The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis

B. Mckinnon, C. J. Deighan, John David Norrie, J. M. Boulton-Jones, N. Sattar, J. G. Fox

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    Introduction: It is well-established that there is an increase in the incidence of cardiovascular mortality in patients with proteinuric renal disease. The magnitude of the increase in risk is unlikely to be explained by traditional risk factors for cardiovascular disease alone. Proteinuria itself may constitute an additional risk factor, and proteinuric patients are known to have a degree of endothelial dysfunction. The nature of this relationship between proteinuria and endothelial function is the subject of intense investigation. Aim: The aim of this study was to examine the relationship between proteinuria and endothelial dysfunction, as reflected by serum von Willebrand factor (vWF), and the soluble cell adhesion molecules VCAM and ICAM, in patients with primary glomerulonephritis (GN). A secondary aim was to discern whether any relationship could be explained by renal function, lipid profile, inflammation or blood pressure. Methods: A cross-sectional study was undertaken in consecutive patients attending a general nephrology clinic with biopsy-proven primary GN. Patients with end-stage renal disease (ESRD), those on immunosuppressive drugs, or with intercurrent infective illnesses were excluded. Blood pressure and body mass index were recorded. Routine lab assays were undertaken for serum creatinine, lipid profile, and 24-hour urinary protein (U-Prot). Additional serum samples were stored at -80degreesC for subsequent measurement of vWF, VCAM, ICAM and sensitive C reactive protein (sCRP). Results: Data were collected from 129 (86 male) patients. Mean (standard deviation) estimated creatinine clearance was 64 (32) ml/min, and median (interquartile range) 24-hour proteinuria was 1.1 (0.22-2.9) g. Mean vWF was 173 (68) IU/dl, median VCAM, ICAM and sCRP were 594 (410-708) ng/ml, 235 (208-286) ng/ml, and 2.33 (0.83-5.68) mg/l, respectively. There was a significant positive correlation between vWF and U-Prot (Spearman rank correlation, r = 0.41, p < 0.001). When split into tertiles, according to U-Prot (0-500 mg, 500-2,000 mg, and > 2,000 mg), there was a significant, stepwise increase in mean vWF (p < 0.001), log VCAM (p < 0.001), and log ICAM (p = 0.002). On multivariate analysis with vWF as the continuous dependent variable, U-Prot, age, total cholesterol and sCRP were the only significantly independent correlates (model-adjusted R-2 = 33%). Conclusion: In patients with primary GN, there is a significant association between endothelial activation as reflected by vWF, VCAM, or ICAM and increasing proteinuria. Elevations in vWF, as well as being related to classical risk factors, are associated with increases in total proteinuria and low-grade inflammation. Thus, future prospective studies should examine the extent to which vWF and other circulating markers of endothelial activation predict coronary heart disease risk in patients with proteinuric renal disease.

    Original languageEnglish
    Pages (from-to)173-180
    Number of pages7
    JournalClinical Nephrology
    Volume63
    Issue number3
    Publication statusPublished - 2005

    Keywords

    • endothelial function
    • inflammation
    • proteinuria
    • primary glomerulonephritis
    • VON-WILLEBRAND-FACTOR
    • CHRONIC-RENAL-FAILURE
    • HEALTHY-SUBJECTS
    • DEPENDENT VASODILATION
    • ADHESION MOLECULES
    • DYSFUNCTION
    • MICROALBUMINURIA
    • DISEASE
    • RISK

    Cite this

    Mckinnon, B., Deighan, C. J., Norrie, J. D., Boulton-Jones, J. M., Sattar, N., & Fox, J. G. (2005). The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis. Clinical Nephrology, 63(3), 173-180.

    The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis. / Mckinnon, B.; Deighan, C. J.; Norrie, John David; Boulton-Jones, J. M.; Sattar, N.; Fox, J. G.

    In: Clinical Nephrology, Vol. 63, No. 3, 2005, p. 173-180.

