title: An unusual association of contralateral congenital small kidney, reduced renal function and hyperparathyroidism in sponge kidney patients: on the track of the molecular basis.
abstract: Of unknown pathogenesis, sponge kidney (SK) is variably associated with nephrocalcinosis, stones, nephronic tubule dysfunctions and precalyceal duct cysts. Amongst 72 unrelated renal SK patients with renal stone disease, we detected one with unilateral bifid renal pelvis and six with unilateral small kidneys (longitudinal diameter difference >15%). Secondary causes of small kidney were excluded. Of the seven cases, four had reduced renal function (67 vs 7% in the entire cohort), and three developed hyperparathyroidism during follow-up (43 vs 4%). The pathogenesis of SK ought to explain why anatomical structures of different embryological origin are involved (the precalyceal and collecting ducts and the nephron) and why there is frequent association with hyperparathyroidism. In embryogenesis, the metanephric blastema synthesizes the chemotactic glial-derived neurotrophic factor (GDNF) to prompt the ureteric bud to branch off from Wolff's mesonephric duct, and to approach and invade the blastema. The bud's tip expresses the GDNF receptor (RET). RET-GDNF binding is crucial not only for the correct formation of ureters and collecting ducts (both of Wolffian origin), but also for nephrogenesis. We advance the hypothesis that SK results from a disruption in the ureteric bud-metanephric blastema interface, possibly due to one or more mutations or polymorphisms of RET or GDNF genes. This would explain: the concurrent alterations in precalyceal ducts and the functional defects in the nephron, the occasional association with size and the functional asymmetry between the two kidneys, some degree of renal dysplasia causing the reduction in the glomerular filtration rate and (given the role of RET in parathyroid cell proliferation) the association with hyperparathyroidism.
authors.affiliation: Divisione di Nefrologia, Dipartimento di Scienze Biomediche e Chirurgiche, Università di Verona, Ospedale Maggiore, Piazzale Stefani 1, 37126 Verona, Italy. giovanni.gambaro@univr.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gambaro
authors.forename: Antonia
authors.initials: A
authors.lastname: Fabris
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Citron
authors.forename: Enrica
authors.initials: E
authors.lastname: Tosetto
authors.forename: Franca
authors.initials: F
authors.lastname: Anglani
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellan
authors.forename: Marilena
authors.initials: M
authors.lastname: Conte
authors.forename: Luciana
authors.initials: L
authors.lastname: Bonfante
authors.forename: Antonio
authors.initials: A
authors.lastname: Lupo
authors.forename: Angela
authors.initials: A
authors.lastname: D'Angelo
mesh_terms: D000328:Adult; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005919:Glomerular Filtration Rate; D006801:Humans; D006961:Hyperparathyroidism / Q000453:epidemiology*; D006984:Hypertrophy; D007668:Kidney / Q000002:abnormalities* / Q000473:pathology; D008297:Male; D007691:Medullary Sponge Kidney / Q000453:epidemiology* / Q000235:genetics*; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D010281:Parathyroid Hormone / Q000097:blood; D011110:Polymorphism, Genetic; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D015513:Oncogene Proteins; D010281:Parathyroid Hormone; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases