Pediatric tubulo-interstitial nephritis
Introduction
Brief introduction of pediatric renal tubule-interstitial nephritis Tubulo-interstitial nephritis (TIN) refers to a group of non-suppurative inflammatory reactions mainly characterized by renal interstitial lesions. The glomeruli are almost free of lesions or occasional mild lesions, and the renal tubules are affected. . basic knowledge The proportion of illness: 0.003% Susceptible people: children Mode of infection: non-infectious Complications: hypertension, anemia, acute renal failure
Cause
Pediatric tubule-interstitial nephritis
Causes
Renal tubulointerstitial nephritis is a large group of kidney diseases caused by various reasons. According to the course of disease, tubulointerstitial nephritis can be divided into two categories: acute and chronic; according to the cause, it is infectious, drug-based, immune Mediated and interstitial nephritis caused by hereditary metabolic disorders.
Infection (20%):
Including bacterial infections (streptococcus, staphylococcus, diphtheria, typhoid bacillus, etc.), Legionella, Leptospira, Toxoplasma protozoa, viral infections, etc., kidney or systemic infections caused by the above pathogens can induce TIN, but not pathogens Directly invade the kidney, but the immune response mechanism.
Drug reaction (15%):
Common antibiotics (such as aminoglycosides, penicillins, cephalosporins, amphotericin, tetracyclines, sulfonamides, doxorubicin, anti-tuberculosis drugs, etc.), non-hormonal anti-inflammatory drugs (indomethacin, Blo Fen, aspirin, etc., long-term exposure to heavy metal salts (such as lead, mercury, etc.), anti-epileptic drugs, anesthetics, central stimulants, immunosuppressants, diuretics, etc.
Urinary tract obstruction (15%):
Renal tubule-interstitial damage caused by urinary tract obstruction or vesical reflux.
Immunological glomerular lesions (20%):
Including anti-glomerular basement membrane antibodies, immune complex deposition and the like.
Vascular disease (10%):
Such as renal arteriosclerosis, renal artery thrombosis or renal vein thrombosis.
Metabolic disease (10%):
Hyperuricemia, urate nephropathy, cystineuria, hypercalcemia, long-term hypokalemia, etc.
Other factors (8%):
(1) genetic factors: familial interstitial nephritis, sponge kidney, congenital polycystic kidney disease.
(2) Tumor: leukemia, lymphosarcoma, multiple myeloma, etc.
(3) Radiation nephritis and the like.
Pathogenesis
1. Immunization mechanisms include cellular immune-mediated acute interstitial nephritis, humoral immune-mediated acute interstitial nephritis, complement activation, ige-mediated (blood ige elevation, blood and urine eosinophil count ) and other mechanisms .
2. Non-immune mechanisms include various systemic infections, drugs, and toxic substances such as dic. Due to large renal blood flow, large renal endothelial cell area, high renal tubular metabolic rate, renal countercurrent doubling system and inhibition of renal enzymes, the kidney is prone to poisoning.
3. Pathological changes
(1) Seen by the naked eye: The size of the kidney is normal or slightly enlarged, and the lesion is mainly in the medulla, which may be focal or diffuse.
(2) seen under the microscope: glomerular more normal, occasional mesangial cell proliferation or crescent formation. Renal tubular epithelial cells swell, necrosis, degeneration, hyperplasia, tubular basement membrane shrinkage and rupture. Significant edema in the interstitial area, a variety of cell infiltration. Immunopathology suggests a moderate amount of fibrinogen, c3, c4, igg deposits in the mesenchymal membrane area.
Prevention
Pediatric tubule-interstitial nephritis prevention
There is not much attention, mainly to find timely treatment in a timely manner.
Complication
Pediatric tubular-interstitial nephritis complications Complications, hypertension, anemia, acute renal failure
Can be complicated by high blood pressure, can occur anemia, acute renal failure, etc., and can coexist with kidney stones.
Symptom
Pediatric tubule-interstitial nephritis symptoms common symptoms nocturia increased lymphadenopathy anorexia joint pain edema fever accompanied by rash high fever abdominal pain polyuria azotemia
The disease can occur in any age group.
1. Typical clinical manifestations of fever, rash, joint pain, triad of AIN, sick children may have varying degrees of edema, nocturia, polyuria, vomiting, diarrhea, anorexia, abdominal pain, children may have microscopic hematuria, Pyuria, severe renal disease can occur, most of the performance is non-oliguric.