    Research output: Contribution to journalArticle

    Mckinnon, B, Deighan, CJ, Norrie, JD, Boulton-Jones, JM, Sattar, N & Fox, JG 2005, 'The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis', Clinical Nephrology, vol. 63, no. 3, pp. 173-180.
    Mckinnon B, Deighan CJ, Norrie JD, Boulton-Jones JM, Sattar N, Fox JG. The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis. Clinical Nephrology. 2005;63(3):173-180.
    Mckinnon, B. ; Deighan, C. J. ; Norrie, John David ; Boulton-Jones, J. M. ; Sattar, N. ; Fox, J. G. / The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis. In: Clinical Nephrology. 2005 ; Vol. 63, No. 3. pp. 173-180.
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    abstract = "Introduction: It is well-established that there is an increase in the incidence of cardiovascular mortality in patients with proteinuric renal disease. The magnitude of the increase in risk is unlikely to be explained by traditional risk factors for cardiovascular disease alone. Proteinuria itself may constitute an additional risk factor, and proteinuric patients are known to have a degree of endothelial dysfunction. The nature of this relationship between proteinuria and endothelial function is the subject of intense investigation. Aim: The aim of this study was to examine the relationship between proteinuria and endothelial dysfunction, as reflected by serum von Willebrand factor (vWF), and the soluble cell adhesion molecules VCAM and ICAM, in patients with primary glomerulonephritis (GN). A secondary aim was to discern whether any relationship could be explained by renal function, lipid profile, inflammation or blood pressure. Methods: A cross-sectional study was undertaken in consecutive patients attending a general nephrology clinic with biopsy-proven primary GN. Patients with end-stage renal disease (ESRD), those on immunosuppressive drugs, or with intercurrent infective illnesses were excluded. Blood pressure and body mass index were recorded. Routine lab assays were undertaken for serum creatinine, lipid profile, and 24-hour urinary protein (U-Prot). Additional serum samples were stored at -80degreesC for subsequent measurement of vWF, VCAM, ICAM and sensitive C reactive protein (sCRP). Results: Data were collected from 129 (86 male) patients. Mean (standard deviation) estimated creatinine clearance was 64 (32) ml/min, and median (interquartile range) 24-hour proteinuria was 1.1 (0.22-2.9) g. Mean vWF was 173 (68) IU/dl, median VCAM, ICAM and sCRP were 594 (410-708) ng/ml, 235 (208-286) ng/ml, and 2.33 (0.83-5.68) mg/l, respectively. There was a significant positive correlation between vWF and U-Prot (Spearman rank correlation, r = 0.41, p < 0.001). When split into tertiles, according to U-Prot (0-500 mg, 500-2,000 mg, and > 2,000 mg), there was a significant, stepwise increase in mean vWF (p < 0.001), log VCAM (p < 0.001), and log ICAM (p = 0.002). On multivariate analysis with vWF as the continuous dependent variable, U-Prot, age, total cholesterol and sCRP were the only significantly independent correlates (model-adjusted R-2 = 33{\%}). Conclusion: In patients with primary GN, there is a significant association between endothelial activation as reflected by vWF, VCAM, or ICAM and increasing proteinuria. Elevations in vWF, as well as being related to classical risk factors, are associated with increases in total proteinuria and low-grade inflammation. Thus, future prospective studies should examine the extent to which vWF and other circulating markers of endothelial activation predict coronary heart disease risk in patients with proteinuric renal disease.",
    keywords = "endothelial function, inflammation, proteinuria, primary glomerulonephritis, VON-WILLEBRAND-FACTOR, CHRONIC-RENAL-FAILURE, HEALTHY-SUBJECTS, DEPENDENT VASODILATION, ADHESION MOLECULES, DYSFUNCTION, MICROALBUMINURIA, DISEASE, RISK",
    author = "B. Mckinnon and Deighan, {C. J.} and Norrie, {John David} and Boulton-Jones, {J. M.} and N. Sattar and Fox, {J. G.}",
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    TY - JOUR

    T1 - The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis

    AU - Mckinnon, B.

    AU - Deighan, C. J.

    AU - Norrie, John David

    AU - Boulton-Jones, J. M.

    AU - Sattar, N.

    AU - Fox, J. G.

