Sex-Related Disparities in CKD Progression

Ana C. Ricardo; Wei Yang; Daohang Sha; Lawrence J. Appel; Jing Chen; Marie Krousel-Wood; Anjella Manoharan; Susan Steigerwalt; Jackson Wright; Mahboob Rahman; Sylvia E. Rosas; Milda Saunders; Kumar Sharma; Martha L. Daviglus; James P. Lash; on behalf of the CRIC Investigators

doi:10.1681/ASN.2018030296

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Figure 1.
Unadjusted rates of ESRD and death were lower in women compared with men across age strata. Unadjusted (A) ESRD and (B) death event rates per 100 person-years of follow-up in women (light gray) versus men (dark gray) stratified by age.
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Figure 2.
Adjusted eGFR slope was similar in women compared with men. Mixed effects models for the difference in eGFR slope in women versus men using a hierarchical modeling approach similar to failure-time regression analyses.

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Table 1.

Baseline characteristics of the Chronic Renal Insufficiency Cohort participants by sex

Characteristics	Women, n=1778	Men, n=2161
Demographic characteristics
Age, yr, mean (SD)	58.0 (11.2)	58.3 (10.9)
Age categories, yr, n (%)
21–45	242 (13.9)	296 (14.0)
46–60	664 (38.1)	777 (36.8)
61–74	836 (48.0)	1039 (49.2)
Race/ethnicity, n (%)
Non-Hispanic white	656 (36.9)^a	982 (45.4)
Non-Hispanic black	844 (47.5)	806 (37.3)
Hispanic	209 (11.8)	288 (13.3)
Other	69 (3.9)	85 (3.9)
Annual household income <$20,000, n (%)	660 (37.1)^a	580 (26.8)
Less than high school education, n (%)	400 (22.5)^a	428 (19.9)
Marital status n (%)
Married/living with partner	752 (42.3)^a	1406 (65.1)
Single	305 (17.2)	263 (12.2)
Widowed/divorced	721 (40.6)	492 (22.8)
Health insurance, n (%)	1456 (81.9)	1782 (82.5)
Ever seen a nephrologist (yes versus no), n (%)	1084 (61.0)^a	1517 (70.2)
Clinical and laboratory characteristics
Hypertension, n (%)	1499 (84.3)^a	1892 (87.6)
Diabetes, n (%)	844 (47.5)	1064 (49.2)
Cardiovascular disease, n (%)	514 (28.9)	802 (37.1)
Family history of CHD, n (%)	932 (65.3)^a	998 (57.7)
Systolic BP, mm Hg, mean (SD)	128.3 (22.7)	128.6 (21.7)
Glycated hemoglobin, %, median (IQR)	6.1 (5.6–7.3)	6.2 (5.6–7.4)
LDL cholesterol, mg/dl, mean (SD)	107.4 (36.5)^a	98.9 (34.4)
HDL cholesterol, mg/dl, mean (SD)	42.7 (12.2)^a	53.4 (17.0)
Triglycerides, mg/dl, median (IQR)	122.5 (86–171)^a	133 (93–197)
FGF23, RU/ml, median (IQR)	165.8 (105.0–276.8)^a	132.0 (90.7–207.9)
Calcium, mg/dl, mean (SD)	9.3 (0.5)^a	9.2 (0.4)
Phosphate, mg/dl, mean (SD)	3.9 (0.6)^a	3.6 (0.7)
Albumin, g/dl, mean (SD)	3.9 (0.45)	4.0 (0.49)
Hemoglobin, g/dl, mean (SD)	13.1 (1.8)^a	12.0 (1.5)
Kidney function measurements
eGFR, ml/min per 1.73 m², mean (SD)	43.9 (17.4)	45.7 (16.4)
eGFR categories, ml/min per 1.73 m², n (%)
<30	405 (22.8)^a	402 (18.6%
30 to <45	627 (35.3)	712 (32.9)
45 to <60	441 (24.8)	650 (30.1)
≥60	305 (17.2)	397 (18.4)
Urine protein, mg/24 h, median (IQR)	113 (60–599)^a	268 (89–1200)
Lifestyle factors
Never smoker, n (%)	944 (53.1)^a	837 (38.7)
Physical activity 30 min/d at least 5 d/wk, n (%)	817 (46.0)^a	1185 (54.8)
Body mass index, kg/m², mean (SD)	33.2 (9.2)^a	31.1 (6.4)
Body mass index categories, kg/m², n (%)
<25	287 (13.3)^a	343 (19.3)
25–<30	753 (35.0)^a	372 (20.9)
30–<35	632 (29.4)^a	393 (22.1)
≥35	481 (22.3)^a	668 (37.6)
Waist circumference, cm, mean (SD)	106.5 (15.9)^a	105.1 (19.4)
Ideal waist circumference, men <102 cm and women <88 cm, n (%)	358 (20.4)^a	928 (43.6)
Medications, n (%)
ACE inhibitor or ARB	1123 (63.7)^a	1566 (72.9)
Aspirin	705 (40.0)^a	972 (45.3)
Statin	922 (52.3)^a	1231 (57.3)
Achievement of guideline-recommended goals, n (%)
BP<130/80 mm Hg	904 (51)	1054 (49.1)
LDL cholesterol <100 mg/dl	834 (47.1)^a	1233 (57.3)
Hemoglobin A1c <7%	1172 (69.3)	1411 (68.3)

