Severe allopurinol hypersensitivity. Association with thiazides and prior renal compromise

Young, J. L.

doi:10.1001/archinte.134.3.553

Cited by 63 publications

(32 citation statements)

References 21 publications

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“…A rare form of allopurinol nephrotoxicity directed at glomeruli has been described in patients and is characterized by a diffuse vasculitis and glomerular crescent formation. 23 ' 24 A similar pattern of renal parenchymal damage has been observed in a model of chronic renal failure after 5/6 nephrectomy, in which there is a better correlation between the level of renal function and the extent of tubulointerstitial injury than to the degree of glomerular damage. 25 An explanation for the enhanced toxicity of allopurinol in the hypertensive rats compared with normotensive controls is not apparent from these experiments.…”

Section: Discussionmentioning

confidence: 65%

Nephrotoxicity of allopurinol is enhanced in experimental hypertension.

1991

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Hyperuricemia is present in 20-40% of pediatric and adult patients with essential hypertension. This metabolic abnormality may represent an additional risk factor for the development of cardiovascular disease. Therefore, we performed the following studies to determine 1) whether hyperuricemia is more prevalent in the spontaneously hypertensive rat (SHR) and 2) whether allopurinol treatment has a beneficial effect on the development of hypertension in this strain, based on its capacity to lower the serum uric acid concentration and to act as an antioxidant agent SHR and control Wistar-Kyoto (WKY) rats were assigned to two groups, one given tap water to drink and the other provided water containing allopurinol (400 mg/1) to furnish an approximate daily dose equal to 100 mg/kg body wt. This treatment was maintained for 15 weeks. The serum uric acid levels were similar in untreated SHR and WKY rats (1.85±0.10 versus 1.66±0.14 mg/dl; p=0.2S). In the control WKY rat strain, allopurinol therapy did not adversely affect weight gain or hematocrit and did not cause an increase in mortality. It resulted in a moderate decrement in kidney function (creatinine clearance: allopurinol-treated group 0.32 ±0.09 versus control group 0.46±0.04 ml/min/100 g body wt, in conjunction with mild-to-moderate tubulointerstitial inflammation (allopurinol-treated group 0.9 ±0.4 versus control group 0). In contrast, administration of allopurinol to SHR resulted in failure to thrive, marked anemia, severe azotemia (creatinine clearance: allopurinol-treated group 0.04 ±0.01 versus control group 0.39±0.04 ml/min/100 g body wt; p<0.001), and severe tubular atrophy and interstitial fibrosis (allopurinol-treated group 2.2±0.2 versus control group 0;p<0.001). These findings indicate that hyperuricemia is not more prevalent in the SHR. Furthermore, allopurinol administration is associated with markedly increased nephrotoxicity characterized by severe tubulointerstitial injury, azotemia, and impaired growth. (Hypertension 1991;17:194-202)

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Section: Discussionmentioning

confidence: 65%

Nephrotoxicity of allopurinol is enhanced in experimental hypertension.

1991

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“…1,6 In fact, AHS may have been avoided in our patient with renal insufficiency if the allopurinol dosage had been reduced appropriately, based on creatinine clearance as described by Hande et al 5 In addition, most patients who develop AHS do not have an appropriate indication for allopurinol treatment. 1 We are unaware of any reports in the literature of elevations in transient pancreatic exocrine enzyme level associated with pancreatic endocrine insufficiency in the setting of AHS.…”

Section: Commentmentioning

confidence: 93%

“…6,7 In addition, thiazide diuretics are a known cause of drug-induced pancreatitis. 8 Our patient's dramatic increase in serum lipase and amylase levels with a concurrent increase in abdominal pain were consistent with acute pancreatitis.…”

Section: Commentmentioning

confidence: 99%

“…10 In conclusion, we describe a case of AHS with unique features including concurrent development of elevations in transient pancreatic exocrine enzymelevelandnew-onsettype1dia-betes mellitus. Acute pancreatitis, while rarely associated with AHS, occurred 6,7 and may have led to endocrineinsufficiencyinourpatient.However, the absence of any evidence for pancreatitis on imaging scans and numerousreportsintheliteratureoftransient elevations in exocrine enzyme level with a rapid onset of diabetes mellitus suggests otherwise. Perhaps AHS induced an immune-mediated pan-pancreatopathy with irreversible ␤-cell injury.…”

Section: Commentmentioning

confidence: 99%

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Allopurinol Hypersensitivity Syndrome Associated With Pancreatic Exocrine Abnormalities and New-Onset Diabetes Mellitus

Sommers

Schoene

2002

Arch Intern Med

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“…Weltweit werden etwa 240 Millionen Einzeldosen pro Jahr verbraucht (10). Es ist bekannt, dass Allopurinol Auslöser schwerer und zum Teil tödlicher Hypersensitivitätsreaktionen, insbesondere bei Patienten mit vorbestehender Nierenerkrankung sein kann (20).…”

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Hypersensitivitätssyndrom unter Therapie mit Allopurinol bei asymptomatischer Hyperurikämie mit tödlichem Ausgang

Hammer

Link²,

Wagner³

et al. 2001

Dtsch med Wochenschr

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The life threatening hypersensitivity syndrome with fever, eosinophilia, hepatitis, renal failure and skin eruptions as severe as epidermal necrolysis is the most dangerous complication of therapy with allopurinol. The trigger seems to be oxipurinol, the main metabolite of allopurinol, which particularly accumulates in patients with renal failure and concomitant therapy with thiazides. There is no specific treatment of the disease. The use of allopurinol in patients with asymptomatic hyperuricaemia is not indicated in most cases. Dose adjustment according to the clearance of creatinine is mandatory.

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Severe allopurinol hypersensitivity. Association with thiazides and prior renal compromise

Cited by 63 publications

References 21 publications

Nephrotoxicity of allopurinol is enhanced in experimental hypertension.

Nephrotoxicity of allopurinol is enhanced in experimental hypertension.

Allopurinol Hypersensitivity Syndrome Associated With Pancreatic Exocrine Abnormalities and New-Onset Diabetes Mellitus

Hypersensitivitätssyndrom unter Therapie mit Allopurinol bei asymptomatischer Hyperurikämie mit tödlichem Ausgang

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