    PY - 2005

    Y1 - 2005

    N2 - Introduction: It is well-established that there is an increase in the incidence of cardiovascular mortality in patients with proteinuric renal disease. The magnitude of the increase in risk is unlikely to be explained by traditional risk factors for cardiovascular disease alone. Proteinuria itself may constitute an additional risk factor, and proteinuric patients are known to have a degree of endothelial dysfunction. The nature of this relationship between proteinuria and endothelial function is the subject of intense investigation. Aim: The aim of this study was to examine the relationship between proteinuria and endothelial dysfunction, as reflected by serum von Willebrand factor (vWF), and the soluble cell adhesion molecules VCAM and ICAM, in patients with primary glomerulonephritis (GN). A secondary aim was to discern whether any relationship could be explained by renal function, lipid profile, inflammation or blood pressure. Methods: A cross-sectional study was undertaken in consecutive patients attending a general nephrology clinic with biopsy-proven primary GN. Patients with end-stage renal disease (ESRD), those on immunosuppressive drugs, or with intercurrent infective illnesses were excluded. Blood pressure and body mass index were recorded. Routine lab assays were undertaken for serum creatinine, lipid profile, and 24-hour urinary protein (U-Prot). Additional serum samples were stored at -80degreesC for subsequent measurement of vWF, VCAM, ICAM and sensitive C reactive protein (sCRP). Results: Data were collected from 129 (86 male) patients. Mean (standard deviation) estimated creatinine clearance was 64 (32) ml/min, and median (interquartile range) 24-hour proteinuria was 1.1 (0.22-2.9) g. Mean vWF was 173 (68) IU/dl, median VCAM, ICAM and sCRP were 594 (410-708) ng/ml, 235 (208-286) ng/ml, and 2.33 (0.83-5.68) mg/l, respectively. There was a significant positive correlation between vWF and U-Prot (Spearman rank correlation, r = 0.41, p < 0.001). When split into tertiles, according to U-Prot (0-500 mg, 500-2,000 mg, and > 2,000 mg), there was a significant, stepwise increase in mean vWF (p < 0.001), log VCAM (p < 0.001), and log ICAM (p = 0.002). On multivariate analysis with vWF as the continuous dependent variable, U-Prot, age, total cholesterol and sCRP were the only significantly independent correlates (model-adjusted R-2 = 33%). Conclusion: In patients with primary GN, there is a significant association between endothelial activation as reflected by vWF, VCAM, or ICAM and increasing proteinuria. Elevations in vWF, as well as being related to classical risk factors, are associated with increases in total proteinuria and low-grade inflammation. Thus, future prospective studies should examine the extent to which vWF and other circulating markers of endothelial activation predict coronary heart disease risk in patients with proteinuric renal disease.

    AB - Introduction: It is well-established that there is an increase in the incidence of cardiovascular mortality in patients with proteinuric renal disease. The magnitude of the increase in risk is unlikely to be explained by traditional risk factors for cardiovascular disease alone. Proteinuria itself may constitute an additional risk factor, and proteinuric patients are known to have a degree of endothelial dysfunction. The nature of this relationship between proteinuria and endothelial function is the subject of intense investigation. Aim: The aim of this study was to examine the relationship between proteinuria and endothelial dysfunction, as reflected by serum von Willebrand factor (vWF), and the soluble cell adhesion molecules VCAM and ICAM, in patients with primary glomerulonephritis (GN). A secondary aim was to discern whether any relationship could be explained by renal function, lipid profile, inflammation or blood pressure. Methods: A cross-sectional study was undertaken in consecutive patients attending a general nephrology clinic with biopsy-proven primary GN. Patients with end-stage renal disease (ESRD), those on immunosuppressive drugs, or with intercurrent infective illnesses were excluded. Blood pressure and body mass index were recorded. Routine lab assays were undertaken for serum creatinine, lipid profile, and 24-hour urinary protein (U-Prot). Additional serum samples were stored at -80degreesC for subsequent measurement of vWF, VCAM, ICAM and sensitive C reactive protein (sCRP). Results: Data were collected from 129 (86 male) patients. Mean (standard deviation) estimated creatinine clearance was 64 (32) ml/min, and median (interquartile range) 24-hour proteinuria was 1.1 (0.22-2.9) g. Mean vWF was 173 (68) IU/dl, median VCAM, ICAM and sCRP were 594 (410-708) ng/ml, 235 (208-286) ng/ml, and 2.33 (0.83-5.68) mg/l, respectively. There was a significant positive correlation between vWF and U-Prot (Spearman rank correlation, r = 0.41, p < 0.001). When split into tertiles, according to U-Prot (0-500 mg, 500-2,000 mg, and > 2,000 mg), there was a significant, stepwise increase in mean vWF (p < 0.001), log VCAM (p < 0.001), and log ICAM (p = 0.002). On multivariate analysis with vWF as the continuous dependent variable, U-Prot, age, total cholesterol and sCRP were the only significantly independent correlates (model-adjusted R-2 = 33%). Conclusion: In patients with primary GN, there is a significant association between endothelial activation as reflected by vWF, VCAM, or ICAM and increasing proteinuria. Elevations in vWF, as well as being related to classical risk factors, are associated with increases in total proteinuria and low-grade inflammation. Thus, future prospective studies should examine the extent to which vWF and other circulating markers of endothelial activation predict coronary heart disease risk in patients with proteinuric renal disease.

    KW - endothelial function

    KW - inflammation

    KW - proteinuria

    KW - primary glomerulonephritis

    KW - VON-WILLEBRAND-FACTOR

    KW - CHRONIC-RENAL-FAILURE

    KW - HEALTHY-SUBJECTS

    KW - DEPENDENT VASODILATION

    KW - ADHESION MOLECULES

    KW - DYSFUNCTION

    KW - MICROALBUMINURIA

    KW - DISEASE

    KW - RISK

    M3 - Article

    VL - 63

    SP - 173

    EP - 180

    JO - Clinical Nephrology

    JF - Clinical Nephrology

    SN - 0301-0430

    IS - 3

    ER -