EXOME SEQUENCING IN MEDULLARY SPONGE KIDNEY - Trial NCT06418230

Timeline & Enrollment

Primary Outcome

Class 3, 4 and 5 variants detected at exome-sequencing

Summary

Medullary sponge kidney is a rare, underdiagnosed renal pathology, characterized by
 precalyceal dilatation of the renal tubes associated with active and recurrent stone disease
 with nephrocalcinosis, hypercalciuria and tubular dysfunction with, for example,
 acidification and urinary concentration defects.
 
 The pathophysiology is poorly understood The prevalence and etiopathogenesis of the disease
 is not known Medullary sponge kidney is often characterized as a congenital pathology with
 delayed expression due to reported cases occurring in early childhood and associations with
 other congenital renal and extra-renal malformative pathologies, such as Wilms tumors,
 horseshoe kidney, contralateral renal hypoplasia, Beckwith-Wiedemann syndrome, Caroli
 disease, or congenital hepatic fibrosis, for example. However, no clear demonstration of the
 congenital nature has been established so far, and it is considered a sporadic disease.
 
 However familial cases have been reported with an autosomal dominant mode.
 
 The pathophysiology may involve disruptions in renal organogenesis, which depends on
 reciprocal inductive interactions necessary to coordinate nephrogenesis between the ureteric
 bud and the metanephric blastema during the 5th week of embryonic development. Some authors
 suggested that the GDNF and RET genes may be involved in the physiopathology of the disease.
 
 For instance 12% of heterozygous patients for rare GDNF variants were identified in an
 Italian cohort of 57 medullary sponge kidney patients.
 
 Other genes have been suggested to be involved in the pathophysiology based on reported
 cases, with no direct relationship demonstrated and their role remain putative Medullary
 sponge kidney disease is a debilitating condition, with the main symptoms being recurrent
 kidney stones and urinary infections.
 
 Additional data are needed to determine the involvement of genetic anomalies in the
 pathophysiology of the condition.
 
 The aim of the study is to describe the genetic variants identified with exome sequencing in
 medullary sponge kidney patients, in order to optimize management, especially for familial
 forms, and therapeutic interventions.

ICD-10 Classifications