Autoregulation of glomerular filtration rate during spironolactone treatment in hypertensive patients with type 1 diabetes: a randomized crossover trial.
BACKGROUND
Autoregulation of GFR, i.e. maintenance of relative constancy of GFR despite variations in mean arterial pressure (MAP) >80 mmHg, is impaired in diabetic kidney disease; furthermore, some antihypertensive drugs may jeopardize autoregulation. The aim of our study was to establish if spironolactone affects the ability to autoregulate GFR.


METHODS
Sixteen hypertensive type 1 diabetic patients with persistent normoalbuminuria (presumed normal autoregulation) completed this randomized, double-masked, crossover trial. After a 4-week wash-out period, patients received spironolactone 25 mg o.d. and matched placebo for 4 weeks in random order. After each treatment period, the ability to autoregulate GFR was determined by measuring GFR ((51)Cr-EDTA clearance) before (basal) and after acute blood pressure reduction by intravenous injection of clonidine.


RESULTS
During placebo, the mean (SE) basal GFR was 115 (5) ml/min/1.73 m(2) and the BP was 146 (4)/81 (2) mmHg corresponding to a MAP of 103 (2) mmHg. Spironolactone did not significantly reduce GFR or BP. Injection of clonidine induced a significant reduction in the MAP of 17 (2) and 19 (1) mmHg during placebo and spironolactone treatment, respectively, and an overall reduction in GFR of 11 and 15 ml/min/1.73 m(2) (both comparisons NS between treatment periods). Signs of impaired autoregulation were present in nine patients during placebo and in nine patients during spironolactone treatment. Relative changes in GFR on placebo treatment correlated with diabetes duration (R = 0.67, P < 0.01) but were not related to duration of hypertension, baseline BP, GFR, HbA1c or to changes in BP.


CONCLUSIONS
Spironolactone did not change the overall ability to autoregulate GFR in 16 hypertensive type 1 diabetic patients with normoalbuminuria. Our data are suggestive that the ability to autoregulate GFR is gradually impaired with increasing diabetes duration, a phenomenon not previously described in normoalbuminuric patients.
Schjoedt
Katrine J
KJ
1Steno Diabetes Center, Niels Steensens Vej 1, 2820 Gentofte, Denmark. kjos@steno.dk
Christensen
Per K
PK
Jorsal
Anders
A
Boomsma
Frans
F
Rossing
Peter
P
Parving
Hans-Henrik
HH
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000209:etiology; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D013148:Spironolactone / Q000627:therapeutic use*
D013148:Spironolactone; D012083:Renin