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Hum Mol Genet. 2016 Sep 1;25(17):3784-3797. doi: 10.1093/hmg/ddw224. Epub 2016 Jul 19.

Progressive development of renal cysts in glycogen storage disease type I.

Author information

1
Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, France.
2
Université de Lyon, Lyon, France.
3
Université Lyon1, Villeurbanne, France.
4
APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Centre de référence des maladies héréditaires du métabolisme hépatique, Clamart, France.
5
Service de pathologie et de neuropathologie Est, Institut de Cancérologie des Hospices Civils de Lyon, Lyon, France.
6
VetAgro Sup, UPSP 2011-03-101, ICE, Marcy L'Etoile, France.
7
UMR 5305 CNRS/Université Claude-Bernard, Biologie tissulaire et Ingénierie thérapeutique, Lyon, France.
8
Exploration Fonctionnelle Rénale, Groupement Hospitalier Edouard Herriot, Hospices civils de Lyon, Lyon, France.
9
APHP, Hôpitaux Universitaires Paris Sud, Hôpital Antoine Béclère, Service de radiologie, Clamart, France.
10
Université Paris Sud, Orsay, France.
11
Institut National de la Santé et de la Recherche Médicale, U1213, Lyon, France fabienne.rajas@univ-lyon1.fr.

Abstract

Glycogen storage disease type I (GSDI) is a rare metabolic disease due to glucose-6 phosphatase deficiency, characterized by fasting hypoglycemia. Patients also develop chronic kidney disease whose mechanisms are poorly understood. To decipher the process, we generated mice with a kidney-specific knockout of glucose-6 phosphatase (K.G6pc-/- mice) that exhibited the first signs of GSDI nephropathy after 6 months of G6pc deletion. We studied the natural course of renal deterioration in K.G6pc-/- mice for 18 months and observed the progressive deterioration of renal functions characterized by early tubular dysfunction and a later destruction of the glomerular filtration barrier. After 15 months, K.G6pc-/- mice developed tubular-glomerular fibrosis and podocyte injury, leading to the development of cysts and renal failure. On the basis of these findings, we were able to detect the development of cysts in 7 out of 32 GSDI patients, who developed advanced renal impairment. Of these 7 patients, 3 developed renal failure. In addition, no renal cysts were detected in six patients who showed early renal impairment. In conclusion, renal pathology in GSDI is characterized by progressive tubular dysfunction and the development of polycystic kidneys that probably leads to the development of irreversible renal failure in the late stages. Systematic observations of cyst development by kidney imaging should improve the evaluation of the disease's progression, independently of biochemical markers.

PMID:
27436577
DOI:
10.1093/hmg/ddw224
[Indexed for MEDLINE]

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