Urinary proteome signature of Renal Cysts and Diabetes syndrome in children.

Abstract

Renal Cysts and Diabetes Syndrome (RCAD) is an autosomal dominant disorder caused by mutations in the HNF1B gene encoding for the transcriptional factor hepatocyte nuclear factor-1B. RCAD is characterized as a multi-organ disease, with a broad spectrum of symptoms including kidney abnormalities (renal cysts, renal hypodysplasia, single kidney, horseshoe kidneys, hydronephrosis), early-onset diabetes mellitus, abnormal liver function, pancreatic hypoplasia and genital tract malformations. In the present study, using capillary electrophoresis coupled to mass spectrometry (CE-MS), we investigated the urinary proteome of a pediatric cohort of RCAD patients and different controls to identify peptide biomarkers and obtain further insights into the pathophysiology of this disorder. As a result, 146 peptides were found to be associated with RCAD in 22 pediatric patients when compared to 22 healthy age-matched controls. A classifier based on these peptides was generated and further tested on an independent cohort, clearly discriminating RCAD patients from different groups of controls. This study demonstrates that the urinary proteome of pediatric RCAD patients differs from autosomal dominant polycystic kidney disease (PKD1, PKD2), congenital nephrotic syndrome (NPHS1, NPHS2, NPHS4, NPHS9) as well as from chronic kidney disease conditions, suggesting differences between the pathophysiology behind these disorders.

• Authors: Pierbruno Ricci, Pedro Magalhães, Magdalena Krochmal, Martin Pejchinovski, Erica Daina, Maria Rosa Caruso, Laura Goea, Iwona Belczacka, Giuseppe Remuzzi, Muriel Umbhauer, Jens Drube, Lars Pape, Harald Mischak, Stéphane Decramer, Franz Schaefer, Joost P Schanstra, Silvia Cereghini, Petra Zürbig
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 2225 (02 18 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 30778115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Peptides
• Proteome

Topics

• Adolescent
• Biomarkers (urine)
• Central Nervous System Diseases (diagnosis, metabolism, urine)
• Child
• Child, Preschool
• Dental Enamel (abnormalities, metabolism)
• Diabetes Mellitus, Type 2 (diagnosis, metabolism, urine)
• Diagnosis, Differential
• Female
• Humans
• Kidney Diseases, Cystic (diagnosis, metabolism, urine)
• Male
• Mass Spectrometry
• Peptides (urine)
• Phenotype
• Proteome
• Proteomics (methods)
• Reproducibility of Results