Renal failure NSAIDs associated

Adverse effects are uncommon, apart from excess of therapeutic effect (electrolyte disturbance and hypotension due to low plasma volume) and those mentioned in the general account for diuretics (below). They include nausea, pancreatitis and, rarely, deafness which is usually transient and associated with rapid i.v. injection in renal failure. NSAIDs, notably indomethacin, reduce frusemide-induced diuresis probably by inhibiting the formation of vasodilator prostaglandins in the kidney. 

Phenylbutazone (Butazolidin) is metabolized to oxy-phenbutazone (Phlogistol), and both compounds have all of the activities associated with the NSAIDs. Their use is accompanied by serious adverse reactions, such as anemia, nephritis, renal failure or necrosis, and liver damage. Because of their toxicity, they are prescribed only for the treatment of pain associated with gout or phlebitis or as a last resort for other painful inflammatory diseases resistant to newer and less toxic treatments. Interactions with a large number of other drugs... 

Because the sulfide may be reoxidized to the inactive prodrug in the kidney, sulindac may inhibit renal COX less than other NSAIDs, though reversible renal failure and nephrotic syndrome have been observed with this drug. Among the more severe reactions, Stevens-Johnson epidermal necrolysis syndrome, thrombocytopenia, agranulocytosis, and nephrotic syndrome have all been observed. Like diclofenac, sulindac may have some propensity to cause elevation of serum aminotransferases it is also sometimes associated with cholestatic liver damage, which disappears or becomes quiescent when the drug is stopped. 

NSAIDs inhibit prostaglandin synthesis, and in so doing can reduce GFR in susceptible patients, including those with cirrhosis. A number of renal complications can occur, including acute renal failure. All NSAIDs have been associated with nephrotoxicity. There is a small amount of data suggesting that renal effects are less likely to occur with sulindac, but studies relate to short-term therapy only, and there have been case reports of acute renal failure developing in high-risk patients [4,27,35]. 

NSAIDs are the most widely used analgesics in human and veterinary medicine, and all have some toxic potential. NSAIDs cause an acute reduction in renal function, which leads to nephrotoxic acute renal failure. The abnormalities related to renal function associated with NS AID... 

A series of 11 spontaneously reported cases in which renal impairment was associated with the use of nimesulide has been described (17). The adverse events were represented by acute renal insufficiency n — 2), acute deterioration of chronic renal insufficiency n — 3), fluid retention n = 4), and oliguria and macro hematuria n = 1 each). The patients had a median age of 57 (range 17-81) years and six had some predisposing condition (chronic renal insufficiency, heart failure, diabetes, use of diuretics) to NSAID-induced functional renal impairment. Apart from one patient, nimesulide was taken for a very short time (less than 8 days). A favorable outcome ensued after withdrawal of therapy in aU patients. The acute deterioration of renal function described in these patients pointed to hemodynamically mediated renal impairment in all cases, with the exception of one man in whom interstitial nephritis was suspected. 

The actual risk of NSAID-associated acute renal dysfunction also continues to be the subject of controversy. There is adequate evidence that underlying renal insufficiency, congestive heart failure, or hepatic cirrhosis are conditions that carry a high risk of NSAID-related renal functional impairment. It is still not known whether old age is a risk factor, whether the risk of renal impairment varies with different NSAIDs, or whether renal function continues to deteriorate, stabilize, or even improve in affected patients with continued use of NSAIDs. Three cases of renal insufficiency caused by topical NSAIDs have been described (SEDA-18,100). 

In recent years, however, several case reports have been published, suggesting an association between the use of 5-ASA and the development of a particular type of chronic tubulo-interstitial nephritis, characterized by an important cellular infiltration of the interstitium [26, 27]. In some cases, it was shown that this cellular infiltration was not disappearing upon arrest of the drug, even after a period of more than one year [28]. Although acute renal failure under non-steroidal antiinflammatory drugs (NSAID) is well documented, the risk for developing chronic lesions remains controversial. 

Tubulointerstitial nephritis can be either acute or chronic in nature. Acute interstitial nephritis is characterized by an acute renal interstitial inflammatory response with urinary eosinophils and nonoliguric acute renal failure. The more common drugs that induce acute interstitial nephritis include penicillins, rifampicin, sulfonamides, and cimetadine. Chronic tubulointerstitial nephritis is most commonly associated with the long term use of large amounts of analgesics and antiinflammatory agents (e.g., NSAIDs). 

The National Kidney Foundation strongly discourages the use of over-the-counter combination analgesic products (e.g., acetaminophen and NSAIDs) because this is associated with an increased prevalence of renal failure. Finally, patients should be warned about potential toxicity if they inadvertently ingest more than the recommended dose when using both nonprescription and prescription products containing acetaminophen. 

NSAIDs are associated with sodium and potassium retention, acute renal failure, interstitial nephritis, and analgesic nephropathy. 

The cases of renal impairment cited emphasise the need to monitor renal function in patients on ACE inhibitors and diuretics. If increases in blood urea and creatinine occur, a dosage reduction and/or discontinuation of the diuretic and/or ACE inhibitor may be required. In a statement, the American Heart Association comments that acute renal failure complicating ACE inhibitor therapy is almost always reversible and repletion of extracellular fluid volume and discontinuation of diuretic therapy is the most efTective approach. In addition, withdrawal of interacting drugs, supportive management of fluid and electrolytes, and temporary dialysis, where indicated, are the mainstays of therapy. Combined use of ACE inhibitors, diuretics and NSAIDs may be particularly associated with an increased risk of renal failure, see ACE inhibitors + NSAIDs , p.28. 

Alcohol may increase the risk of gastrointestinal haemorrhage associated with NSAIDs. The skills related to driving are impaired by indometacin and phenylbutazone and this is made worse if patients drink alcohol while taking phenylbutazone, but this does not appear to occur with indometacin. A few isolated reports attribute acute renal failure to the concurrent use of NSAIDs and acute excessive alcohol consumption. 

Syndromes of renal failure associated with NSAID... 

Acute renal failure associated with NSAID falls into several categories (1) acute interstitial nephritis with glomerular abnormalities, (2) functional acute renal failure, probably haemodynamic in nature, (3) papillary necrosis, and (4) phenylbutazone anuria. 

Meloxicam is only available in oral formulations. An IV formulation is not available for human use but has been employed for pain management in veterinary medicine. Despite studies demonstrating improved tolerability, meloxicam, like other NSAIDs, is associated with the potential for serious gastrointestinal and wound site bleeding. Treatment with meloxicam may worsen renal function or precipitate acute renal failure. 

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the clearance of MTX (121). However, the effect is relatively small and does not appear to have a clinically significant effect (118,122,123). Conversely, if NSAIDs induce acute renal failure, high levels of MTX and toxicity can be encountered. We have observed two patients who developed severe MTX-induced leukopenia associated with NSAID-induced renal failure. 

---