Papillary necrosis

NSAIDs can cause renal insufficiency when administered to patients whose renal function depends on prostaglandins. Patients with chronic renal insufficiency or left ventricular dysfunction, the elderly, and those receiving diuretics or drugs that interfere with the renin-angiotensin system are particularly susceptible. Decreased glomerular filtration also may cause hyperkalemia. NSAIDs rarely cause tubulointerstitial nephropathy and renal papillary necrosis. 

Genitourinary Renal papillary necrosis, hematuria, hyposthenuria, proteinuria, nephritic syndrome, tubular dysfunction,... 

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... 

Acute exposure of rats to high concentrations (up to 40,000 ppm) has resulted in convulsions, pulmonary edema, respiratory arrest, and death. In rats repeatedly exposed at 600 ppm, death was attributed to renal papillary necrosis renal toxicity was not present in rabbits similarly exposed. Exposure of rabbits to 300 or 600 ppm resulted in convulsions and hyperactivity, moderate inflammation of nasal tissues, and some inflammation of the trachea or bronchi. Subchronic studies found that rats exposed at 3 00 ppm had mottled incisor teeth, minimal renal effects, pulmonary histiocytosis, inflammation of nasal tissues, and cerebral vacuolation. 

Renal effects Acute renal insufficiency, interstitial nephritis with hematuria, nephrotic syndrome, proteinuria, hyperkalemia, hyponatremia, renal papillary necrosis, and other renal medullary changes may occur. 

Adverse effects that are not unequivocally related to inhibition of prostaglandin synthesis include hepatic effects (hepatitis, hepatic necrosis, cholestatic jaundice, increased serum aminotransferases), dermal effects (photosensitivities, Stevens-Johnson syndrome, toxic epidermal necrolysis, onycholysis), central nervous system (CNS) effects (headaches, dizziness, tinnitus, deafness, drowsiness, confusion, nervousness, increased sweating, aseptic meningitis), ocular effects (toxic amblyopia, retinal disturbances), and certain renal effects (acute interstitial nephritis, acute papillary necrosis). 

Hemolytic anemia and methemoglobinemia are very rare adverse events. Interstitial nephritis and papillary necrosis—serious complications of phenacetin—have not occurred nor has gastrointestinal bleeding. Caution is necessary in patients with any type of liver disease. 

Brix AE Renal papillary necrosis. Toxicol Pathol 2002 30 672. [PMID 12512867]... 

Degenerative changes occur in many organs of rats after administration of aziridine by various routes, including inhalation (lARC, 1975). Acute renal papillary necrosis is produced in rats and dogs administered aziridine. At low doses in rats, there was necrosis of interstitial cells, thin limbs of the loops of Henle and vasa recta, while collecting ducts were spared. At higher doses, there was total papillary necrosis (Ellis et al., 1973 Ellis Price, 1975 Axelsen, 1978). 

Axelsen, R.A. (1978) Experimental renal papillary necrosis in the rat the selective vulnerability of medullary structures to injury. Virchows Arch. A. Pathol. Anal, 381,79-84... 

Ellis, B.G. Price, R.G. (1975) Urinary enzyme excretion during renal papillary necrosis induced in rats with ethyleneimine. Chem.-biol. Interact., 11, 473-482... 

Hemolytic anemia and methemoglobinemia, reported with the use of phenacetin, are rarely noted with acetaminophen. Interstitial nephritis and papillary necrosis—serious complications of phenacetin—although anticipated with widespread chronic use of acetaminophen, have not occurred. Gastrointestinal bleeding does not occur. Caution should be exercised in patients with liver disease. 

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). 

S.D. Lenz, and W.W. Carlton, Diphenylamine-induced renal papillary necrosis and necrosis of the pars recta in laboratory rodents. Vet. Pathol. 27 71-178, 1990. 

Small numbers of lipid droplets (representing neutral lipid, lipoprotein or phospholipid) are considered normal in dogs, cats, mice and humans (Gross et al. 1991 Streather et al. 1993 Finco 1997). Increased excretion of lipid droplets (which may cause increased urine turbidity) may indicate glomerular injury (de Mendoza et al. 1976 Gherardi and Calandra 1982). Increased urinary phospholipid excretion (confirmed by thin layer chromatography) may indicate early papillary injury/renal papillary necrosis in rodents (Thanh etal. 2001). 

Thanh NTK, Stevenson G, Obatomi DK et al. (2001) Urinary lipid change during the development of chemically induced renal papillary necrosis. A study using mefenamic acid and N-phenylantranihc acid. Biomarkers 6 417-427 Weingand K, Brown G, Hall R et al. (1996) Harmonization of animal clinical pathology testing in toxicity and safety studies. Fund Appl Toxicol 29 198-201... 

In laboratory animals, papillary necrosis due to non-narcotic analgesic has been extremely difficult to produce. However, papillary necrosis has been demonstrated following administration of 2-bromoethylamine 2-bromoethylamine has been used to demonstrate the role of urinary concentrating mechanisms in the etiology of 2-bromoethylamine-induced papillary necrosis. Maneuvers that produce large volumes of dilute urine, such as diuretic therapy, lack of antidiuretic hormone (Brattleboro rats), or volume expansion with 5% glucose, prevent papillary necrosis due to... 

Rodenticide A pesticide or other agent used to kill rats and other rodents or to prevent them from damaging food, crops, or forage RPN Renal papillary necrosis RRRs (3R) Reduce, reuse, and recycle RUP See Restricted-use pesticide... 

Large doses of acetaminophen can cause renal and hepatic toxicity in rats and mice. Toxicity is characterized by renal tubular necrosis in the proximal tubules (Schnellmann, 2001). Acetaminophen toxicity has also been reported in humans. Generally, toxicosis is a result of large overdoses which result in proximal tubular necrosis. Aspirin, ibuprofen, and acetaminophen are the important analgesics, which are reported to cause toxicosis in veterinary medicine. Renal lesions including renal tubular necrosis and papillary necrosis have been reported in dogs. 

Gunson, D.E., Soma, L.R. (1983). Renal papillary necrosis in horses after phenylbutazone and water deprivation. Vet. Pathol. 20(5) 603-10. 

Renal papillary necrosis and interstitial nephritis with the nephrotic syndrome have been documented (27,28). Other cases of the nephrotic syndrome, with or without renal insufficiency, which were apparently due to minimal-change nephropathy (which is relatively more common in NSAID users), have been reported (29,30). The unusual feature of diclofenac-associated renal interstitial mucinosis has been described (SEDA-17, 109). 

Interstitial nephritis with the nephrotic sjmdrome and one case of renal papillary necrosis have been recorded (SEDA-12, 86) (SEDA-17, 110). Flurbiprofen can cause a membranous nephropathy (SEDA-21,105). 

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