Allergic acute tubulointerstitial nephritis

　　First, the cause of the disease

　　The following drugs can cause acute interstitial nephritis (ATIN), and the specific drugs in each type are arranged according to the incidence rate of ATIN they cause.

　　1, Antibiotics

　　(1) Beta-lactam antibiotics: dicloxacillin, oxacillin, penicillin, cloxacillin, carbenicillin, new penicillin No. 2, ethoxynaphthylpenicillin, and ampicillin.

　　(2) Cephalosporins: cefalotin, cefradine, cefaloridine, cefoxitin, cefazolin, cefaloridine.

　　(3) Other antibiotics: rifampin, minocycline, doxycycline, gentamicin, vancomycin, lincomycin, mezlocillin, chloramphenicol.

　　2, Sulfonamide potentiators such as sulfamethizole, sulfamethizole, sulfathiazole, and sulfamethoxazole.

　　3, Non-steroidal anti-inflammatory drugs such as fenoprofen (Fenoprofen), ibuprofen, naproxen, Glafenenin, sodium tolfenamic acid (Tolmetin), sodium propyfenate (Zomepirac), indomethacin (Indomethacin), diflunisal, phenylbutazone, sulindac, phenazone, sulfinpyrazone, and aminopyrine.

　　4, Anticonvulsants such as phenytoin sodium, phenobarbital, and carbamazepine (Carbamazepine).

　　5, Anticoagulants such as phenindione and warfarin.

　　6, Diuretics such as thiazides, furosemide, triamterene, and chlorothiazide.

　　7, Immunosuppressants such as nitrogen mustard and cyclosporin.

　　8, Other drugs such as allopurinol, cimetidine, captopril (Captopril), clofibrate (Clofibrate), amphetamine, gamma-aminosalicylic acid.

　　Currently, many types of drugs have been found to cause acute allergic interstitial nephritis, of which antibiotics account for 2/3. However, only a few drugs are commonly reported to cause AIN. Methicillin is usually considered to be a common drug causing AIN and is now less commonly used. Drugs strongly associated with acute interstitial nephritis include: methicillin (Novocillin I), penicillins, cefalotin (先锋霉素I), non-steroidal anti-inflammatory drugs, and cimetidine. Drugs possibly related include: carbenicillin (carbenicillin), cephalosporins, oxacillin (Novocillin II), sulfonamides, rifampicin, thiazides, furosemide, interleukins, phenylbutazone. Weakly related include: phenytoin, tetracyclines, probenecid, captopril, allopurinol, erythromycin, chloramphenicol, and clofibrate (Clofibrate). In recent years, allergic interstitial nephritis caused by Chinese herbal medicine has been reported in China and abroad, and should be paid attention to.

　　Second, pathogenesis

　　The pathogenesis of drug-induced acute interstitial nephritis is an immune mechanism, including humoral immunity and cell-mediated immunity. This type of acute renal failure is generally caused by hypersensitivity, and has little to do with direct toxic effects of drugs, because acute interstitial nephritis occurs only in a few patients taking the drug, which may be due to the high sensitivity of the body to the drug and is unrelated to the dose of the drug. In addition to type II and I hypersensitivity reactions, type III hypersensitivity reactions may also play a role in some drug-induced interstitial nephritis.

　　Evidence of the pathogenesis of this disease comes from human studies, and there is currently no satisfactory experimental model. In some cases of this disease, the serum IgE level is elevated, a large number of mononuclear cells including lymphocytes, monocytes, and multinucleated giant cells are present in the renal interstitium, and occasionally, IgG and C3 are deposited linearly along the TBM. These findings are three basic factors for establishing the pathogenesis hypothesis of this disease.

　　The first step in the pathogenesis of this disease may be the binding of drug hapten to the structural protein of renal interstitium and/or tubular basement membrane (TBM), thereby forming a stable hapten-protein complex. This binding antigen should be able to initiate antibody-mediated reactions and delayed hypersensitivity reactions, and then cause renal damage through humoral immunity or cell-mediated immunity.

　　Some studies have shown that antibodies bind in situ to tubular interstitial antigens, which may activate complement to cause inflammation, or induce chemotactic reactions to directly mediate inflammation, or produce direct toxic effects on tubular cells, or act as a bridge between antigen-antibody-dependent cell-mediated cytotoxicity.

　　In a few cases, humoral immune response generates IgE antibodies, which can directly bind to specific receptors on tissue eosinophils, basophils, and mast cells, causing these cells to degranulate and release proteases, histamine, PAF, leukotrienes, prostaglandins, and peroxidases, directly causing local tissue damage.

　　Observation hints that there is a cell-mediated immune mechanism in the pathogenesis of ATIN caused by drugs. The majority of cases show cell infiltration dominated by mononuclear cells, containing epithelial cells and multinucleated giant cells, and this lesion is not related to immunoglobulins.

