Modest systolic blood pressure reductions to 160-180 mm Hg led to a striking resolution of vascular and glomerular malignant nephrosclerosis injury (injury score 35 vs 9, P<0.0001).
Does blood pressure reduction below a critical threshold prevent and repair malignant nephrosclerosis in stroke-prone spontaneously hypertensive rats?
Lowering blood pressure below a critical threshold prevents and rapidly repairs malignant nephrosclerosis in a hypertensive rat model, regardless of the antihypertensive class used.
Absolute Event Rate: 9% vs 35%
p-value: p=<0.0001
Most patients with essential hypertension do not exhibit substantial renal damage. Renal autoregulation by preventing glomerular transmission of systemic pressures has been postulated to mediate this resistance. Conversely, malignant nephrosclerosis (MN) has been postulated to develop when severe hypertension exceeds a critical ceiling. If the concept is valid, even modest blood pressure (BP) reductions to below this threshold regardless of antihypertensive class (1) should prevent MN and (2) lead to the healing of the already developed MN lesions. Both predicates were tested using BP radiotelemetry in the stroke-prone spontaneously hypertensive rats receiving 1% NaCl as drinking fluid for 4 weeks. Severe hypertension (final 2 weeks average systolic BP, >200 mm Hg) and MN (histological damage score 36±5; n=27) developed in the untreated stroke-prone spontaneously hypertensive rats but were prevented by all antihypertensive classes (enalapril n=15, amlodipine n=13, or a hydralazine/hydrochlorothiazide combination n=15) if the final 2-week systolic BP remained <190 mm Hg. More impressively, modest systolic BP reductions to 160 to 180 mm Hg (hydralazine/hydrochlorothiazide regimen) initiated at ≈4 weeks in additional untreated rats after MN had already developed (injury score 35±4 in the right kidney removed before therapy) led to a striking resolution of the vascular and glomerular MN injury over 2 to 3 weeks (post-therapy left kidney injury score 9±2, P <0.0001; n=27). Proteinuria also declined rapidly from 122±9.5 mg/24 hours before therapy to 20.5±3.6 mg 1 week later. These data clearly demonstrate the barotrauma-mediated pathogenesis of MN and the striking capacity for spontaneous and rapid repair of hypertensive kidney damage if new injury is prevented.
Griffin et al. (Tue,) conducted a other in Malignant nephrosclerosis and severe hypertension (n=97). Antihypertensive therapy (enalapril, amlodipine, or hydralazine/hydrochlorothiazide) vs. Untreated / Pre-therapy baseline was evaluated on Histological damage score (p=<0.0001). Modest systolic blood pressure reductions to 160-180 mm Hg led to a striking resolution of vascular and glomerular malignant nephrosclerosis injury (injury score 35 vs 9, P<0.0001).