Renal Papillary Necrosis

Brix, Amy E.

doi:10.1080/01926230290166760

Cited by 49 publications

(29 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been suggested that the renal papilla of rats and dogs are more susceptible to xenobiotic insult due to sluggish regional blood flow that may predispose to COX-mediated ischemia. The interstitial cells of the renal papilla in the dog and rat have similar expression levels of COX-1 and COX-2, and may be the earliest targets of NSAID inhibition (Brix, 2002). While monkeys developed some renal lesions after treatment, these were attributable to the precipitation of the drug into the renal tubules, and have been previously described (Leach et al, 1999) and were not likely pharmacologically mediated.…”

Section: Discussionmentioning

confidence: 95%

“…RPN caused by NSAIDs in humans is rare, and is often associated with concomitant factors such as heart disease, hypertension, and dehydration (Brix, 2002). In contrast to humans, the renal medullary arterial blood flow is entirely postglomerular in laboratory animals, therefore changes in glomerular perfusion have effects not only at the cortical level, but also at the medullary level (Brix, 2002;Khan and Alden, 2002). The mechanisms of renal papillary necrosis are uncertain, but are believed to be at least in part due to decreased renal blood flow.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Interspecies Differences in the Nephrotoxic Response to Cyclooxygenase Inhibition

Sellers¹,

Senese²,

Khan³

2004

Drug and Chemical Toxicology

View full text Add to dashboard Cite

In contrast to cyclooxygenase-1 (COX-1), the basal expression of renal cyclooxygenase-2 (COX-2) varies among species. High basal levels of COX-2 in the renal cortex and papilla in dogs compared with monkeys suggest that COX-2 inhibition may lead to distinct nephrotoxic responses. In this study, we compared the renal effects of COX inhibition between dogs and cynomolgus monkeys (n = 6/group) following the administration of naproxen sodium, a non-selective COX-1/COX-2 inhibitor. Dogs and monkeys were treated with 50 or 150 mg/kg/day naproxen sodium, respectively, for 2 to 6 weeks. Naproxen doses used in this study resulted in equivalent inhibition of COX activity in both species as measured by reductions in urinary prostaglandin E2 (PGE2) and 6-keto-PGF1-alpha levels. There was prominent reduction in renal blood flow (43%) and urinary sodium excretion (62%) in dogs but no alterations in renal blood flow and only minimal change (19%) in urinary sodium excretion in monkeys. The canine but not monkey kidney showed prominent COX-2 expression in the macula densa, thick ascending limb of Henle and papillary interstitial cells by immunohistochemistry. After treatment, the canine but not monkey kidneys had mild to moderate renal tubular atrophy and interstitial fibrosis and renal papillary necrosis. Obstructive nephropathy secondary to intra-tubular drug accumulation was seen in monkeys but not in dogs. Collectively, these data demonstrate species differences in the renal response to COX inhibition. The nature of functional and morphologic changes suggests a more prominent role of COX-2 in renal hemodynamics and natriuresis in dogs than in monkeys.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Interspecies Differences in the Nephrotoxic Response to Cyclooxygenase Inhibition

Sellers¹,

Senese²,

Khan³

2004

Drug and Chemical Toxicology

View full text Add to dashboard Cite

show abstract

“…Ultimately, these patients may develop hypertension, cardiac disease, and chronic renal failure. 3,7 In this case, the patient presented with some of these symptoms: general malaise, gastrointestinal complaints, irritative voiding symptoms, and renal colic; however, her imaging was highly unusual as it appeared as an obstructing bladder mass most consistent with an invasive malignancy. As her RPN progressed, the sloughed debris obstructed her left ureter that resulted in renal colic.…”

Section: Discussion and Literature Reviewmentioning

confidence: 90%

“…1 Still, it is likely that several different pathways are at play depending on the underlying cause, and that RPN represents a final common pathway of multiple courses. 1,7–9 Our patient had known diabetes that likely represented her biggest risk factor for RPN. Furthermore, her history of recurrent UTI raises the question of subclinical pyelonephritis preceding her presentation and further increasing her risk for papillary necrosis.…”