　　Some people speculate according to the research results that the pathogenesis of renal damage in this disease involves multiple links from the deposition of pathogenic drugs along the tubular basement membrane (TBM) and/or the interstitium to the sensitization of drugs by lymphocytes, followed by the infiltration of renal tissue lymphocytes, leading to the release of various lymphokines and other mediators that cause tissue damage. The research results suggest that the haptenic drugs may bind to the surface of tubular cells, and thus they may also act as cell lysis or antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by T cells.

　　Immunohistological studies have found that in some cases, T lymphocytes predominate in the infiltrating cells. In acute interstitial infiltration, CD4+ and CD8+ T lymphocyte subsets are common. In cases of drug-induced acute tubulointerstitial nephritis caused by antibiotics and NSAIDs, CD8+ cell infiltration is particularly prominent, while in cases caused by other drugs, CD4+ cell infiltration is predominant.

　　The above evidence supports the immunological basis of the pathogenesis of drug-induced ATIN, but it has not explained the specific steps and whether the disease is mediated by humoral immunity or cell immunity.

　　VanYpersele combined various conclusions on the pathogenesis of the disease obtained from previous experiments with various immunological disturbances observed in clinical observations, proposing a hypothesis: These drugs accumulated in the interstitium may be diffused through damaged TBM, may be concentrated around the capillaries of the tubules, or may bind to the haptens of TBM.

　　According to immunological principles, humoral immunity can be systemic, manifested as the formation of circulating antibodies against the corresponding drug or TBM, or it can be local, manifested as interstitial infiltration of monocytes, lymphocytes, and plasma cells. These cells can synthesize immunoglobulins locally and form in situ complexes. Delayed hypersensitivity reactions can lead to interstitial infiltration of lymphocytes activated by macrophages. Therefore, an acceptable view is that the same drug can cause the same tubulointerstitial damage through different immune mechanisms, and the type of reaction is determined by the patient's innate immune reactivity, the degree and characteristics of immune stimulation, and the amount of etiological factors.

　　The pathogenesis of ATIN caused by non-steroidal anti-inflammatory drugs is different from that caused by other drugs, as they are mediated through mechanisms such as the inhibition of prostaglandin synthesis.

　　It mainly complications with metabolic acidosis, heart failure, and acute renal failure.

　　1, Metabolic acidosis is the most common type of acid-base imbalance, caused by an increase in extracellular H+ or a loss of HCO3-, leading to a primary decrease in HCO3-.

　　2, Acute renal failure, abbreviated as ARF, is a clinical critical illness. The disease is an acute renal injury caused by various etiologies, which can cause a sharp decline in the regulatory function of renal units within a few hours to several days, resulting in the inability to maintain fluid and electrolyte balance and excrete metabolic products, leading to hyperkalemia, metabolic acidosis, and acute uremic syndrome. This syndrome is clinically known as acute renal failure.

　　Drug-induced acute interstitial nephritis can occur in people of all ages, but NSAID-induced ATIN mainly occurs in the elderly (64.6 years ± 2.1 years).

　　The duration of drug exposure before the onset of allergic ATIN varies, generally around 15 days, and ATIN caused by NSAIDs often occurs several months later.

　　The clinical symptoms of onset of the disease are often fever, rash, and hematuria. In about 1/3 of drug-induced ATIN cases, rash, fever, and joint pain may occur simultaneously. A few cases may have obvious lumbar pain, which is less common in ATIN caused by NSAIDs. 95% of patients have hematuria, 1/3 cases have gross hematuria, and about 86% of patients have more than 30% eosinophils in their urine leukocytes; however, in ATIN caused by NSAIDs, only 5% of patients have eosinophiluria. Most patients generally only have mild proteinuria, less than 1.5g in 24h quantification, and proteinuria reaching the range of nephrotic syndrome is uncommon, unless it is ATIN caused by NSAIDs with minimal change glomerulonephritis, and experimental examination has or does not have elevated serum IgE (only half of patients confirmed by renal biopsy can find elevated serum IgE levels, so negative results cannot exclude the diagnosis of the disease). 60% to 80% of cases may have a short-term increase in eosinophils, which is of great help in the diagnosis of the disease.

　　The disease often occurs with acute renal failure, of which 20% to 50% of cases are oliguric or anuric. Many cases have urine examination results similar to acute tubular necrosis (ATN), with varying degrees of renal failure, among which more than 30% of patients need dialysis treatment.

　　In most reported early drug-induced ATIN cases, the correlation between acute renal damage and clinical manifestations of acute allergic reaction can suggest the diagnosis of the disease. Multicenter prospective studies have evaluated the value of immediate hypersensitivity symptoms in predicting ATIN, among which increased blood eosinophils are of the greatest significance for predicting ATIN.

