Abstract
The involvement of the kidneys, or lupus nephritis, develops in 30–50 % of patients with systemic lupus erythematosus and is a major cause of morbidity and mortality. Although some clinical variables have prognostic value, histological information obtained from biopsies continues to be indispensable for classification and outcome prediction, including the status of renal vascular lesions. In this chapter, we describe main histological patterns of vasculopathies by using routine methods for light microscopy, electron microscopy, and direct immunofluorescence. Lastly, we report more sensitive and specific methods for immunohistochemistry detection of platelet aggregates. These procedures could help to better identify vascular involvement in patients with lupus nephritis.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAbbreviations
- aCL antibodies:
-
Anticardiolipin antibodies
- ADAMTS-13:
-
Disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
- ANXA5:
-
Annexin A5
- aPL antibodies:
-
Antiphospholipid antibodies
- APS:
-
Antiphospholipid syndrome
- APSN:
-
APS nephropathy
- CEC:
-
Circulating endothelial cell
- CV:
-
Cardiovascular
- DIF:
-
Direct immunofluorescence
- EM:
-
Electron microscopy
- GN:
-
Glomerulonephritis
- GP:
-
Glycoproteins
- H&E:
-
Hematoxylin and eosin
- HUS:
-
Hemolytic uremic syndrome
- IC:
-
Immunocomplex
- IF:
-
Immunofluorescence
- IHC:
-
Immunohistochemistry
- LA:
-
Lupus anticoagulant
- LM:
-
Light microscopy
- LN:
-
Lupus nephritis
- MHA:
-
Microangiopathic hemolytic anemia
- PAS:
-
Periodic acid-Schiff
- RAS:
-
Renal artery stenosis
- SLE:
-
Systemic lupus erythematosus
- sTM:
-
Soluble thrombomodulin
- TMA:
-
Thrombotic microangiopathy
- TTP:
-
Thrombotic thrombocytopenic purpura
- VCAM-1:
-
Vascular cell adhesion molecule-1
- VWFCP:
-
Von Willebrand factor-cleaving protease
References
Appel GB, Pirani CL, D’Agati V. Renal vascular complications of systemic lupus erythematosus. J Am Soc Nephrol. 1994;4:1499–515.
Arbustini E, Dal Bello B, Morbini P, et al. Immunohistochemical characterization of coronary thrombi in allograft vascular disease. Transplantation. 2000;69:1095–101.
Austin 3rd HA, Boumpas DT, Vaughan EM, et al. High-risk features of lupus nephritis: importance of race and clinical and histological factors in 166 patients. Nephrol Dial Transplant. 1995;10:1620–8.
Balow JE, Austin 3rd HA. Renal disease in systemic lupus erythematosus. Rheum Dis Clin N Am. 1988;14:117–33.
Banfi G, Bertani T, Boeri V, et al. Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). Am J Kidney Dis. 1991;18:240–8.
Bruschi M, Sinico RA, Moroni G, et al. Glomerular autoimmune multicomponents of human lupus nephritis in vivo: alpha-enolase and annexin AI. J Am Soc Nephrol. 2014;25:2483–98.
Cameron JS. Lupus nephritis. J Am Soc Nephrol. 1999;10:413–24.
Cederholm A, Frostegard J. Annexin A5 in cardiovascular disease and systemic lupus erythematosus. Immunobiology. 2005;210:761–8.
Clancy R, Marder G, Martin V, et al. Circulating activated endothelial cells in systemic lupus erythematosus: further evidence for diffuse vasculopathy. Arthritis Rheum. 2001;44:1203–8.
Cohen D, Koopmans M, Kremer Hovinga IC, et al. Potential for glomerular C4d as an indicator of thrombotic microangiopathy in lupus nephritis. Arthritis Rheum. 2008;58:2460–9.
Cohen D, Buurma A, Goemaere NN, et al. Classical complement activation as a footprint for murine and human antiphospholipid antibody-induced fetal loss. J Pathol. 2011;225:502–11.
