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Clinical Epidemiology
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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 and on behalf of the CRIC Investigators
JASN January 2019, 30 (1) 137-146; DOI: https://doi.org/10.1681/ASN.2018030296
Ana C. Ricardo
1Department of Medicine, Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois;
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Wei Yang
2Departments of Medicine and Epidemiology and Biostatistics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania;
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Daohang Sha
2Departments of Medicine and Epidemiology and Biostatistics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania;
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Lawrence J. Appel
3Department of Medicine, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland;
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Jing Chen
Departments of 4Medicine and
5Epidemiology, Tulane University, New Orleans, Louisiana;
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Marie Krousel-Wood
Departments of 4Medicine and
5Epidemiology, Tulane University, New Orleans, Louisiana;
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Anjella Manoharan
1Department of Medicine, Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois;
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Susan Steigerwalt
6Department of Medicine, University of Michigan, Ann Arbor, Michigan;
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Jackson Wright
7Department of Medicine, Case Western University, University Hospitals Case Medical Center, Cleveland, Ohio;
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Mahboob Rahman
7Department of Medicine, Case Western University, University Hospitals Case Medical Center, Cleveland, Ohio;
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Sylvia E. Rosas
8Department of Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts;
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Milda Saunders
9Department of Medicine, University of Chicago, Chicago, Illinois; and
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Kumar Sharma
10Department of Medicine, University of California, San Diego, California
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Martha L. Daviglus
1Department of Medicine, Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois;
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James P. Lash
1Department of Medicine, Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois;
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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=1778Men, n=2161
    Demographic characteristics
     Age, yr, mean (SD)58.0 (11.2)58.3 (10.9)
     Age categories, yr, n (%)
      21–45242 (13.9)296 (14.0)
      46–60664 (38.1)777 (36.8)
      61–74836 (48.0)1039 (49.2)
     Race/ethnicity, n (%)
      Non-Hispanic white656 (36.9)a982 (45.4)
      Non-Hispanic black844 (47.5)806 (37.3)
      Hispanic209 (11.8)288 (13.3)
      Other69 (3.9)85 (3.9)
     Annual household income <$20,000, n (%)660 (37.1)a580 (26.8)
     Less than high school education, n (%)400 (22.5)a428 (19.9)
     Marital status n (%)
      Married/living with partner752 (42.3)a1406 (65.1)
      Single305 (17.2)263 (12.2)
      Widowed/divorced721 (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)a1517 (70.2)
    Clinical and laboratory characteristics
     Hypertension, n (%)1499 (84.3)a1892 (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)a998 (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)a98.9 (34.4)
     HDL cholesterol, mg/dl, mean (SD)42.7 (12.2)a53.4 (17.0)
     Triglycerides, mg/dl, median (IQR)122.5 (86–171)a133 (93–197)
     FGF23, RU/ml, median (IQR)165.8 (105.0–276.8)a132.0 (90.7–207.9)
     Calcium, mg/dl, mean (SD)9.3 (0.5)a9.2 (0.4)
     Phosphate, mg/dl, mean (SD)3.9 (0.6)a3.6 (0.7)
     Albumin, g/dl, mean (SD)3.9 (0.45)4.0 (0.49)
     Hemoglobin, g/dl, mean (SD)13.1 (1.8)a12.0 (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 (%)
      <30405 (22.8)a402 (18.6%
      30 to <45627 (35.3)712 (32.9)
      45 to <60441 (24.8)650 (30.1)
      ≥60305 (17.2)397 (18.4)
     Urine protein, mg/24 h, median (IQR)113 (60–599)a268 (89–1200)
    Lifestyle factors
     Never smoker, n (%)944 (53.1)a837 (38.7)
     Physical activity 30 min/d at least 5 d/wk, n (%)817 (46.0)a1185 (54.8)
     Body mass index, kg/m2, mean (SD)33.2 (9.2)a31.1 (6.4)
     Body mass index categories, kg/m2, n (%)
      <25287 (13.3)a343 (19.3)
      25–<30753 (35.0)a372 (20.9)
      30–<35632 (29.4)a393 (22.1)
      ≥35481 (22.3)a668 (37.6)
     Waist circumference, cm, mean (SD)106.5 (15.9)a105.1 (19.4)
     Ideal waist circumference, men <102 cm and women <88 cm, n (%)358 (20.4)a928 (43.6)
    Medications, n (%)
     ACE inhibitor or ARB1123 (63.7)a1566 (72.9)
     Aspirin705 (40.0)a972 (45.3)
     Statin922 (52.3)a1231 (57.3)
    Achievement of guideline-recommended goals, n (%)
     BP<130/80 mm Hg904 (51)1054 (49.1)
     LDL cholesterol <100 mg/dl834 (47.1)a1233 (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

    ModelVariables Included in Regression ModelsESRD50% Decline in eGFR from BaselineDevelopment of CKD Stage 5 (eGFR<15 ml/min per 1.73 m2)
    Model 1Clinical site, age, race/ethnicity, baseline eGFR, and urine protein-to-creatinine ratio0.83 (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 insurance0.82 (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 circumference0.88 (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 hemoglobin0.74 (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 statin0.74 (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 phosphorus0.72 (0.59 to 0.87)0.82 (0.69 to 0.96)0.84 (0.74 to 0.94)
    Model 6P value for interaction sex × age0.010.030.53
    Age strata–specific multivariable regression analyses
     Model 621–45 yr1.15 (0.81 to 1.64)1.34 (0.96 to 1.86)—
     Model 646–60 yr0.69 (0.52 to 0.90)0.78 (0.62 to 0.99)—
     Model 661–74 yr0.58 (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

    ModelVariables Included in Regression ModelsDeath from Any CauseDeath from Any Cause (ESRD as a Censoring Event)
    Model 1Clinical site, age, race/ethnicity, baseline eGFR, and urine protein-to-creatinine ratio0.69 (0.60 to 0.80)0.78 (0.70 to 0.86)
    Model 2+Education, marital status, nephrology care, health insurance0.61 (0.51 to 0.73)0.70 (0.62 to 0.79)
    Model 3+Smoking status, physical activity, BMI, waist circumference0.65 (0.54 to 0.80)0.76 (0.66 to 0.86)
    Model 4+Systolic BP, diabetes, CVD, LDL, HDL, triglycerides, albumin, and hemoglobin0.65 (0.52 to 0.81)0.67 (0.58 to 0.78)
    Model 5+ACEi/ARB, aspirin, and statin0.65 (0.52 to 0.81)0.68 (0.58 to 0.78)
    Model 6+Serum FGF23, calcium, and phosphorus0.56 (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.

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January 2019
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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
JASN Jan 2019, 30 (1) 137-146; DOI: 10.1681/ASN.2018030296

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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
JASN Jan 2019, 30 (1) 137-146; DOI: 10.1681/ASN.2018030296
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