TY - JOUR

T1 - Variability in response to albuminuria-lowering drugs

T2 - true or random?

AU - Petrykiv, Sergei I

AU - de Zeeuw, Dick

AU - Persson, Frederik

AU - Rossing, Peter

AU - Gansevoort, Ron T

AU - Laverman, Gozewijn D

AU - Heerspink, Hiddo J Lambers

N1 - © 2016 The British Pharmacological Society.

PY - 2017/6

Y1 - 2017/6

N2 - AIMS: Albuminuria-lowering drugs have shown different effect size in different individuals. Since urine albumin levels are known to vary considerably from day-to-day, we questioned whether the between-individual variability in albuminuria response after therapy initiation reflects a random variability or a true response variation to treatment. In addition, we questioned whether the response variability is drug dependent.METHODS: To determine whether the response to treatment is random or a true drug response, we correlated in six clinical trials the change in albuminuria during placebo or active treatment (on-treatment) with the change in albuminuria during wash-out (off-treatment). If these responses correlate during active treatment, it suggests that at least part of the response variability can be attributed to drug response variability. We tested this for enalapril, losartan, aliskiren, atrasentan and paricalcitol.RESULTS: No correlation between the on- and off-treatment albuminuria change was observed in the placebo arm of all clinical trials (R(2) < 0.01). However, we observed significant associations between the on- and off-treatment response (R(2) 0.14 to 0.57; all P < 0.015) for different albuminuria lowering drugs. Additionally, the albuminuria responses strongly correlated when the same individual was re-exposed to the same drug at the same dose: lisinopril 10 mg day(-1) (R(2) = 53%; P < 0.01), losartan 50 mg day(-1) (R(2) = 63%; P < 0.01).CONCLUSION: The degree of albuminuria lowering with antialbuminuric drugs varies between patients. This variability in response appears drug-class independent. Identifying which factors determine this initial short-term variation in drug response appears important since the degree of albuminuria lowering is related to subsequent long-term renoprotection.

AB - AIMS: Albuminuria-lowering drugs have shown different effect size in different individuals. Since urine albumin levels are known to vary considerably from day-to-day, we questioned whether the between-individual variability in albuminuria response after therapy initiation reflects a random variability or a true response variation to treatment. In addition, we questioned whether the response variability is drug dependent.METHODS: To determine whether the response to treatment is random or a true drug response, we correlated in six clinical trials the change in albuminuria during placebo or active treatment (on-treatment) with the change in albuminuria during wash-out (off-treatment). If these responses correlate during active treatment, it suggests that at least part of the response variability can be attributed to drug response variability. We tested this for enalapril, losartan, aliskiren, atrasentan and paricalcitol.RESULTS: No correlation between the on- and off-treatment albuminuria change was observed in the placebo arm of all clinical trials (R(2) < 0.01). However, we observed significant associations between the on- and off-treatment response (R(2) 0.14 to 0.57; all P < 0.015) for different albuminuria lowering drugs. Additionally, the albuminuria responses strongly correlated when the same individual was re-exposed to the same drug at the same dose: lisinopril 10 mg day(-1) (R(2) = 53%; P < 0.01), losartan 50 mg day(-1) (R(2) = 63%; P < 0.01).CONCLUSION: The degree of albuminuria lowering with antialbuminuric drugs varies between patients. This variability in response appears drug-class independent. Identifying which factors determine this initial short-term variation in drug response appears important since the degree of albuminuria lowering is related to subsequent long-term renoprotection.

KW - Journal Article

U2 - 10.1111/bcp.13217

DO - 10.1111/bcp.13217

M3 - Journal article

C2 - 28002889

VL - 83

SP - 1197

EP - 1204

JO - British Journal of Clinical Pharmacology, Supplement

JF - British Journal of Clinical Pharmacology, Supplement

SN - 0264-3774

IS - 6

ER -