Collins AB, Schneeberger EE, Pascual MA, et al. Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries. J Am Soc Nephrol. 1999;10:2208–14.
Crespo-Leiro MG, Veiga-Barreiro A, Domenech N, et al. Humoral heart rejection (severe allograft dysfunction with no signs of cellular rejection or ischemia): incidence, management, and the value of C4d for diagnosis. Am J Transplant. 2005;5:2560–4.
Daugas E, Nochy D, Huong DL, et al. Antiphospholipid syndrome nephropathy in systemic lupus erythematosus. J Am Soc Nephrol. 2002;13:42–52.
de Kort H, Munivenkatappa RB, Berger SP, et al. Pancreas allograft biopsies with positive c4d staining and anti-donor antibodies related to worse outcome for patients. Am J Transplant. 2010;10:1660–7.
Descombes E, Droz D, Drouet L, et al. Renal vascular lesions in lupus nephritis. Medicine (Baltimore). 1997;76:355–68.
Distelmaier K, Adlbrecht C, Jakowitsch J, et al. Local complement activation triggers neutrophil recruitment to the site of thrombus formation in acute myocardial infarction. Thromb Haemost. 2009;102:564–72.
El-Banawy HS, Gaber EW, Maharem DA, et al. Angiopoietin-2, endothelial dysfunction and renal involvement in patients with systemic lupus erythematosus. J Nephrol. 2012;25:541–50.
Erdbruegger U, Woywodt A, Kirsch T, et al. Circulating endothelial cells as a prognostic marker in thrombotic microangiopathy. Am J Kidney Dis. 2006;48:564–70.
Esdaile JM, Federgreen W, Quintal H, et al. Predictors of one year outcome in lupus nephritis: the importance of renal biopsy. Q J Med. 1991;81:907–18.
Fakhouri F, Noel LH, Zuber J, et al. The expanding spectrum of renal diseases associated with antiphospholipid syndrome. Am J Kidney Dis. 2003;41:1205–11.
Faurschou M, Dreyer L, Kamper AL, et al. Long-term mortality and renal outcome in a cohort of 100 patients with lupus nephritis. Arthritis Care Res (Hoboken). 2010;62:873–80.
Galindo M, Gonzalo E, Martinez-Vidal MP, et al. Immunohistochemical detection of intravascular platelet microthrombi in patients with lupus nephritis and anti-phospholipid antibodies. Rheumatology (Oxford). 2009;48:1003–7.
Gonzalez-Crespo MR, Lopez-Fernandez JI, Usera G, et al. Outcome of silent lupus nephritis. Semin Arthritis Rheum. 1996;26:468–76.
Gonzalo E, Toldos O, Martinez-Vidal MP, et al. Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis. Arthritis Res Ther. 2012;14:R126.
Gungor T, Furlan M, Lammle B, et al. Acquired deficiency of von Willebrand factor-cleaving protease in a patient suffering from acute systemic lupus erythematosus. Rheumatology (Oxford). 2001;40:940–2.
Hamasaki K, Mimura T, Kanda H, et al. Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report and literature review. Clin Rheumatol. 2003;22:355–8.
Hu WX, Liu ZZ, Chen HP, et al. Clinical characteristics and prognosis of diffuse proliferative lupus nephritis with thrombotic microangiopathy. Lupus. 2010;19:1591–8.
Kant KS, Pollak VE, Weiss MA, et al. Glomerular thrombosis in systemic lupus erythematosus: prevalence and significance. Medicine (Baltimore). 1981;60:71–86.
Kim SH, Jeong HJ. Glomerular C4d deposition indicates in situ classic complement pathway activation, but is not a marker for lupus nephritis activity. Yonsei Med J. 2003;44:75–80.
Klemperer P, Pollack AD, Baehr G. Landmark article May 23, 1942: diffuse collagen disease. Acute disseminated lupus erythematosus and diffuse scleroderma. By Paul Klemperer, abou D. Pollack and George Baehr. JAMA. 1984;251:1593–4.
Magro CM, Pope Harman A, Klinger D, et al. Use of C4d as a diagnostic adjunct in lung allograft biopsies. Am J Transplant. 2003;3:1143–54.
