D007: Pharmacogenomic treatment of hypertensive patients with polycystic kidney disease according to genotypes of renin angiotensin system

• Published in: American journal of hypertension 2000-04, Vol.13 (S2), p.75A-75A
• Main Authors: Aranda, P., Reyes, A., Aranda, F.J., Dieguez, J.L., Lopez-Novales, E.
• Format: Article
• Language: English
• Subjects: Genotypes of RAS; polycystic kidney disease; Renin angiotensin system
• ISSN: 0895-7061; 1941-7225
• DOI: 10.1016/S0895-7061(00)00845-1

To search for the link between the pathogenetic role of activation of the RAS in the development and progression of renal damage and the therapeutic response to its pharmacologic block either with ACEI or AT1 receptor Antagonists (AT1rA) according to genetic polimorphism of the RAS. In a group of 60 hypertensive patients with ADPKD (34/56.7% women. Mean age: 43.2 ± 15 years. Mean time since diagnosis: 81 ± 14 months, and mean serum creatinine (sCr): 1.59 ± 0.93 mg/dl), we determined by PCR techniques, the genetic polimorphisms of angiotensinogen (ATG) and angiotensin converting enzyme (ACE) as well as we analyzed, the therapeutic effects of blocking the RAS either with ACEIs or AIIRAs on renal function and proteinuria during a retrospective period of 5 years. All patients followed a moderate protein restriction diet and were treated with ACEIs (80%) or AIIRAs (20%) either in monotherapy (15%) or in combination with CCB (36.6%), diuretics (35%), betablockers (23.3%) and/or alphablockers (30%). There were no statistically significant differences between the different subgroups of genotypes regarding mean age, or mean treated BP (mean: 134.8 ± 8.5/85.2 ± 5 mmHg). After the analysis of the data we found: We conclude that among hypertensive patients with ADPKD those with the TT (ATG) or II (ACE) genotypes have the best renal prognosis. Patients with MM (ATG) or DD (ACE) genotypes showed a good response in slowing renal damage progression when blocking RAS, while the MT (ATG) and ID (ACE) patients had a worse response. (See Table) Genotype s (%) ATG ACE MM (43,3) MI (41,7) TT (15) DD (41,7) ID (35) II (23,3) SCr1 1,85 ± 1,5 1,79 ± 1,1 1,12 ± 0,2 1,87 ± 1,3 1,9 ± 1,0 1,17 ± 0,4 (P) n.s. * ** ns * ns SCr2 2,28 ± 1,7 3,47 ± 2,8 1,32 ± 0,5 2,05 ± 2,6 3,72 ± 2,6 1,32 ± 0,6 Proteinuria (n-%) 10–38,5 7–28 0 10–40 9–42,8 0 Proteinuria1 0,58 ± 0,5 0,47 ± 0,7 0 0,81 ± 0,8 0,36 ± 0,4 0 Proteinuria2 0,12 ± 0,2 0,21 ± 0,3 0 0,21 ± 0,5 0,68 ± 0,7 0 sCr1: Initial sCr (mg/dL), sCr2: 60 months sCr (mg/dL). Proteinuria 1: values initial; Proteinuria 2: values at 60 months; *p < 0.001; **p < 0.01.