Overview of allergic acute tubulointerstitial nephritis (AATIN)
Acute tubulointerstitial nephritis due to hypersensitive, also known as drug-induced acute interstitial nephritis, is an acute disease caused by multiple drugs, with interstitial edema and inflammatory cell infiltration as the main pathological changes.
Acute tubulointerstitial nephritis (due to hypersensitive), also known as drug-induced acute interstitial nephritis, refers to a group of clinicopathological syndromes caused by a variety of drugs, acute onset of disease, renal interstitial edema and inflammatory cell infiltration as the main pathological changes, with renal tubular dysfunction and accompanied by a decline in filtration function as the main clinical features.
Etiology
At present, it is found that there are many kinds of drugs causing allergic acute tubulointerstitial nephritis, and the common ones are as follows:
1. Penicillins
Almost all kinds of penicillins have been reported to cause this disease, but those caused by dimethoate penicillin have been reported most frequently. In recent years, there has been an increase in the number of cases caused by amoxicillin and oxpiperazine penicillin. The incubation period is from 2 days to several weeks, usually 2 weeks. It is common in children, and the dose of the drug is not related to the onset of the disease.
2. Cephalosporins
The nephrotoxicity of this class of drugs alone is not very high, but the combined use of aminoglycoside antibiotics can cause acute tubular necrosis and acute interstitial nephritis.
3.Aminoglycosides
The nephrotoxicity of this class of drugs is greatest with neomycin, followed by gentamicin and butylcarbamate, tobramycin and ethylcissomycin, and streptomycin is the lightest. The severity of the disease is proportional to the dosage and duration of treatment, and the nephrotoxicity increases significantly when combined with other nephrotoxic drugs, cephalosporins, pre-existing renal insufficiency, advanced age and pre-existing liver disease.
4. Anti-tuberculosis drugs
Commonly used anti-tuberculosis drugs can cause this disease, such as rifampicin, ethambutol and isoniazid, among which rifampicin is the most common. Intermittent use, or re-use after stopping the drug, sometimes even adding another dose of rifampicin, can cause acute interstitial nephritis.
5. Sulfonamides
Both antibacterial sulfonamides and diuretic sulfonamides can cause acute interstitial nephritis. Combined use of drugs such as cotrimoxazole or dihydrochlorothiazide and amphotericin is closely related to the development of this disease. Typically, it occurs within a few days of administration, but in cases of acute interstitial nephritis caused by sulfonamides, the symptoms may reappear within a few hours.
6. Other antibiotics
Such as tetracyclines, amphotericin B, vancomycin, quinolones, etc., can cause acute interstitial nephritis.
7. Non-steroidal anti-inflammatory drugs
This class of drugs can cause acute interstitial nephritis, of which Fenoprofen is the most likely to cause the disease in this class of drugs. The onset of the disease can be several days to months after the use of the drug.
8. Allopurinol
Acute interstitial nephritis caused by this drug often develops in about 3 weeks of drug use. In addition, the vast majority have skin and liver function damage. The vast majority of cases occur in conventional therapeutic doses, so it is thought to be related to allergic reactions.
9. Histamine H2 receptor antagonists and proton pump inhibitors
The former includes almost all histamine H2 receptor antagonists, such as cimetidine and ranitidine. Proton pump inhibitors such as omeprazole may also cause acute interstitial nephritis.
10. Angiotensin-converting enzyme inhibitors
Angiotensin-converting enzyme inhibitors, such as mercaptomethylpropionic acid, cause acute interstitial nephritis is not uncommon.
11. Herbal medicines
Particularly aristolochic acid and its related herbs, especially when overdosed for a long period of time, cause this disease should be a cause for concern.
