Carotid Intima-Media Thickness in Children with CKD: Results from the CKiD Study

Tammy M. Brady; Michael F. Schneider; Joseph T. Flynn; Christopher Cox; Joshua Samuels; Jeffrey Saland; Colin T. White; Susan Furth; Bradley A. Warady; Mark Mitsnefes

doi:10.2215/CJN.03130312

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Figure 1.
Box-percentile plots illustrating the distribution of cIMT measurements in 101 Children of the CKiD and in 97 healthy controls. The numerical values of the 50th percentile are shown. The 2.5th, 5th, 10th, 25th, 75th, 90th, 95th, and 97.5th percentiles of the distribution are denoted. cIMT values <2.5th percentile or >97.5th percentile are denoted by closed circles. cIMT, carotid artery intima-medial thickness; CKiD, Chronic Kidney Disease in Children study.

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Table 1.

Descriptive statistics at the 12-month follow-up visit^a of the 101 children in the cIMT substudy included in analyses and the remaining 366 children in the CKiD cohort

Characteristic	cIMT Substudy Cohort^b (n=101)	CKiD Cohort without cIMT (n=366)	P Value
Age (yr)	12.4 (8.5–15.3)	11.7 (8.2–15.9)	0.60
Male sex	71 (70)	211 (58)	0.02
White race	80 (79)	243 (66)	0.01
Height (m)	1.48 (1.24–1.63)	1.43 (1.23–1.60)	0.15
Tanner stage II–V	59 (58)	176 (48)	0.07
Birth weight ≥2500 g	82 (81)	297 (81)	0.90
Duration of CKD (yr)	8.9 (5.0, 12.4)	7.1 (4.0–10.7)	0.01
Nonglomerular CKD etiology	86 (85)	284 (78)	0.10
GFR (ml/min per 1.73 m²)	42.9 (28.9–54.0)	44.6 (33.7–58.2)	0.07
BMI z score	0.09 (−0.55 to 1.08)	0.38 (−0.38 to 1.08)	0.20
BMI ≥85th percentile	26 (26)	95 (26)	0.90
Dyslipidemia^c	56 (55)	159 (43)	0.03
HDL cholesterol <40 mg/dl	28 (28)	67 (18)	0.04
HDL cholesterol (mg/dl)	45 (39–53)	48 (41–57)	0.06
Non-HDL cholesterol >160 mg/dl	18 (18)	56 (15)	0.50
Non-HDL cholesterol (mg/dl)	128 (109–151)	125 (106–146)	0.30
Triglycerides >130 mg/dl	41 (41)	117 (32)	0.10
Triglycerides (mg/dl)	119 (86–162)	102 (73–141)	0.01
Hypertension^d	77 (76)	274 (75)	0.80
Systolic BP (mmHg)^e	109 (102–114)	106 (99–112)	0.02
Systolic BP index^f	0.90 (0.84–0.94)	0.88 (0.83–0.93)	0.09
Diastolic BP (mmHg)^e	64 (58–69)	66 (60–72)	0.03
Diastolic BP index^f	0.80 (0.74–0.87)	0.84 (0.76–0.93)	0.001
Taking antihypertensive medication^g	71 (70)	248 (68)	0.60
Calcium^e, mg/dl	9.7 (9.5–9.9)	9.6 (9.4–9.9)	0.70
Phosphorus^e, mg/dl	4.8 (4.2–5.1)	4.6 (4.2–5.0)	0.10

Data are median (interquartile range) or n (%). cIMT, carotid intima-media thickness; CKiD, Chronic Kidney Disease in Children study; BMI, body mass index.
↵a Used baseline data if data were missing at 12-month follow-up visit.
↵b Cincinnati Children’s Hospital and Medical Center (Cincinnati, OH; n=26), University of Texas (Houston, TX; n=26), British Columbia Children’s Hospital (Vancouver, BC; n=24), Children’s Mercy Hospital (Kansas City, MO; n=19), and Nationwide Children’s Hospital (Columbus, OH; n=13).
↵c HDL cholesterol <40 mg/dl, non-HDL cholesterol ≥160 mg/dl, or triglycerides ≥130 mg/dl.
↵d Defined as having an average systolic or diastolic BP from the baseline and 12-month follow-up visits ≥95th age-, sex-, and height-specific percentile, or if the participant reported hypertension at baseline or the 12-month follow-up visit, or if the participant reported using antihypertensive medication at baseline or at the 12-month follow-up visit.
↵e Average of values from baseline and 12-month follow-up.
↵f Measured systolic or diastolic BP/95th age-, sex-, and height-specific percentile BP; a value ≥1 is elevated. The average index from the baseline and 12-month follow-up is reported.
↵g Used antihypertensive medication at the baseline or 12-month follow-up visit.

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Table 2.

