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Red Blood Cell Distribution Width: Useful Predictor for Treatment Response in Primary Glomerular Diseases

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Biomarkers in Kidney Disease

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Abstract

Red blood cell distribution width (RDW) shows the variation in size of erythrocytes in the circulation and it is obtained easily by automated blood cell counters. RDW is associated with systemic inflammation. Clinical or subclinical inflammation is usually present in pathogenesis of primary glomerular diseases (PGDs). Control of many of PGDs can be achieved by immune modulator agents and this supports the underlying systemic inflammatory process. Treatment response cannot be achieved in some patients. There is neither a standard dose nor a standard dose reduction protocol for immunosuppressive treatment in PGDs. In this aspect, use of predictive biomarkers for treatment response can protect patients from side effects of unnecessary immunosuppressive drugs. New biomarkers are essential in prediction of treatment response and prognosis of PGDs. So, studies have been focused to investigate potential clinical importance of RDW in prediction of prognosis and clinical outcome of PGDs. RDW is assessed as part of the complete blood count which is a quite cheap test, and therefore, it may be a useful novel marker for evaluation of treatment response in nephrotic syndrome due to PGDs.

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Abbreviations

Anti-PLA2R:

Phospholipase A2 receptor

CRP:

C-reactive protein

FSGS:

Focal segmental glomerulosclerosis

FSP1+:

Fibroblast-specific protein 1-positive

IgAN:

IgA nephropathy

IgG:

Immunoglobulin G

IgM:

Immunoglobulin M

L FABP:

L fatty-acid-binding protein

MCD:

Minimal change disease

MG:

Membranous glomerulopathy

MPGN:

Type 1 membranoproliferative glomerulonephritis

MPV:

Mean platelet volume

NAG:

N-acetyl-beta-glucosaminidase

NHANES:

National health and nutrition examination survey

NS:

Nephrotic syndrome

PGDs:

Primary glomerular diseases

RBC:

Red blood cell

RDW:

Red blood cell distribution width

SOCS:

Suppressors of cytokine signaling

α1M:

α1-microglobulin

β2M:

β2-microglobulin

References

  • Abdullahi H, Osman A, Rayis DA, et al. Red blood cell distribution width is not correlated with preeclampsia among pregnant Sudanese women. Diagn Pathol. 2014;9:29.

    Article  PubMed Central  PubMed  Google Scholar 

  • Afonso L, Zalawadiya SK, Veeranna V, et al. Relationship between red cell distribution width and microalbuminuria: a population-based study of multiethnic representative US adults. Nephron Clin Pract. 2011;119:277–82.

    Article  Google Scholar 

  • Appel GB, D’Agati VD. Primary and secondary (non-genetic) causes of focal and segmental glomerulosclerosis. In: Johnson RJ, Feehally J, Floege J, editors. Comprehensive clinical nephrology. 5th ed. Philadelphia: Elsevier Saunders; 2015. p. 218–30.

    Google Scholar 

  • Arbel Y, Weitzman D, Raz R, et al. Red blood cell distribution width and the risk of cardiovascular morbidity and all-cause mortality. A population-based study. Thromb Haemost. 2014;111:300–7.

    Article  CAS  PubMed  Google Scholar 

  • Atkins RC, Nikolic-Paterson DJ, Song Q, et al. Modulators of crescentic glomerulonephritis. J Am Soc Nephrol. 1996;7:2271–8.

    CAS  PubMed  Google Scholar 

  • Badid C, Desmoulière A, McGregor B, et al. Interstitial alpha-smooth muscle actin: a prognostic marker in membranous nephropathy. Clin Nephrol. 1999;52:210–7.

