Porphyrias and the Kidney

Day, R.S.; Eales, L; Disler, Peter

doi:10.1159/000182215

Cited by 36 publications

(20 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the presented model allows evaluation of both hepatic and renal porphyrin biosynthesis, in this respect, it is interesting to note the high kidney porphyrin content in oxadiazon-treated rats ( fig. 1), as well as the possible contribution of the kidney to porphyrin excretion in porphyria (Day et al 1981). Also, the intact rodent model accurately reproduces the excretion pattern of human acute porphyrias, a positive result is indicated not only by elevated levels of porphyrins, but also by increased accumulation and excretion of porphobilinogen and 5-aminolevulinic acid.…”

Section: Discussionmentioning

confidence: 75%

Effect of Tiagabine and Topiramate on Porphyrin Metabolism in an in vivo Model of Porphyria

Krijt

Krijtová

Sanitrák

2001

Pharmacology & Toxicology

View full text Add to dashboard Cite

Administration of many antiepileptic drugs to patients with porphyria can precipitate an acute porphyric crisis. Information on the porphyrogenic activity of new antiepileptic drugs is still limited. In the presented study, the effects of tiagabine and topiramate on porphyrin metabolism were evaluated in an in vivo model of porphyria. Administration of the protoporphyrinogen oxidase inhibitor oxadiazon (12.5 mg/kg/day) for four days to male Wistar rats caused a partial block of porphyrin biosynthesis, thus mimicking the condition of quiescent variegate porphyria. Administration of phenobarbital (75 mg/kg/day) to oxadiazon-pretreated rats increased liver porphyrin content, liver porphobilinogen content (means 480 nmol/g, control less than 20 nmol/g) and urinary excretion of porphobilinogen (means 1000 mmol/l, control less than 20 mmol/l). Tiagabine (75 mg/kg/day) and topiramate (75 mg/kg/day) increased liver porphobilinogen content (means 33 and 53 nmol/g respectively) and urinary porphobilinogen concentration (240 and 490 mmol/l respectively). Similar results were obtained in oxadiazon-treated BALB/c mice. In untreated rats, tiagabine and topiramate caused a moderate increase of hepatic pentoxyresorufin-O-dealkylase activity (approximately 100 and 200 pmol/min./mg respectively, controls 15 pmol/min./mg). These data demonstrate that administration of tiagabine or topiramate to oxadiazontreated animals can provoke a condition resembling an acute porphyric attack and suggest that administration of these drugs to patients with suspected porphyria should be avoided. However, 5-day administration of both tiagabine and topiramate (75 mg/kg) is considerably less porphyrogenic than phenobarbital administered at the same dose.

show abstract

Section: Discussionmentioning

confidence: 75%

Effect of Tiagabine and Topiramate on Porphyrin Metabolism in an in vivo Model of Porphyria

Krijt

Krijtová

Sanitrák

2001

Pharmacology & Toxicology

View full text Add to dashboard Cite

show abstract

“…There is also disagreement on whether pseudoporphyria has a completely normal porphyrin profile or may have elevated plasma porphyrins in the setting of renal failure. [10][11][12][13] Plasma porphyrins may increase because of impaired excretion of these molecules and inefficient clearance by dialysis since porphyrins have too high molecular weight to be cleared by the hemodialysis membrane. Thus, it is better to investigate patients' porphyrin profile by fractionation of fecal porphyrins.…”

Section: Discussionmentioning

confidence: 99%

Pseudoporphyria Associated with Chronic Renal Failure: The Outcome from Oral N-Acetylcysteine Treatment in Three Cases

Ada¹,

Şenel²

2012

Turkiye Klinikleri J Med Sci

View full text Add to dashboard Cite

1122 seudoporphyria is a rare and acquired bullous disorder with clinical and histopathological features similar to those of porphyria cutanea tarda (PCT) despite a normal porphyrin metabolism. It is associated with chronic renal failure, excessive sun exposure and numerous medications such as furosemide, hydrochlorothiazide, tetracycline and naproxen. 1 So far, there has been no specific treatment for pseudoporphyria, although sun protection and discontinuation of the offending drugs may provide some benefit.Oral N-acetylcysteine has recently been reported as an effective treatment option in five cases. [2][3][4][5][6] This paper was aimed to share our experience on and present outcome of N-acetylcysteine treatment option in three pseudoporphyria patients associated with chronic renal failure. Pseudoporphyria Associated with ChronicRenal Failure: The Outcome from Oral N-Acetylcysteine Treatment in Three Cases A AB BS ST TR RA AC CT T Pseudoporphyria is a rare and acquired bullous disorder with clinical and histopathological features identical to porphyria cutanea tarda, despite a normal porphyrin metabolism. It is associated with chronic renal failure, excessive sun exposure and various medications. There is no specific treatment for pseudoporphyria, but sun protection and discontinuation of the offending drugs may provide some benefit. Oral N-acetylcysteine has recently been reported as an effective treatment option in five cases in the literature. Here, we described our experience with N-acetylcysteine treatment in three patients with pseudoporphyria due to chronic renal failure. K Ke ey y W Wo or rd ds s: : Kidney failure, chronic; therapy; acetylcysteine Ö ÖZ ZE ET T Psödoporfiri, klinik ve histopatolojik olarak porfiriya kutanea tardaya benzeyen, ancak porfirin metabolizmasının normal olduğu, nadir görülen, edinsel, büllöz bir deri hastalığıdır. Kronik böbrek yetmezliği, aşırı güneş maruziyeti ve çeşitli ilaçlarla ilişkilendirilmektedir. Psödoporfirinin spesifik bir tedavisi olmamakla birlikte, güneşten korunma ve sorumlu ilacın kesilmesi kısmi yarar sağlayabilmektedir. Literatürde, yakın zamanda beş olguda oral N-asetilsistein'in etkili bir tedavi seçeneği olabileceği bildirilmiştir. Burada kronik böbrek yetmezliği zemininde gelişen üç psödoporfiri olgusunda oral N-asetilsistein tedavi deneyimimizi sunmaktayız. Ya zış ma Ad re si/Cor res pon den ce:

show abstract

“…Stimulation of hepatic heme synthesis (e.g., by certain drugs) in the absence of deficiency of any heme-synthesis enzymes can lead to increased coproporphyrin excretion. The kidney (primarily the epithelium of the proximal tubules) has been identified as a major source of porphyrins (primarily coproporphyrin) in the urine of normal and porphyric individuals as well as leadand mercury-poisoned individuals (84)(85)(86)(87) (99,100); others noted the presence of abdominal colic and muscle weakness during the acute phase (102). Follow-up studies up to 30 years later reported that a majority of the patients studied had cutaneous residua, arthritic deformities, thyromegaly (particularly in women), and neurologic manifestations including weakness, paresthesias, and sensory shading; smaller proportions of patients had myotonia or cogwheel rigidity without other extrapyramidal signs (103)(104)(105)(106).…”

Section: Porphyrias With Neurologic Manifestationsmentioning

confidence: 99%