Table S1:Tracking Over Time of Differences Associated with Low Urine Urea Nitrogen

SupplementaryMaterial

Table S1:Tracking over time of differences associated with low urine urea nitrogen.

Table S2:Baseline descriptive statistics by sex-specific quintile of urine urea nitrogen.

Figure S1:Non-adjusted analysis of mortality by quintile of urine urea nitrogen.

Figure S2:Adjusted analysis of mortality by quintile of estimated protein intake.

Figure S3:Non-adjusted analysis ofgreat eGFR decline by quintile of urine urea nitrogen.

Figure S4:Adjusted analysis ofgreat eGFR decline by quintile of estimated protein intake.

Figure S5:Adjusted analysis ofgreat eGFR decline by baseline eGFR and by quintile of estimated protein intake.

Table S1. Tracking over time of differences associated with low urine urea nitrogen (UUN).Mean or prevalencein persons taking part in all exams and of adult age since the 1983-85 exam.

Baseline UUN
Low / Non-low
N persons / 330 / 1668
P value*
Plasma urea nitrogen, mg/dL / 1983-85 exam / 15.9 / 16.5 / 0.006
1989-92 exam / 15.6 / 17.1 / <0.001
2001-07exam / not measured
Urine sodium/potassium ratio / 1983-85 exam / 3.70 / 4.19 / <0.001
1989-92 exam / 3.91 / 4.64 / <0.001
2001-07 exam / not measured
Habitual alcohol intake, g/d / 1983-85 exam / 35.0 / 33.7 / 0.578
1989-92 exam / 26.4 / 22.6 / 0.039
2001-07 exam / 20.9 / 16.9 / 0.006
Obesity, % / 1983-85 exam / 7.3% / 17.3% / <0.001
1989-92 exam / 8.8% / 21.5% / <0.001
2001-07 exam / 11.6% / 23.5% / <0.001
Underweight, % / 1983-85 exam / 2.7% / 0.9% / 0.005
1989-92 exam / 1.5% / 0.4% / 0.010
2001-07 exam / 1.2% / 0.5% / 0.163

* for comparison between low UUN and non-low UUN by ANOVA or chi-square analysis

Table S2. Baseline descriptive statistics by sex-specific quintile of urine urea nitrogen (UUN). Mean or prevalence.

UUN quintile
1 / 2 / 3 / 4 / 5
UUN, g/h / 0.227** / 0.351 / 0.433 / 0.524 / 0.780
Number of persons (% men) / 861 (45.3%) / 860 (45.1%) / 863 (45.3%) / 864 (45.3%) / 859 (45.3%)
Age, y
Age ≥ 65 y, % (n) / 51.6**
31.6%** / 50.3
28.1% / 48.3
21.0% / 48.9
22.1% / 50.2
20.4%
Plasma urea nitrogen, mg/dL / 16.0** / 16.3 / 16.7 / 17.5 / 18.4
Protein intake, g/d
Protein intake, g/d per kg of ideal weight
Protein intake <0.8 g/d per kg of ideal weight, % (n) / 34.0**
0.60**
93.4%** / 52.7
0.92
14.0% / 65.0
1.12
0.0% / 78.6
1.36
0.0% / 117.0
2.03
0.0%
Urine sodium, mmol/h / 4.36** / 5.46 / 6.48 / 7.67 / 9.58
Urine potassium, mmol/h / 1.20** / 1.40 / 1.60 / 1.74 / 2.11
Urine sodium/potassium ratio / 4.03** / 4.29 / 4.47 / 4.92 / 5.03
Intake of alcohol, g/d / 25.4** / 21.7 / 20.8 / 20.4 / 21.6
Intake of milk or yogurt, mL/day / 76.2 / 75.4 / 82.9 / 81.5 / 78.5
Intake of caffeine-containing beverages, n/d / 1.69 / 1.73 / 1.66 / 1.76 / 1.73
Habitual physical activity, h/d / 0.220** / 0.258 / 0.289 / 0.312 / 0.334
eGFR, mL/min x 1.73 m2
reduced eGFR, % (n) / 82.8**
62.6%** / 84.1
62.2% / 87.1
54.9% / 88.7
52.9% / 89.6
48.8%
Body mass index, kg/m2
Obesity, % (n)
Underweight, % (n) / 25.5**
12.3%**
2.1%** / 26.0
15.5%
1.0% / 26.5
18.0%
0.7% / 27.4
24.0%
0.5% / 28.2
31.0%
0.5%
Smoking, % (n) / 31.6% / 33.0% / 29.2% / 28.0% / 24.8%
Ex-smoker, % (n) / 22.4% / 24.8% / 19.9% / 22.6% / 23.6%
Hypertension, % (n) / 37.6% / 34.1% / 31.9% / 33.7% / 36.1%
Hypercholesterolemia, % (n) / 29.3% / 31.3% / 29.9% / 29.2% / 32.7%
Diabetes, % (n) / 4.6% / 4.2% / 3.4% / 5.9% / 8.0%
Previous cardiovascular disease, % (n) / 6.4% / 5.5% / 5.4% / 4.7% / 3.7%

