Toxic side effects of drugs and kidney damage In human life, no matter big or small diseases, we can’t live without drugs, and in old age, when diseases are haunting us, we take more drugs. Proper medication can relieve illness, relieve symptoms, improve mental, physical, appetite, sleep and other discomforts, and improve the quality of life of living with illness. Inappropriate medication can bring various adverse reactions, organ damage, and even life-threatening to those who take it. When patients are allergic, certain drugs can lead to different degrees of allergic reactions, which can be life-threatening in serious cases. Drug-related adverse reactions may occur when patients do not use the medication correctly according to medical advice, such as a single dose that is too large, a course of treatment that is too long, or incorrect usage, incorrect route of administration, too many combined medications, and the existence of contraindications to the combination of drugs, leading to tissue damage and abnormal function of the corresponding organs. Why do drugs have nephrotoxicity? As we all know, kidney is an important excretory organ in human body, but it is also one of the main organs for drug metabolism. Most drugs are metabolized by the liver and then excreted from the kidneys, and some drugs are only metabolized and excreted in the kidneys, and the concentration of certain drugs gathered in the kidneys is much higher than the concentration of drugs in the blood. When renal insufficiency occurs, the excretion of drugs from the kidneys slows down, resulting in higher blood drug concentrations and higher chances of toxic side effects; or the drugs accumulate and precipitate in the kidney tissues, resulting in local damage to the kidney tissues. The main mechanisms of nephrotoxic effects are the direct toxic effects of drugs, the immune response of drugs leading to kidney damage, the deposition of drugs in the kidney blocking the renal tubules and damaging the renal interstitium, and the indirect effects of drugs damaging the kidney. Which drugs can be nephrotoxic? Drugs that are clearly nephrotoxic include aminoglycosides, amphotericin B, and peptide (vancomycin, polymyxins) antibiotics, which can directly damage renal tubular epithelial cells. Drugs that cause renal damage indirectly such as sulfonamides and methotrexate can increase the formation of renal stones; β-lactam antibiotics (penicillins, cephalosporins), rifampin, methylsulfoxypyrimidine, and hydrazinebendazole can cause renal damage due to immune response; other drugs such as diuretics, ACEI, and NSAIDs can cause renal damage by affecting renal hemodynamics. In addition, contrast agents and mannitol can damage the kidney due to high permeability; cyclosporine, mitomycin, 5-fluorouracil, and oral contraceptives can cause microangiopathic kidney damage and similar manifestations of hemolytic-uremic syndrome. Who is prone to adverse drug reactions? When the patient is in hypotension, hypovolemia, dehydration, when the patient has coexisting diabetic nephropathy, moderate and severe renal artery stenosis, and existing renal insufficiency, the kidney blood perfusion is low at this time, and it is sensitive to the toxic side effects of the drugs, when the application of drugs with clear nephrotoxicity, if the dose is not adjusted, the chance of kidney damage is great. If the dose of drugs that are mainly metabolized in the kidney is not adjusted according to the glomerular filtration function, there is a possibility of drug accumulation and increase in blood concentration, leading to an increase in the incidence of various adverse reactions. Therefore, for the elderly, diabetic nephropathy, combined with severe hypoproteinemia, cardiac insufficiency, abnormal liver and kidney function, low blood volume, the use of drugs must be considered comprehensively, according to the patient’s own specific circumstances, choose the appropriate drugs, appropriate dose and medication interval and course of treatment. The doctor must individualize the medication, and the patient should not rely only on the drug instructions to take the medication, or increase the drug dose at will. Why are elderly people more likely to have drug-related acute kidney injury? Elderly patients are in a state of reduced reserve function of various organs, that is, on the surface it seems to function normally, but under various stressful conditions, such as inflammation, surgery, drugs and other factors, they show abnormalities in the function of various systems and are prone to acute kidney injury or acute renal failure. We often say that the elderly have hidden renal insufficiency, meaning that the indicators we commonly use to measure kidney function, serum creatinine and urea indicators, are within the normal range from the laboratory results, and thus people think that the kidney function is normal. However, in fact, their real glomerular filtration function has decreased to 30-40% of normal people. With age, especially above 80 years old, the glomerular filtration rate is mostly 20-30 ml/min. Because the serum creatinine level is significantly related to the muscle volume and muscle metabolism in the body, in elderly patients, the activity is reduced, muscle atrophy and muscle metabolism is slowed down, so the serum creatinine is produced less and the increase is smaller, so the serum creatinine cannot represent the real kidney filtration function of the elderly, but Instead, creatinine clearance or glomerular filtration rate should be used to measure the renal filtration function of elderly patients. What are the clinical manifestations of drug-related kidney damage? When you are a young or middle-aged patient applying a drug without nephrotoxicity, usually no problem occurs, while applying a drug with nephrotoxicity, the same dose and course used in young and elderly people, different results will occur, especially in elderly patients over 75 years old, when applying a drug with nephrotoxicity, if the dose is not reduced or the interval between doses is extended, most of the milder patients have no complaints of discomfort. A transient urinalysis abnormality, such as the appearance of proteinuria and/or hematuria, or an increase in urinary tubular epithelial cells, or an increase in urinary NAG enzymes, urinary β2 microglobulin, and nocturia, etc., is found during close monitoring of urinary routine, and the urine may return to normal if the drug is discontinued in time. If the drug continues to be applied, elevated serum urea and creatinine may gradually appear, and in severe cases, oliguria and anuria may occur, leading to acute kidney injury and acute renal failure. Some patients may be accompanied by nausea, loss of appetite, weakness and other discomforts. Therefore, only by actively monitoring urine routine and paying attention to recording urine volume, it is possible to detect the occurrence of kidney injury early. Especially when applying drugs with clear nephrotoxicity. How to prevent the occurrence of drug-related kidney injury? Many drug-related kidney injuries are of medical origin. It is caused by the physician’s lack of awareness of the toxic effects of the drugs used, or failure to individualize the medication. In order to reduce the occurrence of adverse drug reactions in the clinic, first of all, each doctor should always check the drug manual or drug instructions to fully understand the adverse drug reactions, drug interactions, drug use, especially the drug dose and interval in renal insufficiency. Make sure that you know the drug by heart and by heart. Next, we should know the patient’s current status, such as renal function (GFR should be emphasized, not serum creatinine), the presence of dehydration, malnutrition, hypotension, cardiac insufficiency, and the presence of co-administration of diuretics, analgesics, and other drugs. Regardless of the application of drugs with or without nephrotoxicity, first of all, before the use of drugs, we should understand the current renal situation, and should conduct urinary routine and renal function tests, and if possible, urinary enzymes, urinary osmolality, and urinary small molecule protein tests to understand renal tubular function. As long as we pay attention to understand the state of kidney function before medication, closely observe the changes of urine volume, urinary routine and kidney function during medication, discover abnormalities early and stop medication early, most drug-induced kidney damage is reversible.