　　In some cases, there may be no allergic symptoms at all, and renal failure can occur alone, especially in 30% to 40% of cases, which is non-oliguric renal failure. In these cases, the diagnosis of the disease is still difficult, so allergic interstitial nephritis is often missed in clinical practice, unless all acute renal failure of unknown etiology is subjected to renal biopsy.

　　It is mainly to use various drugs that are likely to trigger the disease with caution. For those with allergic diseases, active symptomatic treatment should be carried out to prevent the occurrence of interstitial nephritis.

　　1. Control dietary structure to avoid excessive intake of acidic substances, which can exacerbate acidic constitution. The acid-base balance of diet is a very important link in the treatment of diabetes and the prevention of complications. In terms of diet, it is necessary to eat more foods rich in plant organic active alkalis, less meat, and more vegetables.

　　1. Participate in aerobic exercise, exercise the body appropriately, do more physical activities and sweat in the sun, which can help to eliminate excess acidic substances in the body, thereby preventing the occurrence of kidney disease.

　　2. Maintain a good mood, do not have excessive psychological stress. Excessive stress can lead to the deposition of acidic substances, affecting the normal progression of metabolism. Appropriate adjustment of mood and personal stress can maintain an alkaline体质, thereby preventing the occurrence of kidney disease.

　　3. Live a regular life. People with irregular lifestyles, such as staying up all night to sing karaoke, play Mahjong, and not going home at night, will worsen the body's acidification.

　　4. Stay away from cigarettes and alcohol. Both are typical acidic foods, and smoking and drinking without restraint can easily lead to acidification of the human body, making kidney disease an opportunity. In daily life, tea can be a drink to prevent and improve nephritis, and it can also regulate the balance of the human body, anti-inflammatory and antibacterial, cool and detoxify, and enhance the body's resistance. This kind of Chinese herbal tea mainly includes honeysuckle, wild chrysanthemum, cordyceps, and so on.

　　5. Avoid contaminated foods such as polluted water, crops, poultry, eggs, and fish. Eat some green organic foods and prevent diseases from entering the body through the mouth.

　　1. Blood routine:Increased eosinophils.

　　2. Urinalysis:Gross or microscopic hematuria; leukocyte urine, mainly eosinophils, if stained with Wright; mild to moderate proteinuria may be present, and massive proteinuria can be produced if the glomeruli are damaged.

　　3. Blood biochemistry:Increased BUN, Sc3, elevated blood immunoglobulin IgE levels, and detectable anti-TBM antibodies in the blood. Some patients may show acute elevation of blood creatinine.

　　4. Renal biopsy case examination:The pathological changes of this disease are diffuse bilateral renal lesions, diffuse or multifocal infiltration of inflammatory cells in the renal interstitium, leading to interstitial edema, and varying degrees of degenerative changes and even necrosis in renal tubules; renal glomeruli are usually normal, and some patients may show deposition of immunoglobulin IgG and complement C3.

　　1. Light microscopy examination:Renal biopsy shows diffuse interstitial edema involving the entire cortex, moderate to severe interstitial infiltration, mainly composed of lymphocytes, plasma cells, and eosinophils. Eosinophils usually appear earlier and disappear rapidly. Since renal biopsies for this disease are often performed late in clinical practice, the increase in eosinophils in the tissue may not be evident. Tubular changes include leukocyte infiltration, characterized by a dense infiltration of small to medium-sized lymphocytes around the tubular wall, while other lymphocytes are located opposite the basement membrane of the tubules and between the tightly connected tubular epithelial cells. Tubular basement membrane damage may or may not be present, and Ooi et al. describe this as tubulitis. The interstitium may appear with granulomas containing macrophages, which are considered a specific manifestation of drug hypersensitivity. In some reports, renal interstitial epithelial cell granulomas are seen in 25% to 50% of drug-induced ATIN. Renal glomeruli and blood vessels are generally normal, but there are also individual case reports of glomerular and vascular lesions.

　　22, Immunofluorescence examination:In some cases, IgG linear deposition can be seen, and occasionally C3 deposition can be seen along the tubular basement membrane, these manifestations are mainly seen in ATIN caused by methicillin, penicillin, or phenytoin, and the corresponding antibody can detect methicillin antigen-dimethoxyphenylacetyl along the TBM in 3 patients with this disease, suggesting a hapten-carrier mechanism. It may be related to the induction of anti-TBM antibodies in these cases. In one patient with ATIN caused by phenytoin sodium, anti-TBM antibodies were detected, and at the same time, phenytoin sodium deposited along the TBM was found, but in most reported cases, immunofluorescence examination did not show immune globulin, complement, and纤维素 deposition in renal tissue.

