Correlation between angiotensin-converting enzyme gene insertion/deletion polymorphism and kidney graft long-term outcome in pediatric recipients: a single-center analysis

Transplantation. 1999 Feb 27;67(4):534-8. doi: 10.1097/00007890-199902270-00008.


Background: Despite numerous advances in the areas of organ preservation, histocompatibility, and immunosuppression, chronic deterioration of organ allograft function, referred to as "chronic rejection," still remains the main obstacle to long-term graft survival. The common feature of chronic rejection is a concentric generalized graft arteriosclerosis associated with interstitial fibrosis that reflects an allogeneic injury to graft arteries, possibly worsened by other alloantigen-independent risk factors. The presence of the angiotensin I-converting enzyme (ACE) gene-deleted (D) allele has been associated, when in homozygosity, with increased risk of cardiovascular diseases and with an accelerated progression of organ damage in a variety of kidney diseases. In this study, we analyzed whether the insertion/deletion polymorphism of the ACE gene, because of its negative prognostic impact on cardiovascular and renal pathology, could have any influence on kidney graft survival in pediatric recipients.

Methods: DNA was isolated from peripheral blood mononuclear cells from 146 pediatric dialysis patients (mean age: 12.9 years) who received a first kidney graft at our center between December 1985 and July 1997. To rule out any bias due to acute graft losses, only 119 patients who reached a minimum of 12 months of graft survival were considered for statistical analysis. The insertion/deletion polymorphism of the ACE gene was detected using a polymerase chain reaction technique with two flanking primers.

Results: The results demonstrated that (i) the distribution of DD and non-DD (ID + II) genotypes was 36.1% (43 patients) and 63.8% (76 patients), respectively; (ii) actuarial graft survival at 7, 8, 9, and 10 years in patients with non-DD genotype was significantly higher than that in patients with DD genotype (7 years: 94.6% vs. 72.4%, P<0.05; 8 years: 94.6% vs. 62%, P<0.025; 9 years: 87.3% vs. 51.4%, P<0.025; 10 years: 76.3% vs. 25.7%, P<0.01).

Conclusions: In conclusion, the above data indicate that DD genotype is associated in pediatric kidney graft recipients with a shorter long-term kidney graft survival and suggest a possible role of this genotype as a cofactor in the progression of nonimmunological injuries leading to chronic kidney graft failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Angiotensin II / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Genotype
  • Humans
  • Kidney Transplantation*
  • Male
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*
  • Renin-Angiotensin System / physiology


  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin II
  • Peptidyl-Dipeptidase A