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The classification of glomerulonephritis in systemic lupus erythematosus revisited
2004; Elsevier BV; Volume: 65; Issue: 2 Linguagem: Inglês
10.1111/j.1523-1755.2004.00443.x
ISSN1523-1755
AutoresJan J. Weening, Vivette D. D’Agati, Melvin M. Schwartz, Surya V. Seshan, Charles E. Alpers, Gerald B. Appel, James E. Balow, Jan A. Bruijn, Terence Cook, Franco Ferrario, Agnes B. Fogo, Ellen M. Ginzler, L Hebert, Gary S. Hill, Prue Hill, J. Charles Jennette, Norella Kong, Philippe Lesavre, Michael D. Lockshin, Lai‐Meng Looi, Hirofumi Makino, Luiz A. Moura, Michio Nagata,
Tópico(s)Systemic Sclerosis and Related Diseases
ResumoThe classification of glomerulonephritis in systemic lupus erythematosus revisited.The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving ≥50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification. The classification of glomerulonephritis in systemic lupus erythematosus revisited.The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving ≥50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification. The morphologic changes in a renal biopsy from a patient with systemic lupus erythematosus (SLE) comprise a spectrum of vascular, glomerular, and tubulointerstitial lesions. The classification of SLE nephritis has evolved over the past 40 years as more lesions were identified and defined. It has been an increasing challenge to apply new pathogenetic insights to the interpretation of the renal biopsy in SLE and to correlate pathologic findings with clinical symptoms, choice of treatment, and prognosis. The current classification, which was advanced in 1982 [1.Churg J. Sobin L.H. Renal Disease: Classification and Atlas of Glomerular Disease. Igaku-Shoin, Tokyo1982Google Scholar] and revised in 1995 [2.Churg J. Bernstein J. Glassock R.J. Renal Disease: Classification and Atlas of Glomerular Diseases. 2nd ed. Igaky-Shoin, New York, Tokyo1995Google Scholar], reflects our understanding of the pathogenesis of the various forms of renal injury in SLE nephritis. However, subsequent clinicopathologic studies have revealed the need for clarification of the different categories and the diagnostic terminology. The classification of lupus nephritis is critical to the issue of patient care and for the comparison of outcome results and therapeutic trials between different clinics. It is imperative that pathologists reach a consensus concerning the definition of the different classes of SLE nephritis and the meaning of the pathologic terminology applied in order to standardize the way biopsies are interpreted and reported between different centers. With these objectives in mind, a group of renal pathologists, nephrologists, and rheumatologists convened to formulate a revised classification of lupus nephritis during a 3-day consensus conference held at Columbia University, New York, New York in May 2002. SLE is a multisystem autoimmune disease whose etiology and pathogenesis are incompletely understood. The development of autoimmunity in SLE has been attributed to a loss of self-tolerance due to inadequate central or peripheral deletion or silencing of autoreactive lymphocytes, leading to multiple autoantibody specificities [3.Mecklenbrauker I. Saijo K. Zheng N.Y. et al.Protein kinase C delta controls self-antigen-induced B-cell tolerance.Nature. 2002; 416: 860-865Crossref PubMed Scopus (225) Google Scholar]. Dysregulated apoptosis and inadequate removal of apoptotic cells and nuclear remnants may contribute to autoimmunity by causing prolonged exposure of the immune system to nuclear and cell membrane components [4.Stuart L. Hughes J. Apoptosis and autoimmunity.Nephrol Dial Transpl. 2002; 17: 697-700Crossref PubMed Scopus (37) Google Scholar]. The characteristic development of autoantibodies to DNA and other nuclear antigens, as well as to membrane phospholipids, support the relevance of both mechanisms [5.Berden J.H. Lupus nephritis.Kidney Int. 1997; 52: 538-558Abstract Full Text PDF PubMed Scopus (195) Google Scholar, 6.Walport M.J. Davies K.A. Botto M. C1q and systemic lupus erythematosus.Immunobiology. 