　　20, Electron microscopy examination:Some literature reports on the electron microscopic findings of drug-induced ATIN, Ooi et al. found that the mitochondria of tubular cells were swollen, the rough endoplasmic reticulum was significantly expanded, the lesions of the distal tubules were more severe than those of the proximal tubules, the peritubular basement membrane of the cortical tubules was thickened and divided into multiple layers, and the cause of thickening may be the proliferation of basement membrane substances. Due to the destruction of the interstitial structure, the lesions in the interstitial region were described as chaotic by Galpin et al., the inflammatory infiltrating cells were composed of lymphocytes, plasma cells, and eosinophils, with a small number of neutrophils. The glomeruli are generally normal, and only in the cases of drug-induced ATIN with nephrotic syndrome, obvious foot process fusion is found.

　　18, Pathological changes of non-steroidal anti-inflammatory drug nephropathy:The pathological changes of ATIN caused by non-steroidal anti-inflammatory drugs are different from those caused by other drugs, often accompanied by glomerular involvement, see non-steroidal anti-inflammatory drug nephropathy.

　　16, Other:Ultrasound examination shows enlargement of the kidney volume.

　　12, What is good for the body for allergic acute tubulointerstitial nephritis patients

　　11, Adequate vitamin supplementation should be provided:Vitamins should be fully supplied, and attention should be paid to supplementing foods rich in B-group vitamins and vitamins A, C, and folic acid. For patients with anemia, it is advisable to supplement B-group vitamins, iron, and folic acid-rich foods, such as animal liver, green leafy vegetables, etc.

　　9, Eat more vegetables:Such as winter melon, luffa, watermelon, bamboo shoots, radish, green vegetables, etc. If accompanied by hypertension, lotus root, corn, celery can be eaten. For those with hematuria and a large number of red blood cells in the urine, wild vegetables such as Stachys sieboldii, Capsella bursa-pastoris, and Stachys sieboldii can be eaten.

　　7, What is bad for the body for allergic acute tubulointerstitial nephritis patients

　　6, Taboo: Fishy and spicy, fried and fried, aquatic products (shrimp, crab), chili, garlic, green onions, coriander, dog meat, horse meat, donkey meat. The diet should be low in salt, light and rich in vitamins. Appropriate amounts of seasoning can be added to various patients, such as a small amount of sesame oil, monosodium glutamate, etc.

　　5, In daily life, it is advisable to quit smoking and drink light tea, and drinking should be moderate, not excessive.

　　4, People with kidney disease should not eat food with high protein and high salt content.

　　Three, Dietotherapy for allergic acute tubulointerstitial nephritis

　　1, Crucian carp and red bean drink:One large crucian carp, 60 grams of red bean, boil and drink the juice, take it all at once. Note that it is not advisable to add salt.

　　2. Pepper egg:7 grains of white pepper, 1 fresh egg. First, make a small hole in the egg, then put the white pepper into the egg, seal the hole with flour, wrap it with wet paper, and steam it in a steamer. When served, peel off the eggshell and eat the egg and pepper together. Adults take 2 eggs a day, children take 1 egg a day. 10 days is a course of treatment, rest for 3 days after taking the first course, and then take the second course.

　　3. Erjiao soup:120 grams of red bean, 9 grams of phytolacca, as a daily dose, add water, boil the soup and drink it, take it continuously for 3-5 days.

　　4. Fish-mercury and plantain herb decoction:60 grams of houttuynia herb, 60 grams of plantain herb, decoct the soup and take it.

　　5. Red bean mulberry bark decoction:60 grams of red bean, 15 grams of mulberry bark, boil in water, remove the mulberry bark, drink the soup and eat the beans.

　　6. Boiled red bean with grass root:250 grams of white grass root, 120 grams of red bean, boil in water until the water is dry, remove the grass root, and chew the beans in several doses.

　　7. Toad and locust gourd powder:2 dried toads, 7 locusts, 15 grams of old gourds, slightly fried, ground into fine powder or made into pills, taken with warm wine, 6 grams each time, 3 times a day.

　　8. Crucian carp soup:500 grams of crucian carp, 1 head of garlic, 3 grams of black pepper, 3 grams of Sichuan pepper, 3 grams of tangerine peel, 3 grams of amomum villosum. Put scallion, sauce, salt, Sichuan pepper, garlic, etc. into the fish belly and cook it into a soup.

　　9. Red sage seed pork soup:30 grams of red sage seeds, 120 grams of lean pork, decoct the soup and eat the meat, take 1 dose a day, divided into 2 doses. For the treatment of chronic nephritis edema and patients with more proteinuria.

　　10. Winter melon crucian carp soup:500 grams of crucian carp, 200 grams of winter melon (cut into pieces), cook together, add 10 grams of chopped scallion and a little salt before serving.

