The Laboratory of Immunopathology and Molecular Biology of the Kidney is part of the Pediatric Nephrology Dialysis and Transplant unit of the Dept. of Women’s and children’s Health of the Azienda Ospedale Università Padova. The Unit is a center of excellence and reference for Pediatric Nephrology and Rare kidney disease. It is also part of the international registries and networks (i.e. ERKNet) for the diagnosis and treatment of kidney rare diseases. Furthermore, it works in close collaboration with various specialists to follow children patients from prenatal diagnosis to kidney transplantation, using a multidisciplinary and comprehensive approach. The Laboratory provides an analysis pattern for the immune-histological classification of primary and secondary pediatric renal diseases and for the follow-up of pediatric kidney transplantation recipients. It also coordinates the management of molecular tests for genetic kidney diseases. Furthermore, the laboratory has a remarkable biobank of paraffin and frozen renal tissues of transplanted pediatric patients. The Pediatric Nephrology Di-alysis and Transplant unit together with the laboratory conduct and coordinate important scientific studies, from the clinical trials to the translational research, in particular concerning kidney trans-plantation, congenital abnormalities of the kidney and urinary tract (CAKUT), nephrotic syndrome, acute kidney injury (AKI) and dialysis in childhood.
Concerning the CAKUT, one of the most severe phenotypes is renal hypodysplasia (RHD), which is a defect in the number and/or normal differentiation of nephronic units with a subsequent impair-ment of kidney function. Even though mutations of at least 17 genes involved in the early stages of kidney development have been associated with RHD, the majority of patients remains without a genetic diagnosis. In the last three years, we have been participating in the University of Padua’s Strategic project “Bioinfogen” with the aim to create new bioinformatics tools to facilitate NGS data analysis in Mendelian diseases. Our unit is investigating RHD genetic causes in 20 patients and their healthy relatives, with whole exome sequencing. To date, we identified a new candidate gene for isolated bilateral RHD (INVS) and validation studies are still ongoing. Furthermore, we highlighted a variant in a candidate gene in 25% of the analysed cases. These results will permit to lay the basis for setting up a perspective RHD diagnostic panel.
Another field of interest of our laboratory is the study of factors affecting the survival of kidney transplantation in the pediatric population. To date, the survival graft rate is about 15 years, un-acceptable for pediatric patients. The gold standard in the diagnosis of renal allograft failure (the main cause of kidney rejection) is the biopsy and the Pediatric Transplant Centre of Padua is a pioneer of protocol biopsy, that allows recognizing the rejection when there are no clinical features. In our lab, we are evaluating the prognostic value of infiltrate cell phenotyping, of the intrarenal presence of the virus, of the dosage of antibody against the donor. Now we are collaborating with many IRP groups with different expertise, to characterize the extracellular vesicles (EVs) isolated from se-rum and urine of our transplanted children. These EVs act as a message delivery system of the graft, and their cargo could be useful to identify novel non-invasive biomarkers predictive of rejection, to personalize the treatment of children with a suspicious of subclinical graft rejection before the damage is detectable in the kidney.
Susanna Negrisolo Lab Manager
Andrea Carraro Post Doctoral Researcher
Nicola Bertazza Partigiani Clinical Researcher
Maria Sangermano Collaborator, Clinical Researcher
Diana Marzenta Lab Technician
Benedetta Antoniello Master student
Iatropoulos P, Daina E, Curreri M, Piras R, Valoti E, Mele C, Bresin E, Gamba S, Alberti M, Breno M, Perna A, Bettoni S, Sabadini E, Murer L, Vivarelli M, Noris M, Remuzzi G; Registry of Membranoproliferative Glomerulonephritis/C3 Glomerulopathy; Nastasi. 2018. Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN. Journal of the American Society of Nephrology, 29(1), pp. 283-294.
Negrisolo, S., Carraro, A., Fregonese, G., Benetti E., Schaefer F., Alberti M., Melchionda S., Fischetto R., Giordano M, Murer L. 2018 Could the interaction between LMX1B and PAX2 influence the severity of renal symptoms? European Journal of Human Genetics 26, pp.1708–1712.
Giglio S, Provenzano A, Mazzinghi B, Becherucci F, Giunti L, Sansavini G, Ravaglia F, Roperto R, Farsetti S, Benetti E, Rotondi M, Murer L., Lazzeri E, Lasagni L, Materassi M, Romagnani P. 2015. Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression. Journal of The American Society of Nephrology, vol. 26; p. 230-236.
Negrisolo S, Benetti E, Centi S, Della Vella M, Ghirardo G, Zanon GF, Murer L, Artifoni L. PAX2 gene mutations in pediatric and young adult transplant recipients: Kidney and urinary tract malformations without ocular anomalies. 2011. Clinical Genetics 80(6), pp. 581-585.
Grenda R. Watson A. Trompeter R. Tönshoff B. Jaray J. Fitzpatrick M. Murer L. Vondrak K. Maxwell H. Van Damme R. ‐Lombaerts Loirat C. Mor E. Cochat P. Milford D. V Brown M. Webb N. J. A. A randomized trial to assess the impact of early steroid withdrawal on growth in pediatric renal transplantation: The twist study. 2010.
Barzon L*- Murer L*, Pacenti M, Biasolo M, Della Vella M, Benetti E, Zanon G, Palù G. 2009. Investigation of intrarenal viral infections in kidney transplant recipients unveils an association between parvovirus B19 and chronic allograft injury. The Journal of Infectious Diseases, VOL. 199, P. 372-380.
Corso Stati Uniti, 4 F
Phone: +39 049 9640111
Fax: +39 049 9640101