Autoregulation of glomerular filtration rate during spironolactone treatment in hypertensive patients with type 1 diabetes: a randomized crossover trial
2009
Background.
Autoregulationof 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
spironolactoneaffects the ability to
autoregulateGFR. 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
spironolactone25 mg o.d. and matched placebo for 4 weeks in random order. After each treatment period, the ability to
autoregulateGFR 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.
Spironolactonedid not significantly reduce GFR or BP. Injection of
clonidineinduced a significant reduction in the MAP of 17 (2) and 19 (1) mmHg during placebo and
spironolactonetreatment, 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
autoregulationwere present in nine patients during placebo and in nine patients during
spironolactonetreatment. 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, HbAlc or to changes in BP. Conclusion.
Spironolactonedid not change the overall ability to
autoregulateGFR in 16 hypertensive type 1 diabetic patients with normoalbuminuria. Our data are suggestive that the ability to
autoregulateGFR is gradually impaired with increasing diabetes duration, a phenomenon not previously described in normoalbuminuric patients.
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