　　11. Raw earth and Chinese yam honey:60 grams of raw earth, 60 grams of Chinese yam, 500 grams of honey. Quickly wash the raw earth and Chinese yam, pour them into an earthen pot, add 3 bowls of cold water, and simmer over low heat for about 40 minutes, then filter out half a bowl of the first decoction. Add another bowl of cold water, simmer for 30 minutes until the decoction is half a bowl, filter out and discard the residue. Mix the first and second decoctions with honey, pour them into a porcelain bowl, cover it, and prevent steam from entering. Steam over high heat for 2 hours, remove from heat, cool, bottle, seal tightly, take 2 times a day, 1 spoon each time, and take it with warm water after meals.

　　First, treatment

　　1. Eliminate the cause:Immediately discontinue the use of drugs that cause allergic reactions and are toxic to the kidneys, and avoid using similar drugs again. For some patients, renal function can recover within a few days after discontinuing the suspected drugs.

　　2. Nutritional and supportive treatment:Acute allergic interstitial nephritis can lead to acute renal failure, and acute renal failure is often accompanied by a high catabolic state of protein, combined with limited intake, which often leads to malnutrition. Although some patients do not show obvious negative nitrogen balance, most patients have varying degrees of net protein catabolism (i.e., the difference between the total protein synthesis and catabolic metabolism in the body is negative), as well as disorders of water and electrolyte balance or acid-base balance. Appropriate nutritional support and supplementary therapy should be provided for patients with acute renal failure who cannot eat.

　　The nutritional supply for acute renal failure patients is generally based on the principle of output and input, providing according to need. The apparent value of urea nitrogen is a commonly used indicator to measure or evaluate the size of a patient's nitrogenous nutritional needs. When the apparent rate of urea nitrogen in the patient is low, such as when the patient is not currently receiving dialysis treatment, providing a diet or extraintestinal nutrition with a lower nitrogen content [such as 20 to 30g/d of essential amino acids or 0.6g/(kg·d) of protein] may be very helpful. As long as it is maintained for 1 to 2 weeks, it can generally maintain a neutral or slightly negative nitrogen balance, reducing the accumulation rate of nitrogenous products in the body to the lowest, thereby significantly reducing or avoiding the need for dialysis treatment in patients. For patients with an apparent rate of urea nitrogen >4 to 5g/d, malnutrition, those undergoing dialysis treatment, or patients who need long-term nutritional support, it is usually necessary to provide a diet or infusion with a considerable amount of protein or amino acids to supply 1 to 2g/(kg·d) of essential amino acids and non-essential amino acids. The intake of a large amount of nitrogen can alleviate the patient's negative nitrogen balance, but the apparent rate of urea nitrogen is almost always increased, and the intake of a large volume of fluid is indispensable for providing an appropriate amount of energy and amino acids, which will increase the patient's need for dialysis treatment significantly. For patients with a larger remaining renal function, higher tolerance to fluid load, and stronger cardiovascular and respiratory system function, they usually have a higher tolerance for large amounts of nitrogenous nutrition intake; for most patients, they can tolerate high nitrogen intake as long as they receive appropriate dialysis treatment.

　　The pathways for patients to intake nutrients include oral intake and nasogastric feeding, as well as intravenous infusion, which is an extraintestinal nutritional method. It is best not to use extraintestinal nutritional methods for patients who can eat or tolerate nasogastric feeding. For patients who obtain nutrients through the gastrointestinal tract, the selected preparations should be based on the principle of providing sufficient protein [such as 1 to 2g/(kg·d) for dialysis treatment patients] while minimizing the liquid volume and the lowest potassium concentration. In addition, consideration should also be given to the rational proportion of essential amino acids and non-essential amino acids contained in the preparations. For malnourished patients who cannot receive gastrointestinal nutrition or those undergoing dialysis treatment, total parenteral nutrition therapy should be adopted to provide 1 to 2g/(kg·d) of essential amino acids and non-essential amino acids. If the patient has severe uremia, or is overloaded with fluid, or the serum electrolyte concentration of the patient is abnormal, or the patient cannot undergo dialysis treatment, then the composition and volume of the nutritional infusion should be adjusted according to the specific situation. Due to the fact that acute renal failure patients usually have varying degrees of negative nitrogen balance, a larger amount of calories should be supplied to reduce the decomposition of proteins and amino acids in the body, improve and reverse the negative nitrogen balance. The approximate caloric needs of these patients are generally 125 to 188kJ/(kg·d). As for the needs of acute renal failure patients for vitamins, the current understanding is not very clear. It is necessary to appropriately supplement water-soluble vitamins, but a cautious attitude should be maintained for the supplementation of fat-soluble vitamins; the supplementation of electrolytes should be based on the changes in serum concentration, which varies from person to person and over time.