Symptoms
Patients have a clear history of drug use, and most patients develop the disease within the second week (2 to 44 days) after drug use, manifested by an acute increase in blood creatinine after the use of a nephrotoxic drug, and a number of patients may have low back pain and pain in the renal region or tenderness to percussion; fever (in 75% of the patients), which usually occurs after the fever of the primary disease has been controlled or after the initiation of drug therapy; rash (less than 50%); arthralgia (15% to 20%); elevated eosinophils (80%); but infrequently acute tubulointerstitial nephritis (ATIN) caused by nonsteroidal anti-inflammatory drug (NSAID) class of medications; urinalysis: mild-to-moderate proteinuria; red blood cells and leukocytes, leukocyte tubulointerstitial pattern; and blood eosinophilia (seen in 86% of cases; ATIN due to NSAID class of medications is uncommon). Nephrotic syndrome is common in those taking NSAIDs that also cause glomerular damage. Non oliguric acute renal failure may occur, while oliguric acute renal failure is more common in those with severe disease.
Examination
1. Blood test
There may be eosinophilia in peripheral blood.
2. Urine routine
Naked eye or microscopic hematuria; leukocyturia, if stained by Wright’s stain, mainly eosinophils; mild to moderate proteinuria, rarely more than 3g/d. If a large amount of proteinuria is produced, glomerular damage should be considered.
3. Blood biochemistry
BUN and Scr are elevated, blood immunoglobulin IgE is occasionally elevated, anti-TBM antibody can be detected in the blood, and acute elevation of blood creatinine can be seen in some patients.
4. Pathologic examination of renal biopsy
The pathological changes of this disease are bilateral diffuse renal lesions, with diffuse or multifocal inflammatory cell infiltration in the renal interstitium, resulting in interstitial edema, and different degrees of degenerative changes and even necrosis of the renal tubules; the glomeruli are mostly normal, and some patients can see the deposition of immunoglobulin IgG and complement C3.
(1) Light microscopy Renal biopsy reveals diffuse interstitial edema involving the entire cortex, moderate to severe interstitial infiltration, mainly composed of lymphocytes, plasma cells and eosinophils, eosinophils usually appear at an early time and disappear rapidly, due to the fact that renal biopsy of cases of this disease is often performed later in the clinic, the eosinophilia in the tissues may not be obvious, tubular changes include leukocyte infiltration, the Tubular changes include leukocyte infiltration, which is characterized by a monolayer of small and medium-sized lymphocytes closely surrounding the outside of the tubules, while other lymphocytes are located on the opposite side of the tubular basement membrane as well as between tightly connected tubular epithelial cells, which may or may not be accompanied by rupture of the tubular basement membrane.
(2) Immunofluorescent examination In some cases, IgG thread-like deposits are seen, and occasionally C3 deposits are seen along the tubular basement membrane. These manifestations are mainly seen in ATIN caused by methicillin, penicillin, or phenytoin.
(3) Electron microscopy: mitochondria of tubular cells are swollen, endoplasmic reticulum is significantly dilated in the rough surface, distal tubular lesions are more severe than proximal tubular lesions, and the peritubular basement membranes of cortical tubules are thickened and divided into multiple layers.
(4) Non-steroidal anti-inflammatory drug nephropathy (NSAID) The pathologic changes of NSAID-induced ATIN are different from those of other drug-induced ATIN as described above, and are often accompanied by glomerular involvement.
5. Other
Ultrasound and nuclear examination show increased volume of both kidneys.
Diagnosis
Diagnosis can be made on the basis of clinical manifestations, medical history and laboratory tests. The clinical diagnostic criteria for acute allergic interstitial nephritis have not been standardized so far, and the more recognized ones are:
1. History of drug use
Recent history of allergic drug use.
2.Systemic allergic reaction
ATIN caused by NSAIDs is uncommon; increased eosinophils in the urine is an important clue to the diagnosis of allergic interstitial nephritis, but the positive rate is often not high, and urine alkalinization helps to detect eosinophils; bilateral or unilateral costal and lumbar pain is uncommon, which may be due to the diffuse enlargement of the kidneys pulling on the renal peritoneum; in the interstitial nephritis infiltrated by inflammatory cells, radioactive gallium citrate In interstitial nephritis with inflammatory cell infiltration, radioactive gallium citrate imaging is often positive, especially in the early stage of the disease, this test seems to be more meaningful.
