Pediatric drug-induced renal impairment
Introduction
Introduction to drug-induced renal damage in children Drug-induced renal damage refers to a kind of disease caused by various kidney damage caused by drugs. The kidney is an important organ for drug metabolism and excretion. The kidney damage caused by drugs is increasing day by day, mainly manifested as nephrotoxic reaction and allergic reaction. Physicians should raise awareness of the role of drug-induced nephrotoxicity in order to reduce the incidence of drug-induced renal damage. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: chronic renal failure, diabetes insipidus, nephrotic syndrome
Cause
Pediatric drug-induced renal damage
(1) Causes of the disease
1. Causes of drug-induced damage in the kidney The kidney is particularly sensitive to drug toxicity, mainly due to:
(1) The blood flow of the kidney is particularly rich: 20% to 25% of the cardiac output, calculated by unit area, is the largest blood flow of each organ, so a large amount of drugs can enter the kidney.
(2) The surface area of the capillaries in the kidney is large: deposition of the antigen-antibody complex is liable to occur.
(3) Excreta concentration: The concentration of excreta acting on the surface of the renal tubule is high, which is caused by the action of the blood flow concentrating system. In addition, the proximal tubule has secretion and reabsorption effects on various drugs, and also increases the drug. Opportunities for interaction with renal tubular epithelial cells.
(4) High metabolic rate of renal tubules: During the process of secretion and reabsorption, drugs are often concentrated on the surface or cells of the renal tubules, which is prone to drug poisoning.
(5) Sensitivity to drugs: The kidneys have a large oxygen consumption and are sensitive to ischemia and hypoxia, so they are sensitive to drugs that affect blood flow.
(6) Susceptibility: Kidney disease increases the susceptibility to drug damage, hypoalbuminemia increases the concentration of free drug, renal insufficiency increases the half-life of the drug, kidney disease and special populations such as infants, old age Human kidney reserve function is low.
2. Common drugs that are easy to cause kidney damage
(1) Antibiotics and sulfonamides: including: 1 aminoglycosides: gentamicin, amikacin (butylamine kanamycin), streptomycin, kanamycin, neomycin, etc. Vegetarian, kanamycin, gentamicin has the strongest toxicity. 2 penicillins: various semi-synthetic penicillins can induce kidney damage. 3 cephalosporins: the first generation of cephalosporin is most obvious. 4 more colistin. 5 tetracycline family: increase protein decomposition, aggravate azotemia. 6 amphotericin B. 7 vancomycin and sulfonamides.
(2) Non-steroidal anti-inflammatory drugs (NSAlDs): including aspirin (acetylsalicylic acid), ibuprofen, phenylbutazone, naproxen (naproxen), indomethacin (indomethacin) , piroxicam (inflammatory pain Xi Kang), Xi Le Bao and so on.
(3) X-ray contrast agent: mainly iodine-containing contrast agent.
(4) Antitumor drugs: including cisplatin, methotrexate, streptomycin, nitrosourea (carmustine, chloroethene, hexyl nitrosourea).
(5) Diuretics: including osmotic diuretics and furosemide.
(6) Chinese herbal medicine: mainly aristolochia, Mutong, anti-self, Magnolia, Asarum, Motherwort and so on.
(7) Other drugs: such as penicillamine, captopril, birth control pills, cyclosporine, adrenaline, etc.
(two) pathogenesis
Mechanism of drug-induced renal damage:
1. Contraction of renal blood vessels, affecting renal hemodynamics, blood flow reduction can reduce renal filtration clearance, and can also lead to renal ischemia and hypoxia, leading to further kidney damage.
2. When the concentration of direct nephrotoxic drugs in the renal tubules increases to the concentration of poisoning, the renal tubular epithelial cells can be directly damaged. The degree of damage is related to the dose. The mechanisms are as follows: (1) Direct damage to the cell membrane, change of membrane permeability and ion transport Features.