    CAS  PubMed  Google Scholar 

  • Bazzi C, Rizza V, Raimondi S, et al. In crescentic IgA nephropathy, fractional excretion of IgG in combination with nephron loss is the best predictor of progression and responsiveness to immunosuppression. Clin J Am Soc Nephrol. 2009;4:929–35.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bazzi C, Rizza V, Casellato D, et al. Urinary IgG and α2-macroglobulin are powerful predictors of outcome and responsiveness to steroids and cyclophosphamide in idiopathic focal segmental glomerulosclerosis with nephrotic syndrome. Biomed Res Int. 2013:941831. doi: 10.1155/2013/941831. Epub 2013 Sep 4.

    Google Scholar 

  • Beck Jr LH, Fervenza FC, Beck DM, et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol. 2011;22:1543–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89e95.

    Google Scholar 

  • Brenchley PE, Coupes B, Short CD, et al. Urinary C3dg and C5b-9 indicate active immune disease in human membranous nephropathy. Kidney Int. 1992;41:933–7.

    Article  CAS  PubMed  Google Scholar 

  • Bright R. Tabular view of the morbid appearances in 100 cases connected with albuminous urine. Guy’s Hosp Rep. 1836;1:338–79.

    Google Scholar 

  • Camici M. The nephrotic syndrome is an immunoinflammatory disorder. Med Hypotheses. 2007;68:900–5.

    Article  CAS  PubMed  Google Scholar 

  • Caro J, Gutiérrez-Solís E, Rojas-Rivera J, et al. Predictors of response and relapse in patients with idiopathic membranous nephropathy treated with tacrolimus. Nephrol Dial Transplant 2015 Mar;30(3):467–74.

    Google Scholar 

  • Cattran DC, Reich HN, Beanlands HJ, Genes, Gender and Glomerulonephritis Group, et al. The impact of sex in primary glomerulonephritis. Nephrol Dial Transplant. 2008;23:2247–53.

    Article  PubMed  Google Scholar 

  • Couser WG, Johnson RJ. The etiology of glomerulonephritis: roles of infection and autoimmunity. Kidney Int. 2014;86:905–14.

    Article  CAS  PubMed  Google Scholar 

  • Deegens JK, Wetzels JF. Fractional excretion of high- and low-molecular weight proteins and outcome in primary focal segmental glomerulosclerosis. Clin Nephrol. 2007;68:201–8.

    Article  CAS  PubMed  Google Scholar 

  • Deveci OS, Kabakci G, Tulumen E, et al. The relationship between microalbuminuria and the presence and extent of coronary atherosclerosis. Angiology. 2010;61(2):184–91.

    Article  CAS  PubMed  Google Scholar 

  • Dillon SC, Taylor GM, Shah V. Diagnostic value of urinary retinol-binding protein in childhood nephrotic syndrome. Pediatr Nephrol. 1998;12:643–7.

    Article  CAS  PubMed  Google Scholar 

  • Feehally J, Floege J. IgA nephropathy and henoch-schönlein nephritis. In: Johnson RJ, Feehally J, Floege J, editors. Comphrensive clinical nephrology. 5th ed. Philadelphia: Elsevier Saunders; 2015. p. 266–77.

    Google Scholar 

  • Ghaffari S. Oxidative stress in the regulation of normal and neoplastic hematopoiesis. Antioxid Redox Signal. 2008;10:1923–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Harada K, Akai Y, Kurumatani N, et al. Prognostic value of urinary interleukin 6 in patients with IgA nephropathy: an 8-year follow-up study. Nephron. 2002;92:824–6.

    Article  CAS  PubMed  Google Scholar 

  • Harada K, Akai Y, Yamaguchi Y, et al. Prediction of corticosteroid responsiveness based on fibroblast-specific protein 1 (FSP1) in patients with IgA nephropathy. Nephrol Dial Transplant. 2008;23:3152–9.

    Article  CAS  PubMed  Google Scholar 

  • Hofstra JM, Deegens JK, Willems HL, et al. Beta-2-microglobulin is superior to N-acetyl-beta-glucosaminidase in predicting prognosis in idiopathic membranous nephropathy. Nephrol Dial Transplant. 2008;23:2546–51.