3. Abnormal urinalysis
Aseptic leukocyturia (including eosinophilic leukocyturia) may be accompanied by leukocyte tubular pattern, microscopic hematuria or hematochezia, and mild to severe proteinuria (often mild proteinuria, but proteinuria may be severe in patients with non-steroidal anti-inflammatory drug induced proteinuria).
4. Progressive renal decompensation in a short period of time
Partial impairment of proximal and/or distal renal tubular function and glomerular impairment.
Ultrasound shows that the size of both kidneys is normal or oversized. Where 1, 2 and 3 and/or 4 above are present, the clinical diagnosis can be established, however, atypical cases (especially those caused by non-steroidal anti-inflammatory drugs) often do not have Article 2, and must rely on renal biopsy to confirm the diagnosis of the pathological changes seen in renal biopsy as bilateral diffuse renal lesions, with diffuse or multifocal renal interstitial infiltration of inflammatory cells, leading to interstitial edema. The renal tubules have different degrees of degenerative changes and even necrosis; the glomeruli are mostly normal, and some patients can see deposits of immunoglobulin IgG and complement C3, or anti-TBM antibodies can be measured in the blood.
Treatment
1. Remove the cause of disease
Immediately stop using the drugs that cause allergic reaction and toxicity to kidneys, avoid using the same kind of drugs again, some patients can recover their renal function within a few days after stopping the suspected drugs.
2. Nutritional and supportive therapy Acute allergic interstitial nephritis can lead to acute renal failure, which is often accompanied by a high catabolic state of protein, coupled with the restriction of the amount of food intake, which can often lead to malnutrition, although some patients do not show significant negative nitrogen balance, but most patients have varying degrees of net protein catabolism (i.e., the difference between the total amount of protein synthesized in the body and that of the total amount catabolized in the body is negative ), as well as water and electrolyte balance or acid-base balance disorders, for patients with acute renal failure who can not eat should be given appropriate nutritional support and supplemental complementary therapies.
3.Drug therapy
For drug tubulointerstitial nephritis, it is generally believed that corticosteroid therapy has some value, prednisone is the most commonly used, 2-6 weeks; the first 2 weeks of ineffective can be added cyclophosphamide; effective gradually reduce the amount of treatment should not exceed 2-4 months, individual can be up to 1 year; 6 weeks of ineffective should be discontinued. For patients with a slight increase in serum creatinine, or patients with significant recovery of renal function 3 to 5 days after discontinuation of the drug, hormones and other special treatments are not necessary, for renal biopsy shows irreversible damage to the kidney, immunosuppressive drug therapy is also unnecessary, for patients with persistent renal failure, treatment should be initiated at an early stage.
4.Correction of water and electrolyte metabolic disorders
Some patients with acute allergic interstitial nephritis may develop oliguric acute renal failure, and the disturbances of fluid, electrolyte, acid-base and nitrogen metabolism must be actively dealt with.
5.Dialysis therapy
If severe acute renal failure occurs in acute allergic interstitial nephritis, dialysis treatment should be considered as early as possible. The dialysis techniques currently used in the treatment of acute renal failure are hemodialysis, hemodiafiltration and peritoneal dialysis, and each of the three dialysis techniques has its own advantages and disadvantages, and can be used appropriately.
6. Chinese medicine treatment
Chinese medicine activates blood circulation and removes blood stasis as well as rhubarb and cordyceps preparations, which have the effect of protecting renal function. On the basis of diagnosis and treatment, targeted selection of traditional Chinese medicine treatment is effective in acute allergic interstitial nephritis, including Chinese herbal medicine aristolochic acid kidney injury.