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Original ArticlesChronic Kidney Disease
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Urinary Fibrinogen as a Predictor of Progression of CKD

Hongtian Wang, Chunxia Zheng, Yinghui Lu, Qi Jiang, Ru Yin, Ping Zhu, Minlin Zhou and Zhihong Liu
CJASN December 2017, 12 (12) 1922-1929; DOI: https://doi.org/10.2215/CJN.01360217
Hongtian Wang
*National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and
†Division of Nephrology, Jinling Hospital, Southern Medical University, Nanjing, China
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Chunxia Zheng
*National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and
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Yinghui Lu
*National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and
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Qi Jiang
*National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and
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Ru Yin
*National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and
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Ping Zhu
*National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and
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Minlin Zhou
*National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and
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Zhihong Liu
*National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and
†Division of Nephrology, Jinling Hospital, Southern Medical University, Nanjing, China
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  • Figure 1.
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    Figure 1.

    Flow chart for selection of 402 patients with kidney biopsies.

  • Figure 2.
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    Figure 2.

    Distributions of urinary fibrinogen-to-creatinine ratios by eGFR and cause of CKD among 402 patients with kidney biopsies. (A) Distributions of urinary fibrinogen-to-creatinine ratios by eGFR. (B) Distributions of urinary fibrinogen-to-creatinine ratios by cause of CKD.

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    Figure 3.

    Correlations of urinary fibrinogen-to-creatinine ratio with (A) urine protein and (B) eGFR among 402 patients with kidney biopsies.

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    Figure 4.

    Survival free of ESRD according to urinary fibrinogen-to-creatinine tertile among 402 patients with kidney biopsies. (A) Patients with CKD due to causes other than diabetes (n=301). (B) Patients with CKD due to diabetes (n=101).

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    Table 1.

    Baseline characteristics of 402 patients with kidney biopsies stratified by urinary fibrinogen-to-creatinine ratio and 50 healthy control subjects

    VariablesHealthy Control Subjects, n=50All Patients with CKD, n=402Patients with CKD by Urinary Fibrinogen-to-Creatinine Ratio
    <313 ng/mg, n=134314–1246 ng/mg, n=134>1247 ng/mg, n=134
    Age, yr35 (22–45)41 (31–50)38 (31–50)41 (31–50)46 (36–52)
    Women, %4642394344
    Systolic BP, mmHg110 (100–122)130 (120–140)128 (119–140)127 (118–140)135 (125–148)
    eGFR, ml/min per 1.73 m2112 (96–128)82 (53–111)94 (59–115)87 (64–114)75 (39–104)
    Urine protein, g/24 h—2.4 (1.0–4.7)0.9 (0.7–1.6)2.6 (1.4–4.5)4.6 (3.3–7.6)
    Serum albumin, g/dl4.3 (4.1–4.5)3.5 (2.6–4.1)4.0 (3.6–4.4)3.3 (2.6–3.9)2.9 (2.3–3.5)
    Urinary fibrinogen to creatinine, ng/mg2 (2–3)536 (191–1461)131 (52–209)608 (458–836)2938 (1683–5782)
    Disease type, n
     IgAN—152894518
     IMN—94223438
     DN—101172757
     Focal segmental GN—5552822
    • —, No data; IgAN, IgA nephropathy; IMN, idiopathic membranous nephropathy; DN, diabetic nephropathy.

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    Table 2.

    Comparison of baseline characteristics of 402 patients with kidney biopsies by development of ESRD during follow-up

    VariablesNon-ESRD, n=334ESRD, n=68P Value
    Age, yr41 (31–50)43(31–51)0.51
    Women, %44340.13
    Follow-up, mo35.8 (24.5–83.1)42.8 (27.1–63.8)0.94
    eGFR ml/min per 1.73 m291 (61–113)57 (34–83)<0.001
    Systolic BP, mmHg129 (120–140)140 (125–150)0.11
    Urine protein, g/24 h1.9 (1.0–4.4)3.7 (2.4–5.6)<0.001
    Serum albumin, g/dl3.5 (2.6–4.1)3.6 (2.7–3.9)0.91
    Urinary fibrinogen to Cr, ng/mg521.1 (177.5–1451.3)1599.9 (654.9–4148.6)<0.001
    Global sclerosis, %8 (0–27)17 (33–58)<0.001
    Segmental sclerosis, %0 (0–7)3 (0–14)0.01
    IFTA1 (1–2)2 (1–2)<0.001
    Disease type, n (%)<0.001
     IgAN130 (39)22 (32)
     IMN89 (27)5 (7)
     DN64 (19)37 (54)
     Focal segmental GN51 (15)4 (6)
    • Cr, creatinine; IFTA, interstitial fibrosis and tubular atrophy; IgAN, IgA nephropathy; IMN, idiopathic membranous nephropathy; DN, diabetic nephropathy.

