Polycystic kidney features of the renal pathology in glycogen storage disease type I: possible evolution to renal neoplasia
- 138 Downloads
Glycogen storage disease type I (GSDI) is a rare genetic pathology characterized by glucose-6 phosphatase (G6Pase) deficiency, translating in hypoglycemia during short fasts. Besides metabolic perturbations, GSDI patients develop long-term complications, especially chronic kidney disease (CKD). In GSDI patients, CKD is characterized by an accumulation of glycogen and lipids in kidneys, leading to a gradual decline in renal function. At a molecular level, the activation of the renin-angiotensin system is responsible for the development of renal fibrosis, eventually leading to renal failure. The same CKD phenotype was observed in a mouse model with a kidney-specific G6Pase deficiency (K.G6pc−/− mice). Furthermore, GSDI patients and mice develop frequently renal cysts at late stages of the nephropathy, classifying GSDI as a potential polycystic kidney disease (PKD). PKDs are genetic disorders characterized by multiple renal cyst formation, frequently caused by the loss of expression of polycystic kidney genes, such as PKD1/2 and PKHD1. Interestingly, these genes are deregulated in K.G6pc−/− kidneys, suggesting their possible role in GSDI cystogenesis. Finally, renal cysts are known to predispose to renal malignancy development. In addition, HNF1B loss is a malignancy prediction factor. Interestingly, Hnf1b expression was decreased in K.G6pc−/− kidneys. While a single case of renal cancer has been reported in a GSDI patient, a clear cell renal carcinoma was recently observed in one K.G6pc−/− mouse (out of 36 studied mice) at a later stage of the disease. This finding highlights the need to further analyze renal cyst development in GSDI patients in order to evaluate the possible associated risk of carcinogenesis, even if the risk might be limited.
We would like to thank the members of Animaleries Lyon Est Conventionnelle et SPF (ALECS, Université Lyon 1, SFR Santé Lyon Est) for the animal care and the members of the Plateforme de Recherche Anatomopathologique– Centre Leon Bérard, Lyon.” We also thank Fabiola Terzi for reading of and editing the article.
This work was supported by research grants from the Agence Nationale de la Recherche (ANR16-CE14-0022-02) and the Association Francophone des Glycogénoses. LM and MG are recipients of funding of the Fondation pour la Recherche Médicale (FRM grant number ECO20160736048) and the Ligue nationale contre le cancer, respectively.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Kishnani PS, Austin SL, Abdenur JE, Arn P, Bali DS, Boney A, Chung WK, Dagli AI, Dale D, Koeberl D et al (2014) Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med e1:16Google Scholar
- Liu Z, Zhu Y, Wang Y, Fu Q, Fu H, Wang Z, Zhang J, Li G, Xu J, Dai B (2017) Prognostic value of granulocyte colony-stimulating factor in patients with non-metastatic clear cell renal cell carcinoma. Oncotarget 8:69961Google Scholar
- Rogers KA, Moreno SE, Smith LA, Husson H, Bukanov NO, Ledbetter SR, Budman Y, Lu Y, Wang B, Ibraghimov-Beskrovnaya O et al (2016) Differences in the timing and magnitude of Pkd1 gene deletion determine the severity of polycystic kidney disease in an orthologous mouse model of ADPKD. Physiol Rep 4Google Scholar
- Walters W, Braasch WF (1934) Surgical aspect of polycystic kidney. Surg Gynec Obstet 58:647–650Google Scholar