Kidney papillary necrosis

The most common adverse effects involve the GI system (gastritis, bleeding, and perforation), kidneys (renal papillary necrosis, reduced creatinine clearance [CLcr]), cardiovascular system (sodium and fluid retention, increased blood pressure), and CNS (impaired cognitive function, headache, dizziness). 

Glomerulonephritis, pyelonephritis, renal infarction, papillary necrosis, renal tumors, kidney stones Pyelonephritis, interstitial nephritis... 

These findings from special renal studies and the clinical trial data indicate that inhibition of Cox-2 does not eliminate the renal effects of NSAIDs because Cox-2-derived prostanoids are involved in normal renal function. However, the kidney contains considerably more Cox-1 than Cox-2, and the localization of the two isoforms is different It is not yet known whether the Cox-2 inhibitors will be safer in subgroups of patients prone to develop acute renal failure with NSAIDs, such as those patients with severe volume depletion, congestive heart failure, or hepatic cirrhosis with ascites (Bosch-Marce et al., 1999). Also, it is not known whether rare events, such as interstitial nephritis or papillary necrosis, will occur with long-term use of Cox-2 inhibitors, although studies in animals suggest that such events may be related to Cox-1 inhibition, since only Cox-1 is found in the papilla. Therefore, Cox-2 inhibitors may not produce these serious adverse effects (Khan etal., 1998). 

McCredie M, Stewart JH, Carter JJ, Turner J, Mahony JF. Phenacetin and papillary necrosis independent risk factors for renal pelvic cancer. Kidney Int 1986 30(1) 81-84. 

By definition, papillary necrosis represents the development of irreversible damage within the parenchyma of the renal papillae. The papillae of the kidney contain the tip portions of the long loops of Henle, together with the terminal portions of the collecting duct complexes, which open in to the minor calyces. The minor calyces of the kidneys representing the first location in the upper renal outflow tract into which mine is collected before it travels into the renal pelvis and into the urinary bladder via the ureters. 

The chronic progression of events that lead to NSAID/analgesic related papillary necrosis are well known since the days of the first descriptions of chronic combined analgesics abuse nephropathy and the subsequent extensive investigations which defined the consequences of chronic (5-20 years) exposure of the kidney to high doses of analgesic combinations such as salicylate and acetaminophen (the metabolite of phenacetin) often with the addition of caffeine [106]. 

Before introduction of hemodialysis in the treatment of chronic renal patients, the kidneys of patients who died of Balkan nephropathy used to be the smallest seen at post mortem examinations, weighing 14.8-80 g each (Figure 2A) the difference between the left and right kidneys being small (5-20 g) [74, 76-78]. Surface of the kidneys is smooth, occasionally wavy but never granulated or roughly nodular. The section shows markedly narrowed cortex, pyramid and Bertin s columns are fairly well preserved, and corticomedular border is well differentiated. Papillary necrosis of the pyramids has not been found. 

Papillary necrosis is a form of chronic interstitial nephritis characterized by necrosis of the renal papillae, which are the regions of the kidney where the collecting ducts enter the renal pelvis. Analgesic use is the most common cause of papillary necrosis, accounting for 36% of all cases. ... 

Segasothy M, Samad SA, Zulfigar A, Bennett WM. Chronic renal disease and papillary necrosis associated with long-term use of nonsteroidal anti-inflammatory drugs as the sole or predominate analgesic. Am J Kidney Dis 1996 24 17-24. 

Atta MG, Whelton A. Acute renal papillary necrosis induced by ibuprofen. Am J Ther 1996 4 55-60 Kincaid-Smith P. Effects of non-narcotic analgesics on the kidney. Drugs 1986 32(Suppl 4) 109-128. 

Bombard, E. M., F. W. FaUcenberg, and I. Loof. 1994. Changes in urinary enzymes and kidney-derived antigens after acute renal papillary necrosis in rats. Kidney International 47 (SuppL) 60-63. 

Bach, P. H., and T. L. Hardy. 1985. Relevance of animal models to analgesic-associated papillary necrosis in humans. Kidney International 28 605-613. 

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