Systemic Lupus Erythematosus (SLE)



This disease chiefly affects young females and is diagnosed by serological evidence of autoanti­bodies to cell nuclear components (ANA’s) and by clinical evidence of inflammatory processes in multiple organs (skin, joints, brain, and kidneys). Five major categories of glomerular histopathol­ogy have been described for SLE nephritis . Virtually all cases of lupus nephritis dis­play a degree of interstitial inflammation uncom­mon for other glomerulopathies. One subset of pa­tients with SLE renal disease has a dominant interstitial lesion with little or no glomerular in­volvement.

In general, the clinical presentation and sever­ity of renal disease in SLE correlate to the under­lying histological lesion. About two thirds of pa­tients will have some clinical evidence of renal disease (proteinuria, microhematuria, or azo­temia) at the time SLE is diagnosed. Virtually all patients will have some evidence of SLE renal dis­ease if studied with renal biopsy.

Renal disease in SLE may present clinically as either nephrosis or nephritis. The former pres­entation is more common, with the nephrotic syn­drome occuring in over half of all patients. Even in these patients, however, considerable overlap of clinical manifestations occurs, and hematuria, hypertension, and azotemia are frequent findings. A smaller number of patients present with a full­blown nephritic picture with a clinical course re­sembling that of RPGN. Renal function may de­teriorate rapidly over a period of only a few weeks. Serum complement activity, both CH50 and C3, are reduced with active renal disease. The serum C4 may be strikingly depressed, indicating activation of the classic complement pathway.

As shown in Table 34-9, the glomerular his-topathology in SLE is similar to that seen in non-SLE diseases for any given lesion. For instance, Type IV, diffuse proliferative lupus glomerulo­nephritis, has similarities to postinfectious AGN. Likewise, Type V, membranous lupus glomeru­lopathy, is indistinguishable from idiopathic membranous nephropathy. It is believed that the pattern of glomerular injury relates to the pres­ence or absence of circulating immune com­plexes; the ability of free antigens to fix to, or lodge in, glomerular structures; and the intensity and pattern of the immune response.

The clinical course and prognosis of lupus ne­phritis correspond to the glomerular lesion. As seen from , the five-year renal survival in untreated patients ranges from more than 80 per cent in patients with Type V, membranous lesion to about 25 per cent in patients with the Type IV, diffuse proliferative lesion. Progression of the renal lesion, for example, from Type III, focal proliferative, to Type IV, diffuse prolifera­tive, has been documented. Regression of lesions to a less ominous pathological picture is also known to occur, especially after vigorous therapy. The indications for renal biopsy either to deter­mine the renal prognosis or to define the need for treatment with steroids or immunosuppressive drugs remain unclear.

Corticosteroid therapy is the mainstay of treat­ment for lupus nephritis. In the absence of ad­vanced renal failure (serum creatinine >6 mg/dl) and extensive glomerular sclerosis, high-dose steroid therapy (prednisone, 40 to 60 mg/day for 6 to 12 months] has had a dramatic effect on sur­vival. The renal survival in diffuse proliferative SLE glomerulopathy with such treatment is up to 80 per cent in five years versus the 25 per cent survival without steroids. There is some evidence to support treatment of Types II and III lupus ne­phritis with low doses (<40 mg prednisone/day) of steroids in an attempt to normalize serum CH50 activity and to prevent progression to Type IV, diffuse proliferative, nephritis. The addition of a cytotoxic drug, such as azathioprine, may allow use of lower doses of prednisone, avoiding com­plications of high-dose steroid therapy but adding those of a cytotoxic agent. The membranous le­sion has been successfully treated with steroids to reduce proteinuria, but an effective treatment to halt the slow progression to renal failure has not been demonstrated.