Cellular and molecular mechanisms underlying pediatric kidney diseases
The Laboratory of Translational Research in Paediatric Nephro-urology (LNUP) directed by Prof. Giovanni Montini and Dr. Federica Collino was born a year ago thanks to the support of various private associations (ImpactSIM SpA, Associazione Bambino Nefropatico and La Nuova Speranza Onlus Foundation).
LNUP is associated to the Ca ‘Granda Foundation IRCCS Ospedale Maggiore Policlinico di Milano and to the Department of Clinical and Community Sciences (UNIMI) and on the basis of a cooperative agreement is localized at the National Institute of Molecular Genetics (INGM).
The Laboratory studies the cellular and molecular mechanisms targeting the functional structures of the kidney, the glomerulus and the renal tubule, in children with pediatric kidney diseases. Their malfunction causes a reduction in the filtering capacity of the kidney or an imbalance of its ability to reabsorb essential substances to our body, which can lead to the development of irreversible kidney damage and the need for dialysis and transplantation.
In this context, the commitment of the LNUP researchers is to determine using -omics technologies and cytofluorimetric techniques, the renal and immune cellular components involved in the onset of pediatric diseases of the kidney and to study the plasma and urinary secretome of these patients, to identify molecules responsible for kidney damage. An important component of the secretome are the extracellular vesicles (EVs), circular structures released by the cells that mediate the crosstalk between the different components of a tissue in both physiological and pathological conditions. In the lab, we study the EV composition and their role in kidney damage propagation, together with their use as exogenous vectors for the delivery of healing molecules. In addition, we have developed a three-dimensional dynamic millifluidic model capable of mimicking the complex structure of the kidney in vitro and we explore the use of different substrates to better mimic the kidney morphology and study its functionality in acute and chronic diseases.
- Role of the immune system alteration in development of the immune-mediated nephrotic syndrome.
- Crosstalk between endothelial and epithelial glomerular cells in patients with steroid-resistant idiopathic nephrotic syndrome and its role in proteinuria development.
- Urinary extracellular vesicles (EVs) in prenatal diagnosis of patients with upper and lower urinary tract obstruction.
- Development of a three-dimensional ex vivo model of the renal tubule for the “delivery” of curative molecules by naïve and engineered EVs.
Giovanni Montini has published over 220 manuscripts in peer-reviewed scientific journals. Its H index (Scopus) is 42. Selection of some of the most relevant publications (from 2005):
- Mesenchymal Stromal Cell-Derived Extracellular Vesicles Pass through the Filtration Barrier and Protect Podocytes in a 3D Glomerular Model under Continuous Perfusion.
Bellucci L, Montini G, Collino F, Bussolati B.
Tissue Eng Regen Med. 2021 Aug;18(4):549-560.
- Urinary Extracellular Vesicles: Uncovering the Basis of the Pathological Processes in Kidney-Related Diseases.
Cricrì G, Bellucci L, Montini G, Collino F.
Int J Mol Sci. 2021 Jun 17;22(12):6507.
- Prevalence of SARS-CoV-2-IgG Antibodies in Children with CKD or Immunosuppression.
Morello W, Mastrangelo A, Guzzo I, Cusinato L, Annicchiarico Petruzzelli L, Benevenuta C, Martelli L, Dall’Amico R, Vianello FA, Puccio G, Massella L, Benetti E, Pecoraro C, Peruzzi L, Montini G;
Clin J Am Soc Nephrol. 2021 Jul;16(7):1097-1099.
- Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome.
Turolo S, Edefonti A, Mazzocchi A, Syren ML, Morello W, Agostoni C, Montini G.
Int J Mol Sci. 2021 May 21;22(11):5452.
- Persistent Abnormalities of Fatty Acids Profile in Children With Idiopathic Nephrotic Syndrome in Stable Remission.
Turolo S, Edefonti AC, Morello W, Syren ML, De Cosmi V, Ghio L, Tamburello C, Demarco EA, Berrettini A, Manzoni G, Agostoni C, Montini G.
Front Pediatr. 2021 Jan 27;8:633470.
- Impact of COVID-19 Pandemic in Children with CKD or Immunosuppression.
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;
Clin J Am Soc Nephrol. 2021 Mar 8;16(3):449-451.
- Results of the PROPINE randomized controlled study suggest tapering of prednisone treatment for relapses of steroid sensitive nephrotic syndrome is not necessary in children.
Gargiulo A, Massella L, Ruggiero B, Ravà L, Ciofi Degli Atti M, Materassi M, Lugani F, Benetti E, Morello W, Molino D, Mattozzi F, Pennesi M, Maringhini S, Pasini A, Gianoglio B, Pecoraro C, Montini G, Murer L, Ghiggeri GM, Romagnani P, Vivarelli M, Emma F.
Kidney Int. 2021 Feb;99(2):475-483.
- Urinary Extracellular Vesicle Protein Profiles Discriminate Different Clinical Subgroups of Children with Idiopathic Nephrotic Syndrome. Santorelli L, Morello W, Barigazzi E, Capitoli G, Tamburello C, Ghio L, Crapella B, Galimberti S, Montini G, Pitto M, Raimondo F.
