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Kidney Int. 2015 Aug;88(2):386-95. doi: 10.1038/ki.2015.97. Epub 2015 Apr 1.

High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

Author information

1
1] INSERM U1147, Centre Universitaire des Saints Pères, Paris, France [2] Service de Biochimie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France [3] Service de Néphrologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France [4] Université Paris Descartes, Paris, France.
2
1] INSERM U1147, Centre Universitaire des Saints Pères, Paris, France [2] Université Paris Descartes, Paris, France.
3
1] Centre Francais des Porphyries, Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris, Colombes, France [2] INSERM U1149, Center for Research on Inflammation (CRI), Site Bichat, Paris, France [3] Université Paris Diderot, Paris, France.
4
1] INSERM U1149, Center for Research on Inflammation (CRI), Site Bichat, Paris, France [2] Université Paris Diderot, Paris, France.
5
Service d'Anatomopathologie, Centre Hospitalo-Universitaire Charles Nicolle, Rouen, France.
6
1] Université Paris Descartes, Paris, France [2] Service d'Anatomopathologie, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France.
7
Service d'Anatomopathologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
8
1] INSERM U702, Paris, France [2] Université Pierre et Marie Curie, Paris, France.
9
1] Service de Néphrologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France [2] Université Paris Descartes, Paris, France.

Abstract

Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis.

PMID:
25830761
DOI:
10.1038/ki.2015.97
[Indexed for MEDLINE]

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