title: New non-renal congenital disorders associated with medullary sponge kidney (MSK) support the pathogenic role of GDNF and point to the diagnosis of MSK in recurrent stone formers.
abstract: Medullary sponge kidney (MSK) is a congenital renal disorder. Its association with several developmental abnormalities in other organs hints at the likelihood of some shared step(s) in the embryogenesis of the kidney and other organs. It has been suggested that the REarranged during Transfection (RET) proto-oncogene and the Glial cell line-Derived Neurotrophic Factor (GDNF) gene are defective in patients with MSK, and both RET and GDNF are known to have a role in the development of the central nervous system, heart, and craniofacial skeleton. Among a cohort of 143 MSK patients being followed up for nephrolithiasis and chronic kidney disease at our institution, we found six with one or more associated non-renal anomalies: one patient probably has congenital hemihyperplasia and hypertrophic cardiomyopathy with adipose metaplasia and mitral valve prolapse; one has Marfan syndrome; and the other four have novel associations between MSK and nerve and skeleton abnormalities described here for the first time. The discovery of disorders involving the central nervous system, cardiovascular system and craniofacial skeleton in MSK patients supports the hypothesis of a genetic alteration on the RET-GDNF axis having a pivotal role in the pathogenesis of MSK, in a subset of patients at least. MSK seems more and more to be a systemic disease, and the identification of extrarenal developmental defects could be important in arousing the suspicion of MSK in recurrent stone formers.
authors: Division of Nephrology, Department of Medicine, University of Verona, Verona, Italy. ria.paolo@gmail.com.
authors: Paolo
authors: http://orcid.org/0000-0002-3964-5135
authors: P
authors: Ria
authors: Division of Nephrology, Department of Medicine, University of Verona, Verona, Italy.
authors: Antonia
authors: A
authors: Fabris
authors: Division of Nephrology, Department of Medicine, University of Verona, Verona, Italy.
authors: Alessandra
authors: A
authors: Dalla Gassa
authors: Division of Nephrology, Department of Medicine, University of Verona, Verona, Italy.
authors: Gianluigi
authors: G
authors: Zaza
authors: Division of Nephrology, Department of Medicine, University of Verona, Verona, Italy.
authors: Antonio
authors: A
authors: Lupo
authors: Division of Nephrology, Department of Medical Sciences, Catholic University of the Sacred Heart, Rome, Italy.
authors: Giovanni
authors: G
authors: Gambaro
mesh_terms: D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000151:congenital / Q000235:genetics; D002490:Central Nervous System / Q000002:abnormalities; D015331:Cohort Studies; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia / Q000151:congenital / Q000235:genetics; D007668:Kidney / Q000002:abnormalities; D007669:Kidney Calculi / Q000209:etiology / Q000235:genetics*; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics; D007691:Medullary Sponge Kidney / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000235:genetics; D055815:Young Adult
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: Diagnosis; Genetic defects; Kidney development; Medullary sponge kidney; Nephrolithiasis