RISK-FACTORS FOR LONG-TERM RENAL SURVIVAL AFTER RENAL-TRANSPLANTATION- A ROLE FOR ANGIOTENSIN-CONVERTING ENZYME (INSERTION DELETION) POLYMORPHISM/

Chronic progressive renal function loss is a main cause of long-term g raft loss after initially successful renal transplantation. Transplant ed kidneys share some risk factors for renal function loss, such as hy pertension or proteinuria, with diseased native kidneys. Recently, it has been shown that renal function loss is influenced by the angiotens in-converting enzyme (ACE) (insertion/deletion [I/D]) genotype in rena l disease in diseased native kidneys. This study examines whether dono r or recipient ACE (I/D) genotype is a risk factor for graft loss afte r renal transplantation. To avoid bias by acute events, graft survival was studied, with patients dying with a functioning graft censored, s tarting at 12 mo after transplantation in a cohort of 367 patients tra nsplanted between 1987 and 1994 with at least 2 yr of follow-up. Mean follow-up was 58 mo. ACE (L/D) genotype was determined by PCR on store d donor and recipient lymphocytes. Neither donor nor recipient ACE (I/ D) genotype was associated with graft survival. However, Cox proportio nal hazards analysis identified recipient, but not donor, ACE (I/D) ge notype D-allele to be independently associated with a shorter time to graft loss in subgroups of patients at high risk for graft loss define d by a creatinine clearance <50 ml/min (n = 108, P = 0.017) or protein uria greater than or equal to 0.5 g/24 h at 12 mo (n = 97, P = 0.0051) after transplantation. In conclusion, recipient ACE (VD) genotype was associated with time to graft loss in a specific high-risk subgroup o f the study population. This suggests that the effect of ACE (VD) geno type on graft survival only becomes apparent when other risk factors a re simultaneously present.