Fwd: NSAIDs and neuropathy/ from H

[Guest guest]

On the Trail of Analgesic Nephropathies

from WebMD Scientific American® Medicine

Posted 12/06/2002

L. Henrich, MD

As the number of new analgesics available for the treatment of inflammatory conditions has grown and as more of these medicines have become available on the over-the-counter market, there has been increasing concern about their potential effects on renal function. The adverse effects of analgesics on kidney function may be either acute or chronic, with chronic damage possibly taking years to develop. Data from laboratory models of this process have not been forthcoming, and this has hindered our understanding of the underlying pathophysiology.

Three general types of analgesic-associated nephropathy are most often described: nephropathy related to classic analgesics, to nonsteroidal anti-inflammatory drugs (NSAIDs), and to the new cyclooxygenase-2 (COX-2) inhibitors.

Classic analgesic nephropathy is characterized by the habitual and long-term consumption of analgesics over a period of years, as well as by tubulointerstitial nephritis. Most countries removed phenacetin from combination analgesic products by the early 1970s, after it became known that the use of phenacetin was associated with nephropathy. Acetaminophen was often substituted instead. This substitution has led to controversy over whether or not classic analgesic nephropathy was adequately addressed, because phenacetin is converted to acetaminophen in one pass through the liver.

There have been a relatively small number of case-control and patient follow-up studies performed over the past several decades to address this point. In the newest and best conducted of these, by Fored and colleagues,[1] a cohort of Swedish patients with chronic renal failure was studied. These individuals--identified on the basis of elevations in serum creatinine concentrations--were queried as to their analgesic histories, and they were compared with age- and gender-matched control patients. The results of this study suggested that the intake of analgesics (acetaminophen and aspirin) increased the risk of kidney disease.

The second form of analgesic-associated kidney disease is linked to the ingestion of nonselective inhibitors of prostaglandin synthesis--NSAIDs. These powerful and effective drugs have many therapeutic uses and are popular as over-the-counter agents. Unfortunately, they have been associated with acute renal failure syndromes in individuals whose effective arterial blood volume is decreased. Thus, patients who have congestive heart failure, cirrhosis, or nephrotic syndrome or who are recovering from major abdominal surgery may be at risk for developing acute renal failure after the ingestion of NSAIDs. These drugs also have an antirenin effect and, therefore, can produce hyperkalemia. Another interesting aspect of these drugs is their propensity to produce an interstitial nephritis characterized by heavy proteinuria--a condition that physicians must be alert for in their patients taking NSAIDs.

The newest class of anti-inflammatory and analgesic medicines are the selective COX-2 inhibitors. These drugs have been designed to inhibit the inducible form of cyclooxygenase, which is in part responsible for the inflammatory response. The renal side-effect profile of these drugs is not fully delineated, but there have been well-described cases of edema and acute renal failure following their ingestion. The overall incidence of these side effects is also not clear but appears to be somewhat less than that found with the nonselective NSAIDs. It is anticipated that in the next several years, the complete side-effect profile of these drugs will be known. For the present, selective COX-2 inhibitors should be used with caution in individuals who would be at risk for developing acute renal failure were they to use nonselective NSAIDs.

An ongoing study of the incidence of analgesic nephropathy in the United States is expected to be completed in the coming months. Its results should shed light on how large a problem classic analgesic nephropathy is in the United States today, and it should provide important information as to the specific analgesics and dosage regimens that are implicated in causing it. For the present, it is prudent to monitor renal function with the serum creatinine and urinalysis every 6 months in those individuals who require long-term analgesic treatment.

For more information, visit http://www.samed.com .