title: A multidrug, antiproteinuric approach to alport syndrome: a ten-year cohort study.
abstract: OBJECTIVE
  Combined ACE inhibitor, angiotensin-receptor-blocker, non-dihydropyridine calcium-channel-blocker, and statin therapy (Remission Clinic) reduced proteinuria and halted progression in non-diabetic nephropathies, but their efficacy in Alport syndrome (AS) nephropathy is unknown.
  
  
  METHODS
  From February 2004 to September 2007, we included nine albuminuric AS adults with creatinine clearance >20 ml/min/1.73 m(2) in a single-center, open-label, prospective, off-on-off academic study. After the 1-month wash-out from RAS inhibition (Run-in), patients entered the 4-month, add-on, treatment period with benazepril (10-20 mg/day), valsartan (80-160 mg/day), diltiazem (60-120 mg/day), and fluvastatin (40-80 mg/day) followed by the 1-month wash-out (Recovery). The primary outcome was albuminuria at month 4. After recovery, patients were kept on the Remission Clinic protocol and followed until July 2014 (Extension).
  
  
  RESULTS
  The median (IQR) albuminuria progressively declined from 657.7 (292.7-1,089.6) μg/min at baseline to 71.4 (21.7-504.9) μg/min at treatment end (p = 0.009) and raised to 404.3 (167.9-446.8) μg/min after recovery. Albumin and IgG fractional clearances significantly (p ≤ 0.005) decreased from 66.9 (53.6-80.8) to 9.4 (4.6-26.0) and from 5.1 (3.0-8.4) to 1.1 (0.6-3.2), and then recovered toward baseline. Blood pressure and lipids significantly decreased on treatment, without changes in inulin-measured GFR or para-aminohippuric-measured RPF. After recovery, one patient refused to enter the extension, one with severe renal insufficiency at baseline reached ESRD, and seven retained normal serum creatinine until the end of the study. At the final visit, three were microalbuminuric and one was normoalbuminuric. Treatment was well tolerated.
  
  
  CONCLUSIONS
  The Remission Clinic approach safely ameliorated albuminuria, blood pressure, lipids, and glomerular selectivity in AS patients and halted long-term progression in those without renal insufficiency to start with.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo & Cele Daccò", Bergamo, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Daina
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo & Cele Daccò", Bergamo, Italy.|Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cravedi
authors.affiliation: CMID, Center of Research on Immunopathology and Rare Diseases, Ospedale S. Giovanni Bosco and University of Torino, Torino, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Alpa
authors.affiliation: CMID, Center of Research on Immunopathology and Rare Diseases, Ospedale S. Giovanni Bosco and University of Torino, Torino, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Roccatello
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo & Cele Daccò", Bergamo, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gamba
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo & Cele Daccò", Bergamo, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo & Cele Daccò", Bergamo, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo & Cele Daccò", Bergamo, Italy.|Unit of Nephrology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Clinical Research Centre for Rare Diseases "Aldo & Cele Daccò", Bergamo, Italy.|Unit of Nephrology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001552:Benzazepines / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D015331:Cohort Studies; D004110:Diltiazem / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000379:methods*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000188:drug therapy*; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy*; D000068756:Valsartan / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D002121:Calcium Channel Blockers; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D000068756:Valsartan; D004110:Diltiazem; C044946:benazepril