Lupus Nephritis

This syndrome may occur with or without lupus nephritis in up to one third of patients with SLE. The syndrome occurs in the absence of any other autoimmune process in 30 to 50% of affected patients. In antiphospholipid antibody syndrome Antiphospholipid Antibody Syndrome (APS) Antiphospholipid antibody syndrome is an autoimmune disorder in which patients have autoantibodies to phospholipid-bound proteins. Venous or arterial thrombi may occur. The pathophysiology is... read more , circulating lupus anticoagulant causes microthrombi, endothelial damage, and cortical ischemic atrophy. Antiphospholipid syndrome nephropathy increases a patient’s risk of hypertension and renal insufficiency or failure compared with lupus nephritis alone.

Treatment is toxic and thus is reserved for nephritis that has the following characteristics:

Activity is estimated by the activity score as well as clinical criteria (eg, urine sediment, increasing urine protein, increasing serum creatinine). Many experts believe that a mild to moderate chronicity score, because it suggests reversibility, should provoke more aggressive therapy than a more severe chronicity score. Nephritis with the potential for deterioration and for reversibility is usually class III or IV; it is unclear whether class V nephritis warrants aggressive treatment.

The activity score describes the degree of inflammation. The score is based on cellular proliferation, fibrinoid necrosis, cellular crescents, hyaline thrombi, wire loop lesions, glomerular leukocyte infiltration, and interstitial mononuclear cell infiltration. The activity score is less well correlated with disease progression, and is used, rather, to help identify active nephritis.

The chronicity index describes the degree of scarring. It is based on presence of glomerular sclerosis, fibrous crescents, tubular atrophy, and interstitial fibrosis. The chronicity index predicts progression of lupus nephritis to renal failure. A mild to moderate chronicity score suggests at least partially reversible disease, whereas more severe chronicity scores may indicate irreversible disease.

Treatment for proliferative lupus nephritis usually combines cytotoxic drugs, corticosteroids, and sometimes other immunosuppressants.

One induction regimen consists of cyclophosphamide, which is usually given in IV boluses (monthly for up to 6 months) beginning with 0.75 g/m² in a saline solution over 30 to 60 minutes and, assuming a white blood cell (WBC) count > 3000/microL, increasing to a maximum of 1 g/m². Oral or IV fluid administration to create rapid urine flow minimizes the bladder toxicity of cyclophosphamide, as does mesna (see table IV Cyclophosphamide Protocols for Systemic Lupus Erythematosus IV Cyclophosphamide Protocols for Systemic Lupus Erythematosus ).

Another induction regimen uses mycophenolate mofetil with a target dose of 3 g/day. Prednisone is also begun at 60 to 80 mg orally once a day and tapered according to response to 20 to 25 mg every other day over 6 to 12 months. The amount of prednisone is determined by the extrarenal manifestations and number of relapses. Relapses are usually treated with increasing doses of prednisone. Both induction regimens are equally efficacious, although systemic toxicity may be less with mycophenolate mofetil than with cyclophosphamide.

Many experts are replacing the more toxic cyclophosphamide maintenance regimens (after induction with 6 or 7 monthly IV cyclophosphamide doses) with protocols using mycophenolate mofetil 500 mg to 1 g orally twice a day or, as a second choice, azathioprine 2 mg/kg orally once a day (maximum 150 to 200 mg/day). Chlorambucil, cyclosporine, and tacrolimus have also been used, but relative efficacies are not clear. Low-dose prednisone 0.05 to 0.2 mg/kg orally once a day is continued and titrated based on disease activity. Duration of maintenance therapy is at least 1 year.

Anticoagulation is of theoretical benefit for patients with antiphospholipid syndrome nephropathy, but the value of such treatment has not been established.

Kidney transplantation Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more is an option for patients with end-stage renal disease due to lupus nephritis. Recurrent disease in the graft is uncommon (< 5%), but risk may be increased in Black people, females, and younger patients.