The renin-angiotensin system in malignant hypertension revisited: plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension.
BACKGROUND
Malignant hypertension is a renin-dependent form of hypertension. However, the variations in renin-angiotensin system (RAS) activation in malignant hypertension are not completely understood. A proposed mechanism for ongoing RAS activation is the presence of microangiopathic hemolysis resulting in renovascular ischemia.


METHODS
We prospectively examined the association between plasma renin activity (PRA), microangiopathic hemolysis, and renal dysfunction in 30 consecutive patients with malignant hypertension (n=18) and severe hypertension (n=12). The PRA and aldosterone were measured in the supine position and before initiating therapy.


RESULTS
The PRA was 8.8 ng angiotensin I (AI)/mL/h (interquartile range [IQR] 4.8-20) in malignant hypertensive patients and 2.8 ng AI/mL/h (IQR 0.6-6.3) in patients with severe hypertension (P<.01). Aldosterone was 1.30+/-1.02 nmol/L in patients with malignant hypertension compared with 0.44+/-0.37 nmol/L in those with severe hypertension (P<.01). In malignant hypertension, PRA highly correlated with lactic dehydrogenase (LDH) (r=0.76, P<.001), meaning that 58% of the variations in PRA could be explained by LDH. The PRA positively correlated with serum creatinine values at presentation (r=0.50, P=.007), but adjustment for LDH abolished the effect of PRA on creatinine (P=.24).


CONCLUSIONS
The PRA and aldosterone were markedly elevated in patients with malignant hypertension but not in severely hypertensive patients despite small differences in blood pressure (BP). The strong logarithmic correlation between PRA, microangiopathic markers, and renal dysfunction suggests a renin-mediated acceleration of vascular damage and renal dysfunction in patients with malignant hypertension.
Department of Internal and Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands. b.j.vandenborn@amc.uva.nl
Bert-Jan H
BJ
van den Born
Richard P
RP
Koopmans
Gert A
GA
van Montfrans
D000328:Adult; D000450:Aldosterone / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006461:Hemolysis / Q000502:physiology*; D006801:Humans; D006974:Hypertension, Malignant / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000502:physiology*; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; D000450:Aldosterone; D003404:Creatinine; D012083:Renin