Descriptive statistics of the 97 healthy controls compared with 101 CKiD cIMT substudy participants

Characteristic	Healthy Controls (n=97)	cIMT Substudy Cohort (n=101)	P Value^a
Age (yr)	10.1 (7.9–13.7)	12.4 (8.5–15.3)	0.08
Male sex	53 (55)	71 (70)	0.02
White race	71 (73)	80 (79)	0.30
Weight (kg)	34.6 (25.7–50.0)	42.9 (26.4–57.8)	0.20
Height (m)	1.41 (1.27–1.59)	1.48 (1.24–1.63)	0.50
BMI (kg/m²)	17.3 (16.1–20.2)	18.9 (16.2–22.7)	0.10
Overweight/obese (BMI ≥85th percentile)	7 (7)	26 (26)	0.001
Systolic BP (mmHg)	104 (98–113)	109 (102–114)	0.01
Diastolic BP (mmHg)	59 (55–64)	64 (58, 69)	<0.001
Systolic BP index^b	0.87 (0.82–0.91)	0.90 (0.84–0.94)	0.01
Diastolic BP index^b	0.76 (0.7–0.81)	0.80 (0.74–0.87)	0.001

Data are median (interquartile range) or n (%). CKiD, Chronic Kidney Disease in Children study; cIMT, carotid intima-media thickness; BMI, body mass index.
↵a P value from Wilcoxon rank sum test when medians were compared, and P value from Pearson χ² when percentages were compared.
↵b Measured systolic or diastolic BP/95th age-, sex-, and height-specific percentile BP; a value ≥1 is elevated.

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Table 3.

Correlates of cIMT in 101 children of the CKiD cohort study

Characteristic	Mean Difference in cIMT, mm (95% CI)
Characteristic	Unadjusted	Adjusted
Age (per 5-yr increase)	0.003 (−0.02 to 0.02)	−0.06 (−0.13 to 0.004)
Male sex (versus female)	−0.01 (−0.04 to 0.02)	−0.03 (−0.06 to 0.01)
Nonwhite race (versus white)	−0.001 (−0.04 to 0.04)	−0.002 (−0.04 to 0.04)
Height (per 0.1-m increase)	0.002 (−0.004 to 0.01)	0.03 (0.003–0.05)
Tanner stage II–V (versus stage I)	0.000 (−0.03 to 0.03)	−0.02 (−0.08 to 0.03)
Birth weight ≥2500 g (versus <2500 g)	0.01 (−0.03 to 0.05)	0.02 (−0.03 to 0.06)
Glomerular CKD etiology (versus nonglomerular)	0.004 (−0.04 to 0.05)	−0.02 (−0.07 to 0.03)
GFR (per 10 ml/min per 1.73 m² decrease)	0.003 (−0.01 to 0.01)	−0.002 (−0.01 to 0.01)
BMI z score	−0.001 (−0.01 to 0.01)	−0.01 (−0.02 to 0.003)
Dyslipidemia^a	0.04 (0.01–0.07)	0.05 (0.01–0.08)
Hypertension^b	0.03 (−0.003 to 0.07)	0.04 (0.003–0.08)
Calcium (per 1-mg/dl increase)	−0.004 (−0.03 to 0.02)	−0.004 (−0.04 to 0.03)
Phosphorus (per 1-mg/dl increase)	−0.01 (−0.03 to 0.01)	−0.01 (−0.04 to 0.01)

Data are median (interquartile range) or n (%). cIMT, carotid intima-media thickness; CKiD, Chronic Kidney Disease in Children study; CI, confidence interval; BMI, body mass index.
↵a HDL cholesterol <40 mg/dl, non-HDL cholesterol >160 mg/dl, or triglycerides >130 mg/dl.
↵b Average systolic or diastolic BP from the baseline and 12-month follow-up visits ≥95th age-, sex-, height-specific percentile, or if the participant reported hypertension at baseline or the 1-month follow-up visit, or if the participant reported using antihypertensive medication at baseline or at the 12-month follow-up visit.

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Table 4.

Univariate and multivariable relationships of components of dyslipidemia and cIMT

Characteristic	Mean Difference in cIMT, mm (95% CI)
Characteristic	Unadjusted	Adjusted
HDL cholesterol <40 mg/dl	0.03 (−0.004 to 0.06)	0.03 (−0.02 to 0.07)
Non-HDL cholesterol >160 mg/dl	−0.01 (−0.05 to 0.03)	−0.01 (−0.06 to 0.03)
Triglycerides >130 mg/dl	0.03 (−0.002 to 0.06)	0.04 (0.01–0.08)

All variables in Table 3, except dyslipidemia, are included in the adjusted model shown here. cIMT, carotid intima-media thickness; CI, confidence interval.

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Table 5.

Univariate and multivariable relationships of components of hypertension variable and cIMT

Characteristic	Mean Difference in cIMT, mm (95% CI)
Characteristic	Unadjusted	Adjusted (Full Model)
Average systolic BP index^a	0.16 (−0.03 to 0.36)	0.20 (−0.04 to 0.45)
Average diastolic BP index^a	0.21 (0.07–0.36)	0.16 (0.002–0.32)
Taking antihypertensive medication (yes/no)	0.04 (0.01–0.07)	0.04 (0.01–0.08)

All variables in Table 3, except hypertension, are included in the adjusted model shown here. cIMT, carotid intima-media thickness; CI, confidence interval.
↵a Measured systolic or diastolic BP/95th age-, sex-, and height-specific percentile BP; a value ≥1 is elevated. The average index from the baseline and 12-month follow-up is used.