1998; 199: 265-285Crossref PubMed Scopus (305) Google Scholar]. In addition to established genetic predisposition, altered immunoregulatory factors or environmental stimuli may trigger autoimmune phenomena in certain populations. Recent studies have ascribed specific genetic linkages to the development of renal disease in SLE among certain ethnic groups, including European American and African American populations, some of which may determine the severity of the glomerular disease [7.Lea J. Lupus nephritis in African Americans.Am J Med Sci. 2002; 323: 85-89Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar]. Although knowledge of the etiology of SLE is incomplete, it is clear from the varied forms of tissue injury that a number of different effector mechanisms may act alone or in concert to produce the pleomorphic patterns of lupus nephritis. Autoantibodies may lead to cell and tissue injury by Fc receptor-mediated inflammation [8.Clynes R. Dumitru C. Ravetch J.V. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis.Science. 1998; 279: 1052-1054Crossref PubMed Scopus (506) Google Scholar] as well as by direct cytotoxicity, which is usually complement-dependent, as has been shown for antibody-mediated hemolytic anemia or thrombocytopenia. In the kidney, intrinsic antigens such as extracellular matrix components or cell surface glycoproteins may serve as targets for autoantibody binding. In addition, renal injury in lupus nephritis may result from autoantibodies that bind to circulating antigens, forming circulating preformed immune complexes, or autoantibodies that bind to antigens deposited from the circulation in glomerular and vessel walls, causing in situ immune complex formation, as has been shown for nucleosomes and antidouble-stranded DNA autoantibodies [5.Berden J.H. Lupus nephritis.Kidney Int. 1997; 52: 538-558Abstract Full Text PDF PubMed Scopus (195) Google Scholar]. Subsequent Fc receptor and complement binding then initiates an inflammatory and cytotoxic reaction. Such cytotoxicity may be directed toward podocytes in the setting of membranous nephropathy, where in situ immune complex formation occurs along the subepithelial aspect of the glomerular basement membrane, or toward endocapillary cells in the case of the endocapillary proliferative and exudative inflammatory reaction that follows subendothelial immune complex formation. In addition to direct immune complex-mediated cell and tissue injury, autoantibodies with antiphospholipid or cryoglobulin activity may also promote thrombotic and inflammatory vascular lesions in SLE [9.Daugas E. Nochy D. Huong Du L.T. et al.Antiphospholipid syndrome nephropathy in systemic lupus erythematosus.J Am Soc Nephrol. 2002; 13: 42-52PubMed Google Scholar]. Antineutrophil cytoplasmic-antigen autoantibodies (ANCA) have been described in a subgroup of patients with lupus nephritis and may initiate vasculitis and glomerulonephritis by “pauci-immune” neutrophil-dependent mechanisms similar to those described for microscopic polyangiitis or Wegener's granulomatosis [10.Marshall S. Dressler R. D'Agati V. Membranous lupus nephritis with antineutrophil cytoplasmic antibody-associated segmental necrotizing and crescentic glomerulonephritis.Am J Kidney Dis. 1997; 29: 119-124Abstract Full Text PDF PubMed Scopus (40) Google Scholar]. Finally, it is also likely that other poorly characterized autoantibodies of unknown specificity (such as anti-endothelial antibodies) may be operant in the pathogenesis of some forms of lupus nephritis. Based on various experimental models of autoimmune and immune complex disease in the kidney and on observations in human renal biopsies, it is now well established that the glomerular patterns of immune complex-mediated injury are related to the site of accumulation of immunoglobulins, their antigen specificity, their capacity to bind and activate complement and other serine proteases, and their ability to evoke a cellular inflammatory response [11.Fries J.W. Mendrick D.L. Rennke H.G. Determinants of immune complex-mediated glomerulonephritis.Kidney Int. 1988; 34: 333-345Abstract Full Text PDF PubMed Scopus (71) Google Scholar]. These patterns of injury can be divided into three groups. In the mesangial pattern, mesangial hypercellularity and matrix accumulation result from mesangial immune complex accumulation, as can occur in IgA nephropathy or in mesangial proliferative lupus nephritis. The endothelial pattern has an exudative component characterized by leukocyte accumulation, endothelial cell injury, and endocapillary proliferation. This pattern is often associated with capillary wall destruction, mild to marked immune complex deposition, and varying degrees of mesangial proliferation and crescent formation. This category is exemplified by severe postinfectious glomerulonephritis, antiglomerular basement membrane (GBM) disease, systemic