Quintiles cutoffs, g/h UUN = men: <0.34, 0.34-0.43, 0.44-0.51, 0.52-0.63, >0.63; women: <0.28,0.28-0.36, 0.37-0.43, 0.44-0.55, >0.55.

Figure S1. Non-adjusted analysis of mortality by quintile of urine urea nitrogen. Hazard ratio (HR) of death over median overnight urine urea nitrogen (UUN) in sex-controlled quintile of UUN. The open symbol indicates the reference subgroup (quintile 3). The line below the abscissa indicates the UUN-derived estimates of protein intake. The top table reports N persons, N persons with events (death), annual % mortality rate, and HR with 95%CI for each quintile.

Figure S2. Adjusted analysis of mortality by quintile of estimated protein intake. Hazard ratio (HR) of death over the median of estimated protein intake in sex-controlled quintile of estimated protein intake. The section Statistics in Methods lists the covariates used for HR adjustment. The open symbol indicates the reference subgroup (quintile 3). The top table reports N persons, N persons with events (death), annual % mortality rate, and adjusted HR with 95%CI for each quintile.

Figure S3. Non-adjusted analysis of great eGFR decline by quintile of urine urea nitrogen. Odds ratio (OR) ofgreat eGFR decline (eGFR change ≤ -1 Z-score, ≤ -20 mL/min x 1.73 m2) over median overnight urine urea nitrogen (UUN) in sex-controlled quintile of UUN. The open symbol indicates the reference subgroup (quintile 3). The line below the abscissa indicates the UUN-derived estimates of protein intake. The top table reports N persons, N persons with event (greateGFR decline), % persons with event, and non-adjusted OR with 95%CI for each quintile.

Figure S4. Adjusted analysis ofgreat eGFR decline by quintile of estimated protein intake. Odds ratio (OR) ofgreat eGFR decline (eGFR change ≤ -1 Z-score, ≤ -20 mL/min x 1.73 m2) over the median of estimated protein intake in sex-controlled quintile of estimated protein intake. The section Statistics in Methods lists the covariates used for OR adjustment. The open symbol indicates the reference subgroup (quintile 3). The top table reports N persons, N persons with events (death), annual % mortality rate, and adjusted OR with 95%CIsì for each quintile.

Figure S5. Adjusted analysis ofgreat eGFR decline by baseline eGFR and by quintile of estimated protein intake. Odds ratio (OR) ofgreat eGFR decline (eGFR change ≤ -1 Z-score, ≤ -20 mL/min x 1.73 m2) over the median over the median of estimated protein intake in sex-controlled quintile of estimated protein intake: comparison between the subgroup with reduced baseline eGFR (left panel, baseline eGFR < 90 mL/min x 1.73 m2) and the subgroup without with reduced baseline eGFR (right panel, baseline eGFR ≥ 90 mL/min x 1.73 m2). The section Statistics in Methods lists the covariates used for OR adjustment. The open symbol indicates the reference subgroup (quintile 3). The top table reports N persons, N persons with event (greateGFR decline), % persons with event, and adjusted OR with 95%CI for each quintile.