Lupus podocytopathy
Abstract
Lupus Erythematosus (SLE) is a systemic autoimmune disease which may affect several organs. Approximately 50% of SLE patients develop clinically overt renal disease, an important cause of morbidity and mortality. Nephrotic syndrome (NS) is frequent in patients suffering from lupus nephritis (LN) and it is usually associated with immune complex deposition on capillary walls accompanied by endocapillary proliferation and necrosis. However, a growing number of reported cases of SLE and NS patients show biopsies which reveal podocyte injury, consisting of pedicel fusion upon electron microscopy and a morphological pattern identical to minimal change disease (MCD), primary focal segmental glomerulosclerosis or mesangial proliferative glomerulonephritis, in absence of immune complex deposition on capillary walls. Although this finding could be explained by the coexistence of LN and MCD, most researchers consider that this fact is not pure coincidence. A new term, lupus podocytopathy, therefore appears to define a distinct entity characterized by T cell activation and the presence of a glomerular permeability factor. This allows to distinguish the group of SLE and NS patients whose biopsies do not show immune complex deposition on capillary walls or signs of renal lupus activity; electron microscopy reveals diffuse pedicel fusion and patients show high responsiveness to corticosteroid treatment. In order to diagnose this new entity, it is necessary to interpret histopathological findings together with data gathered from immunofluorescence and electron microscopy.References
D’Agati VD. Renal disease in systemic lupus erythematosus, mixed connective tissue disease, Sjogren’s syndrome, and rheumatoid arthritis. En: Heptinstall’s pathology of the kidney. 7th ed. Philadelphia : Wolters Kluwer Health/Lippincott Williams & Wilkins, 2015. P. 608-9.
Appel GB, Silva FG, Pirani CL, Meltzer JI, Estes D. Renal involvement in systemic lupud erythematosus (SLE): a study of 56 patients emphasizing histologic classification. Medicine (Baltimore). 1978;57(5):371-410.
Seshan SV, Jennette JC. Renal disease in systemic lupus erythematosus with emphasis on classification of lupus glomerulonephritis: advances and implications. Arch Pathol Lab Med. 2009;133(2):233-48.
Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018;93(4):789-96.
Wilhelmus S, Alpers CE, Cook HT, Ferrario F, Fogo AB, Haas M, et al. The Revisited Classification of GN in SLE at 10 Years: Time to Re-Evaluate Histopathologic Lesions. J Am Soc Nephrol. 2015;26(12):2938-46.
Bomback AS, Markowitz GS. Lupus Podocytopathy: A Distinct Entity. Clin J Am Soc Nephrol. 2016;11(4):547-8.
Trivedi S, Zeier M, Reiser J. Role of podocytes in lupus nephritis. Nephrol Dial Transplant. 2009;24(12):3607-12.
Hu W, Chen Y, Wang S, Chen H, Liu Z, Zeng C, et al. Clinical-Morphological Features and Outcomes of Lupus Podocytopathy. Clin J Am Soc Nephrol. 2016;11(4):585-92.
Markowitz GS, D’Agati VD. Classification of lupus nephritis. Curr Opin Nephrol Hypertens. 2009;18(3):220-5.
Appel GB, Valeri A. The course and treatment of lupus nephritis. Annu Rev Med. 1994;45:525-37.
Dube GK, Markowitz GS, Radhakrishnan J, Appel GB, D’Agati VD. Minimal change disease in systemic lupus erythematosus. Clin Nephrol. 2002;57(2):120-6.
Hertig A, Droz D, Lesavre P, Grünfeld JP, Rieu P. SLE and idiopathic nephrotic syndrome: coincidence or not? Am J Kidney Dis. 2002;40(6):1179-84.
Kraft SW, Schwartz MM, Korbet SM, Lewis EJ. Glomerular podocytopathy in patients with systemic lupus erythematosus. J Am Soc Nephrol. 2005;16(1):175-9.
Huong DL, Papo T, Beaufils H, Wechsler B, Blétry O, Baumelou A, et al. Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center. Medicine (Baltimore). 1999;78(3):148-66.
Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore). 1993;72(2):113-24.
Nam KH, Cha YJ, Kwon YE, Kim YL, Park KS, An SY, et al. Minimal change disease in systemic lupus: another renal manifestation of lupus? Ewha Med J. 2013;36(2):139-43.
Wang Y, Yu F, Song D, Wang SX, Zhao MH. Podocyte involvement in lupus nephritis based on the 2003 ISN/RPS system: a large cohort study from a single centre. Rheumatology (Oxford). 2014;53(7):1235-44.
Han TS, Schwartz MM, Lewis EJ. Association of glomerular podocytopathy and nephrotic proteinuria in mesangial lupus nephritis. Lupus. 2006;15(2):71-5.
Deji N, Sugimoto T, Kanasaki M, Aoyama M, Tanaka Y, Sakaguchi M, et al. Emerging minimalchange nephrotic syndrome in a patient with chronic mesangial proliferative lupus nephritis. Intern Med. 2007;46(13):991-5.
Lech M, Anders HJ. The pathogenesis of lupus nephritis. J Am Soc Nephrol. 2013;24(9):1357-66.
Desai N, Cimbaluk D, Lewis EJ, Whittier WL. Proteinuria in membranous lupus nephritis: the pathology is in the podocyte. Lupus. 2013;22(5):461-8.
Ma R, Jiang W, Li Z, Sun Y, Wei Z. Intrarenal macrophage infiltration induced by T cells is associated with podocyte injury in lupus nephritis patients. Lupus. 2016;25(14):1577-86.
Shalhoub RJ. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet. 1974;2(7880):556-60.
Sahali D, Pawlak A, Valanciuté A, Grimbert P, Lang P, Remy P, et al. A novel approach to investigation of the pathogenesis of active minimal-change nephrotic syndrome using subtracted cDNA library screening. J Am Soc Nephrol. 2002;13(5):1238-47.
Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G, et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol. 2007;2(3):445-53.
