Renoprotection with and without blood pressure reduction.
BACKGROUND
AT1-receptor blockade dose dependently lowers blood pressure (BP) and albuminuria. Reduction of BP and albuminuria are independent treatment targets for renoprotection, but whether this requires similar dose titration is unknown.


METHODS
We tested this in two studies designed to find the optimal antialbuminuric dose of losartan in type 1 diabetic (DM, N= 50) and nondiabetic renal patients (ND, N= 12). After baseline, treatment followed with losartan 50, 100, and 150 mg/day, each dose for eight (DM) or six weeks (ND). At the end of each period, albuminuria (24-hour samples) and mean arterial pressure (MAP) were measured. Patients were divided into "good" and "poor" BP responders (BP+, BP-) according to BP response above or below group median.


RESULTS
Baseline MAP in the BP- groups was 102 (97, 104) mm Hg in DM (median, 95% CI) and 91 (80, 108) mm Hg in ND. The top of the dose response for BP (obtained at losartan 100 mg) in the BP- groups was -2 (-4, 3) mm Hg in DM and -1 (-6, 2) mm Hg in ND, versus -15 (-18, -12) mm Hg and -16 (-26, -18) mm Hg in BP+ groups (both P < 0.05). Albuminuria was reduced dose dependently both in BP- and BP+: with 100 mg, the reduction in albuminuria in DM BP- was -32% (-49, 13) versus -45% (-60, -38) in DM BP+ and -45% (-70,-7) versus -25% (-58, -6) in ND BP- and BP+ (all P > 0.05). Moreover, in patients in whom BP fell below the recommended treatment target of 130/80 mm Hg (13 in DM and 10 in ND), albuminuria was progressively reduced, with further increasing the dose of losartan in most patients.


CONCLUSIONS
Absence of BP response to losartan does not preclude a reduction in albuminuria, and optimal reduction of albuminuria may require titration beyond the predefined BP target.
Laverman
Gozewijn Dirk
GD
Division of Nephrology, Department of Internal Medicine, and Department of Clinical Pharmacology, University of Groningen, Groningen, The Netherlands. gd_laverman@hotmail.com
Andersen
Steen
S
Rossing
Peter
P
Navis
Gerjan
G
de Zeeuw
Dick
D
Parving
Hans-Henrik
HH
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006977:Hypertension, Renal / Q000188:drug therapy*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged
D000959:Antihypertensive Agents; D019808:Losartan