　　3. Medication:Both experimental and clinical applications suggest that adrenal cortical hormones are often effective in achieving diuresis, improving renal function, and lowering blood creatinine levels to normal. For patients with only slightly elevated serum creatinine levels, or those whose renal function significantly recovers within 3～5 days after drug discontinuation, additional special treatment such as hormones is often unnecessary. For patients with irreversible renal damage shown by renal biopsy, immunosuppressive drug treatment is also not necessary. For patients with persistent renal failure, treatment should be initiated early. It is recommended to administer short-term hormone therapy, with the dose of oral prednisone recommended to be 30～60 mg/d, and it should be used continuously for at least 4 weeks. For severe renal failure patients, intravenous administration is preferable, usually methylprednisolone 0.5～1g/d for 3 days. There are also reports that methylprednisolone 240mg/d is sufficient for the treatment of acute allergic interstitial nephritis, and the dose should be gradually reduced, with a course of 2～4 weeks, followed by oral prednisone for 2～4 months. For patients who are not suitable for renal biopsy but have highly suggestive clinical symptoms of acute interstitial nephritis, prednisone can be administered orally at a dose of 1mg/(kg·d) for 2～3 weeks as diagnostic treatment. If the patient's serum creatinine levels show little change after hormone therapy, or if renal biopsy shows mild or no interstitial fibrosis, cytotoxic drugs such as cyclophosphamide 2mg/(kg·d) can be added to the treatment within 2 weeks of corticosteroid therapy. If the efficacy remains poor, immunosuppressive drugs should be gradually reduced and discontinued within 5～6 weeks. If the glomerular filtration rate improves, cyclophosphamide can be continued for 1～2 months, and the dose of corticosteroids should be gradually reduced. However, renal biopsy is recommended before the use of immunosuppressive drugs to confirm AIN, as interstitial fibrosis may appear within 10～14 days of the onset of the disease, and the use of immunosuppressive drugs may be more harmful than beneficial at this stage. The use of cytotoxic drugs should not be prolonged during the treatment of acute allergic interstitial nephritis to prevent complications caused by medication.

　　4. Correction of water and electrolyte metabolism disorders:Part of the patients with acute allergic interstitial nephritis may present with oliguric acute renal failure, requiring active management of fluid, electrolyte, acid-base, and nitrogen metabolism disorders.

　　(1) Water intoxication with left heart failure: The fluid replacement volume for 24 hours is the sum of the apparent and insensible fluid losses minus the endogenous water production. The following points can serve as indicators for moderate fluid replacement:

　　① No signs of dehydration or edema under the skin.

　　② Daily weight does not increase; if it exceeds 0.5 kg or more, it suggests excessive body fluid.

　　③ Low serum sodium concentration, with no salt loss basis, indicates fluid retention.

　　④ Central venous pressure is normally between 0.59～0.98 kPa (6～10 cmH2O); if it is higher than 1.17 kPa (12 cmH2O), it suggests excessive body fluid.

　　⑤ Chest X-ray shows vascular shadows; if signs of pulmonary congestion are present, it indicates fluid retention.

　　⑥ Rapid heart rate, increased blood pressure, and rapid breathing; if there are no signs of infection, excessive body fluid should be suspected.

　　In addition, maintaining fluid balance by measuring body weight every day is a simple and practical method. Patients with acute renal failure may experience high-volume left heart failure, mainly requiring dialysis methods and resolving excessive fluid overload.

　　(2) Potassium balance disorder (hyperkalemia): Mildly elevated blood potassium levels (6.5mmol/L, especially when there are changes in the electrocardiogram, should be treated emergently.

　　① Injection of calcium: Calcium can counteract the toxic effects of potassium on the heart. A common method is to slowly inject 10% calcium gluconate 10 to 20ml intravenously, paying close attention to heart rate and rhythm changes.

　　② Alkaline drugs: Alkaline drugs can transfer potassium in the blood to the inside of cells, thereby lowering blood potassium levels; especially for patients with metabolic acidosis, they should be considered as the first choice. A common method is to use 250ml of 5% sodium bicarbonate for intravenous infusion.

　　③ Infusion of glucose and insulin: A common method is to use 250ml of 25% to 50% glucose solution, adding 1U of insulin for intravenous infusion per 6g of glucose. Immediate preparation for hemodialysis treatment should be made.

　　(3) Metabolic acidosis: If not very severe, acid-base imbalance generally does not cause serious consequences to the patient and therefore does not require emergency treatment. For patients with mild imbalance, it is important to pay attention to why acid-base imbalance occurs, because even a slight imbalance may hide a series of serious diseases. Metabolic acidosis caused by renal failure is mostly inorganic acid, and renal failure without complications rarely causes severe acidosis. However, if there is increased acid production due to high catabolic metabolism or large losses of bases (diarrhea, etc.), severe metabolic acidosis may occur. These patients must be supplemented with bicarbonate, and dialysis correction of metabolic acidosis is very effective. However, if dialysis is not sufficient to fully correct the acidosis, or if renal failure is secondary to decreased renal perfusion due to hypovolemia, bicarbonate infusion should be considered. The initial dose can be estimated based on the distribution volume of 50% of body weight to gradually increase the serum bicarbonate concentration. The osmolarity of isotonic bicarbonate is 1.3%, and the commonly used sodium bicarbonate solution is usually hypertonic. If it is not used in combination with other hypotonic solutions, it can lead to hypernatremia. Regardless of the form of bicarbonate used, it must be carefully observed and efforts must be made to avoid possible complications, such as volume overload, decreased free calcium concentration, and rare hypokalemia.

