Exosomal miRNAs in Urine Associated with Children’s Cardiorenal Parameters: a Cross-Sectional Study

Figures & data

Table 1. Demographic characteristics of the 88 children participating in this PROGRESS subcohort at 4–6 years of age.

Demographic	Category	n (%)
Sex
	Female	47 (53)
	Male	41 (47)
Indoor tobacco smoke exposure
	Yes	28 (32)
	No	60 (68)
Socioeconomic status
	Low	46 (52)
	Medium	35 (40)
	High	7 (8)
		Mean ± SD (range), n
Age, years		4.7 ± 0.5 (4.0–6.4), 88
BMI, kg/m^2		15.6 ± 1.7 (12.8–21.9), 88
Urine creatinine, mg/dl		72.0 ± 34.3 (10.4–156.0), 87
Urine specific gravity, kg/m^3		1.02 ± 0.01 (1.01–1.03), 88
Urine osmolality, mmol/kg		653 ± 201 (272-1100), 86
Systolic blood pressure, mmHg		84 ± 7.6 (70–120), 88
Diastolic blood pressure, mmHg		52 ± 6.5 (35–76), 88
Urinary sodium, mmol/l		130 ± 49 (15–268), 86
Urinary potassium, mmol/l		74.9 ± 40.4 (15.5–207.6), 86
Urinary sodium-to-potassium ratio		2.29 ± 1.49 (0.09–8.21), 86
Serum cystatin C, age 8–10 years, mg/l		0.74 ± 0.19 (0.39–1.59), 68
eGFRCysC, 8–10 years, ml/min/1.73 m^2		99.3 ± 24.3 (46.8–170), 68

eGFR_CysC: Estimated glomerular filtration rate using the cystatin C-based equation; SD: Standard deviation.

Table 2. Association between exo-miRs and urinary sodium concentration.^†

Names	β (95% CI)	Uncorrected p-value	FDR-corrected p-value
hsa-miR-1180-3p	12.9 (6.2–19.6)	0.0002	0.03
hsa-miR-34a-3p	9.8 (3.9–15.7)	0.0011	0.07
hsa-miR-32-5p	19.8 (7.9–31.8)	0.0012	0.07

Regression coefficients reflect changes in urinary sodium concentration per doubling of exo-miR concentration.

† Models were adjusted for age, sex, BMI, indoor tobacco smoke exposure, socioeconomic status and specific gravity.

exo-miRs: Exosomal miRNAs; FDR: False discovery rate.

Table 3. Association between exo-miRs and urinary sodium-to-potassium ratio.^†

Names	β (95% CI)	Uncorrected p-value	FDR-corrected p-value
hsa-miR-32-5p	0.6 (0.3–1.0)	0.0002	0.02
hsa-miR-378a-5p	0.5 (0.2–0.8)	0.0003	0.02
hsa-miR-34a-3p	0.4 (0.2–0.6)	0.0004	0.02
hsa-miR-223-3p	0.2 (0.1–0.3)	0.0014	0.07
hsa-miR-31-3p	0.2 (0.1–0.3)	0.0028	0.09
hsa-miR-16-5p	0.2 (0.1–0.4)	0.0044	0.09
hsa-miR-375	0.2 (0.1–0.4)	0.0055	0.09
hsa-miR-328-3p	0.3 (0.1–0.4)	0.0057	0.09
hsa-miR-15b-5p	0.2 (0.1–0.3)	0.0057	0.09
hsa-miR-128-3p	0.3 (0.1–0.4)	0.0061	0.09
hsa-miR-195-5p	0.4 (0.1–0.8)	0.0062	0.09
hsa-miR-15a-5p	0.3 (0.1–0.5)	0.0067	0.09
hsa-miR-25-3p	0.2 (0.1–0.4)	0.0070	0.09
hsa-miR-1180-3p	0.3 (0.1–0.6)	0.0073	0.09
hsa-miR-148a-3p	0.2 (0.1–0.4)	0.0078	0.09
hsa-miR-340-3p	0.3 (0.1–0.5)	0.0079	0.09
hsa-miR-424-5p	0.3 (0.1–0.5)	0.0083	0.09

Regression coefficients reflect changes in the ratio per doubling of exo-miR concentration.

† Models were adjusted for age, sex, BMI, indoor tobacco smoke exposure, socioeconomic status and specific gravity.

exo-miRs: Exosomal miRNAs; FDR: False discovery rate.

Table 4. Association between exo-miRs and eGFR assessed at 8–10 years old.^†

Names	β (95% CI)	Uncorrected p-value	FDR-corrected p-value
hsa-miR-520e	-12.1 (-18.6 to -5.6)	0.0003	0.05
hsa-miR-425-3p	-6.1 (-10.5 to -1.6)	0.0073	0.71
hsa-miR-645	-3.6 (-6.7 to -0.6)	0.0202	0.94
hsa-miR-140-3p	-10.8 (-20.6 to -1.0)	0.0303	0.94

Regression coefficients reflect changes in eGFR from a doubling of exo-miR concentration.

† Models were adjusted for age at urine collection and eGFR measurement, sex, BMI, indoor tobacco smoke exposure, socioeconomic status and specific gravity.

exo-miRs: Exosomal miRNAs; FDR: False discovery rate.

Figure 1. Representative plots of highlighted associations between exo-miRs and cardiorenal outcomes.

Representative plots of the top (based on lowest p-value) associations between exo-miRs and cardiorenal outcomes, including (A) urinary sodium and miR-1180 (n = 59), (B) urinary sodium-to-potassium ratio and miR-32-5p (n = 27), (C) systolic blood pressure and miR-150-5p (n = 53) and (D) eGFR and miR-520e (n = 27). The plots are unadjusted regression lines.

eGFR: Estimated glomerular filtration rate; exo-miRs: Exosomal miRNAs.

Data sharing statement

Access to the data is limited because of a data sharing agreement approved by the institutional review board at Mount Sinai. However, the data from this study are accessible to qualified researchers upon reasonable request pursuant to the following restrictions to ensure the privacy of human subjects. Researchers interested in accessing PROGRESS data must send their resume or curriculum vitae and Collaborative Institutional Training Initiative training certificate to the institutional review board chair, I Wilets ([email protected]). They must also send a data analysis plan to the principal investigators for PROGRESS, RO Wright ([email protected]), M Tellez-Rojo ([email protected]) and AA Baccarelli ([email protected]). When this process is completed and the request is approved, the PROGRESS data analyst, N McRae ([email protected]), will send a de-identified dataset via the secure data sharing platform box.