antigens/antibodies. The common ones are:
1, serum autoantibody assay: ANA, dsDNA, anti-histone, Sm, Sm/RNP, ScL-70, SS-A, SS-B, adhesin, Jo-1.
2. Autoantibodies against kidney tissue structures: anti-GBM antibodies and anti-TBM antibodies. High titers of anti-GBM antibodies can help diagnose pulmonary-renal syndrome or other anti-GBM nephritis. 50-70% of patients with anti-GBM nephritis may also have anti-TBM antibodies with significant tubulointerstitial nephritis. Anti-TBM antibodies are closely related to the development of tubulointerstitial nephritis.
3. Anti-neutrophil cytoplasmic antibody (ANCA): It is a serological marker of primary vasculitis. C-ANCA target antigens are mainly proteinase 3 (PR3). p-ANCA target antigens are mainly myeloperoxidase (MPO), elastase, histone G, lysosomes, etc. C-ANCA positivity is mainly seen in Wegener’s granulomatosis (WG). p- ANCA positivity is mainly associated with multiple microarteritis and is less common in patients with WG. P-ANCA potency correlates with disease activity. In addition, P-ANCA is also seen in rheumatic and collagenous diseases (such as RA, SLE, SS and polymyositis dermatomyositis), glomerulonephritis, ulcerative colitis and primary biliary cirrhosis.
4, immunological tests related to infectious agents of kidney disease: mainly for post-infectious glomerulonephritis. These include: bacteria (streptococcus, staphylococcus, pneumococcus, etc.), viruses (chickenpox, mumps, hepatitis B virus (HBV), EBV, etc.), protozoa (malaria), spirochetes (syphilis), mycoplasma, and fungi.
Transdermal kidney biopsy (renal biopsy)
The examination in the early 1950s (used clinically in China in 1958) has obtained a lot of information about the histopathology, etiology and classification of kidney diseases that cannot be obtained by other methods, which is important for clarifying the etiology, immunopathogenesis, pathological typing, diagnosis, guiding treatment, estimating prognosis and observing the evolution of the disease. The revision rate of renal biopsy on clinical diagnosis is 34%-63%. The revision rate of treatment plan reaches 19%-36% The revision rate of prognosis estimation reaches 32%-36%.
I. Classification: (1) open kidney biopsy: first reported by Gwyn in 1923, is the most primitive method and has been largely unused. Only those who cannot undergo percutaneous renal puncture biopsy and estimated risk of bleeding can be considered. (2) Percutaneous renal puncture biopsy: first applied by Alwall in 1944 and promoted after 1950, 22 hospitals in China performed it in 1983, with 1613 punctures. It is the most widely used kidney biopsy method at home and abroad. (3) Transvenous renal biopsy: introduced by Mal in 1990, the biggest advantage is that blood still flows into the blood circulation when trauma bleeds.
II. Indications: Various primary and secondary renal diseases (glomerular and/or tubulointerstitial diseases) such as glomerulonephritis, nephrotic syndrome, asymptomatic proteinuria/hematuria, SLE, vasculitis, etc. Prompt puncture should also be performed for acute renal failure where the etiology cannot be determined clinically and laboratory. If rejection occurs in patients after renal transplantation, the decision to remove the transplanted kidney can be based on renal biopsy.
Contraindications: obvious bleeding tendency that cannot be corrected, psychiatric illness or uncooperative operation, isolated kidney, fixed kidney or small kidney are absolute contraindications to kidney biopsy. Hypertension, renal tumor, abscess or infection, uremia, excessive obesity, high edema, and severe anemia are relative contraindications.
IV. Indications for repeat renal biopsy: severe glomerular disease, such as crescentic nephritis; hormone-sensitive nephrotic syndrome that becomes resistant after multiple relapses and suspected pathological type transformation; those who are ineffective in hormone therapy, in order to track the progress of the lesion and estimate the prognosis; drug therapy (such as CsA) monitoring, tubulointerstitial fibrosis, and transplanted kidney.
