Objectives: 

The most important risk factor for both cardiovascular and chronic kidney disease is hypertension. Early detection of hypertensive end organ damage and secondary diseases are key determinants of cardiovascular prognosis. Recently, multiple biomarkers have been suggested to play a role in cardiovascular and renal disease, but biomarkers for the detection of the occurrence of vascular and organ (heart, kidney, retina) damage in hypertensive patients remain still unidentified. Consequently, our aim is to try to find a new biomarker able to identify the occurrence of vascular and organ damage due to hypertension.

Materials: 

We have analysed the urinary excretion of the serine protease kallikrein-related peptidase 9 (KLK9), a member of the kinin-kallikrein system, mainly expressed in submaxillar glands and whose function remains unknown, in different models of hypertension in rats (spontaneously hypertensive rats -SHR-, N-nitro-l-arginine-methyl-ester (L-NAME)-induced hypertension, SHR treated with antihypertensive drugs and Wistar rats).

Results: 

We observed in our experimental models (SHR, L-NAME-induced hypertension), that the urinary excretion of KLK9 is increased in the presence of hypertension. KLK9 urinary excretion appears before the onset of hypertensive nephropathy. We found that KLK9 expression is not increased in the kidney, heart, liver, lungs or blood serum in the presence of hypertension. Urinary KLK9 excretion in the presence of hypertension may have its origin in a decreased tubular reabsorption. KLK9 urinary excretion is strongly correlated to both cardiac hypertrophy and aortic wall thickening. The ACE inhibitor trandolapril significantly reduced the arterial pressure and the expression of KLK9 in urine.

Conclusions: 

In summary, KLK9 appears in the urine in the presence of consolidated hypertension prior to the onset of hypertensive nephropathy. KLK9 may be an indicator of the presence of target organ damage (cardiac hypertrophy, arterial wall thickening) associated with hypertension.