Urinary and Plasma Levels of Vasohibin-1 Can Predict Renal Functional Deterioration in Patients with Renal Disorders

Abstract

Vasohibin-1 (VASH-1) is a negative feedback regulator of angiogenesis, and a small vasohibin-binding protein (SVBP) serves as its secretory chaperone and contributes to its antiangiogenic effects. In the present study, we aimed to define the clinical significance of VASH-1 and SVBP in patients with chronic kidney disease (CKD). We recruited 67 Japanese hospitalized patients with renal disorders with (n = 45) or without (n = 22) renal biopsy samples and 10 Japanese healthy controls. We evaluated the correlations between the plasma and urinary levels of VASH-1/VASH-1-SVBP complex/SVBP and the clinicopathological parameters. The plasma levels of VASH-1 were inversely correlated with age and systolic and diastolic blood pressure and positively correlated with crescent formation. Increased plasma and urinary levels of VASH-1 and VASH-1-SVBP complex were significantly correlated with worse renal outcomes. These results demonstrate an association between elevated urinary and plasma levels of VASH-1 and progressive decline of the renal function, thus suggesting a potential role for VASH-1 in predicting a worse renal prognosis in patients with renal disease, including CKD.

Novel Link between Inhibition of Angiogenesis and Tolerance to Vascular Stress

“…A similar situation has been documented in cases of disease associated with augmented cellular stress, namely, chronic renal disease (CKD) 62,63) . Importantly, one study determined the concentrations of VASH1 in CKD patients using ELISA; the results revealed that the plasma levels of VASH1 positively correlate with tracheal administration of adenoviral vectors encoding human VASH1 (AdhVASH1), paraquat-induced acute lung injury is almost completely prevented.…”

“…This disorder was also found to be associated with glomerular basement membrane thickening and a reduction in the slit diaphragm density. Furthermore, renal hypertrophy and the glomerular accumulation of the mesangial matrix and type IV collagen are exacerbated in diabetic VASH1 ( / ) mice versus their diabetic wild-type littermates 38) .…”

“…Due to the more serious paraquat-induced acute organ damage noted in VASH1 ( / ) mice versus their wild-type littermates 6) , the role of endogenous VASH1 in vascular diseases was further clarified by comparing the incidence and progression of STZ-induced diabetic vascular disease in VASH1 ( / ) mice with that seen in their wild-type littermates 38) . The results indicated that albuminuria is significantly exacerbated in diabetic VASH1 ( / ) mice compared with that observed in their diabetic wild-type littermates.…”

“…None. crescent formation and that increased plasma and urinary levels of VASH1 correlate with worse renal outcomes 62) . Therefore, elevated plasma and urinary levels of VASH1 may be markers predicting a worse prognosis in patients with CKD.…”

Increased vasohibin-1 expression is associated with metastasis and poor prognosis of renal cell carcinoma patients

“…In fact, urinary and plasma levels of VASH1 were reported to be useful for prediction of renal functional deterioration in patients with chronic renal disease. 33 Because VASH1 was associated with progression and resistance to sunitinib treatment of ccRCCs, quantification of VASH1 expression by RNA-based detection and/or liquid biopsy specimen using urine samples would be an easier method to predict the disease progression and useful for the choice of molecular targeted therapy in the future.…”