Official reprint from UpToDate www.uptodate.com ©2016 UpToDate Diagnosis and classification of r enal disease in systemic lupus erythematosus Authors: Andrew S Bomback, MD, MPH, Gerald B Appel, MD Section Editors: Richard J Glassock, MD, MACP, David S Pisetsky, MD, PhD Deputy Editor: Albert Q Lam, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through:  Oct 2016. | This topic last updated:  Mar 24, 2016. INTRODUCTION — Renal involvement is common in systemic lupus er ythematosus (SLE). An abnormal urinalysis with or without an elevated plasma creatinine concentration is present in a large proportion of patients at the time of diagnosis of lupus nephritis. The most fr equently observed abnormality in patients with lupus nephritis is proteinuria [ 1 ]. Clinical findings underestimate the true frequency of renal involvement, as some patients may (rarely) have significant pathologic abnormalities without any clinical signs of r enal involvement. (See 'Silent lupus nephritis' below.) There are several types of renal disease in SLE (most commonly , immune complex-mediated glomerular disease), which are usually differentiated with a renal biopsy. In addition, renal diseases that are unrelated to lupus may be seen [ 2,3 ]. An overview of the epidemiology , pathogenesis, and classification of lupus nephriti s will be presented here. The indications for renal biopsy and the approach to therapy in the different types of lupus nephritis ar e discussed separately. (See "Indications for renal biopsy in patients w ith lupus nephritis" and "Therapy of diffuse or focal proliferative lupus nephritis" and "Clinical features and therapy of lupus membranous nephropathy" .) PATHOGENESIS  — The pattern of glomerular injur y seen in systemic lupus erythematosus (SLE) (and in other immune complex-mediated glomerular diseases) is primarily r elated to the site of formation of the immune deposits, which are primarily due to anti-double-stranded DNA antibodies (anti-dsDNA, or anti-DNA). These antibodies bind DNA in various forms, such as DNA in the form of nucleosomes, which consist of dsDNA wound around a core histone octamer [ 4 ]. Anti-DNA immune complex formation  — These immune complexes are primarily composed of DNA and anti-DNA. However, immune complexes may also have as their components chromatin, C1q, laminin, Sm, La (SS-B), Ro (SS- A), ubiquitin, and ribosomes [ 5-12 ]. In addition to forming immune complexes with DNA, some anti-DNA antibodies may bind directly to components of the gl omerular basement membrane (GBM) and mesangium [ 13,14 ]. The immune deposits in lupus nephritis can occur in the mesangium, subendothelial, and/or subepithelial compartments of the glomerulus. Deposits in the mesangium and subendothelial space are proximal to the GBM and are therefore in communication with the vascular space. As a result, activation of complement (typically via the classical pathwa y) with the generation of the chemoattractants, C3a and C5a, r esults in the influx of neutrophils and mononuclear cells. These changes are manifest histologically by a mesangial or focal or diffuse pr oliferative glomerulonephritis and clinically by an active urine sediment (red cells, white cells, and cellular and granular casts), proteinuria, and, often, an acute decline in renal function. ® ®