2. A variety of clinical manifestations
(1) Acute TIN: caused by infection, drug allergy, vascular disease or drug nephrotoxicity, a few are idiopathic, ATIN is characterized by acute onset, often accompanied by fever, rash and bladder irritation, more Allergic drugs, severe cases can show acute renal failure, pathologically mainly metamorphic exudation, interstitial edema, infiltration of inflammatory cells vary by etiology and pathogenesis, TIN patients can be due to edema in the kidney, kidney capsule Stretching, patients feel low back pain, physical examination has renal pain, the common clinical manifestations are patients with different degrees of acute renal failure, and according to different causes can appear corresponding performance:
1 infection caused: more chills and fever, body aches, loss of appetite and other symptoms of poisoning, blood neutrophils, antibacterial treatment is effective.
2 drug allergy caused: a history of useful drugs, rash, fever, joint pain and lymphadenopathy and other allergic symptoms in the course of medication or shortly after withdrawal, blood eosinophilia and IgE increased, urine sediment check 1 / 3 patients can find eosinophils.
3 drug nephrotoxicity caused by: most patients have a clear history of medication, renal tubular epithelial cells can appear in the urine.
(2) Chronic TIN: mainly manifested as renal tubular insufficiency, such as proximal tubule involvement, manifested as type II renal tubular acidosis and Fanconi syndrome, such as severe distal tubule involvement, can be expressed as type I or IV Renal tubular acidosis.
Clinical features of 1CTIN: clinical manifestations are not as obvious as ATIN, patients can have no symptoms, careful examination can find a variety of renal tubular dysfunction, blood pressure can be normal or elevated, often mild proteinuria, when a large amount of proteinuria When prompted for glomerular disease, some CTIN and kidney stones coexist, Balkan nephropathy or abuse of analgesics can occur urinary tract malignant tumors, renal papillary necrosis can be complicated by abuse of analgesics, sickle cell disease or chronic urinary tract obstruction The resulting CTIN is characterized by fever, hematuria and renal colic. Occasionally, necrotic tissue is excreted from the urine. Anemia is not proportional to the degree of azotemia. It is common in medullary cyst disease, abuse of analgesics and multiple myeloma. Increased nocturia is an important diagnostic clue for many CTINs.
The characteristic pathological manifestations of 2CTIN: interstitial fibrosis, tubule atrophy and mononuclear cell infiltration, late kidney shrinkage, irregular shape (a manifestation of scar presence), single or multiple corpus callosum expansion, due to fibrosis Wrapped, the tubule is deformed, the basement membrane of the tubule is thickened, and there may be secondary glomerular changes and renal vascular disease in the later stage. Because of the more interstitial medulla, the medulla and nipple are seriously affected because of the renal tubule Each segment has the function of reabsorbing sodium ions. Therefore, any segmental renal tubular epithelial cell damage caused by primary CTIN can reach a certain degree, which can cause inappropriate loss of sodium ions, which is clinically worthy of clinical evaluation. The doctor's attention is: primary CTIN generally does not occur sodium retention, and CTIN caused by secondary CTIN and vascular disease often accompanied by sodium retention, manifested as edema and hypertension, please consult the history to find TIN Causes or causes, typical clinical manifestations such as fever, rash, joint pain triad; or unexplained renal failure, allergic systemic symptoms; laboratory tests for elevated serum IgE, increased peripheral blood eosinophil count Urine 2 microglobulin increased, hypokalemia; urine has red blood cells, white blood cells and white blood cell casts; renal dysfunction, if necessary, need to do a kidney biopsy to confirm the diagnosis.
Examine
Pediatric tubule-interstitial nephritis
The kidney has five major functions, namely excretion of metabolic waste, reabsorption of useful filtration substances, water and electrolyte balance, acid-base balance and endocrine function. The tubulointerstitial system accounts for about 95% of the total kidney volume, and the tubulointerstitial is the main site for accomplishing these functions. Therefore, TIN can be expressed as a defect of these five functions.
1. General urine test
(1) urine sediment examination: the change of urine sediment varies with the primary disease. Generally, urine sediment can be seen in moderate red blood cells, white blood cells, renal tubular epithelial cells and casts. Renal tubular epithelial cells and their casts are of great value in the diagnosis of TIN. Renal tubular epithelial cells are not easily seen in normal human urine sediments, and if found, are direct evidence of tubular damage. Normal people can only see a small amount of transparent cast in concentrated acidic urine. In any case, a tubular cast or a granular cast in the urine, a transparent cast in a non-concentrated acidic urine, or a large number of transparent casts in concentrated acidic urine all indicate damage to the renal parenchyma. Infected by infection, there are more white blood cells in the urine, and the middle urine culture can be positive. Caused by drug allergy, 1/3 of patients have eosinophils in the urine sediment, and blood eosinophils can also be increased.
(2) Urine protein analysis: The daily urine protein content of TIN is usually less than 1.5g, and it is a small tubular proteinuria, which can be used for quantitative detection of small proteins or urinary protein disk electrophoresis.
2. In renal function test ATIN, renal function loss is mostly transient; while CTIN is negative for renal function loss. The impairment of tubule interstitial function is particularly significant. The form and extent of functional impairment are related to the location and extent of damage to the tubulointerstitial by virulence factors.
