OVERVIEW
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of anti-inflammatory drugs other than steroidal hormones that have antipyretic, analgesic, anti-inflammatory, and antirheumatic effects. Application of NSAIDs may cause kidney damage called NSAID nephropathy. There are several ways in which renal damage can occur, including acute renal failure due to altered renal hemodynamics, causing tubulointerstitial nephritis leading to direct nephrotoxic manifestations such as proteinuria and hypertensive syndrome.
Etiology.
NSAIDs include several categories: (i) salicylic acid The representative drugs are aspirin and diflunisal; (ii) acetic acid The representative drugs are diclofenac, indomethacin, sulindac, and etofenamate; (iii) propionic acid The representative drugs are ibuprofen, ketobuprofen, fenbufen, naproxen, oxaprozin, oxaprozin, and oxaprozin, and so on; (iv) xylocon The classes of piroxicam, meloxicam, tinocoxib, and ronoxacin; (v) xyloxacin The classes of celecoxib, Rofecoxib; (6) Pyrazolones: Anakinra, aminopyrine, prednisone, oxybutazone; (7) Others: Nimesulide.
The anti-inflammatory mechanism of action of NSAIDs is to inhibit the cyclooxygenase (COX) enzyme, which is required for the synthesis of prostaglandins. there are two types of isoenzymes for COX, COX-1 and COX-2. COX-1 is found in normal tissues such as the gastrointestinal tract, kidneys, platelets, etc., and has the effect of maintaining normal physiological functions such as the maintenance of renal blood flow, while COX-2 is mainly found in inflamed tissues. Once COX-1 is inhibited by drugs, normal physiological functions are impaired and renal damage can easily occur. Therefore a more ideal NSAIDS should selectively inhibit COX-2 and weakly inhibit COX-1.
Symptoms
Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause two different types of acute renal failure, hemodynamically regulated renal failure and acute interstitial nephritis (often accompanied by nephrotic syndrome), both of which are directly related to NSAIDs-induced reduction in PG synthesis. The following clinical signs are often present: ① Acute renal failure including congestive heart failure, elderly patients (age >65 years), hypovolemia or shock, sepsis, and hypertension. ② Chronic kidney damage. ③ Disturbed water-electrolyte balance and increased blood pressure. ④ Atherosclerotic disease. ⑤ Malignant tumor.
Examination
1. Blood test
Blood eosinophilia, hyperkalemia, acute renal insufficiency manifested by significant increase in blood urea nitrogen and creatinine.
2. Urine examination
Urinalysis may be normal or sterile pyuria and/or mild proteinuria (<1.5g/d), increase in urinary eosinophils, individual may have more proteinuria, even to the extent of nephrotic syndrome, a large amount of proteinuria may be the release of sensitive lymphocytes, synthesis of lymphokine activator, so that the glomerular basement membrane permeability increases, but tubular damage is not obvious; urinary sodium decreases.
3.Renal biopsy histopathology examination
Usually similar to other drug-induced acute interstitial nephritis pathology, short-term use of drugs to the tubulointerstitial pathology is dominated by changes in the tubular interstitium, there may be interstitial edema and diffuse inflammatory cell infiltration, generally no eosinophils, acute interstitial nephritis with nephrotic syndrome glomerulopathy is often mild, biopsy confirmed as a small lesion, but also membranous nephropathy, interstitial mainly T lymphocyte infiltration, focal interstitial fibrosis, immunofluorescence examination is often not available, but the results of the study are very clear, the results of the study are very clear. Immunofluorescence examination is often not specific, but in some cases, immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM) and C3 staining can be seen in the interstitium, and weakly positive. Light microscopy, immunofluorescence and electron microscopy in patients with long-term drug-induced nephrotic syndrome show morphology similar to that of microscopic glomerulopathy, with the most prominent histologic changes still confined to the interstitium and tubules.
4. Radiologic examination
Intravenous pyelography and CT scanning are mainly used to diagnose or exclude NSAID nephropathy, which can present with partial and total renal papillary necrosis in 25% to 40% of patients; the majority of the remaining patients present with a shrunken kidney and blunted calyces similar to chronic pyelonephritis. Intravenous pyelography has some limitations for the diagnosis of ischemic nephropathy (low sensitivity and potential nephrotoxicity in patients with impaired renal function). The diagnosis of ischemic nephropathy is somewhat limited by intravenous pyelography (low sensitivity and potential nephrotoxicity in patients with impaired renal function).
5. Ultrasound
to rule out other causes of renal failure.
Diagnosis
Diagnosis can be confirmed on the basis of etiology, history, clinical manifestations and intravenous pyelogram and other tests.
Treatment
1. Symptomatic treatment
First of all, the use of such drugs should be stopped, including the discontinuation of topical use of such drugs.
2. Glucocorticoid therapy
Once it is clear that kidney damage is caused by NSAIDs, the drug should be stopped immediately and treated with glucocorticoids, prednisone orally for about 3 months. There is no clear evidence to confirm the benefit of glucocorticoid therapy. However, a course of prednisone (prednisone) should be considered in patients whose renal failure persists for 1 to 2 weeks after discontinuation of NSAIDs.NSAIDs cause microscopic lesions and nephrotic syndromes, and it is not clear whether corticosteroid use can provide relief, but there are uncontrolled studies confirming the effectiveness of hormone therapy.
3. Angiotensin-converting enzyme inhibitor treatment
The use of angiotensin-converting enzyme inhibitors (ACEIs) such as enalapril orally reduces urinary protein quickly in most patients after discontinuation of the drug; however, there are reports that the combined use of ACEIs and NSAIDs will aggravate the nephrotoxicity of NSAIDs. The reason is that NSAIDs inhibit the vasodilator effect of prostaglandins, resulting in glomerular inlet and outlet arterioles constriction, after the use of ACEI, the constriction effect of the outlet arterioles is inhibited so that the glomerular filtration rate (GFR) to further decline.
4. Hemodialysis or abdominal dialysis
If renal insufficiency occurs, alternative treatment such as hemodialysis or abdominal dialysis should be performed.