title: Effects of add-on fluvastatin therapy in patients with chronic proteinuric nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial.
abstract: OBJECTIVE
  This open, prospective, randomized trial aimed to assess the effects of statins in chronic kidney disease patients on optimized antiproteinuric treatment with combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade.
  
  
  METHODS
  After 1-month benazepril therapy followed by 1-month benazepril-valsartan combined therapy (run-in), 186 consenting patients with residual proteinuria >0.5 g/24 h were randomized to 6-month benazepril-valsartan therapy alone or combined with fluvastatin. Between-groups changes in proteinuria (primary outcome), serum lipids, and GFR were compared by ANCOVA. Analyses were blinded and by intention to treat.
  
  
  RESULTS
  During the run-in, proteinuria decreased more on benazepril-valsartan than on benazepril alone. Proteinuria reduction correlated with concomitant reduction in total, LDL, and HDL cholesterol, and apolipoprotein B and apolipoprotein A levels. After randomization, median proteinuria similarly decreased from 1.2 (0.6 to 2.2) to 1.1 (0.5 to 1.7) g/24 h on fluvastatin and from 1.5 (0.8 to 2.7) to 1.0 (0.5 to 2.4) g/24 h on benazapril-valsartan therapy alone. Fluvastatin further reduced total and LDL cholesterol and apolipoprotein B versus benazepril-valsartan alone, but did not affect serum triglycerides and GFR. Treatment was well tolerated.
  
  
  CONCLUSIONS
  In chronic kidney disease patients with residual proteinuria despite combined angiotensin-converting enzyme inhibitor and angiotensin receptor blockade therapy, add-on fluvastatin does not affect urinary proteins, but further reduces serum lipids and is safe. Whether combined angiotensin-converting enzyme inhibitor, angiotensin receptor blockade, and statin therapy may improve cardiovascular outcomes in this high-risk population is worth investigating.
authors.affiliation: Clinical Research Center for Rare Diseases Aldo & Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.forename: Giacomina
authors.initials: G
authors.lastname: Loriga
authors.forename: Nicola
authors.initials: N
authors.lastname: Motterlini
authors.forename: Nadia
authors.initials: N
authors.lastname: Rubis
authors.forename: Franca
authors.initials: F
authors.lastname: Ledda
authors.forename: Stefano
authors.initials: S
authors.lastname: Rota
authors.forename: Andrea
authors.initials: A
authors.lastname: Satta
authors.forename: Antonio
authors.initials: A
authors.lastname: Granata
authors.forename: Giovanni
authors.initials: G
authors.lastname: Battaglia
authors.forename: Francesco
authors.initials: F
authors.lastname: Cambareri
authors.forename: Salvatore
authors.initials: S
authors.lastname: David
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.forename: Nadia
authors.initials: N
authors.lastname: Stucchi
authors.forename: Sergio
authors.initials: S
authors.lastname: Carminati
authors.forename: Bogdan
authors.initials: B
authors.lastname: Ene-Iordache
authors.forename: Paolo
authors.initials: P
authors.lastname: Cravedi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure; D016009:Chi-Square Distribution; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D005919:Glomerular Filtration Rate; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007558:Italy; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008055:Lipids; D013777:Tetrazoles; D000077340:Fluvastatin; D000068756:Valsartan; D014633:Valine; C044946:benazepril