vasculitis, and endocapillary proliferative forms of lupus glomerulonephritis. Within the endothelial pattern of glomerular injury, a diffuse and global form can often be separated from a focal segmental form (as seen in microscopic polyangiitis), in which different pathogenetic mechanisms may prevail. The endothelial pattern of injury can also be caused by nonimmunologic mechanisms, such as shear-stress in malignant hypertension, bacterial toxins in verocytotoxin-induced thrombotic microangiopathy, and thrombotic events in SLE-associated lupus anticoagulant syndrome. Persistent accumulation of immune complexes in the subendothelial space may lead to more severe injury and chronic changes, including cellular interposition and replication of the GBM. These endocapillary changes usually occur in association with mesangial pathology because the mesangium is in direct continuity with the subendothelial space and is accessible to circulating immune complexes. This combined mesangiocapillary or membranoproliferative pattern of injury is particularly common in the chronic phase of lupus nephritis. In the epithelial pattern, antibodies and complement inflict cytotoxic injury on the podocyte, resulting in a nonexudative, nonproliferative capillary wall lesion, as can be seen in idiopathic and SLE-associated forms of membranous glomerulopathy. The usual clinical manifestations of these three major morphologic patterns can be predicted based on the topography and character of the glomerular lesions. Mesangial pathology leads to a syndrome of microscopic hematuria and subnephrotic proteinuria with well-preserved or minimally reduced glomerular filtration rate (GFR); the endocapillary pattern is characterized by an acute reduction in GFR, hematuria, and mild to moderate proteinuria; and the membranous pattern is associated with significant proteinuria, often with nephrotic syndrome, and with preservation or gradual reduction in GFR. These three patterns of injury, which encompass the spectrum of most glomerular diseases regardless of etiology, also apply to the major subtypes of glomerular involvement in SLE. In lupus glomerulonephritis, as in other glomerular diseases, it is not uncommon for several different morphologic patterns to coexist, leading to a more complex clinical expression of disease. The introduction of renal biopsy in the 1950s, the application of immunofluorescence and electron microscopic techniques in the 1960s, and increasing knowledge about mechanisms of immune-mediated glomerular injury derived from experimental studies on serum sickness and other models formed the basis of the recognition and classification of the various patterns of renal injury in SLE. As early as 1964, focal segmental glomerulitis, diffuse proliferative glomerulonephritis, and membranous glomerulopathy were recognized as separate entities [12.Pollak V.E. Pirani C. Schwartz F.D. The natural history of the renal manifestations of systemic lupus erythematosus.J Lab Clin Med. 1964; 63: 537-550PubMed Google Scholar, 13.Baldwin D.S. Lowenstein J. Rothfield N.J. et al.The clinical course of proliferative and membranous forms of lupus nephritis.Ann Intern Med. 1970; 73: 929-942Crossref PubMed Scopus (219) Google Scholar], followed by the identification of mesangial lesions in the 1970s [14.Baldwin D.S. Gluck M.C. Lowenstein J. et al.Lupus nephritis: Clinical course as related to morphologic forms and their transitions.Am J Med. 1977; 62: 12-30Abstract Full Text PDF PubMed Scopus (259) Google Scholar]. The first World Health Organization (WHO) classification was formulated by Pirani and Pollak in Buffalo, New York in 1974 and was first used in publications in 1975 [15.Mccluskey R.T. Lupus nephritis.in: Sommers S.C. Kidney Pathology Decennial 1966–1975. Appleton-Century-Crofts, East Norwalk, CT1975: 450-535Google Scholar] and 1978 [16.Appel G.B. Silva F.G. Pirani C.L. Renal involvement in systemic lupus erythematosus (SLE): A study of 56 patients emphasizing histologic classification.Medicine. 