    Article  CAS  PubMed  Google Scholar 

  • Huang YL, Hu ZD, Liu SJ, et al. Prognostic value of red blood cell distribution width for patients with heart failure: a systematic review and meta-analysis of cohort studies. PLoS One. 2014;18(9):e104861.

    Article  Google Scholar 

  • Irazabal MV, Eirin A, Lieske J, et al. Low- and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy: a prospective study. Nephrol Dial Transplant. 2013;28:137–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ishiguro C, Yaguchi Y, Funabiki K, et al. Serum IgA/C3 ratio may predict diagnosis and prognostic grading in patients with IgA nephropathy. Nephron. 2002;91:755–8.

    Article  PubMed  Google Scholar 

  • Keskin KR, Aras Z, Silfeler DB, et al. Relationship of red cell distribution width with the presence and severity of preeclampsia. Clin Appl Thromb Hemost 2015 Mar; 21(2):128–31.

    Google Scholar 

  • Kocyigit I, Yilmaz MI, Simşek Y, et al. The role of platelet activation in determining response to therapy in patients with primary nephrotic syndrome. Platelets. 2013;24:474–9.

    Article  CAS  PubMed  Google Scholar 

  • Lippi G, Targher G, Montagnana M, et al. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med. 2009;133:628–32.

    CAS  PubMed  Google Scholar 

  • Mastroianni Kirsztajn G, Nishida SK, Silva MS, et al. Urinary retinol-binding protein as a prognostic marker in the treatment of nephrotic syndrome. Nephron. 2000;86:109–14.

    Article  CAS  PubMed  Google Scholar 

  • Mathew R, Pai VR, Vijayakumar T. Comparison of microalbuminuria with biochemical and hematological parameters as a marker for renal involvement in patients at high risk for chronic kidney disease-Apilot study. Int J Sci Eng Res. 2014;5:97–100.

    Google Scholar 

  • Ostalska-Nowicka D, Smiech M, Jaroniec M, et al. SOCS3 and SOCS5 mRNA expressions may predict initial steroid response in nephrotic syndrome children. Folia Histochem Cytobiol. 2011;49:719–28.

    Article  CAS  PubMed  Google Scholar 

  • Ozcan F, Turak O, Durak A, et al. Red cell distribution width and inflammation in patients with non-dipper hypertension. Blood Press. 2013;22:80–5.

    Article  PubMed  Google Scholar 

  • Patel KV, Mohanty JG, Kanapuru B, et al. Association of the red cell distribution width with red blood cell deformability. Adv Exp Med Biol. 2013;765:211–6.

    Article  CAS  PubMed  Google Scholar 

  • Peters HP, van den Brand JA, Wetzels JF. Urinary excretion of low-molecular-weight proteins as prognostic markers in IgA nephropathy. Neth J Med. 2009;67:54–61.

    CAS  PubMed  Google Scholar 

  • Pierce CN, Larson DF. Inflammatory cytokine inhibition of erythropoiesis in patients implanted with a mechanical circulatory assist device. Perfusion. 2005;20:83–90.

    Article  PubMed  Google Scholar 

  • Pillai S. Rethinking mechanisms of autoimmune pathogenesis. J Autoimmun. 2013;45:97–103.

    Article  CAS  PubMed  Google Scholar 

  • Piyaphanee N, Ma Q, Kremen O, et al. Discovery and initial validation of α 1-B glycoprotein fragmentation as a differential urinary biomarker in pediatric steroid-resistant nephrotic syndrome. Proteomics Clin Appl. 2011;5:334–42.

    Article  CAS  PubMed  Google Scholar 

  • Price-Jones C. The variation in sizes of red blood cells. Br Med J. 1910;2:1418.

    Article  Google Scholar 

  • Rezende SM, Lijfering WM, Rosendaal FR, et al. Hematologic variables and venous thrombosis: red cell distribution width and blood monocyte count are associated with an increased risk. Haematologica. 2014;99:194–200.

