SP0100 Pathologic classification of lupus nephritis
Authors: D Ferluga
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> A myriad of autoantibodies, particularly those against dsDNA, have been found to be involved in the production of a large heterogeneous set of immune complexes whose deposition in various organs, especially kidneys, appears to play a major role in triggering tissue lesions and an inflammatory response in systemic lupus erythematosus (SLE). In our series of 379 kidney biopsy and autopsy samples from SLE patients, immune deposits were demonstrated by traditional immunofluorescence in the glomeruli (99.0%) and characteristically also in the tubulo-interstitial compartment (57.4%) and extraglomerular vessels (64.4%). Other pathogenetic immune mechanisms, e.g. anti-phospholipid antibodies and anti-neutrophil cytoplasmatic antibodies, appear to be additionally involved, especially in triggering thrombosis and/or necrotizing glomerular lesions, respectively. Furthermore, nonimmune mechanisms, hyperperfusion and hyperfiltration associated with arterial hypertension and severe proteinuria as well as hyperlipidemia, play a more or less significant role in the progression of lupus renal disease. Several parameters provided by semiquantitative evaluation of the kidney biopsy by different techniques have been established to be not only of prognostic significance but also of particular clinical importance in decision making about the most appropriate therapeutic approach in SLE patients. The now widely accepted original WHO classification of lupus glomerulonephritis (GN) basically separates normal glomerular histology class I (14–5.2%), mild mesangiopathy class II (40–15.0%) and mostly fairly indolent membranous GN class V (31–11.6%) from severe forms of renal disease, strictly requiring immunosuppressive therapy, focal segmental class III (65–24.3%) and particularly diffuse proliferative class IV (117–43.8%) lupus GN. Up to 50% of WHO class transformations have been demonstrated by our biopsy follow-up study of 155 SLE patients treated according to agreed standards. By considering additionally the histomorphologic pattern of glomerular inflammatory reaction in our 370 biopsy cases, mixed membranous and proliferative type of GN was confirmed to be particularly characteristic for SLE (141–38.1%). Furthermore, our studies provided evidence for a heterogeneity of GN types related at least to some extent to differences in pathogenesis in WHO classes III and IV. A mesangial-transmembranous immune deposit distribution pattern has been found characteristic for SLE (55.9%) especially when the deposits contain »fingerprints« (17.3%). Our studies confirmed that prominent subendothelial immune deposits are among the most objective evidence of the activity of lupus GN. Furthermore, we share the opinion that kidney biopsy monitoring of the activity index and chronicity index, introduced in the early eighties into clinical trials by a group from NIH, can usefully contribute to planning the most appropriate therapy and biopsy follow-up evaluation. Various immune mechanisms, including those related to extraglomerular deposits, as well as nonimmune mechanisms, play a role in the development and progression of tubulo-interstitial lesions, which have been confirmed to correlate best with the clinical parameters of renal insufficiency. Extraglomerular vascular changes of various histopathological characteristics and pathogenesis have been far less extensively studied than glomerular despite the fact that they may also significantly influence the course and prognosis of lupus GN. Three main forms of vascular lesions were confirmed in our study of kidney tissue samples in 261 SLE patients 1. immune deposit (153–56.4%) accompanied by lupus microangiopathy, uncomplicated and hyalinizing, and vasculitis 2. premature arteriosclerosis (101–38.0%) and 3. thrombosis and thrombotic microangiopathy frequently related to positive anti-cardiolipin antibodies in the sera (11–4.1%). <h3>References</h3> Ferluga D, Jerše M, Vizjak A, <i>et al</i>. Correlation among WHO classes, histomorphologic patterns of glomerulonephritis and glomerular immune deposits in SLE. Wien Klin Wochenschr. 2000;112:692–701 Kashgarian M. The role of the kidney biopsy in the treatment of lupus nephritis. Ren Fail. 1996;18:765–73