Section: Discussion and Literature Reviewmentioning

confidence: 95%

Renal Papillary Necrosis Appearing as Bladder Cancer on Imaging

Dagrosa

Ghali

Gormley

2016

Journal of Endourology Case Reports

View full text Add to dashboard Cite

A 79-year-old woman with a history of diabetes mellitus and recurrent urinary tract infections (UTIs) presented with acute onset left lower quadrant pain, left-sided back pain, vomiting, and dysuria. Abdominopelvic CT scan revealed left hydroureteronephrosis to the level of the left ureterovesical junction (UVJ) where a bladder mass appeared to be obstructing the left ureteral orifice. The obstruction was ultimately found to be the result of a sloughed renal papilla lodged in the distal ureter, which created an inflammatory mass at the UVJ. Her history of diabetes and frequent UTIs likely predisposed her to the development of renal papillary necrosis (RPN) that resulted in sloughing of a renal papilla, distal ureteral obstruction with subsequent bladder inflammation that mimicked a bladder mass on imaging. RPN is a condition associated with many etiologies and likely represents a common final pathway of several diseases. Although several hypotheses exist, it is primarily thought to be ischemic in nature and is related to the underlying physiology of the renal papillae. We present a case of hydroureteronephrosis and bladder mass secondary to a sloughed renal papilla from RPN.

show abstract

“…In preclinical studies, almost all of the nonsteroidal anti-inflammatory drugs produced papillary necrosis in experimental animal models (Whelton and Hamilton, 1991). A possible mechanism of papillary necrosis is ischemic injury through the direct inhibition of cyclooxygenase-mediated production of prostaglandins (Brix, 2002). However, the inhibition of cyclooxygenase mediated by ZP might not contribute to ZP-induced kidney injury because papillary necrosis was not observed in this injury.…”

Section: Downloaded Frommentioning

confidence: 98%

Zomepirac Acyl Glucuronide Is Responsible for Zomepirac-Induced Acute Kidney Injury in Mice

Iwamura

Watanabe

Akai

et al. 2016

Drug Metabolism and Disposition

View full text Add to dashboard Cite

Glucuronidation, an important phase II metabolic route, is generally considered to be a detoxification pathway. However, acyl glucuronides (AGs) have been implicated in the toxicity of carboxylic acid drugs due to their electrophilic reactivity. Zomepirac (ZP) was withdrawn from the market because of adverse effects such as renal toxicity. Although ZP is mainly metabolized to acyl glucuronide (ZP-AG) by UDP-glucuronosyltransferase, the role of ZP-AG in renal toxicity is unknown. In this study, we established a ZP-induced kidney injury mouse model by pretreatment with tri-o-tolyl phosphate (TOTP), a nonselective esterase inhibitor, and L-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor. The role of ZP-AG in renal toxicity was investigated using this model. The model showed significant increases in blood urea nitrogen (BUN) and creatinine (CRE), but not alanine aminotransferase. The ZP-AG concentrations were elevated by cotreatment with TOTP in the plasma and liver and especially in the kidney. The ZP-AG concentrations in the kidney correlated with values for BUN and CRE. Upon histopathological examination, vacuoles and infiltration of mononuclear cells were observed in the model mouse. In addition to immune-related responses, oxidative stress markers, such as the glutathione/ disulfide glutathione ratio and malondialdehyde levels, were different in the mouse model. The suppression of ZP-induced kidney injury by tempol, an antioxidant agent, suggested the involvement of oxidative stress in ZP-induced kidney injury. This is the first study to demonstrate that AG accumulation in the kidney by TOTP and BSO treatment could explain renal toxicity and to show the in vivo toxicological potential of AGs.

show abstract

Renal Papillary Necrosis

Cited by 49 publications

References 24 publications

Interspecies Differences in the Nephrotoxic Response to Cyclooxygenase Inhibition

Interspecies Differences in the Nephrotoxic Response to Cyclooxygenase Inhibition

Renal Papillary Necrosis Appearing as Bladder Cancer on Imaging

Zomepirac Acyl Glucuronide Is Responsible for Zomepirac-Induced Acute Kidney Injury in Mice

Contact Info

Product

Resources

About