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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These preliminary results suggest a possible influence of CYP2C9 genotype on proteinuria and blood pressure in Caucasian CKD patients treated with losartan.
Joy
Melanie S
MS
Division of Nephrology and Hypertension, School of Medicine, UNC Kidney Center, University of North Carolina, Chapel Hill, NC, USA. Melanie_Joy@med.unc.edu
Dornbrook-Lavender
Kimberly
K
Blaisdell
Joyce
J
Hilliard
Tandrea
T
Boyette
Tammy
T
Hu
Yichun
Y
Hogan
Susan L
SL
Candiani
Corina
C
Falk
Ronald J
RJ
Goldstein
Joyce A
JA
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects*; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011507:Proteinuria / Q000517:prevention & control*; D044465:White People / Q000235:genetics
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D019808:Losartan