Abstract 4362827: Urine biomarkers predict declining kidney function and risk of cardiovascular disease

Introduction/Background: Urine biomarkers of kidney function may predict the progression of kidney dysfunction and risk of cardiovascular disease. Methods: We measured 14 urine biomarkers in 2948 Framingham Heart Study (FHS) participants (mean age 59, 53% women )at a routine examination in 1995-1998. Fourteen urine biomarkers (indexed to urine creatinine) (Table 1) were tested for association with new-onset of: 1) chronic kidney disease (CKD), 2) microalbuminuria, 3) coronary heart disease (CHD), 4) atherosclerotic cardiovascular disease (asCVD) , 5) congestive heart failure (CHF), 6) stroke, 7) cancer, and 8) all-cause mortality. We applied age-specific estimated glomerular filtration rate (eGFR) cut-points to define CKD (eGFRcr values of 70, 60, 45 (ml/min/1.73m2 ) for age groups: <55, 55-65, >= 65, respectively). We applied Cox models to assess associations with outcomes by quartile of urine biomarkers and tested for trend across quartiles after adjusting for age, sex, blood pressures, hypertension treatment, total and HDL cholesterol, lipid treatment, diabetes, cigarette smoking, alcohol use, eGFRcr, and dip-stick albuminuria. Statistical significance was defined by linear trend p value <0.05. Results: Higher urine TFF3 was associated with risk of new-onset CKD (Fig-1). Higher A1M, CTGF, KIM1, NGAL, TIMP1, and VEGF were associated with risk of microalbuminuria. Higher A1M, KIM1, and NGAL were associated with risk of CHF. OPN was inversely associated with new-onset stroke (Fig-1). Nine biomarkers were associated with all-cause death (Fig- 2). Conclusions: Multiple kidney-related biomarkers were associated with new-onset kidney dysfunction, CHF, and death and suggest value of urine biomarkers to identify risk for kidney dysfunction and CVD.