title: Antiproteinuric efficacy of fosinopril after renal transplantation is determined by the extent of vascular and tubulointerstitial damage.
abstract: BACKGROUND
  Angiotensin converting enzyme (ACE) inhibitors have been successfully used for treatment of proteinuria after renal transplantation (RTx). Factors possibly responsible for the great inter-patient variance of the antiproteinuric effect (APE) have not yet been investigated in renal-transplanted patients.
  
  
  METHODS
  28 patients after RTx with a persistent proteinuria of more than 1.25 g/d were treated prospectively with does of fosinopril (10-15 mg/d) which were not effective on systemic arterial blood pressure. Prior to initiation of fosinopril, renal graft biopsy was performed in all patients and renal graft artery stenosis was excluded by duplex ultrasound. Serum creatinine and proteinuria were measured prior to, as well as 3 and 8 months after initiation of ACE inhibition, mean arterial pressure was controlled via 24-h measurement and repeated spot measurements. Reduction of proteinuria was correlated with renal histology, serum creatinine, creatinine clearance, mean arterial blood pressure, sodium excretion before therapy and the relative changes of these parameters during therapy respectively.
  
  
  RESULTS
  Therapy had to be stopped in 8/28 patients due to side effects including rise of serum creatinine (n = 4). Three patients were excluded due to non-compliance. In the remaining patients (n = 17) proteinuria was reduced from 2.94 +/- 1.66 to 1.82 +/- 1.39 and 2.48 +/- 3.05 g/d after 3 and 8 months respectively, in the mean +/- SD. There was a significant inverse correlation between the APE and the extent of benign nephrosclerosis, interstitial fibrosis and tubular atrophy. No correlation of the APE to any of the other parameters could be demonstrated.
  
  
  CONCLUSIONS
  Fosinopril can be administered effectively in a subgroup of proteinuric renal transplant recipients. However, because of a high proportion of patients developing side effects, careful monitoring is obligatory. Our results show that the lesser the degree of chronic morphological injury, the greater is the antiproteinuric effect. Thus, the degree of pre-existing histologically proven damage of the graft may serve as an indicator for the antiproteinuric efficacy of ACE inhibitor therapy after RTx.
authors.affiliation: Abt. Nephrologie, Gastroenterologie, Zentrum Innere Medizin und Dermatologie, Medizinische Hochschule, Hannover, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Lufft
authors.forename: V
authors.initials: V
authors.lastname: Kliem
authors.forename: A
authors.initials: A
authors.lastname: Hamkens
authors.forename: J S
authors.initials: JS
authors.lastname: Bleck
authors.forename: U
authors.initials: U
authors.lastname: Eisenberger
authors.forename: R
authors.initials: R
authors.lastname: Petersen
authors.forename: G
authors.initials: G
authors.lastname: Ehlerding
authors.forename: H
authors.initials: H
authors.lastname: Maschek
authors.forename: R
authors.initials: R
authors.lastname: Pichlmayr
authors.forename: R
authors.initials: R
authors.lastname: Brunkhorst
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D017328:Fosinopril / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017328:Fosinopril