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Abstract Several novel urinary kidney damage biomarkers predict the progression of kidney disease. However, the relations of these biomarkers to atherosclerosis, a major consequence of kidney disease, are less studied. Urinary levels of several biomarkers, including kidney injury molecule-1 (KIM-1), osteopontin, epidermal growth factor, and Dickkopf-3, were assessed in participants enrolled in the Swedish CArdioPulmonary BioImage Study. The study included 9,628 individuals with a mean age of 57.5 years, of which 52.4% were women. The presence of coronary artery stenosis and the coronary artery calcium score (CACS) were determined using coronary computed tomography angiography. To analyze the associations between coronary atherosclerosis and urinary biomarker levels, an ordered logistic regression model adusting for confounding factors was employed. KIM-1 was the only biomarker associated with both coronary stenosis and CACS after adjusting for established cardiovascular risk factors (odds ratio [95% confidence intervals], 1.23[1.05–1.44] and 1.25[1.07–1.47]). These results were consistent in sensitivity analyses of individuals without hypertension, diabetes, or known cardiovascular disease and with normal kidney function. Urinary KIM-1, a specific marker of proximal tubular damage, was robustly linked to coronary atherosclerosis even in apparently healthy individuals, which suggests that the detrimental interplay between the kidney and cardiovascular system begins before clinically overt kidney disease. Additional studies are warranted to evaluate the urinary KIM-1 to predict kidney and cardiovascular disease.

Background: Endostatin, cleaved from collagen XVIII in the extracellular matrix, is a promising circulating biomarker for cardiovascular damage. It possesses anti-angiogenic and anti-fibrotic functions and has even been suggested to be involved in blood pressure regulation. Less is known if endostatin levels relate to circadian blood pressure patterns. In the present paper we studied the association between circulating levels of endostatin and nocturnal dipping in blood pressure. Methods: We used the CARDIPP-study, a cohort of middle aged, type 2 diabetics (n = 593, 32% women), with data on both 24-hour and office blood pressure, serum-endostatin, cardiovascular risk factors, and incident major cardiovascular events. Nocturnal dipping was defined as a >10% difference between day- and night-time blood pressures. Results: Two-hundred four participants (34%) were classified as non-dippers. The mean endostatin levels were significantly higher in non-dippers compared to dippers (mean ± standard deviation: 62.6 ± 1.8 µg/l vs. 58.7 ± 1.6 µg/l, respectively, p = .007). Higher serum levels of endostatin were associated with a diminished decline in nocturnal blood pressure adjusted for age, sex, HbA1c, mean systolic day blood pressure, hypertension treatment, glomerular filtration rate, and prevalent cardiovascular disease (regression coefficient per SD increase of endostatin −0.01, 95% CI, −0.02–(−0.001), p = .03). Structural equation modelling analyses suggest that endostatin mediates 7% of the association between non-dipping and major cardiovascular events. Conclusion: We found an independent association between higher circulating levels of endostatin and a reduced difference between day- and night-time systolic blood pressure in patients with type 2 diabetes. Yet endostatin mediated only a small portion of the association between non-dipping and cardiovascular events arguing against a clinical utility of our findings.