UCSF

Objective

Endothelial dysfunction is a possible mechanism to explain the association between atherosclerosis and kidney disease. This study evaluated circulating soluble endothelial cell-selective adhesion molecule (sESAM), a marker of endothelial dysfunction, as a risk factor for kidney function decline and albuminuria.

Approach and results

In the Heart and Soul Study, we measured sESAM from baseline serum samples and defined elevated levels of sESAM by the highest quartile (quartile 4 [Q4]: >65.4 ng/mL). We evaluated the associations of high sESAM with baseline estimated glomerular filtration rate (eGFR) and ratio of urine albumin to creatinine (ACR), and with longitudinal changes in eGFR and ACR. Among 990 participants with sESAM measurements, median sESAM was 54.5 ng/mL (interquartile range, 45.3-65.8). After multivariable adjustment, elevated levels of sESAM were strongly and independently associated with baseline reduced eGFR <60 mL/min per 1.73 m(2) (odds ratio [OR], 11.44; P<0.0001) and ACR ≥30 mg/g (OR, 5.23; P<0.0001). Associations of sESAM (Q4 versus quartile 1 [Q1]) with change in ACR (β=54.47; P<0.0001) were also significant after full adjustment. The association with change in eGFR (1.56%; P=0.0049) was not statistically significant after application of the Bonferroni correction for multiple markers. In unadjusted models, sESAM was associated with rapid kidney function loss, defined as 3% annual eGFR decline (OR, 2.28; P=0.0003), although this was attenuated by adjustment (OR, 2.11; P=0.0095).

Conclusions

sESAM is associated with albuminuria and reduced kidney function in both cross-sectional and longitudinal analyses. These findings implicate endothelial dysfunction as a potential contributor to the elevated kidney disease risk in persons with cardiovascular disease.