V. Initial processing of specimens: including (1) kidney tissue determination. (2) Splitting of kidney specimens. (3) Fixation of light microscopy specimens in 10% formalin solution, electron microscopy with 3% glutaraldehyde, and immunofluorescence specimens wrapped in saline gauze and placed in ice vials for rapid delivery.
VI. Success rate and complications: success rate 93-100%. The key to success is to strictly grasp the indications, precise positioning, ideal puncture needle and skillful operation, and simultaneous puncture of both kidneys is strictly prohibited. Complications include: ① Hematuria: almost every case, with <5% carnal hematuria. (ii) Perirenal hematoma: the incidence is 48-85%, mostly small hematoma, no clinical symptoms, and self absorption within 1-2 weeks. ③ Arteriovenous fistula: incidence 0.1%-0.5%.
VII. Common histopathological items and significance: including LM (HE, PAS, PASM, Masson, etc.), IF, EM.
In conclusion, nephrologists should base on the combination of clinical, histopathological, and renal functional status assessment, which is the key to obtain the correct diagnosis and treatment of renal diseases.
Selection of the diagnosis of renal disease status and the principles
involves both structural and functional aspects, including the estimation of the degree of injury, the nature of injury and the site of injury, etc.
I. Experimental diagnosis related to structural damage of kidney tissue
(a) Glomerular filtration barrier damage: mAlb, uTf, urine immunoglobulin; 24-hour urine protein quantification, urine P/Cr. In addition, electron microscopy has been used to observe the amount and distribution of negatively charged substances in the glomerular capillary wall to reflect the integrity of the glomerular barrier. Recently, it has been used to indirectly understand GBM injury by detecting urinary podocytes and their markers.
(ii) Glomerular thylakoid injury: The markers of glomerular thylakoid tissue include type IV collagen, fibronectin, laminin, etc. The dynamic changes can reflect the synthesis of extracellular matrix collagen and its related substances, especially in diabetic nephropathy, which can be one of the important indications for studying early pathological changes. At present, it is mainly detected by immunofluorescence, immunohistochemistry and glomerular microisolation in situ reverse transcription, which has not been promoted in clinical practice.
(iii) Renal tubular injury
1, renal tubular cellular structure injury: urine sediment microscopy (abnormal tangible fraction, such as red and white blood cells, tubular type, crystals, etc.), renal histopathology.
2, renal tubular subcellular structure injury.
(1) Lysosomal injury: urinary NAG, urinary lysozyme.
(2) Brush border injury: alanine aminopeptidase (AAP), glutamyl transferase (γ-GT), leucine aminopeptidase (LAP).
(iv) Other antigens and proteins associated with injury: THP, urinary fibrin degradation products, basement membrane antigen, brush border protein and CHIP28 water channel protein may also reflect early renal injury changes.
Second, the experimental diagnosis related to renal impairment
(a) Glomerular filtration injury: Scr, BUN, Ccr, CysC, isotope measurement; in addition, serum 5-hydroxy creatinine/creatinine ratio can reflect the degree of renal oxidative stress injury. Fingernail creatinine can reflect the Scr and renal function status of the patient 3 months ago, which is helpful to differentiate acute and chronic renal failure. Carbamoylhemoglobin (CarHb) can reflect the mean BUN of patients several weeks ago, which can help to distinguish acute and chronic renal failure, and can be used to observe the effect of hemodialysis treatment in patients with renal failure.
(II) Renal tubular impairment
1, proximal renal tubular injury: mostly mild proteinuria. Measurement of urinary low molecular weight protein (LMWP): a group of LMWP such as a1-MG, b2-MG, RBP and certain urinary enzymes (e.g., Lys, NAG, γ-GT, AAP, LAP, glutathione S-transferase, etc.) are predominant. In addition, urinary protein-1 or Clara cell protein has been considered one of the most sensitive indicators of early and mild damage to the proximal tubule.
Measurement of renal tubular reabsorption function: urinary amino acid excretion, urinary glucose excretion, and urinary sodium and filtered sodium excretion fraction are commonly used to reflect proximal tubular reabsorption function.
2.Distal tubular function: including renal concentration and dilution test, diurnal urine specific density test and 3h urine specific density test, urine osmolality and free water clearance measurement, etc.