title: A Pilot Study of IL2 in Drug-Resistant Idiopathic Nephrotic Syndrome.
abstract: Tregs infusion reverts proteinuria and reduces renal lesions in most animal models of nephrotic syndrome (i.e. Buffalo/Mna, Adriamycin, Promycin, LPS). IL2 up-regulates Tregs and may be an alternative to cell-therapy in this setting. To evaluate a potential role of IL2 as Tregs inducer and proteinuria lowering agent in human nephrotic syndrome we treated 5 nephrotic patients with 6 monthly cycles of low-dose IL2 (1x106 U/m2 first month, 1.5x106 U/m2 following months). The study cohort consisted of 5 children (all boys, 11–17 years) resistant to all the available treatments (i.e. steroids, calcineurin inhibitors, mycophenolate, Rituximab). Participants had Focal Segmental Glomerulosclerosis (3 cases) or Minimal Change Nephropathy (2 cases). IL2 was safe in all but one patient who had an acute asthma attack after the first IL2 dose and did not receive further doses. Circulating Tregs were stably increased (>10%) during the whole study period in 2 cases while were only partially modified in the other two children who started with very low levels and partially responded to single IL2 Proteinuria and renal function were not modified by IL2 at any phase of the study. We concluded that low-dose IL2 given in monthly pulses is safe and modifies the levels of circulating Tregs. This drug may not be able to lower proteinuria or affect renal function in children with idiopathic nephrotic syndrome. We were unable to reproduce in humans the effects of IL2 described in rats and mice reducing de facto the interest on this drug in nephrotic syndrome.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02455908.
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bonanni
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bertelli
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Di Donato
authors.affiliation: Division of Nephrology, University of Calgary, 1403-29th Street NW, Calgary, Alberta, T2N 2T9, Canada.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.affiliation: Division of Nephrology, Dialysis, Transplantation and Laboratory on Physiopathology of Uremia, Giannina Gaslini Children Hospital, Genoa, Italy.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000276:immunology; D010865:Pilot Projects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2