　　5. Dialysis therapy:Acute allergic interstitial nephritis can lead to acute renal failure. If the condition is mild without obvious complications, non-surgical therapy can show signs of improvement in the short term and dialysis treatment is not required. However, if the patient's condition is severe and progressive, and non-surgical treatment is ineffective or difficult to perform, dialysis treatment should be considered as soon as possible. Clinically, the dialysis techniques currently used for the treatment of acute renal failure are hemodialysis, hemofiltration, and peritoneal dialysis. Each of the three dialysis techniques has its own advantages and disadvantages and can be used for the rescue and treatment of acute renal failure patients with different clinical backgrounds. However, due to the significant overall efficiency of hemodialysis and its high level of popularity, hemodialysis is still the most commonly used dialysis treatment technique for the rescue and treatment of acute renal failure in clinical practice. Because of their respective advantages and disadvantages, they can generally be used for different clinical situations. Renal dialysis should be actively considered for creatinine levels ≥500μmol/L or accompanied by hyperkalemia.

　　(1) Hemodialysis: Can be considered for the treatment of acute renal failure patients in the following clinical situations.

　　① Catabolic type acute renal failure.

　　② Patients with acute renal failure who urgently need solute clearance, such as those with symptoms of hyperkalemia or hypercalcemia.

　　③ Patients who have ingested toxic substances that can be cleared by dialysis.

　　④ Patients with acute renal failure who have failed peritoneal dialysis or hemofiltration (usually due to insufficient clearance), or cannot perform hemofiltration due to the inability to establish an appropriate vascular access or receive necessary anticoagulant measures, as well as patients who cannot perform peritoneal dialysis due to abdominal surgery or infection.

　　(2) Hemofiltration: Can be considered for the following situations.

　　① Patients with unstable hemodynamic conditions who need ultrafiltration and drainage and/or solute clearance.

　　② Patients with constant urine output but needing ultrafiltration in non-oliguric cases.

　　③ Patients who need to perform ultrafiltration and drainage every day.

　　④ Patients who need urgent dialysis treatment but do not have conditions for hemodialysis and peritoneal dialysis.

　　(3) Peritoneal dialysis: Can be considered for the same situations as hemofiltration, including: ① Patients who cannot establish an appropriate vascular access or cannot receive necessary anticoagulant treatment; ② Clinical environments without conditions for hemodialysis and hemofiltration; ③ Patients with unstable hemodynamic conditions who need dialysis treatment.

　　(4) Dialysis treatment during acute renal failure: The first problem to be solved is to clarify the treatment indications. The indications that can be relieved by dialysis therapy before death are absolute indications for dialysis treatment. These absolute indications can be appropriately extended to become relative indications for dialysis treatment in patients with acute renal failure.

　　① Absolute indications: Hyperkalemia: Hyperkalemia associated with myocardial toxicity has always been a recognized indication for initiating dialysis therapy in patients with acute renal failure. The occurrence and harmfulness of hyperkalemia vary with the etiology and complications that cause acute renal failure. Hyperkalemia is the main cause of death in patients with oliguric acute renal failure during the oliguria period, so it should be corrected promptly once it occurs. When non-surgical treatment measures cannot control the potassium concentration at the level of 6.5～7.0 mmol/L, hemodialysis treatment must be used. Among all the methods for correcting hyperkalemia, hemodialysis is the fastest and most effective method.

　　Excessive blood volume: Even in patients with non-oliguric acute renal failure, who start to limit fluid intake appropriately in the early stage of renal failure, excessive blood volume may still occur. The clinical manifestations caused by fluid overload can be divided into two categories. One is hypertension and congestive heart failure caused by expansion of intravascular volume, and the other is the clinical manifestations caused by excessive extravascular fluid, which itself cannot be used as a criterion for whether dialysis treatment should be performed. However, pulmonary edema before respiratory failure can be an absolute indication for urgent dialysis treatment in patients with acute renal failure.

　　Uremia: It is an absolute indication for dialysis treatment, and it is currently trending towards early dialysis treatment, i.e., prophylactic dialysis treatment. In all complications of acute renal failure that are indicated for dialysis treatment, the most obvious improvement is in the central nervous system function after dialysis treatment.

