title: Achieving remission of proteinuria in childhood CKD.
abstract: A multidrug treatment strategy that targets urinary proteins with an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) up-titrated to the respective maximum tolerated dose combined with intensified blood pressure (BP) control has been found to prevent renal function loss in adults with proteinuric nephropathies. Herein, we investigated the effects of this treatment protocol in the pediatric patient population.
  
  
  
  From May 2002 to September 2014 we included in this observational, longitudinal, cohort study 20 consecutive children with chronic nephropathies and 24-h proteinuria of >200 mg who had received ramipril and losartan up-titrated to the respective maximum approved and tolerated doses [mean (﻿standard deviation) dose:2.48 (1.37) mg/m2and 0.61 (0.46) mg/kg daily, respectively]. The primary efficacy endpoint was a >50 % reduction in 24-h proteinuria to <200 mg (remission). Secondary outcomes included changes in proteinuria, serum albumin, BP, and glomerular filtration rate (GFR).
  
  
  
  Mean (± standard deviation) patient age at inclusion was 13.8 ± 2.8 years, and the median [interquartile range (IQR)] serum creatinine level and proteinuria were 0.7 (0.6-1.0) mg/dl and 690 (379-1270) mg/24 h or 435 (252-711) mg/m2/24 h, respectively. Proteinuria significantly decreased by month 6 of follow-up, and serum albumin levels increased over a median follow-up period of 78 (IQR 39-105) months. In the nine children who achieved remission, proteinuria reduction persisted throughout the whole follow-up without rebounds. The GFR improved in those children who achieved remission and worsened in those who did not. The mean GFR slopes differed significantly between these two groups (p < 0.05), being positive in those children with remission and negative in those without remission (+0.023 ± 0.15 vs.-0.014 ± 0.23 ml/min/1.73 m2/month, respectively), whereas BP control was similar between the two groups. Hyperkalemia was observed in two children.
  
  
  
  Combination therapy with maximum approved doses of ACE inhibitors and ARBs is a safe strategy which may achieve proteinuria remission with kidney function stabilization or even improvement in a substantial proportion of children with proteinuric nephropathies.
authors.affiliation: Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò", IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.|Unit of Nephrology, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.affiliation: Department of Medicine, Recanati Miller Transplant Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cravedi
authors.affiliation: Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò", IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Chianca
authors.affiliation: Unit of Nephrology, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: MariaRosa
authors.initials: M
authors.lastname: Caruso
authors.affiliation: Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò", IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy. giuseppe.remuzzi@marionegri.it.|Unit of Nephrology, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy. giuseppe.remuzzi@marionegri.it.|Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. giuseppe.remuzzi@marionegri.it.|Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy. giuseppe.remuzzi@marionegri.it.
authors.forename: Giuseppe
authors.identifier: 0000-0002-6194-3446
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000293:Adolescent; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D020714:Maximum Tolerated Dose; D011507:Proteinuria / Q000188:drug therapy*; D017257:Ramipril / Q000008:administration & dosage*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D019808:Losartan; D017257:Ramipril
keywords: ACE inhibitor; Angiotensin receptor blocker; Children; Chronic nephropathy; Proteinuria