    • View popup
    Table 3.

    Cox regression analysis for incident ESRD according to baseline variables among 402 patients with kidney biopsies

    VariablesUnivariableMultivariable
    HR (95% CI)P ValueHR (95% CI)P Value
    Age, yr1.01 (0.99 to 1.03)0.23
    Sex1.50 (0.91 to 2.48)0.12
    Systolic BP, >140 mmHg1.03 (1.02 to 1.04)<0.0011.00 (0.99 to 1.02)0.68
    eGFR, ≥15 ml/min per 1.73 m20.96 (0.95 to 0.97)<0.0010.98 (0.97 to 0.99)<0.001
    Disease type<0.001<0.001
     IgAN1.0 (Reference)1.0 (Reference)
     IMN0.54 (0.13 to 0.98)0.0010.15 (0.03 to 0.70)0.02
     DN3.61 (1.75 to 5.42)0.0013.13 (1.59 to 6.18)0.001
     Focal segmental GN3.32 (1.26 to 10.23)0.022.10 (0.56 to 7.85)0.27
    Serum albumin, g/dl1.02 (0.99 to 1.05)0.16
    Log10 urine protein3.36 (1.83 to 6.12)<0.0012.63 (1.36 to 6.45)0.002
    Log10 urinary fibrinogen to Cr2.72 (1.91 to 3.87)<0.0012.12 (1.31 to 3.26)0.003
    IFTA3.41 (2.47 to 4.72)<0.0011.76 (1.22 to 2.52)0.002
    Global sclerosis1.19 (1.00 to 1.43)0.06
    Segmental sclerosis1.10 (0.55 to 2.20)0.80
    • HR, hazard ratio; 95% CI, 95% confidence interval; IgAN, IgA nephropathy; IMN, idiopathic membranous nephropathy; DN, diabetic nephropathy; Cr, creatinine; IFTA, interstitial fibrosis and tubular atrophy.

    • View popup
    Table 4.

    Prediction of ESRD among 402 patients with kidney biopsies

    VariablesAll Patients with CKD, n=402Subgroup with CKD Due to Cause Other Than Diabetes, n=301Subgroup with CKD Due to Diabetes, n=101
    Model 1Model 1 + Log10 (Urinary Fibrinogen to Cr)Model 1Model 1 + Log10 (Urinary Fibrinogen to Cr)Model 1Model 1 + Log10 (Urinary Fibrinogen to Cr)
    AUC0.730.760.840.850.710.74
    LR test0.003a0.07a0.02a
    AIC333.6326.9b141.1139.9133.9130.6b
    IDI0.02 (95% CI, 0.01 to 0.04); P<0.01a0.01 (95% CI, <−0.01 to 0.01); P=0.20a0.05 (95% CI, <0.01 to 0.09); P=0.04a
    NRI0.43 (95% CI, 0.17 to 0.69); P=0.001a0.13 (95% CI, −0.27 to 0.53); P=0.34a0.48 (95% CI, 0.07 to 0.88); P=0.02a
    • Model 1 included eGFR, urine protein, and BP (adjusted for age and sex); model 2 included panel + log10 (urinary fibrinogen to Cr). Cr, creatinine; AUC, area under the curve; LR, likelihood ratio; AIC, Akaike information criterion; IDI, integrated discrimination improvement; 95% CI, confidence interval; NRI, net reclassification improvement.

    • ↵a P value (model 1 versus model 2).

    • ↵b Significant between models 1 and 2.

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Clinical Journal of the American Society of Nephrology: 12 (12)
Clinical Journal of the American Society of Nephrology
Vol. 12, Issue 12
December 07, 2017
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Urinary Fibrinogen as a Predictor of Progression of CKD
Hongtian Wang, Chunxia Zheng, Yinghui Lu, Qi Jiang, Ru Yin, Ping Zhu, Minlin Zhou, Zhihong Liu
CJASN Dec 2017, 12 (12) 1922-1929; DOI: 10.2215/CJN.01360217

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Urinary Fibrinogen as a Predictor of Progression of CKD
Hongtian Wang, Chunxia Zheng, Yinghui Lu, Qi Jiang, Ru Yin, Ping Zhu, Minlin Zhou, Zhihong Liu
CJASN Dec 2017, 12 (12) 1922-1929; DOI: 10.2215/CJN.01360217
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Keywords

  • chronic kidney disease
  • fibrinogen
  • predictor
  • progression
  • Glomerulonephritis, IGA
  • Podocytes
  • Glomerulonephritis, Membranous
  • risk factors
  • diabetic nephropathies
  • creatinine
  • blood pressure
  • Glomerulosclerosis, Focal Segmental
  • glomerular filtration rate
  • Confidence Intervals
  • renal insufficiency, chronic
  • Blood Pressure Determination
  • Disease Progression
  • Kidney Failure, Chronic

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