title: Diverse effects of increasing lisinopril doses on lipid abnormalities in chronic nephropathies.
abstract: BACKGROUND
  Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria.
  
  
  RESULTS
  In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients.
  
  
  CONCLUSIONS
  In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.
authors.affiliation: Clinical Research Center for Rare Diseases Aldo and Cele Daccò, Mario Negri Institute, Bergamo, Italy. manuelap@marionegri.it
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.forename: Naobumi
authors.initials: N
authors.lastname: Mise
authors.forename: Roberto
authors.initials: R
authors.lastname: Pisoni
authors.forename: Federica
authors.initials: F
authors.lastname: Arnoldi
authors.forename: Anna
authors.initials: A
authors.lastname: Pezzotta
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.forename: Dario
authors.initials: D
authors.lastname: Cattaneo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D002908:Chronic Disease; D004232:Diuretics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D034141:Hypoalbuminemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D007022:Hypotension / Q000139:chemically induced; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007677:Kidney Function Tests; D017706:Lisinopril / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008137:Longitudinal Studies; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology; D012982:Sodium, Dietary; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004232:Diuretics; D012982:Sodium, Dietary; D014280:Triglycerides; D002784:Cholesterol; D017706:Lisinopril