Protective Effects of Reducing Renal Ischemia-reperfusion Injury During Renal Hilar Clamping: Use of Allopurinol as a Nephroprotective Agent

Keel, Christopher; Wang, Zijun; Colli, Janet; Grossman, Leah; Majid, Dewan S. A.; Lee, Benjamin R.

doi:10.1016/j.urology.2012.08.016

Cited by 16 publications

(9 citation statements)

References 18 publications

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“…The protective effect of the Allopurinol on the kidney as evidenced by decreased levels of Cystatin C and NGAL was statistically significant beginning at 30 minutes after reperfusion. Our findings are congruent with previous studies demonstratiting the benefits of Allopurinol in guarding against ischemia and reperfusion injuries, 10 and in animal studies involving transplant kidneys, those pretreated with allopurinol have been shown to suffer less damage from ischemia. 15 It is believed that xanthine oxidase may give rise to free radicals during ischemia-repurfusion injury; allopurinol is an inhibitor of xanthine oxidase.…”

Section: Discussionsupporting

confidence: 92%

Urinary Cystatin C and NGAL as Early Biomarkers for Assessment of Renal Ischemia-Reperfusion Injury: A Serum Marker to Replace Creatinine?

Woodson¹,

Wang²,

Mandava³

et al. 2013

Journal of Endourology

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Introduction and ObjectiveAcute kidney injury is the result of many potential factors: acute obstructive uropathy, nephrotoxic medications, hypovolemia, urosepsis, intrinsic factors such as glomerulonephritis, acute tubular necrosis or renal surgery and post obstructive causes such as benign prostatic hyperplasia, calculus disease or obstruction. Partial nephrectomy for renal cell carcinoma usually involves temporarily clamping the renal artery, rendering the kidney ischemic during tumor resection. While decreasing hemorrhage and improving visualization of the resection site, the tradeoff is exposing the kidney to effects of warm ischemia and reperfusion injury. Currently, predominate methods of assessing global renal function include measuring serum creatinine and in turn, estimating glomular filtration rate. In a patient with a normal contralateral kidney, serum creatinine measurement may appear normal due to systemic measurements.Urinary cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) represent potential early biomarkers of acute kidney injury. Our hypothesis was to first determine if urinary cystatin C and NGAL levels can quantitate renal damage secondary to warm ischemia through experiments on in a solitary kidney animal model. A second goal was to investigate use of allopurinol for renoprotective abilities in this same animal model, using cystatin C and NGAL findings to quantify the protective effects.Finally, we evaluated the clinical utility of cystatin C in a clinical series of patients who underwent robotic partial nephrectomy. Our hypothesis was that cystatin C could be used as a clinical biomarker following surgery to assess acute kidney injury post operatively. Unfortunately, our hospital lab does not have the ability to quantitate NGAL levels, and thus only Cystatin C was studied in our surgical population.

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Section: Discussionsupporting

confidence: 92%

Urinary Cystatin C and NGAL as Early Biomarkers for Assessment of Renal Ischemia-Reperfusion Injury: A Serum Marker to Replace Creatinine?

Woodson¹,

Wang²,

Mandava³

et al. 2013

Journal of Endourology

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“…The 8-isoprostane levels were lower in the group treated with allopurinol, thus denoting a reduction in oxidative stress in that group. A later study by Keel et al 6 reported similar findings, which led us to believe that the protective effect of allopurinol manifests when ischaemia lasts longer than 60 minutes.…”

Section: Effect Of Allopurinol On the Kidney Function Histology And mentioning

confidence: 62%

“…Xanthine According to some studies, allopurinol and its active metabolite oxipurinol exhibit a protective effect against myocardial ischaemia-reperfusion injury 5 . The specific mechanism underlying this effect has not yet been elucidated; however, it is believed to involve the inhibition of XO 6 .…”