(2) Destroy the cytoplasmic mitochondria, inhibit enzyme activity and protein synthesis, cause calcium influx, destruction of cytoskeletal structure, and necrosis of epithelial cells.
(3) Oxygen free radicals are generated.
(4) acting on epithelial DNA, causing cross-linking, or inhibiting DNA replication-related enzyme activity, and suppressing renal tubular epithelial cell metabolism.
(5) Direct damage to high permeability.
3. Immunoinflammatory reactions include: (1) Cell-mediated immune mechanisms: play an important role in acute allergic interstitial nephritis.
(2) Inducing anti-tubular basement membrane antibodies to mediate immune damage.
(3) The drug interacts with the renal tubule or renal interstitial protein to make it a hapten or an antigen, induces an antibody, forms an immune complex, and stimulates an immune inflammatory response.
(4) idiopathic inflammatory response.
4. Obstructive nephropathy sulfa crystal deposition occlusion of renal tubules, epithelial cell degeneration, necrotic interstitial cell infiltration, high-dose methotrexate, and hyper-dose immunoglobulin can cause kidney damage through obstruction.
5. Induced aggravating factors include: (1) renal dysfunction, prolonged drug half-life.
(2) Hypoproteinemia increases the drug freeness, which makes the drug more toxic to the toxic dose. The above-mentioned several renal damage mechanisms can exist alone or simultaneously by a single drug.
Prevention
Pediatric drug-induced renal damage prevention
1. Emphasis on drug-induced renal damage: To achieve early diagnosis and improve the alertness of the disease, due to the lack of understanding of the kidney damage caused by drugs by clinicians, and the lack of characteristic clinical manifestations of renal diseases caused by certain drugs. And the kidney has a huge reserve of compensation, so that drug-induced nephropathy is not easy to find early, often the symptoms of poisoning of drugs are mistaken for the symptoms of renal insufficiency uremia, resulting in delays in diagnosis and treatment, and even develop into irreversible end-stage renal failure, It is worth noting that some drugs for treating kidney disease have nephrotoxicity. Therefore, we should improve our understanding of this disease. During the treatment process, we should carefully observe, improve alertness, early detection, early withdrawal, and early treatment.
2. Understand the characteristics of the drug: rational use of drugs should be familiar with the large dose of contrast agents in order to avoid or reduce the pharmacological characteristics and pharmacokinetic characteristics of kidney damage, fully understand the drug's nephrotoxicity and other adverse reactions to reduce drug-induced renal function The occurrence of damage, especially the variety of new drugs, the clinician often lacks understanding of the composition of the drugs used, the in vivo process, the pharmacokinetic characteristics, and the use of other drugs, resulting in improper medication, some doctors in primary hospitals on antibiotics, especially Some antibiotics with nephrotoxic effects, more random, and often combined with more than two drugs that are toxic to the kidney, increasing the incidence of kidney damage, clinicians should pay attention to strengthen the prevention of the disease, master the drug related Knowledge, rational use of drugs.
3. Personalized treatment: Many clinicians are mechanically rigid when using drugs, and cannot be personalized according to the specific conditions of patients. For example, patients with advanced age, blood loss or chronic damage to the kidneys have not been reduced. Drug dosage or prolonged medication interval, in the future should emphasize personalized treatment to reduce the incidence of drug-induced renal damage.
4. The timing of treatment of drug-induced renal damage: The timing and treatment of drug-induced renal injury have an important impact on the prognosis. Generally speaking, if it can be treated promptly and correctly, most patients with drug-induced renal damage can turn to safety and even kidney function. It is expected to return to normal, but some medical units are not very active in the treatment of drug-induced renal damage. They only stop the drug and do not seize the opportunity to give necessary excretion and kidney-protecting drugs, unconditionally or not timely. The blood purification treatment also affects the therapeutic effect on drug-induced renal damage, so attention should be paid to the timely treatment of active treatment.
Complication
Pediatric drug-induced renal damage complications Complications chronic renal failure diabetes insipidus nephrotic syndrome
Can be complicated by acute kidney failure, diabetes insipidus, allergic disease, nephrotic syndrome and so on.
Symptom
Pediatric drug-induced renal damage symptoms common symptoms leukocyte edema edema nephrotic syndrome hematuria renal failure urine collapse hypoproteinemia uric acid crystallization hypertension
Drug-induced renal damage can be manifested in a variety of clinical syndromes, related to the type of drug, the mechanism of damage, the time of use and the state of the body.
1. Acute renal failure (ARF): It is more common that ARF caused by X-ray contrast agent appears within 48 hours after angiography. ARF caused by toxic substances such as sulfonamides and aminoglycosides is mainly found in 5 to 7 days after administration or 24 to 48 hours after one-time high-dose administration. Allergic reactions are caused by penicillins, and renal damage occurs within 24 hours after administration. Depletion.
2. Renal tubule-interstitial disease: Penicillin can cause acute allergic interstitial nephritis and manifest as hematuria, leukocyteuria, proteinuria, urinary leukocytes with more eosinophils (>30%), accompanied by kidney Insufficient function, fever, drug eruption, elevated eosinophils in the blood, chronic interstitial nephritis can be caused by non-steroidal anti-inflammatory drugs and Chinese herbal medicines containing aristolochic acid, which often lasts for more than a few months, kidney Toxic antibiotics (aminoglycosides and cephalosporins) and anti-tumor (cisplatin), in addition to direct damage to renal tubular epithelial cells, can also cause chronic interstitial nephritis; in recent years, chronic due to captopril Interstitial nephritis is also gradually increasing; in addition, amphotericin, tetracycline and some traditional Chinese medicine can cause renal tubular acidosis, Fanconi syndrome, renal diabetes insipidus and other tubular diseases.
3. Nephrotic syndrome: manifested as a large amount of proteinuria, edema, hypoproteinemia, etc., penicillamine, NSAID, etc. can cause nephrotic syndrome.
4. Nephritis syndrome: manifested as hematuria, proteinuria, hypertension.
5. Simple hematuria and/or proteinuria: Various nephrotoxic drugs such as aminoglycosides, cephalosporins, sulfonamides, NSAIDs, and anti-tumor drugs can be caused.
6. Chronic Renal Failure: Renal damage caused by Chinese herbal medicines containing aristolochic acid, such as Mutong, Fangji, Motherwort, etc., manifested as progressively difficult to reverse renal failure.
7. Obstructive renal damage: mainly caused by a large number of sulfonamide crystals blocking the renal tubules, tumor chemotherapy drugs can also cause uric acid crystals to block the renal tubules.
8. Hemolytic uremic syndrome (HUS): The contraceptive, cyclosporine, FK506, quinine, etc. can cause secondary HUS.
Examine
Pediatric drug-induced renal damage examination
1. Blood: In patients with allergic interstitial nephritis, blood eosinophils are elevated, IgG and histamine are elevated; different clinical manifestations may show corresponding changes in blood biochemistry, and blood concentration monitoring for cyclosporine Kidney damage, aminoglycoside renal damage and cisplatin nephrotoxicity have certain diagnostic value, such as cyclosporine safe blood concentration <250ng/ml whole blood, beyond this concentration, the possibility of renal damage is greater.
2. Urine: urinary, proteinuria, hematuria, leukocyteuria and renal tubular function changes may occur depending on the type of performance. When sulfa drug is kidney-damaged, a large amount of sulfonamide crystals may appear in the urine; in allergic interstitial nephritis, urine Eosinophils may occur. In addition, the osmolality of the urine is significantly lower than normal, and some small molecular proteins such as retinol binding protein (RBP), 2 microglobulin, and lysozyme, which reflect renal tubular function, are elevated. Urinary N-acetyl--D glucosaminidase (NAG) levels are also elevated.
