ANTIPROTEINURIC EFFICACY OF FOSINOPRIL AFTER RENAL-TRANSPLANTATION ISDETERMINED BY THE EXTENT OF VASCULAR AND TUBULOINTERSTITIAL DAMAGE

Background: angiotensin converting enzyme (ACE) inhibitors have been s uccessfully used for treatment of proteinuria after renal transplantat ion (RTx), Factors possibly responsible for the great interpatient var iance of the antiproteinuric effect (APE) have not yet been investigat ed in renal-transplanted patients. Methods: 28 patients after RTx with a persistent proteinuria of more than 1.25 g/d were treated prospecti vely with doses 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 arter y stenosis was excluded by duplex ultrasound. Serum creatinine and pro teinuria were measured prior to, as well as 3 and 8 months after initi ation 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 cle arance, mean arterial blood pressure, sodium excretion before therapy and the relative changes of these parameters during therapy respective ly. Results: therapy had to be stopped in 8/28 patients due to side ef fects including rise of serum creatinine (n = 4). Three patients were excluded due to non-compliance. In the remaining patients (n = 17) pro teinuria was reduced from 2.94 +/- 1.66 to 1.82 +/- 1.39 and 2.38 +/- 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 o f benign nephrosclerosis, interstitial fibrosis and tubular atrophy. N o correlation of the APE to any of the other parameters could be demon strated. 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 moni toring is obligatory. Our results show that the lesser the degree of c hronic 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 A CE inhibitor therapy after RTx.