Section: Introductionmentioning

confidence: 99%

Effect of allopurinol on the kidney function, histology and injury biomarker (NGAL, IL 18) levels in uninephrectomised rats subjected to ischaemia-reperfusion injury

et al. 2014

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PURPOSE:To investigate whether allopurinol exerts a protective effect on kidneys by measuring new kidney injury biomarkers (NGALp, NGALu, KIM-1 and IL-18) and analysing the renal function and histology in uninephrectomised rats subjected to ischaemia-reperfusion injury. CONCLUSION: Allopurinol did not exert protective or damaging effects on the kidneys of rats subjected to ischaemia-reperfusion injury. METHODS:

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“…Several studies have shown that allopurinol, a non-selective purine analogue XO inhibitor, has renoprotective effects [22,23]. These beneficial effects were hypothesized to be due to reduced plasma uric acid levels, because uric acid itself has been shown to generate oxidative stress in adipocytes, vascular endothelial cells, and vascular smooth muscle cells [24,25,26].…”

Section: Discussionmentioning

confidence: 99%

Febuxostat Ameliorates Diabetic Renal Injury in a Streptozotocin-Induced Diabetic Rat Model

Lee

Jeong²,

Kim³

et al. 2014

Am J Nephrol

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Background: Oxidative stress and inflammation are known to play central roles in the development of diabetic nephropathy (DN). Febuxostat is a novel non-purine xanthine oxidase (XO)-specific inhibitor developed to treat hyperuricemia. In this study, we investigated whether febuxostat could ameliorate DN via renoprotective mechanisms such as alleviation of oxidative stress and anti-inflammatory actions. Methods: Male Sprague-Dawley rats were divided into three groups: a normal group, a diabetes group (DM group), and a febuxostat-treated diabetes group (DM+Fx group). We administered 5 mg/kg of febuxostat to experimental rats for 7 weeks and evaluated clinical and biochemical parameters and XO and xanthine dehydrogenase (XDH) activity in hepatic tissue. The degree of oxidative stress and extent of inflammation were evaluated from urine samples and renal tissue collected from each group. Results: Diabetic rats (DM and DM+Fx groups) had higher blood glucose and kidney weight relative to body weight than normal rats. Albuminuria was significantly reduced in febuxostat-treated diabetic rats compared with untreated diabetic rats. Quantitative analysis showed that hepatic XO and XDH activities were higher in the DM groups, but decreased after treatment with febuxostat. Urinary 8-OHdG concentrations and renal cortical nitrotyrosine also indicated reduced oxidative stress in the DM+Fx group relative to the DM group. The number of ED-1-stained cells in the glomerulus and tubule of diabetic renal tissue decreased in febuxostat-treated diabetic rats relative to that of non-treated diabetic rats. Diabetic rats also expressed higher transcript levels of inflammatory genes (E-selectin and VCAM-1), an inflammation-induced enzyme (COX-2), and inflammatory mediators (ED-1 and NF-κB) than control rats; expression of these genes was significantly reduced by treatment with febuxostat. Conclusions: Febuxostat prevents diabetic renal injury such as albuminuria. This renoprotective effect appears to be due to attenuation of the inflammatory and oxidative effects of diabetes-induced renal damage through inhibition of XO and XDH activities.

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Protective Effects of Reducing Renal Ischemia-reperfusion Injury During Renal Hilar Clamping: Use of Allopurinol as a Nephroprotective Agent

Cited by 16 publications

References 18 publications

Urinary Cystatin C and NGAL as Early Biomarkers for Assessment of Renal Ischemia-Reperfusion Injury: A Serum Marker to Replace Creatinine?

Urinary Cystatin C and NGAL as Early Biomarkers for Assessment of Renal Ischemia-Reperfusion Injury: A Serum Marker to Replace Creatinine?

Effect of allopurinol on the kidney function, histology and injury biomarker (NGAL, IL 18) levels in uninephrectomised rats subjected to ischaemia-reperfusion injury

Febuxostat Ameliorates Diabetic Renal Injury in a Streptozotocin-Induced Diabetic Rat Model

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