LUPUS NEPHRITIS
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.
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