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 Syndrome (APS) Antiphospholipid syndrome is an autoimmune disorder characterized by venous and arterial thrombosis or pregnancy complications (eg, recurrent miscarriage) and persistent autoantibodies to phospholipid-bound... 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 guided by the histologic classification of the lupus nephritis, the degree of disease activity and chronicity, and the presence of concomitant kidney disorders.

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 combines corticosteroids with other immunosuppressants (1, 2 Treatment references Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). Clinical findings include hematuria, nephrotic-range proteinuria, and, in advanced stages, azotemia. Diagnosis... read more ).

Induction therapy for focal or diffuse lupus nephritis usually consists of corticosteroids in combination with either mycophenolate mofetil or intravenous cyclophosphamide (see table ). Prednisone is typically begun at 60 to 80 mg orally once a day and tapered according to response over 6 to 12 months. There is no consensus regarding the optimal corticosteroid dosing regimen. Lower starting doses of prednisone followed by faster tapers may also be used. Relapses are usually treated with increasing doses of prednisone and sometimes a change in the adjunctive immunosuppressive agent. Cyclophosphamide and mycophenolate mofetil are equally efficacious, although systemic toxicity may be less with mycophenolate mofetil than with cyclophosphamide (3 Treatment references Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). Clinical findings include hematuria, nephrotic-range proteinuria, and, in advanced stages, azotemia. Diagnosis... read more ). Reasonable alternatives for induction therapy include mycophenolate mofetil in combination with either a calcineurin inhibitor (tacrolimus or voclosporin) or belimumab (4, 5 Treatment references Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). Clinical findings include hematuria, nephrotic-range proteinuria, and, in advanced stages, azotemia. Diagnosis... read more ). Belimumab may also been used in combination with cyclophosphamide.

After an appropriate renal response has been achieved with induction therapy, immunosuppressive therapy is continued for at least 2 years and often longer. When cyclophosphamide is used as initial therapy, patients are switched to mycophenolate for maintenancetherapy to limit toxicity from cyclophosphamide. Mycophenolate is also preferred over azathioprine for maintenance therapy because of higher rates of relapse observed with azathioprine use. However, azathioprine is preferred for patients who want to become pregnant. Azathioprine is also a reasonable option for patients who are intolerant to mycophenolate or have limited access due to cost. Low-dose prednisone (eg, 0.05 to 0.2 mg/kg orally once a day) is continued in most patients and titrated based on disease activity.

For patients with pure lupus membranous nephropathy, there is a lack of consensus regarding the role of immunosuppressive therapy, and some experts limit its use depending on the degree of proteinuria and findings on kidney biopsy Renal biopsy Biopsy of the urinary tract requires a trained specialist (nephrologist, urologist, or interventional radiologist). Indications for diagnostic biopsy include unexplained nephritic or nephrotic... read more . However, patients who have concurrent lupus membranous nephropathy and focal or diffuse lupus nephritis are treated using the same approach as for focal or diffuse lupus nephritis alone.

Anticoagulation is of theoretical benefit for patients with antiphospholipid syndrome nephropathy, but the value of such treatment has not been established. However, patients with antiphospholipid syndrome Antiphospholipid Syndrome (APS) Antiphospholipid syndrome is an autoimmune disorder characterized by venous and arterial thrombosis or pregnancy complications (eg, recurrent miscarriage) and persistent autoantibodies to phospholipid-bound... read more (APS) and a definite thrombotic event should be anticoagulated in accordance with preferred agents for APS.

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 kidney 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.