Mannucci PM, Vanoli M, Forza I, et al. Von Willebrand factor cleaving protease (ADAMTS-13) in 123 patients with connective tissue diseases (systemic lupus erythematosus and systemic sclerosis). Haematologica. 2003;88:914–8.
Meehan SM, Limsrichamrern S, Manaligod JR, et al. Platelets and capillary injury in acute humoral rejection of renal allografts. Hum Pathol. 2003;34:533–40.
Mok CC. Prognostic factors in lupus nephritis. Lupus. 2005;14:39–44.
Navratil JS, Manzi S, Kao AH, et al. Platelet C4d is highly specific for systemic lupus erythematosus. Arthritis Rheum. 2006;54:670–4.
Neil DA, Hubscher SG. Current views on rejection pathology in liver transplantation. Transpl Int. 2010;23:971–83.
Nochy D, Daugas E, Droz D, et al. The intrarenal vascular lesions associated with primary antiphospholipid syndrome. J Am Soc Nephrol. 1999;10:507–18.
Nzerue CM, Hewan-Lowe K, Pierangeli S, et al. “Black swan in the kidney”: renal involvement in the antiphospholipid antibody syndrome. Kidney Int. 2002;62:733–44.
Rieger M, Mannucci PM, Kremer Hovinga JA, et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood. 2005;106:1262–7.
Salmon JE, Girardi G, Lockshin MD. The antiphospholipid syndrome as a disorder initiated by inflammation: implications for the therapy of pregnant patients. Nat Clin Pract Rheumatol. 2007;3:140–7. quiz 141 p following 187.
Seligman VA, Lum RF, Olson JL, et al. Demographic differences in the development of lupus nephritis: a retrospective analysis. Am J Med. 2002;112:726–9.
Tektonidou MG, Sotsiou F, Nakopoulou L, et al. Antiphospholipid syndrome nephropathy in patients with systemic lupus erythematosus and antiphospholipid antibodies: prevalence, clinical associations, and long-term outcome. Arthritis Rheum. 2004;50:2569–79.
Tsai HM. Autoimmune thrombotic microangiopathy: advances in pathogenesis, diagnosis, and management. Semin Thromb Hemost. 2012;38:469–82.
Wierzbicki P, Klosowska D, Wyzgal J, et al. Beta 3 integrin expression on T cells from renal allograft recipients. Transplant Proc. 2006;38:338–9.
Xing GQ, Chen M, Liu G, Zheng X, E J, Zhao MH. Differential deposition of C4d and MBL in glomeruli of patients with ANCA-negative pauci-immune crescentic glomerulonephritis. J Clin Immunol. 2010;30:144–56.
Yang N, Isbel NM, Nikolic-Paterson DJ, et al. Local macrophage proliferation in human glomerulonephritis. Kidney Int. 1998;54:143–51.
Yao G, Liu ZH, Zheng C, et al. Evaluation of renal vascular lesions using circulating endothelial cells in patients with lupus nephritis. Rheumatology (Oxford). 2008a;47:432–6.
Yao GH, Liu ZH, Zhang X, et al. Circulating thrombomodulin and vascular cell adhesion molecule-1 and renal vascular lesion in patients with lupus nephritis. Lupus. 2008b;17:720–6.
Yung S, Cheung KF, Zhang Q, et al. Anti-dsDNA antibodies bind to mesangial annexin II in lupus nephritis. J Am Soc Nephrol. 2010;21:1912–27.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media Dordrecht
About this entry
Cite this entry
Galindo-Izquierdo, M., Gonzalo-Gil, E., Toldos, O., Pablos-Álvarez, J.L. (2016). Biomarkers of Renal Microthrombosis in Lupus Nephritis. In: Patel, V., Preedy, V. (eds) Biomarkers in Kidney Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7699-9_6
Download citation
DOI: https://doi.org/10.1007/978-94-007-7699-9_6
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-7698-2
Online ISBN: 978-94-007-7699-9
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences