Interventional therapy, widely used in cardiovascular and cerebrovascular diseases, the incidence of drug-induced kidney injury is increasing year by year. According to relevant data, acute kidney injury caused by drugs up to 28.9%, patients over 60 years of age accounted for 51%, combined with underlying diseases of chronic kidney disease is the most common, accounting for about 20%. In addition to causing acute renal failure, drug-related kidney injury can also cause acute interstitial nephritis, acute nephritis syndrome, nephrotic syndrome, acute obstructive nephropathy, chronic kidney damage, etc. If early detection and timely treatment, it can be reversed. Otherwise, it can progress to chronic renal failure, and serious cases need long-term dialysis treatment, causing serious harm to patients.
What are the drugs that cause kidney damage?
There are thousands of drugs that cause kidney injury, which are described as follows.
(1) Aminoglycosides, such as gentamicin, kanamycin, streptomycin, butamycin, etc.
(2) Contrast agent drugs, such as pancystic glucosamine, etc.
(3) Analgesics and non-steroidal drugs, such as paracetamol, aspirin, indomethacin, pautazone, ibuprofen, etc.
(4) Aristolochic acid drugs, such as Guanmutong, Hanfangji, Houpao, etc. in traditional Chinese medicine.
(5) anti-cancer drugs, such as cisplatin, mitomycin, methotrexate, etc.
(6) antifungal drugs, such as amphotericin B, etc.
(7) sulfonamides, such as sulfadiazine, sulfamethoxazole, etc.
(8) immunosuppressive drugs, such as cyclosporine A, cyclophosphamide, etc.
(9) anti-tuberculosis drugs, such as rifampicin, etc.
(10) Penicillin family drugs, such as methylpenicillin, benzisoxazole penicillin, carbenzylpenicillin, ampicillin, etc.
(11) Cephalosporins, such as cefamisin, cefadroxil, cefazolin, cefradine, etc.
(12) antihypertensive drugs, such as converting enzyme inhibitors, etc.
(13) biological products, such as interleukin 2, interferon, penicillamine and allopurinol, etc.
(14) Anti-thyroid drugs, such as propylthiouracil, etc.
(15) Lipid-lowering drugs, such as statins, etc. The most common drugs in clinical practice are antibiotics, contrast agents and painkillers.
3, the causes and mechanisms of drug-related kidney injury
(1) direct nephrotoxicity. Some drugs and their metabolites are excreted by the kidneys, which can directly cause nephrotoxicity. The renal tubules, especially the proximal tubules, due to its concentration and reabsorption function, so that it is exposed to high concentrations of toxins, vulnerable to drug toxicity. Some drugs can cause tubular cytotoxic reactions by impairing mitochondrial function, interfering with tubular transport, enhancing oxidative stress or generating free radicals, resulting in tubular epithelial cell necrosis. The extent of such damage is dose dependent.
(2) Drugs cause renal ischemic injury by affecting renal vascular and hemodynamic changes. Such as non-steroidal drugs, converting enzyme inhibitors and immunosuppressive drugs such as cyclosporine A, tacrolimus, etc.
(3) Immunoinflammatory response. Drugs can act as semi-antigens and deposit in the glomerular and tubular basement membranes, thus activating complement to cause immune injury and leading to acute interstitial nephritis. The injured renal intrinsic cells, including the necrotic tubular epithelial cells, can produce new antigens, resulting in the production of autoantibodies and aggravating the injury. For example, penicillin-induced kidney injury. This kind of injury and drug dose and drug time is not related.
(4) Some drugs themselves or metabolites are easy to form crystals in the kidney tissue, deposited in the lumen of the distal tubule, blocking the urinary flow, stimulating interstitial reaction, causing obstructive nephropathy, such as sulfonamide antibiotics caused by kidney injury.
(5) Metabolic disorders. Anti-tumor drugs can cause tumor cell lysis syndrome with deposition of uric acid and calcium and phosphorus crystals, manifesting as hyperuricemia and hypercalcemia, leading to kidney injury. Vitamin D causes disorders of calcium and phosphorus metabolism can cause interstitial nephritis and renal calcification, and diuretics can cause water-electrolyte disorders, which can lead to kidney injury.
(6) Rhabdomyolysis. Some drugs can induce rhabdomyolysis through direct toxic effects on myocytes, or indirect damage to myocytes, resulting in the release of myoglobin and creatine kinase into the blood, myoglobin through direct toxic effects and blockage of renal tubules, resulting in acute renal failure. Such as lipid-lowering drugs of statins.
(7) Thrombotic microangiopathy. Thrombotic microangiopathy organ damage, often associated with platelet thrombosis in the microcirculation, the mechanism is immune-mediated and direct endothelial toxicity, commonly used drugs such as antiplatelet drugs.
4, the clinical manifestations of drug-related kidney injury
(1) acute renal tubular necrosis. Drug nephrotoxicity caused by acute tubular necrosis, acute renal failure is mostly non-oliguric type, manifested as a rapid increase in blood creatinine, urea nitrogen, creatinine clearance rate decreased, urine specific gravity and urine osmolality decreased, metabolic acidosis and electrolyte disorders. In severe cases, the disease is often unrecoverable and gradually evolves into chronic renal failure, or worse, requires long-term dialysis to maintain life. Aminoglycoside antibiotics cause the most, followed by cephalosporin antibiotics and amphotericin B class.
(2) Acute interstitial nephritis. Caused by drug allergy, clinical manifestations appear after the use of drugs.
(i) systemic allergic reaction: mainly drug fever, drug rash, generalized lymph node enlargement, arthralgias, elevated blood eosinophils and blood IgE.
②Renal allergic reaction, manifested as aseptic leukocyturia; renal tubular function damage may lead to acute renal failure. At this time, if the drug can be timely discontinued or apply hormones and desensitizing drugs, the renal function can be restored to normal. Often caused by penicillins and cephalosporins.
(3) Acute nephritis syndrome or nephrotic syndrome. The clinical manifestations are proteinuria, hematuria, elevated blood pressure and edema, and in a few cases, high edema and nephrotic syndrome. Common steroids, reserpine, penicillamine and biological products caused by kidney damage.
(4) Chronic kidney damage. Long-term use of analgesics, calcium antagonists or lithium may lead to chronic kidney damage.
5, drug-related kidney damage how to determine?
Drug-related kidney damage if early detection, early treatment may restore kidney function. Therefore, the use of drugs must be closely observed, once there is little or no urine, hematuria, unexplained edema, lumbar swelling and pain, unexplained increase in blood creatinine should be highly suspicious of the possibility of drug-induced kidney damage, must immediately stop using the suspected drugs, can be judged according to the following two points.
(1) the history of drug use that may produce kidney damage, including the specific drug type, dose regimen, the interval between drug use and the occurrence of kidney injury, and the recovery of the kidney after stopping the drug.
(2) Early laboratory tests for drug-related kidney injury include: urine β2 microglobulin, urine microalbumin, transferrin, NAG enzyme, protein/creatinine ratio, endogenous creatinine clearance, serum CystatinC, NGAL, and renal injury molecule-1. Serum CystatinC is highly sensitive in the diagnosis of drug-related kidney injury. Urine microalbumin mainly reflects glomerular filtration function, and γ-glutamyl transferase is an indicator of renal tubular injury. The combination of the two tests is conducive to the early detection of renal injury and determine whether it is glomerular or tubular injury and the degree of drug-related kidney injury is a more ideal screening index for drug-related kidney injury.
6, drug-related kidney injury case, the patient, male, 45 years old, chronic glomerulonephritis history of 12 years, blood creatinine 356umol/l, urea nitrogen 17mmol/l, due to elevated blood lipids, out-of-hospital use of statin lipid-lowering drugs, 10 days after taking the drug, oliguria, muscle pain, blood creatinine 1260umol/l, urea nitrogen 40.6mmol/l, creatine kinase 12,000 IU/L, alkaline phosphatase 37,900 IU/L, all muscle enzymes were elevated and the diagnosis was.
(i) rhabdomyolysis syndrome.
② chronic renal failure combined with acute renal failure.
(iii) chronic glomerulonephritis. After 1 month of dialysis and symptomatic treatment, the urine volume gradually increased, and the blood creatinine was checked and decreased to 460umol/l and urea nitrogen decreased to 23mmol/l. All creatinine returned to normal.
7, drug-related kidney injury prevention and control measures
(1) Close observation of clinical manifestations, close monitoring of urinary enzymes, urinary protein, urinary microalbumin, blood creatinine and CystatinC and other indicators of change, once identified as drug-related kidney injury, immediately stop or replace the drug to prevent further aggravation of kidney damage, except aristolochic acid nephropathy, most early kidney damage can be reversed.
(2) Promote drug excretion, protect renal function, support treatment, correct electrolyte and acid-base balance imbalance, and renal replacement therapy should be performed in patients with severe acute renal failure.
(3) Early judgment and timely treatment of drug-related kidney injury is the key to improving the prognosis. Some preventive measures can reduce the incidence of drug-related kidney injury, such as the formation of crystals in the urine of sulfonamide drugs need to drink more water and alkalinize the urine during the drug use period; the use of amphotericin B, cyclosporine A can be used at the same time calcium antagonists to reduce its impact on the kidney; such as allergy-induced interstitial nephritis can be short-term application of adrenocorticotropic hormone and prohibit the use of allergenic drugs and derivatives of the drug.
8.How to use drugs correctly in patients with kidney disease?
(1) Patients with underlying renal disease are prohibited from taking aminoglycosides such as gentamicin, kanamycin, streptomycin and the Chinese medicine Guanmutong.
(2) When using drugs in patients with kidney disease, the metabolic pathway of drugs should be clarified, and the dose of drugs should be reduced and the duration of drugs should be prolonged according to the degree of renal impairment by renal excretion.
(3) For patients older than 60 years old, diabetic patients, glomerular filtration rate <60ml>265umol/l should be used with caution when using converting enzyme inhibitors.
(4) Contrast agents should be used with caution when there is underlying renal disease. If there is renal insufficiency combined with acute myocardial infarction requiring interventional therapy, coronary angiography should be done first after hemodialysis, and then hemodialysis and hydration therapy after angiography.
(5) Patients with primary nephrotic syndrome presenting with elevated blood creatinine should try not to use cyclosporine A, tretinoin and other kidney-damaging drugs.
(6) The history of drug allergy must be inquired before using the drugs, and the indications and side effects of the drugs must be strictly grasped to avoid abuse. Pay attention to the dosage and therapeutic course in drug application, and when multiple drugs are used in combination, pay attention to the related effects of drugs.
(7) In patients with renal impairment, try to use equivalent drugs with less nephrotoxicity.