CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases

Abstract

Losartan is used for anti-proteinuric as well as blood pressure effects in chronic kidney disease (CKD). It is metabolized by cytochrome P450 (CYP) 2C9 to active E-3174. Single nucleotide polymorphisms in CYP2C9 that reduce catalytic activity could reduce clinical benefits. The study aims were to determine whether CYP2C9 variant alleles (*2 and *3) altered urinary protein excretion, glomerular filtration rate, and blood pressure in Caucasian patients prescribed losartan. Differences between baseline and 6-month follow-up outcomes were compared by CYP2C9 genotypes in 59 patients using unpaired t test or Mann-Whitney U test. Primary renal disease patients had a trend toward less favorable antiproteinuric response (-31.7 +/- 156 vs. -125 +/- 323%; p = 0.123) when carrying variant alleles. Patients with secondary renal diseases had less favorable diastolic blood pressure (9.8 +/- 16.0 vs. -3.2 +/- 10.6 mmHg; p = 0.043) and systolic blood pressure (16.2 +/- 27.1 vs. -5.5 +/- 17.5 mmHg; p = 0.044) with CYP2C9 variants. These preliminary results suggest a possible influence of CYP2C9 genotype on proteinuria and blood pressure in Caucasian CKD patients treated with losartan.