Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1R and ecNOS
A. Basset El-Essawy1,2, P. Berthoux1,2, S. Cécillon2, C.Deprèle1,2, D. Thibaudin1,2, J.-P. De Filippis1, E.Alamartine1,2, F. Berthoux1,2
1 Nephrology, Dialysis and Renal Transplantation Department, Hôpital Nord, CHU de Saint-Etienne, 2 Research Group on Glomerulonephritides and Renal Transplantation, Faculty of Medicine, Saint-Etienne, France
DOI 10.5414/CNP57192
Abstract
Background: Arterial hypertension (HT), secondary to cyclosporine A (CsA) used as main immunosuppressive treatment in renal transplantation (RTx), is very frequent (70%), usually severe and explained mostly by vasoconstriction of the glomerular afferent arteriole with secondary sodium and water retention. Material and methods: In a retrospective study, we have analyzed 294 consecutive recipients receiving a first renal cadaveric allograft and all treated with CsA (the majority with triple therapy). We studied, by molecular biology, the polymorphism of genes previously implicated in essential HT such as: angiotensin-converting enzyme (ACE: II, ID and DD), angiotensinogen (AGT: MM, MT and TT), angiotensin II type 1 receptor (AT1-R: AA, AC and CC) and endothelial constitutive nitric oxide synthase (ecNOS: aa, ab and bb), and correlated the data to the prevalence and severity of post-Tx HT. This cohort included 195 (66%) males and 99 females with a mean age of 42 years at time of Tx. The presence and severity of post-Tx HT were indicated by initial persistent blood pressure over 140/90 mmHg with the need for at least one anti-hypertensive drug and by the number of anti-HT medications required to achieve its control. Results: The distribution of the specific alleles and genotypes for ACE, AGT, AT1-R, and ecNOS was not different in transplant recipients compared to 181 controls. At 5 years post-Tx, the prevalence of HT was 72% (169 out of 235) among functioning grafts. There was no significant difference for ACE, AGT, AT1R and ecNOS genotypes distribution between hypertensive vs non-HT recipients. The number of anti-hypertensive drugs prescribed was not different among ACE, AGT, and AT1-R genotypes. However, the a allele and the non-bb genotype (aa + ab) for ecNOS were significantly (p = 0.001) associated with a less severe HT, needing fewer anti-HT drugs. At 10 years post-Tx, the HT prevalence remained high 78% (67 out of 86) among functioning Tx. However, the limited numbers did not allow further correlation. Conclusions: This study produced mainly negative results except for ecNOS-a allele, which seems to protect against severe hypertension. The explanation remains speculative but probably relates to the known cyclosporine-induced upregulation of ecNOS gene and enzyme activity.
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- 1 Nephrology, Dialysis and Renal Transplantation Department, Hôpital Nord, CHU de Saint-Etienne,
- 2 Research Group on Glomerulonephritides and Renal Transplantation, Faculty of Medicine, Saint-Etienne, France
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Citation
A. Basset El-Essawy, P. Berthoux, S. Cécillon, C.Deprèle, D. Thibaudin, J.-P. De Filippis, E.Alamartine, and F. Berthoux.Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1R and ecNOS. 2002; 57: 192-200. doi: 10.5414/CNP57192.