(1) Decreased active excretion function of renal tubules: When some substances (organic anions) are excreted from the kidneys, the proximal tubules are also actively excreted while the glomerulus is filtered. After the renal tubular active excretion function declines, blood uric acid concentration may increase, and the renal excretion rate of some anionic drugs also slows down. The clearance rate was reduced when the phenol red excretion test was performed clinically. At present, the phenol red excretion test is more commonly used in clinical practice. It is generally considered that the abnormality of the test results indicates that the excretion function of the proximal tubular epithelial cells is decreased. In the actual clinical application process, the phenol red excretion test has the following defects:
1 is affected by effective renal plasma flow.
2 is affected by the number of healthy kidney units [or glomerular filtration rate (GFR)]. Total phenol red excretion rate = single nephron phenol red excretion rate x total nephron total phenol red excretion rate = single nephron phenol red excretion rate x total number of nephrons.
3 is limited by the accuracy of the method of retention of urine.
(2) Decreased renal tubular reabsorption: Under normal circumstances, small molecules of glomerular filtration, such as amino acids, glucose, and small molecule globulin, are almost reabsorbed through the proximal tubules and are rarely lost. After the proximal tubule is damaged, the reabsorption function is reduced, and small molecular proteinuria, amino aciduria or diabetes can occur. In severe cases, the proximal tubular reabsorption function collapses completely, manifesting as Fanconi syndrome (a simultaneous reabsorption of glucose, amino acids, and carbonates). Current methods commonly used to examine renal tubular reabsorption are:
1 Urinary 2 microglobulin excretion rate: In the case of normal serum 2 microglobulin concentration, increased urinary excretion suggests a decrease in the function of proximal tubular reabsorption of small molecules. The clinical significance of urine lysozyme examination is similar to that of 2 microglobulin. However, in mild to moderate chronic renal failure, a decrease in the number of nephrons can sometimes counteract the effects of decreased proximal myocardial reabsorption of small molecular proteins: total 2 microglobulin excretion = single nephron 2 microglobulin excretion rate × Total nephron total 2 microglobulin excretion rate = single nephron 2 microglobulin excretion rate × total nephron total 2 microglobulin excretion rate = single nephron 2 microglobulin excretion rate × total number of nephrons total 2 micro Globulin excretion rate = single nephron 2 microglobulin excretion rate × total number of nephrons.
2 Urine protein disc electrophoresis: Urine protein disc electrophoresis (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) shows small protein-based proteinuria when there is no abnormal increase in plasma small molecule protein concentration. It suggests that the proximal tubule reabsorbs the function of small molecular proteins.
3 glucose maximum reabsorption test: from the proximal tubule to the distal tubule have the function of reabsorbing glucose, but mainly in the proximal tubule. Therefore, the renal tubule is damaged, and it is easy to cause renal glucose and urine. Similar to the principle of 2 microglobulin excretion rate, the maximum reabsorption function of glucose is affected by the total number of nephrons and single tubule function. Therefore, the exact clinical significance of the abnormal or normal glucose reabsorption test results should be specifically analyzed.
4 urine amino acid examination: the amino acid excretion in the urine increased significantly after the renal tubular amino acid reabsorption function decreased.
Diagnosis
Diagnosis and diagnosis of renal tubular-interstitial nephritis in children
diagnosis
1. Understand the cause of TIN can cause a lot of TIN causes, in addition to idiopathic TIN, all TIN have a cause can be found, understanding the cause is an important prerequisite for the correct and timely diagnosis of TIN.
2. Find the diagnosis clue of TIN in time. Patients should consider the possibility of TIN when the following conditions occur, and conduct a comprehensive renal examination to confirm or exclude the diagnosis of TIN.
(1) Patients with unexplained renal anemia, renal hypertension (secondary TIN), nocturia.
(2) There is no shock, acute blood volume deficiency, etc. Sudden oliguria or non-oliguric acute renal failure.
(3) Acute renal failure occurs on the basis of chronic renal failure (basic serum creatinine concentration <250mol/L, daily serum creatinine rises above 45mol/L; basic serum creatinine concentration>250moL /L, serum creatinine concentration rises by 90mol/L per day Above), or subacute renal failure (increased serum creatinine concentration per day, but not at the rate of acute renal failure), acute renal failure may be oliguria or non-oliguric.
(4) Chronic renal failure with renal tubular interstitial function impairment.
(5) Necrotic tissue was found in the urine.
3. Find evidence of TIN If necessary, do a kidney biopsy.
Differential diagnosis
1. Renal biopsy can identify ATIN and CTIN.
2. Need to identify a variety of primary and secondary nephritis.
3. Patients with renal failure need to be differentiated from renal failure caused by prerenal, post-renal or other renal pathogenesis.