CHD, coronary heart disease; IQR, interquartile range; FGF23, fibroblast growth factor 23; ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; hemoglobin A1c, glycated hemoglobin.
↵a P<0.05.

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Table 2.

Hazard ratios with 95% confidence intervals from multivariable regression analyses of the association of sex (women versus men) with renal outcomes

Model	Variables Included in Regression Models	ESRD	50% Decline in eGFR from Baseline	Development of CKD Stage 5 (eGFR<15 ml/min per 1.73 m²)
Model 1	Clinical site, age, race/ethnicity, baseline eGFR, and urine protein-to-creatinine ratio	0.83 (0.72 to 0.96)	0.85 (0.75 to 0.96)	0.93 (0.86 to 1.02)
Model 2	+Education, marital status, nephrology care, health insurance	0.82 (0.71 to 0.95)	0.85 (0.74 to 0.97)	0.91 (0.82 to 1.00)
Model 3	+Smoking status, physical activity, BMI, waist circumference	0.88 (0.75 to 1.04)	0.91 (0.79 to 1.05)	0.94 (0.85 to 1.04)
Model 4	+Systolic BP, diabetes, CVD, LDL, HDL, triglycerides, albumin, and hemoglobin	0.74 (0.61 to 0.88)	0.82 (0.70 to 0.96)	0.89 (0.79 to 1.00)
Model 5	+ACEi/ARB, aspirin, and statin	0.74 (0.62 to 0.89)	0.83 (0.70 to 0.97)	0.88 (0.78 to 0.98)
Model 6	+Serum FGF23, calcium, and phosphorus	0.72 (0.59 to 0.87)	0.82 (0.69 to 0.96)	0.84 (0.74 to 0.94)
Model 6	P value for interaction sex × age	0.01	0.03	0.53
Age strata–specific multivariable regression analyses
Model 6	21–45 yr	1.15 (0.81 to 1.64)	1.34 (0.96 to 1.86)	—
Model 6	46–60 yr	0.69 (0.52 to 0.90)	0.78 (0.62 to 0.99)	—
Model 6	61–74 yr	0.58 (0.44 to 0.76)	0.73 (0.57 to 0.93)	—

BMI, body mass index; CVD, cardiovascular disease; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; FGF23, fibroblast growth factor 23; —, not applicable.

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Table 3.

Hazard ratios with 95% confidence intervals from multivariable regression analyses of the association of sex (women versus men) with all-cause mortality

Model	Variables Included in Regression Models	Death from Any Cause	Death from Any Cause (ESRD as a Censoring Event)
Model 1	Clinical site, age, race/ethnicity, baseline eGFR, and urine protein-to-creatinine ratio	0.69 (0.60 to 0.80)	0.78 (0.70 to 0.86)
Model 2	+Education, marital status, nephrology care, health insurance	0.61 (0.51 to 0.73)	0.70 (0.62 to 0.79)
Model 3	+Smoking status, physical activity, BMI, waist circumference	0.65 (0.54 to 0.80)	0.76 (0.66 to 0.86)
Model 4	+Systolic BP, diabetes, CVD, LDL, HDL, triglycerides, albumin, and hemoglobin	0.65 (0.52 to 0.81)	0.67 (0.58 to 0.78)
Model 5	+ACEi/ARB, aspirin, and statin	0.65 (0.52 to 0.81)	0.68 (0.58 to 0.78)
Model 6	+Serum FGF23, calcium, and phosphorus	0.56 (0.44 to 0.70)	0.64 (0.55 to 0.74)

BMI, body mass index; CVD, cardiovascular disease; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; FGF23, fibroblast growth factor 23.