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Renal hemodynamic effects of candesartan in normal and impaired renal function in humans.

Hanneke Buter, GJ Navis, Dick de Zeeuw, P E de Jong

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Abstract

The effects of angiotensin II type I receptor antagonist candesartan cilexitil, 8 mg once daily, were studied after single dose and after five days treatment in 17 hypertensive patients [median mean arterial pressure (MAP) 118 mm Hg, range 84 to 134] with renal function impairment of different severity [glomerular filtration rate (GFR) 60 ml/min, range 11 to 161]. The MAP fell by -8% (-14 to -5) and -11 (-16 to -5)% after single and multiple dose, respectively (both P < 0.02). Effective renal plasma flow (ERPF) increased by 13% (7 to 19) and 10% (3 to 14) after single and multiple dose, respectively (both P < 0.02), while the GFR did not change. Filtration fraction (FF) fell by -11% (-14 to -5) and -12% (-13 to -4) after single and multiple doses, respectively (both P < 0.02). After a single dose the % change in ERPF (r = 0.58) and FF (r = -0.52, both P < 0.05) positively correlated with pretreatment GFR, indicating a more pronounced response in patients with normal GFR. After five days of treatment these correlations were absent, indicating similar renal vasodilation in patients with normal and impaired renal function. Thus, multiple dose candesartan cilexitil had a favorable renal hemodynamic profile, irrespective of pretreatment renal function. Further studies are needed to establish whether this provides long-term renoprotection as well.

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What this paper is about

The effects of angiotensin II type I receptor antagonist candesartan cilexitil, 8 mg once daily, were studied after single dose and after five days treatment in 17 hypertensive patients [median mean arterial pressure (MAP) 118 mm Hg, range 84 to 134] with renal function impairment of different severity [glomerular filtration rate (GFR) 60 ml/min, range 11 to 161]. The MAP fell by -8% (-14 to -5) and -11 (-16 to -5)% after single and multiple dose, respectively (both P < 0.02). Effective renal plasma flow (ERPF) increased by 13% (7 to 19) and 10% (3 to 14) after single and multiple dose, respectively (both P < 0.02), while the GFR did not change. Filtration fraction (FF) fell by -11% (-14 to -5) and -12% (-13 to -4) after single and multiple doses, respectively (both P < 0.02). After a single dose the % change in ERPF (r = 0.58) and FF (r = -0.52, both P < 0.05) positively correlated with pretreatment GFR, indicating a more pronounced response in patients with normal GFR. After five days of treatment these correlations were absent, indicating similar renal vasodilation in patients with normal and impaired renal function. Thus, multiple dose candesartan cilexitil had a favorable renal hemodynamic profile, irrespective of pretreatment renal function. Further studies are needed to establish whether this provides long-term renoprotection as well.

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Available abstract

The effects of angiotensin II type I receptor antagonist candesartan cilexitil, 8 mg once daily, were studied after single dose and after five days treatment in 17 hypertensive patients [median mean arterial pressure (MAP) 118 mm Hg, range 84 to 134] with renal function impairment of different severity [glomerular filtration rate (GFR) 60 ml/min, range 11 to 161]. The MAP fell by -8% (-14 to -5) and -11 (-16 to -5)% after single and multiple dose, respectively (both P < 0.02). Effective renal plasma flow (ERPF) increased by 13% (7 to 19) and 10% (3 to 14) after single and multiple dose, respectively (both P < 0.02), while the GFR did not change. Filtration fraction (FF) fell by -11% (-14 to -5) and -12% (-13 to -4) after single and multiple doses, respectively (both P < 0.02). After a single dose the % change in ERPF (r = 0.58) and FF (r = -0.52, both P < 0.05) positively correlated with pretreatment GFR, indicating a more pronounced response in patients with normal GFR. After five days of treatment these correlations were absent, indicating similar renal vasodilation in patients with normal and impaired renal function. Thus, multiple dose candesartan cilexitil had a favorable renal hemodynamic profile, irrespective of pretreatment renal function. Further studies are needed to establish whether this provides long-term renoprotection as well.

Key concepts: Effective renal plasma flow, Candesartan, Renal function, Filtration fraction, Medicine, Renal blood flow, Internal medicine, Urology

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