Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension

Abstract

Background and objectives: Malignant hypertension (MHT) characterized by acute hypertension with retinopathy or multiorgan damage, is a severe form of hypertensive emergency and associated with target organ involvement and poor kidney outcome. However, the underlying mechanisms are unclear. Methods: Eighty-four patients with acute severe hypertension from the Nephrology Department and Emergency Department in a single center during January 2016 and December 2017 were prospectively enrolled and divided into MHT (n = 48) and non-MHT (n = 36) subgroups according to target organ evaluation. Forty healthy controls were recruited. Serum soluble Fms-like tyrosine kinase-1 (sFlt-1) levels and plasma ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity were examined at baseline and 12-month follow-up. Renal endpoints were defined as a significant decrease in the estimated glomerular filtration rate (eGFR) of more than 40% or the occurrence of end-stage renal disease. Results: Serum sFlt-1 levels were persistently elevated in MHT. Baseline serum sFLT-1 levels were correlated with plasma ADAMTS13 activity and markers of target organ damage. Plasma ADAMTS13 activity was reduced in both MHT and non-MHT patients and recovered to the normal range at 12-month follow-up. During an average follow-up time of 53 ± 13 months, the restoration of reduced ADAMTS13 activity was correlated with the improvement of kidney function and independently reduced the risk of renal endpoints. Conclusions: Abnormal angiogenesis and endothelial damage are involved in the pathophysiology of hypertensive emergency. Evaluation of ADAMTS13 and sFlt-1 may help in the diagnosis and assessment of MHT. Recovery of ADAMTS13 predicts better renal outcome in patients with hypertensive emergencies.