Patients afflicted with systemic lupus erythematosus(SLE) manifest some form of renal involvement. Renal disease in SLE is variable, and involvement may range from mild changes of the urinary sediment to nephrotic syndrome to acute nephritis or renal failure. The degree of renal involvement is classified by the World Health Organization (WHO) classification.
Class I disease describes a completely normal kidney by light microscopy, immunofluorescence (IF) and electron microscopy (EM). Clinically, these patients are entirely asymptomatic. This is an uncommon stage of renal disease in lupus patients.
Class II disease (mesangial) entails renal involvement restricted to the mesangial space between the glomerular capillary loops. Class II disease is further subdivided into Class IIa and IIb disease. Class IIa refers to renal biopsy specimens which reveal immune complex deposition restricted to the mesangial region on IF and EM. When biopsy specimens also demonstrate an increased number of glomerular mesangial cells on light microscopy, the involvement of renal disease is Class IIb. Class II disease may manifest clinically as proteinuria, although this only occurs in about one-third of patients. When proteinuria is present, it is never in the range of the nephrotic syndrome. Hypertension, an elevated serum creatinine and a decreased GFR are all uncommon.
Class III disease (focal segmental proliferative) is characterized by focal proliferative nephritis. The lesions are usually focal (involving some glomeruli) and segmental (involving portions of the glomerular tufts), and they involve proliferation of glomerular cells, leukocyte infiltration, areas of nuclear pyknosis or karyorrhexis (fragmentation), and fibrinoid necrotizing lesions. Less than 50% of the glomerular surface shows involvement. Immune-type deposits in the subendothelium and mesangium are evident on IF and EM. Clinically, these patients may have hypertension, proteinuria (may be in the nephrotic syndrome range), a decreased GFR, and an elevated serum creatinine.
Class IV disease (diffuse proliferative nephritis) is similar to the above-mentioned Class III disease. However, with Class IV disease more than 50% of the glomerular surface is involved as compared to Class III disease in which less than 50% of the glomerular surface is involved. Also, with Class IV disease areas of necrosis and endocapillary plus extracapillary proliferation in Bowmans space (crescent formation) occur more frequently than with Class III disease. IF and EM demonstrate subendothelial deposits involving most capillary loops. It is believed by some investigators that Class IV disease merely represents extensive Class III disease. Clinically, these patients manifest hypertension, proteinuria (approximately half of patients manifest nephrotic syndrome), active urinary sediment, and renal dysfunction more commonly than patients afflicted with Class III disease. This stage of renal involvement has the worst prognosis overall.
Class V disease (membranous) describes a membranous pattern of nephritis. With membranous disease, IF and EM demonstrate subepithelial immune deposits along the outer aspect of the glomerular basement membrane. The glomerular capillaries may be thickened by deposits, with outgrowths of the basement membrane (spike formation) located in between these deposits. Clinically, patients present with proteinuria (many suffer from nephrotic syndrome). Hypertension, active urinary sediment, and decreased renal function are not common manifestations. Patients with Class V disease and nephrotic syndrome are the only group of patients with SLE with a high incidence of renal vein thrombosis. Thrombosis of the renal vein rarely results in worsening renal function; however, shortness of breath, pleuritic chest pain, and hemoptysis should all serve to alert physicians to the possibility of pulmonary embolism.
Class VI disease describes biopsy specimens that demonstrate advanced and sclerosing glomerulonephritis. This lesion is the result of long-standing disease. These patients may show active urinary sediment although many demonstrated burnt-out disease with no signs of active disease. Clinically, these patients manifest hypertension and proteinuria (both of which are the residua of former disease) along with an elevated serum creatinine level and a decreased GFR. In many cases, despite inactive clinical disease these patients progress to renal failure. This progression of disease is believed to be secondary to compensatory hyperfiltration and hypertrophy of normal nephrons.
Other lesions seen on renal biopsy not described by the WHO classification include tubulointerstitial lesions (either interstitial inflammation or fibrosis and scarring), immune deposits along the tubular basement membranes or interstitial blood vessels, and glomeruli or vascular lesions (lesions range from isolated immune deposits to fibrinoid necrotizing changes to vasculitis). Some patients manifest thrombi of the glomeruli or microcirculation as a result of anticardiolipin antibodies or thrombotic microangiopathy syndrome.
Therapy is based on the degree of renal involvement. Class I and Class II disease requires no therapy. Patients with Class III and Class IV disease require aggressive therapy for the nephritis. Therapy for Class V disease is unclear. A 4 to 6 month trial with aggressive therapy in patients with Class V disease who manifest heavy proteinuria is prudent. However, if therapy proves ineffective, it may be advisable to reduce the regimen of therapy. Medications used to treat lupus nephritis include daily or alternate-day high-dose corticosteroids, azathioprine, chlorambucil, intravenous pulse steroids, plasmapheresis, total lymphoid irradiation, thromboxane inhibitors, oral cyclophosphamide, IV cyclophosphamide, and cyclosporine.