Research Area: Genetica e malattie rare
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 Padua University Hospital. The Unit is a center of excellence and reference for Pediatric Nephrology and rare kidney disease. It is also part of international registries and networks (i.e. ERKNet; Certain; Transplantchild) for the diagnosis and treatment of kidney rare diseases. Furthermore, it works in close collaboration with various specialists to follow children 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 renal tissues from transplanted or native kidneys. Pediatric Nephrology Unit and the Laboratory coordinate important scientific studies, from the clinical trials to the translational research, concerning kidney transplantation, congenital abnormalities of the kidney and urinary tract (CAKUT), nephrotic syndrome and other pediatric kidney diseases.
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 impairment of kidney function. Even though mutations of at least 17 genes involved in the early stages of kidney development have been associated with RHD, most patients remain without a genetic diagnosis. In the last three years, the Lab has 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 Lab 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 analyzed cases. These results will permit to lay the basis for setting up a perspective RHD diagnostic panel.
The main 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 15-20 years, a too short period for a pediatric patient. The gold standard in the diagnosis of renal allograft failure (the main cause of kidney rejection) is the biopsy and the Pediatric Renal Transplant Centre of Padua, which also resides at the Pediatric Nephrology Unit, is a pioneer of protocol biopsy. Protocol biopsy allows to identify rejection before the onset of clinical features. Three main topics that are on study are: 1. the prognostic value of infiltrate cell phenotyping in renal transplant biopsies; 2. the relevance and the prognostic value of intrarenal positivity of viruses; 3. the dosage and the role of antibody against the donor (HLA and non-HLA). We are collaborating with Transplantation Immunology Lab (Prof Cozzi) to explore the impact of non -HLA antibodies anti AT1R and ETAR and to assess the possible causative role of anti-ETAR immunity in premature pediatric renal transplant failure. Furthermore, we are collaborating with many IRP groups with different expertise, to characterize the extracellular vesicles (EVs) isolated from serum 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.
The Lab is also involved in the ORCHESTRA project. ORCHESTRA is funded by the European Union’s Horizon 2020 research and innovation programme under the ERAvsCORONA Action Plan which was developed jointly by Commission services and national authorities. ORCHESTRA is a European 3-years project (2020-2023) aimed to deliver scientific evidence to improve the prevention and treatment of the infections caused by SARS-CoV-2. The project builds up on existing and new large scale population cohorts in Europe (France, Germany, Spain, Italy, Belgium, Romania, Netherlands, Portugal, Luxemburg, and Slovakia) and in 9 non-European countries. The main outcome of ORCHESTRA is the creation of a new pan-European cohort including SARS-CoV-2 infected and non-infected individuals of all ages and conditions. The cohort involves four different populations: members of the general population, COVID-19 patients, fragile individuals (children, elderly, transplanted, oncological, HIV infected individuals, and those with Parkinson disease and rheumatologic disease). This cohort will apply homogenous protocols for data collection, data sharing, sampling, and follow-up to rapidly advance the knowledge on the control and management of COVID-19.
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
• Benetti E, Caridi G, Malaventura C, Dagnino M, Leonardi E, Artifoni L, Ghiggeri GM, Tosatto SC, Murer L. A novel WT1 gene mutation in a three-generation family with progressive isolated focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2010 Apr;5(4):698-702.
• 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.
• Meneghesso D, Parolin M, Longo G, Gamba P, Battistel M, Benetti E. Mid-aortic syndrome. Kidney Int. 2021 Oct;100(4):952.
• Ghidini F, De Corti F, Fascetti Leon F, Vidal E, Rancan A, Parolin M, Zadra N, Grazzini M, Antoniello LM, Ganarin A, Maita S, Tognon C, Mognato G, Castagnetti M, Benetti E, Gamba P, Dall’Igna P. Extraperitoneal kidney transplantation: a comparison between children weighting ≤ 15 kg and > 15 kg. experience of a single institution. Transpl Int. 2021 Aug 19.
• Mastrangelo A, Morello W, Vidal E, Guzzo I, Annicchiarico Petruzzelli L, Benetti E, Materassi M, Giordano M, Pasini A, Corrado C, Puccio G, Chimenz R, Pecoraro C, Massella L, Peruzzi L, Montini G; COVID-19 Task Force of the Italian Society of Pediatric Nephrology; Impact of COVID-19 Pandemic in Children with CKD or Immunosuppression. Clin J Am Soc Nephrol. 2021 Mar 8;16(3):449-451.
Corso Stati Uniti, 4 F
Phone: +39 049 9640111
Fax: +39 049 9640101
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