3. Radionuclide examination (SPECT): static imaging of 67 gallium (67Ga) in both kidneys. In interstitial nephritis, gallium absorption in both kidneys is uniform and high in concentration, and the right absorption is the most in 48h, and the interstitiality caused by diagnostic drugs. Nephritis has a greater help, 99mTc diethylenetriamine pentaacetic acid (DTPA) three-phase dynamic imaging, in renal tubular-interstitial lesions showed good renal perfusion, but renal parenchymal absorption is poor, renal tubular function is impaired, 131I - OIH with dynamic renal imaging is unclear and is particularly sensitive, with a diagnostic compliance rate of 95%.
4. X-ray: X-ray films continue to have dense shadows, which is a sensitive indicator of contrast-induced renal toxicity, but lacks specificity.
5. B-ultrasound: Acute interstitial nephritis caused by drugs, B-ultrasound often shows an increase in the volume symmetry of the two kidneys.
6. Drug-specific lymphocyte transformation test: The principle is to use drug specific antigen in vitro culture to stimulate the sensitized lymphocyte transformation of patients, according to the level of drug antigens of lymphocytes, to identify whether it is A drug allergy, this test is an in vitro test, no adverse damage to the patient, another advantage is that it has high specificity, rare false positive, but the negative result can not rule out the possibility of allergic to a certain drug, the general stimulation index 2 is positive and <1.9 is negative.
Diagnosis
Diagnosis and diagnosis of drug-induced renal damage in children
diagnosis
According to the history of medication, clinical manifestations and laboratory tests of renal damage, the diagnosis is not difficult, but the early identification of slowly occurring kidney damage still has some difficulties. Therefore, the use of these drugs should pay attention to the renal function before and after treatment, urine changes As well as some changes in urine small molecular proteins and urinary enzymes, early diagnosis and avoid the occurrence of irreversible damage.
Differential diagnosis
1. Non-drug acute tubular necrosis: drug-induced renal damage is the most common acute tubular necrosis, and must be differentiated from acute tubular necrosis caused by other causes. If there is a clear history of medication, the creatinine clearance rate during or after administration is higher. Normally decreased by more than 50%, B-mode ultrasound showed double kidney enlargement or normal, and drug-induced renal tubular necrosis should be considered in the exclusion of pre-renal and post-renal azotemia.
2. Acute renal failure: acute renal failure caused by drugs should be associated with acute renal failure caused by acute glomerulonephritis, acute nephritis, primary nephrotic syndrome and lupus nephritis and small vasculitis-associated nephritis Phase discrimination, the main point of identification is that the above-mentioned non-drug acute renal failure has a common manifestation of decreased glomerular filtration rate, but each has its characteristic features of primary disease, and the pathological changes also have corresponding characteristics. Occurs before using the drug.
3. Acute interstitial nephritis: Drug-induced acute interstitial nephritis has a history of suspected allergy medications, systemic allergy, urine test can be seen as sterile leukocyte urine, of which eosinophils account for 1/3 and/or protein Urine, renal function test glomerular filtration function in a short-term progressive decline, with partial damage of proximal and / or distal renal tubular function, elevated blood IgE is helpful for diagnosis, renal biopsy helps Confirmed diagnosis.
4. Acute glomerulonephritis: drug-induced renal damage can sometimes be manifested as acute nephritis syndrome, proteinuria, hematuria, elevated blood pressure and edema, similar to the clinical manifestations of acute glomerulonephritis, sometimes difficult to identify, but acute nephritis Often appear after infection, and drug-induced renal damage has a clear history of medication.
5. Benign small arteriosclerosis: Some drugs such as analgesics have relatively slow progression of renal damage, clinical manifestations of mild proteinuria, decreased urinary concentrating function and elevated blood pressure, and benign small arteriopathic nephrosclerosis caused by hypertension Confusion, but benign small arteriosclerosis has a history of hypertension, slow onset, and renal damage occurs 5 to 10 years after the history of hypertension.