　　Acidosis: Metabolic acidosis is usually present in the formation of acute renal failure, unless the patient has chronic vomiting or is receiving nasogastric tube drainage. Before the pH drops below 7.2, the clinical symptoms caused by acidosis are not prominent. When the acidosis state is below pH 7.2, the remaining alkaline buffering capacity is very small, so even a slight decrease in blood bicarbonate can lead to extreme acidosis and severe cardiovascular effects. In such cases, dialysis therapy is the best treatment method, generally speaking, for patients with rapid acidification due to high catabolic metabolism, hemodialysis is undoubtedly the preferred treatment method.

　　② Relative indications: The relative indications for dialysis treatment of acute renal failure are some usually non-life-threatening metabolic disorders that can often be controlled with non-surgical therapy, plus a lower degree of volume overload or expected to develop hypernutrition, moderate neurologic dysfunction, or the need for surgery.

　　(5) Termination of dialysis treatment for acute renal failure with oliguria: For patients with oliguric acute renal failure, dialysis treatment can be terminated when the minimum daily urine output reaches about 800ml, as this level of urine output usually indicates that the patient's own renal function is sufficient to achieve the level of urea clearance that dialysis treatment can achieve. Changes in serum creatinine concentration before and after each dialysis session can also be used to evaluate the recovery of renal function, especially for patients with non-oliguric acute renal failure, if the serum creatinine concentration before dialysis is not significantly different from or even lower than that after the previous dialysis session, it indicates that the patient's own renal function has recovered, and the dialysis catheter should be removed and dialysis treatment terminated as soon as possible.

　　In summary, almost all patients will improve quickly after discontinuing nephrotoxic drugs or after treatment with corticosteroids. However, renal function may not fully recover. Therefore, diagnosis and treatment should be carried out as soon as possible to minimize renal damage.

　　II. Prognosis

　　Most cases of acute allergic interstitial nephritis are reversible if diagnosed and medication is discontinued promptly. Generally, the prognosis is good, although more than 35% of the cases have severe renal function failure with a long duration, requiring dialysis treatment, but the mortality rate is low; some patients have residual renal insufficiency, eventually progressing to end-stage renal failure. In the case of drug-induced acute interstitial nephritis, the clinical syndrome of acute interstitial nephritis can spontaneously resolve after the discontinuation of the causative drug, while complete recovery of renal function may require several months. If diagnosis is delayed or the drug is misused again, resulting in severe allergic reactions and severe acute renal failure, the prognosis is poor, and patients with renal interstitial fibrosis and tubular atrophy on renal biopsy have poor prognosis.

　　The prognosis of acute allergic interstitial nephritis depends on several factors:

　　1. The extent and severity of inflammatory cell infiltration in the cortical areas; patients with diffuse infiltration have poor prognosis.

　　2. The prognosis is poor for those with a high proportion of neutrophils in the infiltrating cells.

　　3. The prognosis is poor for those without improvement in renal function after treatment and for those with sustained increase in blood creatinine levels.

　　4. The prognosis is poor for lesions involving glomeruli and blood vessels.

　　5. The treatment plan is closely related to the prognosis. The combination of adrenal cortical hormone therapy with dialysis therapy can greatly improve the prognosis.

　　In a prospective study, Kleinknecht and his collaborators compared the main characteristics of drug-induced acute tubular necrosis (ATN) and drug-induced ATIN, and found that non-oliguric ARF, clinical and biological manifestations of hypersensitivity, prolonged renal failure time, and persistent renal damage are more common in ATIN patients.

　　Whether the recovery is good is related to the duration of renal failure before treatment. The study by Laberke and Bohle shows that ATIN with ARF lasting 3 weeks or more has a significantly poorer prognosis than those without ARF, or those with ARF lasting 2 weeks or less. The presence or absence of diffuse infiltration is also related to the recovery of renal function, and diffuse infiltration often leads to the persistent existence of renal function damage.

　　The types of drugs that cause ATIN can also affect the long-term prognosis of patients, NSAIDs are more commonly associated with irreversible chronic renal failure.

　　Chronic or untreated interstitial damage often leads to irreversible chronic interstitial fibrosis.

　　Early consideration of drug-induced ATIN, determination and removal of the causative drug, is an important factor in achieving rapid and complete recovery of renal function in patients.

　　The significance of corticosteroid drugs in accelerating the recovery of this disease or improving the prognosis is not yet certain. The evidence of effective prednisone (Prednisone) treatment comes only from a few non-randomized studies and case reports with lack of strict control.

　　Neilson does not believe that persistent interstitial nephritis is a particularly favorable lesion and believes that for acute interstitial damage that persists for more than 1 week after withdrawal of the causative drug and is confirmed by renal biopsy, cautious consideration should be given to a short course of high-dose prednisone (Prednisone) treatment. Corticosteroids may be effective in cases where serum creatinine levels increase for more than 1 week but renal failure does not last for several weeks. If there is no response after 3 to 4 weeks of treatment, steroid treatment should be stopped.