    Article  PubMed Central  PubMed  Google Scholar 

  • Roy RR, Roy E, Rahman MH, et al. Serum immunoglobulin G, M and IgG:IgM ratio as predictors for outcome of childhood nephrotic syndrome. World J Pediatr. 2009;5:127–31.

    Article  CAS  PubMed  Google Scholar 

  • Rumana J, Hanif M, Muinuddin G, et al. Correlation of fractional excretion of magnesium with steroid responsiveness in children with nephrotic syndrome. Saudi J Kidney Dis Transplant. 2014;25:830–6.

    Article  Google Scholar 

  • Santín S, Tazón-Vega B, Silva I, FSGS Spanish Study Group, et al. Clinical value of NPHS2 analysis in early- and adult-onset steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2011;6:344–54.

    Article  PubMed Central  PubMed  Google Scholar 

  • Schena FP, Alpers CE. Membranoproliferative glomerulonephritis and cryoglobulinemic glomerulonephritis. In: Johnson RJ, Feehally J, Floege J, editors. Comphrensive clinical nephrology. 5th ed. Philadelphia: Elsevier Saunders; 2015. p. 253–60.

    Google Scholar 

  • Schmieder RE, Schutte R, Schumacher H, ONTARGET/TRANSCEND Investigators, et al. Mortality and morbidity in relation to changes in albuminuria, glucose status and systolic blood pressure: an analysis of the ONTARGET and TRANSCEND studies. Diabetologia. 2014;57:2019–29.

    Article  CAS  PubMed  Google Scholar 

  • Segarra-Medrano A, Jatem-Escalante E, Carnicer-Cáceres C, et al. Evolution of antibody titre against the M-type phospholipase A2 receptor and clinical response in idiopathic membranous nephropathy patients treated with tacrolimus. Nefrologia. 2014;34:491–7.

    PubMed  Google Scholar 

  • Shimizu A, Takei T, Uchida K, et al. Predictors of poor outcomes in steroid therapy for immunoglobulin A nephropathy. Nephrology (Carlton). 2009;14:521–6.

    Article  CAS  Google Scholar 

  • Shin JR, Kim SM, Yoo JS, et al. Urinary excretion of β2-microglobulin as a prognostic marker in immunoglobulin A nephropathy. Korean J Intern Med. 2014;29:334–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Simel DL, DeLong ER, Feussner JR, et al. Erythrocyte anisocytosis. Visual inspection of blood films vs automated analysis of red blood cell distribution width. Arch Intern Med. 1988;148:822–4.

    Article  CAS  PubMed  Google Scholar 

  • Skjelbakken T, Lappegård J, Ellingsen TS, et al. Red cell distribution width is associated with incident myocardial infarction in a general population: the Tromsø Study. J Am Heart Assoc. 2014;18(3):e001109.

    Article  Google Scholar 

  • Song CS, Park DI, Yoon MY, et al. Association between red cell distribution width and disease activity in patients with inflammatory bowel disease. Dig Dis Sci. 2012;57:1033–8.

    Article  CAS  PubMed  Google Scholar 

  • Spiropoulos A, Goussetis E, Margeli A, et al. Effect of inflammation induced by prolonged exercise on circulating erythroid progenitors and markers of erythropoiesis. Clin Chem Lab Med. 2010;48:199–203.

    Article  CAS  PubMed  Google Scholar 

  • Su C, Liao LZ, Song Y, et al. The role of red blood cell distribution width in mortality and cardiovascular risk among patients with coronary artery diseases: a systematic review and meta-analysis. J Thorac Dis. 2014;6:1429–40.

    PubMed Central  PubMed  Google Scholar 

  • Torres DD, Rossini M, Manno C, et al. The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine predicts renal prognosis in IgA nephropathy. Kidney Int. 2008;73:327–33.

    Article  CAS  PubMed  Google Scholar 

  • Troyanov S, Roasio L, Pandes M, et al. Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int. 2006;69:1641–8.