1978; 75: 371-410Google Scholar]Table 1. This classification addressed glomerular lesions only. Class I was applied to renal biopsies showing no detectable glomerular abnormalities by light, fluorescence, or electron microscopy. Class II was defined as purely mesangial immune deposition and was subdivided into two subclasses depending on whether mesangial hypercellularity was present. Class III lesions were defined as proliferative glomerulonephritis affecting fewer than 50% of the glomeruli (i.e., focal), whereas class IV was defined as proliferative glomerulonephritis affecting more than 50% of the glomeruli (i.e., diffuse). No qualitative differences between class III and class IV lesions were described. Membranous lupus nephritis was classified as class V. Tubulointerstitial and vascular lesions were not included in the classification system.Table 1Original World Health Organization (WHO) classification of lupus nephritis (1974)Class INormal glomeruli (by LM, IF, EM)Class IIPurely mesangial diseasea. Normocellular mesangium by LM but mesangial deposits by IF or EMb. Mesangial hypercellularity with mesangial deposits by IF or EMClass IIIFocal proliferative glomerulonephritis (<50%)Class IVDiffuse proliferative glomerulonephritis (≥50%)Class VMembranous glomerulonephritisAbbreviations are: LM, light microscopy; IF, immunofluorescence; EM, electron microscopy. Open table in a new tab Abbreviations are: LM, light microscopy; IF, immunofluorescence; EM, electron microscopy. In 1982, the WHO classification was modified by the International Study of Kidney Diseases in Children [1.Churg J. Sobin L.H. Renal Disease: Classification and Atlas of Glomerular Disease. Igaku-Shoin, Tokyo1982Google Scholar]Table 2. Class I was applied to normocellular glomeruli and was now divided into two subclasses based on whether mesangial immune deposits were identified. Class II was applied to purely mesangial proliferative glomerulonephritis and was divided into two subcategories based on the severity of the mesangial hypercellularity. Class III now denoted focal segmental glomerulonephritis with necrotizing lesions and class IV was used for diffuse glomerulonephritis, without stipulating criteria for the percentage of affected glomeruli. Within class IV, there were subdivisions of variants with severe mesangial proliferation, membranoproliferative features, or extensive subendothelial immune deposits in the absence of endocapillary proliferation. In addition, the 1982 classification introduced subdivisions for class III and IV based on the presence of active, chronic, or mixed types of glomerular injury. Class V denoted membranous glomerulonephritis but was subdivided based on the presence of mesangial hypercellularity and overlaps with focal proliferative (class III) and diffuse proliferative (class IV) lupus nephritis. Class VI was introduced to denote advanced sclerosing glomerulonephritis, although the percentage of glomeruli requiring sclerosis was not stipulated. The use of numerous subcategories and the handling of mixed classes made this modified classification cumbersome for some pathologists to use and impeded effective communication with the clinicians. These drawbacks prompted many pathologists to continue to work with the older 1974 WHO classification.Table 2World Health Organization (WHO) morphologic classificiation of lupus nephritis (modified in 1982)Class INormal glomerulia) Nil (by all techniques)b) Normal by light microscopy, but deposits by electron or immunofluorescence microscopyClass IIPure mesangial alterations (mesangiopathy)a) Mesangial widening and/or mild hypercellularity (+)b) Moderate hypercellularity (++)Class IIIFocal segmental glomerulonephritis (associated with mild or moderate mesangial alterations)a) With “active” necrotizing lesionsb) With “active” and sclerosing lesionsc) With sclerosing lesionsClass IVDiffuse glomerulonephritis (severe mesangial, endocapillary, or mesangio-capillary proliferation and/or extensive subendothelial deposits)a) Without segmental lesionsb) With “active” necrotizing lesionsc) With “active” and sclerosing lesionsd) With sclerosing lesionsClass VDiffuse membranous glomerulonephritisa) Pure membranous glomerulonephritisb) Associated with lesions of category II (a or b)c) Associated with lesions of category III (a–c)d) Associated with lesions of category IV (a–d)Class VIAdvanced sclerosing glomerulonephritis Open table in a new tab The concept of active and chronic renal lesions was first introduced by Pirani, Pollak, and Schwartz [17.Pirani C.L. Pollak V.E. Schwartz F.D. The reproducibility of semiquantitative analysis of renal histology.Nephron. 