LAUSR

Abstract Purpose: Subclinical chronic kidney disease is known to exacerbate hypertension and progression of kidney damage. In order to initiate timely interventions, early biomarkers for this vicious circle are needed. Our aim was to describe the cross-sectional associations of urinary orosomucoid and urinary N-acetyl-β-D-glucosaminidase (NAG) with blood pressure and the longitudinal associations of urinary orosomucoid and NAG to hypertension after 7 years, and to compare the strength of these associations to the urinary albumin excretion (UAE). Material and methods: The Tromsø Study is a population-based, prospective study of inhabitants of the municipality of Tromsø, Northern Norway. Morning spot urine samples were collected on three consecutive days in the Tromsø 6 survey (2007–2008). We assessed the cross-sectional associations of urinary orosomucoid, NAG and UAE with blood pressure in Tromsø 6. In a cohort of participants attending Tromsø 6 and Tromsø 7 (2015–2016), we studied whether urinary biomarkers were longitudinally associated with hypertension. Results: A total of 7197 participants with a mean age of 63.5 years (SD 9.2), and a mean blood pressure of 141/78 mmHg (SD 23.0/10.6), were included in the study. Orosomucoid and UAE, but not NAG, was significantly associated with systolic and diastolic blood pressure in all the crude and multivariable cross-sectional analyses. Orosomucoid had consistently, although marginally, stronger associations with blood pressure. Incident hypertension at follow-up (Tromsø 7) was consistently significantly associated with urinary orosomucoid, but not urinary NAG or UAE. However, the standardized regression coefficients for orosomucoid were only marginally stronger than the standardized regression coefficients for ACR. Conclusion: In a cohort from the general population urine orosomucoid had a stronger cross-sectional association with blood pressure than UAE. After 7 years, urine orosomucoid showed the strongest association with incident hypertension. There were varying and weak associations between U-NAG, blood pressure and hypertension. PLAIN LANGUAGE SUMMARY What is the context? There is a relationship between high blood pressure and cardiovascular and kidney disease. Hypertension is defined as the level of blood pressure at which the benefits of treatment outweigh the risks of treatment. Hypertension is a risk factor for developing kidney disease, and kidney disease is a risk factor for developing hypertension. Today, kidney function is assessed by blood and urine samples (estimated glomerular filtration rate and urinary albumin excretion). However, today's blood and urine samples are not sensitive enough to capture kidney damage due to hypertension at a stage when prevention may be most effective. What is new? In this study, we assessed if urine orosomucoid and N-acetyl-β-D-glucosaminidase (NAG) are more strongly associated with blood pressure and hypertension than urinary albumin excretion. In the population-based study of residents in Tromsø, Northern Norway, we assessed the relationship between the urine biomarkers and blood pressure, and the development of hypertension after 7 years. In the general population urine orosomucoid had a stronger relationship with blood pressure than urinary albumin excretion. After 7 years, urine orosomucoid had the strongest relationship with the development of hypertension. There were only varying and weak relationships between NAG, blood pressure and hypertension. What is the impact? Orosomucoid showed a stronger relationship with blood pressure and the development of hypertension than urinary albumin excretion. Urine orosomucoid may aid targeted prevention and treatment in hypertension, but further prospective clinical studies are needed to assess if orosomucoid is a clinically useful biomarker in hypertension.