Diagnostics (Basel). 2021 Mar 6;11(3):456.
- Is Shigatoxin 1 protective for the development of Shigatoxin 2-related hemolytic uremic syndrome in children? Data from the ItalKid-HUS Network.
Ardissino G, Possenti I, Vignati C, Daprai L, Capone V, Brigotti M, Luini MV, Consonni D, Montini G.
Pediatr Nephrol. 2020 Oct;35(10):1997-2001.
- Born with a solitary kidney: at risk of hypertension.
La Scola C, Marra G, Ammenti A, Pasini A, Taroni F, Bertulli C, Morello W., Ceccoli M, Mencarelli F, Guarino S, Puccio G, Montini G.
Pediatr Nephrol. 2020 Aug;35(8):1483-1490.
- Post-transplant recurrence of steroid resistant nephrotic syndrome in children: the Italian experience.
Morello W, Puvinathan S, Puccio G, Ghiggeri GM, Dello Strologo L, Peruzzi L, Murer L, Cioni M, Guzzo I, Cocchi E, Benetti E, Testa S, Ghio L, Caridi G, Cardillo M, Torelli R, Montini G.
J Nephrol. 2020 Aug;33(4):849-857.
- Antibiotic Prophylaxis for Urinary Tract Infection-Related Renal Scarring: A Systematic Review.
Hewitt IK, Pennesi M, Morello W, Ronfani L, Montini G.
Pediatrics. 2017 May;139(5): e20163145.
- A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group.
Luyckx VA, Perico N, Somaschini M, Manfellotto D, Valensise H, Cetin I, Simeoni U, Allegaert K, Vikse BE, Steegers EA, Adu D, Montini G, Remuzzi G, Brenner BM; writing group of the Low Birth Weight and Nephron Number Working Group.
Lancet. 2017 Jul 22;390(10092):424-428.
- Mitochondrial dysfunction in inherited renal disease and acute kidney injury.
Emma F, Montini G, Parikh SM, Salviati L.
Nat Rev Nephrol. 2016 May;12(5):267-80.
- Congenital Solitary Kidney in Children: Size Matters.
La Scola C, Ammenti A, Puccio G, Lega MV, De Mutiis C, Guiducci C, De Petris L, Perretta R, Venturoli V, Vergine G, Zucchini A, Montini G.
J Urol. 2016 Oct;196(4):1250-6.
- Renal involvement in mitochondrial cytopathies.
Emma F, Bertini E, Salviati L, Montini G.
Pediatr Nephrol. 2012 Apr;27(4):539-50.
- Febrile urinary tract infections in children.
Montini G, Tullus K, Hewitt I.
N Engl J Med. 2011 Jul 21;365(3):239-50.
- Strict blood-pressure control and progression of renal failure in children.
ESCAPE Trial Group, Wühl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Möller K, Wigger M, Peruzzi L, Mehls O, Schaefer F.
N Engl J Med. 2009 Oct 22;361(17):1639-50.
- Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1.
Montini G, Zucchetta P, Tomasi L, Talenti E, Rigamonti W, Picco G, Ballan A, Zucchini A, Serra L, Canella V, Gheno M, Venturoli A, Ranieri M, Caddia V, Carasi C, Dall’amico R, Hewitt I.
Pediatrics. 2009 Feb;123(2):e239-46.
- Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial.
Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A, Gobber D, Cecchin D, Pavanello L, Molinari PP, Maschio F, Zanchetta S, Cassar W, Casadio L, Crivellaro C, Fortunati P, Corsini A, Calderan A, Comacchio S, Tommasi L, Hewitt IK, Da Dalt L, Zacchello G, Dall’Amico R; IRIS Group.
Pediatrics. 2008 Nov;122(5):1064-71.
- Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials.
Hewitt IK, Zucchetta P, Rigon L, Maschio F, Molinari PP, Tomasi L, Toffolo A, Pavanello L, Crivellaro C, Bellato S, Montini G.
Pediatrics. 2008 Sep;122(3):486-90.
- Early coenzyme Q10 supplementation in primary coenzyme Q10 deficiency.
Montini G, Malaventura C, Salviati L.
N Engl J Med. 2008 Jun 26;358(26):2849-50.
- Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial.
Montini G, Toffolo A, Zucchetta P, Dall’Amico R, Gobber D, Calderan A, Maschio F, Pavanello L, Molinari PP, Scorrano D, Zanchetta S, Cassar W, Brisotto P, Corsini A, Sartori S, Da Dalt L, Murer L, Zacchello G.
BMJ. 2007 Aug 25;335(7616):386.
- Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: a CoQ10-responsive condition.
Salviati L, Sacconi S, Murer L, Zacchello G, Franceschini L, Laverda AM, Basso G, Quinzii C, Angelini C, Hirano M, Naini AB, Navas P, DiMauro S, Montini G.
Neurology. 2005 Aug 23;65(4):606-8.