    Article  CAS  PubMed  Google Scholar 

  • Turgutalp K, Kıykım A, Bardak S, et al. Is the red cell distribution width strong predictor for treatment response in primary glomerulonephritides? Ren Fail. 2014;36:1083–9.

    Article  CAS  PubMed  Google Scholar 

  • Vajpayee N, Graham SS, Bem S. Basic examination of blood and bone marrow. In: McPherson RA, Pincus MR, editors. Henry’s clinical diagnosis and management by laboratory methods. 22nd ed. Philadelphia: Elsevier/Saunders; 2011. p. 30.

    Google Scholar 

  • Van Es LA, de Heer E, Vleming LJ, et al. GMP-17-positive T-lymphocytes in renal tubules predict progression in early stages of IgA nephropathy. Kidney Int. 2008;73:1426–33.

    Article  PubMed  Google Scholar 

  • Veeranna V, Zalawadiya SK, Panaich S, et al. Comparative analysis of red cell distribution width and high sensitivity C-reactive protein for coronary heart disease mortality prediction in multi-ethnic population: findings from the 1999–2004 NHANES. Int J Cardiol. 2013;168:5156–61.

    Article  PubMed  Google Scholar 

  • Yamaguchi M, Ando M, Yamamoto R, et al. Patient age and the prognosis of idiopathic membranous nephropathy. PLoS One. 2014;9:e110376.

    Article  PubMed Central  PubMed  Google Scholar 

  • Yoshimoto K, Wada T, Furuichi K, et al. CD68 and MCP-1/CCR2 expression of initial biopsies reflect the outcomes of membranous nephropathy. Nephron Clin Pract. 2004;98:25–34.

    Article  Google Scholar 

  • Yu FT, Armstrong JK, Tripette J, et al. A local increase in red blood cell aggregation can trigger deep vein thrombosis: evidence based on quantitative cellular ultrasound imaging. J Thromb Haemost. 2011;9:481–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, School of Medicine, Mersin University, Mersin, 33079, Turkey

    Kenan Turgutalp, Simge Bardak, Serap Demir & Ahmet Kıykım

Authors
  1. Kenan Turgutalp
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  2. Simge Bardak
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  3. Serap Demir
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  4. Ahmet Kıykım
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Correspondence to Kenan Turgutalp .

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Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

Definitions

Antibodies

An immunoglobulin, a specialized immune protein, produced due to the introduction of an antigen into the body which possesses the significant capability to combine with the antigen that triggers its production. The production of antibodies is a major function of the immune system and is carried out by a type of white blood cell called a B cell (B lymphocyte).

Biomarkers

A predictor that can be used to measure the presence or progress of a disease or the effects of treatment. For example, prostate-specific antigen is a biomarker for prostate cancer.

End-stage renal disease

End-stage renal disease is the stage of kidney impairment which is irreversible, cannot be controlled by conservative management alone, and requires dialysis or kidney transplantation to maintain life.

Inflammation

A protective tissue response of the organism to injury which serves to remove injurious insult and to mediate the healing process.

Primary glomerular diseases

Primary glomerular diseases consist of a group of disorders characterized by pathologic alterations in normal glomerular structure and function, independent of systemic disease courses. This distinction is important because the clinical presentation and pathologic findings of glomerulopathy secondary to systemic diseases may mimic primary glomerular disorders, yet the correct diagnosis of the underlying systemic disease may significantly alter the treatment of the patient.

Proteinuria

The presence of abnormally large amounts of protein in the urine, usually resulting from kidney diseases, but sometimes results from fever, excessive exercise, and other abnormal conditions. It is often defined as an amount in excess of 300 mg per day.

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Turgutalp, K., Bardak, S., Demir, S., Kıykım, A. (2015). Red Blood Cell Distribution Width: Useful Predictor for Treatment Response in Primary Glomerular Diseases. In: Patel, V. (eds) Biomarkers in Kidney Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7743-9_11-1

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  • DOI: https://doi.org/10.1007/978-94-007-7743-9_11-1

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  • Online ISBN: 978-94-007-7743-9

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