ACE gene D/D genotype as a risk factor for chronic nephrotoxicity from calcineurin inhibitors in liver transplant recipients

Lorenzo Gallon, Enver Akalin, Patrick Lynch, Laura Rothberg, Michele Parker, Thomas Schiano, Michael Abecassis, Barbara Murphy

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background. Chronic renal failure (CRF) is a major cause of morbidity and mortality after orthotopic liver transplantation (OLTX) and is predominantly caused by calcineurin inhibitors (CI)-induced nephrotoxicity. The activation of the renin angiotensin system (RAS) has been implicated in the pathogenesis of chronic nephrotoxicity from CI. Methods. We retrospectively investigated the genes coding for components of the RAS (ACE gene, Angiotensin II receptor 1 gene, Angiotensinogen gene) in 233 liver transplant recipients receiving Cyclosporine (CsA) or Tacrolimus (Tac) as maintenance immunusuppressant. All patients with serum creatinine (sCr) <1.0 mg/dL (n=143) before orthotopic liver transplantation (OLTX) were included in the final analysis. Patients were than categorized into two groups based upon their most recent postliver transplant sCr level: Group 1 (n = 83) with sCr <1.5 mg/dL (mean 1.1±0.2) and group 2 (n=60) with sCr ≥1.5 mg/dL (mean 2.5±1.3) Results. ACE D/D genotype was found in 57% of patients with sCr ≥1.5 mg/dL compared to 20% of patients with sCr <1.5 mg/dL (P<0.0001) Conclusions. Our analysis strongly suggests that liver transplant patients with ACE gene D/D genotype are at a significant higher risk of developing CI-induced chronic nephrotoxicity.

Original languageEnglish (US)
Pages (from-to)463-468
Number of pages6
JournalTransplantation
Volume81
Issue number3
DOIs
StatePublished - Feb 2006
Externally publishedYes

Fingerprint

Creatinine
Genotype
Liver
Serum
Genes
Renin-Angiotensin System
Liver Transplantation
Gene Components
Transplants
Angiotensinogen
Angiotensin Receptors
Tacrolimus
Cyclosporine
Chronic Kidney Failure
Calcineurin Inhibitors
Transplant Recipients
Maintenance
Morbidity
Mortality

Keywords

  • Gene polymorphism
  • Liver transplantation
  • Nephrotoxicity

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

ACE gene D/D genotype as a risk factor for chronic nephrotoxicity from calcineurin inhibitors in liver transplant recipients. / Gallon, Lorenzo; Akalin, Enver; Lynch, Patrick; Rothberg, Laura; Parker, Michele; Schiano, Thomas; Abecassis, Michael; Murphy, Barbara.

In: Transplantation, Vol. 81, No. 3, 02.2006, p. 463-468.

Research output: Contribution to journalArticle

Gallon, Lorenzo ; Akalin, Enver ; Lynch, Patrick ; Rothberg, Laura ; Parker, Michele ; Schiano, Thomas ; Abecassis, Michael ; Murphy, Barbara. / ACE gene D/D genotype as a risk factor for chronic nephrotoxicity from calcineurin inhibitors in liver transplant recipients. In: Transplantation. 2006 ; Vol. 81, No. 3. pp. 463-468.
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AU - Abecassis, Michael

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N2 - Background. Chronic renal failure (CRF) is a major cause of morbidity and mortality after orthotopic liver transplantation (OLTX) and is predominantly caused by calcineurin inhibitors (CI)-induced nephrotoxicity. The activation of the renin angiotensin system (RAS) has been implicated in the pathogenesis of chronic nephrotoxicity from CI. Methods. We retrospectively investigated the genes coding for components of the RAS (ACE gene, Angiotensin II receptor 1 gene, Angiotensinogen gene) in 233 liver transplant recipients receiving Cyclosporine (CsA) or Tacrolimus (Tac) as maintenance immunusuppressant. All patients with serum creatinine (sCr) <1.0 mg/dL (n=143) before orthotopic liver transplantation (OLTX) were included in the final analysis. Patients were than categorized into two groups based upon their most recent postliver transplant sCr level: Group 1 (n = 83) with sCr <1.5 mg/dL (mean 1.1±0.2) and group 2 (n=60) with sCr ≥1.5 mg/dL (mean 2.5±1.3) Results. ACE D/D genotype was found in 57% of patients with sCr ≥1.5 mg/dL compared to 20% of patients with sCr <1.5 mg/dL (P<0.0001) Conclusions. Our analysis strongly suggests that liver transplant patients with ACE gene D/D genotype are at a significant higher risk of developing CI-induced chronic nephrotoxicity.

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