SLE is an autoimmune disease character-ized by overproduction of antibodies to self-antigens, which are mostly derived from cell components like the nucleus, cytoplasm, ribosomes, and cell membranes. Most affected patients are women of childbearing age. In the United States, SLE is more common in black people. Clinical symptoms include polyarthral-gias, malar rash, photosensitivity, alope-cia, serositis, myocarditis and endocarditis, anemia, and thrombocytopenia. Although about 50–70 percent of SLE cases will have renal involvement (abnormal urinalysis, hematuria, proteinuria, or pyuria), the incidence may actually reach 100 percent because kidney biopsies on patients with-out clinical evidence of lupus nephritis often show mesangial and even prolif-erative glomerulonephritis. Hypertension and renal insufficiency occur in later stage of the disease. The degree of proteinuria correlates with the severity of the renal disease. Nephrotic-range proteinuria is more common in membranous and dif-fuse proliferative forms.
Immune complex deposits in the glomeruli are primarily responsible for the inflammatory process that causes glo-merular damage. If deposited into the mesangium and subendothelial space, immune complexes will activate the com-plement (cause hypocomplementemia) and generate chemoattractants (C3a and C5a). The result is an influx of neutro-phils and mononuclear cells that secrete proteases, reactive oxygen species, and cytokines, causing glomerular injury. His-tologically, these can be seen in mesan-gial, focal, or diffuse proliferative lesions. However, subepithelial deposits do not cause influx of inflammatory cells because of the restriction of the chemoattractants from reaching the subepithelial space. The urine sediment is benign. Protein-uria is often in the nephrotic range and is mainly seen in membranous type (Roseet al. 2007). Immune complexes identified in lupus nephritis include DNA-anti-DNA, nucleosomes, chromatin, C1q, laminin, Sm, La (SS-B), Ro (SS-A), ubiquitin, and ribosomes. On electron microscopy, tubu-loreticular structures can be identified in lupus nephritis. These inclusions are made of ribonucleoproteins and membranes and appear to be synthesized in response to interferon-alpha. Similar structures can be seen in HIV-nephropathy, a renal disease that has high levels of circulating inter-feron-alpha.
Lupus nephritis is currently classified into six types based on kidney biopsy find-ings. Class I refers to presence of mesangial deposits without mesangial hypercellular-ity. Class II refers to presence of mesangial deposits with mesangial hypercellular-ity. Class III refers to focal glomerulone-phritis (involving <50 percent of the total number of glomeruli). Class IV refers to diffuse glomerulonephritis (involving >50 percent of the total number of glomeruli) with either segmental class (Class IV-S) or global (Class IV-G). Class V refers to membranous nephropathy. Class VI refers to advanced sclerosing lesions. The latter may have features similar to that of end-stage renal disease.
The clinical course and treatment of lupus nephritis depends on the kidney biopsy findings and presence of systemic symptoms. Class I and II lesions have good prognosis and do not require treatment. In class V disease, steroids and cytotoxic agents can be used to induce and main-tain remission. Likewise, class III and IV require more aggressive treatment with pulse steroids and cyclophosphamide, fol-lowed by oral steroids and mycophenolate mofetil or azathioprine. Concurrent treat-ment of hypertension, dyslipidemia, and proteinuria (with low-protein diet and ACE inhibitors, or ARBs) is also indicated. If treated early, renal function may stabi-lize and prevents patients from reaching end-stage renal disease.