title: Randomized controlled trial: lisinopril reduces proteinuria, ammonia, and renal polypeptide tubular catabolism in patients with chronic allograft nephropathy.
abstract: BACKGROUND
  Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure. Data in renal transplantation remain limited. A negative effect on glomerular filtration rate was concluded in a recent systematic review.
  
  
  METHODS
  In this novel randomized controlled trial, 47 patients with chronic allograft nephropathy, severe renal impairment, and more than or equal to 1 g/24 hr proteinuria were randomized to lisinopril (group A) or other hypotensives (group B) for 1 year. Sodium bicarbonate was given to all patients to treat metabolic acidosis prophylactically (acidosis increases significantly with lisinopril). The annual rate of decline of graft function was measured isotopically (primary outcome) and 24 hr proteinuria, genotyping, radiolabeled polypeptide aprotinin proximal tubular catabolic studies (in group A only) as secondary outcome measurements were undertaken.
  
  
  RESULTS
  At baseline, groups were comparable except for greater proteinuria in group A. After 1 year, the rate of decline of graft function and graft survival were comparable in both groups. Proteinuria decreased significantly in group A patients only. Lisinopril also significantly reduced radiolabeled aprotinin uptake and metabolism, plasma aldosterone, and ammonia excretion. Plasma potassium, bicarbonate, and mean arterial pressures were comparable in both groups. Patients with more than or equal to 30% reduction in proteinuria had a significant association with rs699 polymorphism in the angiotensinogen gene.
  
  
  CONCLUSIONS
  The rate of decline of renal graft function in patients with chronic allograft nephropathy was not adversely affected by lisinopril therapy given for 1 year. Lisinopril significantly reduced proteinuria, renal proximal tubular polypeptide catabolism, plasma aldosterone, and ammonia excretion suggesting relative preservation of graft function. Treating metabolic acidosis allowed safe and prolonged use of angiotensinogen-converting enzyme inhibitors.
authors.affiliation: Pathophysiology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Alieu B
authors.initials: AB
authors.lastname: Amara
authors.forename: Asheesh
authors.initials: A
authors.lastname: Sharma
authors.forename: John L
authors.initials: JL
authors.lastname: Alexander
authors.forename: Ana
authors.initials: A
authors.lastname: Alfirevic
authors.forename: Atif
authors.initials: A
authors.lastname: Mohiuddin
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: Graeme L
authors.initials: GL
authors.lastname: Close
authors.forename: Steve
authors.initials: S
authors.lastname: Grime
authors.forename: Paul
authors.initials: P
authors.lastname: Maltby
authors.forename: Howida
authors.initials: H
authors.lastname: Shawki
authors.forename: Sally
authors.initials: S
authors.lastname: Heyworth
authors.forename: Alan
authors.initials: A
authors.lastname: Shenkin
authors.forename: Linda
authors.initials: L
authors.lastname: Smith
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Abdel
authors.initials: A
authors.lastname: Hammad
authors.forename: Rana
authors.initials: R
authors.lastname: Rustom
mesh_terms: D000641:Ammonia / Q000652:urine*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002102:Cadaver; D003404:Creatinine / Q000097:blood; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D016030:Kidney Transplantation / Q000401:mortality / Q000473:pathology / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D017706:Lisinopril / Q000627:therapeutic use*; D019520:Living Donors; D020641:Polymorphism, Single Nucleotide; D011507:Proteinuria / Q000235:genetics / Q000517:prevention & control*; D016019:Survival Analysis; D017741:Survivors; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000473:pathology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000641:Ammonia; D003404:Creatinine; D017706:Lisinopril