ABSTRACT Background Evaluation of renal function and of factors associated with its decline are important public health issues. Besides markers of glomerular function [e.g. glomerular filtration rate (GFR)], those of tubular functions are rarely evaluated. Urea, the most abundant urinary solute, is markedly concentrated in urine when compared with plasma. We explored the urine-to-plasma ratio of urea concentrations (U/P urea ratio) as a marker of tubular functions. Methods We evaluated the relationship of the U/P urea ratio with eGFR at baseline in 1043 participants (48 ± 17 years) from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) population-based cohort, using mixed regression. In 898 participants, we assessed the relation between U/P urea ratio and renal function decline between two study waves 3 years apart. We studied U/P ratios for osmolarity, Na, K and uric acid for comparison. Results In a transversal study at baseline, estimated GFR (eGFR) was positively associated with U/P-urea ratio [βscaled = 0.08, 95% CI (0.04; 0.13)] but not with the U/P ratio of osmolarity. Considering separately participants with renal function >90 or ≤90 mL/min × 1.73 m2, this association was observed only in those with reduced renal function. In the longitudinal study, eGFR declined at a mean rate of 1.2 mL/min per year. A significant association was observed between baseline U/P urea ratio and eGFR decline [βscaled = 0.08, 95% CI (0.01; 0.15)]. A lower baseline U/P urea ratio was associated with a greater eGFR decline. Conclusion This study provides evidence that the U/P urea ratio is an early marker of kidney function decline in the general adult population. Urea is easy to measure with well-standardized techniques and at low cost. Thus, the U/P urea ratio could become an easily available tubular marker for evaluating renal function decline.