1964; 1: 230-237Crossref PubMed Scopus (88) Google Scholar] and subsequently refined by Morel-Maroger et al[18.Morel-Maroger L. Mery J.P. Droz D. et al.The course of lupus nephritis: Contribution of serial renal biopsies.Adv Nephrol Necker Hosp. 1976; 6: 79-118PubMed Google Scholar]. Austin et al[19.Austin 3rd, H.A. Muenz L.R. Joyce K.M. et al.Diffuse proliferative lupus nephritis: Identification of specific pathologic features affecting renal outcome.Kidney Int. 1984; 25: 689-695Abstract Full Text PDF PubMed Scopus (552) Google Scholar] devised a system of applying semiquantitative scores for activity and chronicity by grading and adding the individual morphologic components in a given biopsy as a guide to treatment and prognosis. Activity and chronicity scores are used as an adjunct to the WHO classification of lupus nephritis by many practicing pathologists, although the reproducibility and the predictability of these indices have been questioned by some [20.Schwartz M.M. Lan S.P. Bernstein J. et al.Irreproducibility of the activity and chronicity indices limits their utility in the management of lupus nephritis. Lupus Nephritis Collaborative Study Group.Am J Kidney Dis. 1993; 21: 374-377Abstract Full Text PDF PubMed Scopus (99) Google Scholar]. In 1995, attention was again drawn to the significance of segmental glomerular capillary wall necrosis [2.Churg J. Bernstein J. Glassock R.J. Renal Disease: Classification and Atlas of Glomerular Diseases. 2nd ed. Igaky-Shoin, New York, Tokyo1995Google Scholar], a lesion also characteristic of glomerular injury in systemic vasculitis. Some investigators consider segmental glomerular necrosis to be the defining feature of class III lesions, regardless of the percentage of glomeruli involved. Subsequent studies by Najafi et al[21.Najafi C.C. Korbet S.M. Lewis E.J. et al.Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis.Kidney Int. 2001; 59: 2156-2163Abstract Full Text Full Text PDF PubMed Google Scholar] revealed the poor outcome of diffuse segmental necrotizing glomerulonephritis involving over 50% of glomeruli, (which these investigators consider a severe form of class III), as compared to other forms of class IV lupus nephritis. In order to accommodate the clinicopathologic and pathogenetic insights that have accumulated since the 1982 and 1995 modifications of the original 1974 WHO classification and to eliminate inconsistencies and ambiguities, we propose a new revised classification Table 3 and Table 4. This revised classification preserves the simplicity of the original WHO classification, incorporates selective refinements concerning activity and chronicity from the 1982 and 1995 revisions, and adds a number of new modifications. Overall, it bears a strong similarity to the 1974 classification, but introduces several important modifications concerning quantitative and qualitative differences between class III and IV lesions. The major objective is to standardize definitions, emphasize clinically relevant lesions, and encourage uniform and reproducible reporting between centers. Like the preceding classifications, this new classification is based exclusively on glomerular pathology. We strongly recommend that any significant vascular and tubulointerstitial pathology be reported as separate entries in the diagnostic line.Table 3International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification of lupus nephritisClass IMinimal mesangial lupus nephritisNormal glomeruli by light microscopy, but mesangial immune deposits by immunofluorescenceClass IIMesangial proliferative lupus nephritisPurely mesangial hypercellularity of any degree or mesangial matrix expansion by light microsocpy, with mesangial immune depositsA few isolated subepithelial or subendothelial deposits may be visible by immunofluorescence or electron microscopy, but not by light microscopyClass IIIFocal lupus nephritisaIndicate the proportion of glomeruli with active and with sclerotic lesions.Active or inactive focal, segmental or global endo- or extracapillary glomerulonephritis involving <50% of all glomeruli, typically with focal subendothelial immune deposits, with or without mesangial alterations Class III (A)Active lesions: focal proliferative lupus nephritis Class III (A/C)Active and chronic lesions: focal proliferative and sclerosing lupus nephritis Class III (C)Chronic inactive lesions with glomerular scars: focal sclerosing lupus nephritisClass IVDiffuse lupus nephritisbIndicate the proportion of glomeruli with fibrinoid necrosis and/or cellular crescents.Active or inactive diffuse, segmental or global endo- or extracapillary glomerulonephritis involving ≥50% of all glomeruli, typically with diffuse subendothelial immune deposits, with or without mesangial alterations. This class is divided into diffuse segmental (IV-S) lupus nephritis when ≥50% of the involved glomeruli have segmental lesions, and diffuse global (IV-G) lupus nephritis when ≥50% of the involved glomeruli have global lesions. Segmental is defined as a glomerular lesion that involves less than half of the glomerular tuft. This class includes cases with diffuse wire loop deposits but with little or no glomerular proliferation. Class IV-S (A)Active lesions: diffuse segmental proliferative lupus nephritis Class IV-G (A)Active lesions: diffuse global proliferative lupus nephritis Class IV-S (A/C)Active and chronic lesions: diffuse segmental proliferative and sclerosing lupus nephritis Class IV-G (A/C)Active and chronic lesions: diffuse global proliferative and sclerosing lupus nephritis Class IV-S (C)Chronic inactive lesions with scars: diffuse segmental sclerosing lupus nephritis Class IV-G (C)Chronic inactive lesions with scars: diffuse global sclerosing lupus nephritisClass VMembranous lupus nephritisGlobal or segmental subepithelial immune deposits or their morphologic sequelae by light microscopy and by immunofluorescence or electron microscopy, with or without mesangial alterationsClass V lupus nephritis may occur in combination with class III or IV in which case both will be diagnosedClass V lupus nephritis may show advanced sclerosisClass VIAdvanced sclerotic lupus nephritis≥90% of glomeruli globally sclerosed without residual activityIndicate and grade (mild, moderate, severe) tubular atrophy, interstitial inflammation and fibrosis, severity of arteriosclerosis or other vascular lesions.a Indicate the proportion of glomeruli with active and with sclerotic lesions.b Indicate the proportion of glomeruli with fibrinoid necrosis and/or cellular crescents. Open table in a new tab Table 4Abbreviated International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification of lupus nephritis (2003)Class IMinimal mesangial lupus nephritisClass IIMesangial proliferative lupus nephritisClass IIIFocal lupus nephritisaIndicate the proportion of glomeruli with active and with sclerotic lesions.Class IVDiffuse segmental (IV-S) or global (IV-G) lupus nephritisbIndicate the proportion of glomeruli with fibrinoid necrosis and cellular crescents.Class VMembranous lupus nephritiscClass V may occur in combination with class III or IV, in which case both will be diagnosed.Class VIAdvanced sclerosing lupus nephritisIndicate and grade (mild, moderate, severe) tubular atrophy, interstitial inflammation and fibrosis, severity of arteriosclerosis or other vascular lesions.a Indicate the proportion of glomeruli with active and with sclerotic lesions.b Indicate the proportion of glomeruli with fibrinoid necrosis and cellular crescents.c Class V may occur in combination with class III or IV, in which case both will be diagnosed. Open table in a new tab Indicate and grade (mild, moderate, severe) tubular atrophy, interstitial inflammation and fibrosis, severity of arteriosclerosis or other vascular lesions. Indicate and grade (mild, moderate, severe) tubular atrophy, interstitial inflammation and fibrosis, severity of arteriosclerosis or other vascular lesions. As a premise, we emphasize that adequacy of the tissue specimen and histopathologic techniques are mandatory for a reliable classification. For accurate pathologic analysis, it is important that the tissue should be optimally preserved, processed by a skilled technician, cut at 3 microns, and sectioned at multiple levels. Proper tissue handling and use of special stains are essential for accurate and complete assessment of glomerular number, cellularity, and capillary wall alterations. In order to reasonably exclude a focal lesion, the biopsy should contain a minimum of 10 glomeruli for light microscopic analysis [22.Corwin H.L. Schwartz M.M. Lewis E. The importance of sample size in the interpretation of the renal biopsy.Am J Nephrol. 1988; 8: 85-93Crossref PubMed Scopus (141) Google Scholar]. Immunofluorescence is required for complete renal biopsy analysis and should include staining for IgG, IgA, and IgM isotypes, kappa and lambda light chains, and complement components C3 and C1q. Glomerular immune deposits attributable to lupus nephritis as detected by immunofluorescence almost always contain dominant polyclonal IgG, as well as C3 and in most instances C1q, with variable codeposits of IgA and IgM. If glomerular immunoglobulin deposits are restricted to IgA or IgM, diagnostic possibilitie
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