Therapy of diffuse or focal proliferative lupus nephritis
- Ronald J Falk, MD
Ronald J Falk, MD
- Allan Brewster Distinguished Professor of Medicine
- Chair, Department of Medicine
- Director, UNC Kidney Center
- Director, Center for Transplant Care
- University of North Carolina-Chapel Hill
- Peter H Schur, MD
Peter H Schur, MD
- Editor-in-Chief — Rheumatology
- Section Editor — Basic Science
- Professor of Medicine
- Harvard Medical School
- Gerald B Appel, MD
Gerald B Appel, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Brad H Rovin, MD
Brad H Rovin, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine and Pathology
- The Ohio State University College of Medicine
The optimal treatment of lupus nephritis (LN) varies with the type of renal histology that is present in renal biopsy specimens. Immunosuppressive therapy is indicated in the great majority of patients with diffuse or focal proliferative LN (class III or IV LN) and in some selected patients with membranous LN (class V LN), including those with a severe nephrotic syndrome, an elevated serum creatinine, and/or associated proliferative disease [1-3]. Immunosuppressive therapy is usually not indicated for minimal mesangial and mesangial proliferative LN. (See "Diagnosis and classification of renal disease in systemic lupus erythematosus", section on 'Classification' and "Clinical features and therapy of membranous lupus nephritis".)
Induction and maintenance immunosuppressive therapy of proliferative LN, as well as nonimmunosuppressive therapies, will be reviewed here. The treatment of resistant or relapsing proliferative LN and issues related to end-stage LN are presented separately. (See "Therapy of resistant or relapsing diffuse or focal proliferative lupus nephritis" and "End-stage renal disease due to lupus nephritis".)
RISK FACTORS FOR PROGRESSION
Even with aggressive therapy, some patients with proliferative lupus nephritis (LN) will have a progressive decline in renal function leading to end-stage renal disease (ESRD). Clinical risk factors for progression, evident at the time of initial presentation, include an elevated serum creatinine, hypertension, nephrotic range proteinuria, anemia with a hematocrit below 26 percent, and black and Hispanic race and ethnicity [4-7]. (See 'Race and ethnicity' below.)
The severity of acute and chronic tubulointerstitial disease and interstitial inflammation as well as the presence of cellular crescents also correlate with long-term prognosis in LN, as they do in many other chronic progressive glomerular diseases [5,6,8,9]. (See "Secondary factors and progression of chronic kidney disease", section on 'Tubulointerstitial fibrosis'.)
Risk factors for progression that become evident after initial presentation and during therapy are the frequency and severity of relapses (renal flares) and the degree to which the abnormal features of renal involvement are controlled (complete or partial remission of proteinuria, hematuria, and the severity of azotemia). (See 'Failure to achieve clinical remission' below.)
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- RISK FACTORS FOR PROGRESSION
- Delayed therapy
- Failure to achieve clinical remission
- - Relapses
- Class of lupus nephritis
- Race and ethnicity
- NONIMMUNOSUPPRESSIVE THERAPY
- IMMUNOSUPPRESSIVE THERAPY
- - Focal proliferative disease
- Criteria for clinical remission
- INDUCTION THERAPY
- Overall approach to initial induction therapy
- - Dosing of glucocorticoids
- - Efficacy
- - Dosing of cyclophosphamide
- Dosing according to ancestry
- Mycophenolate mofetil
- - Synopsis of MMF trials
- Less preferred therapies
- - Tacrolimus
- - Rituximab
- - Costimulatory blockade with CTLA4-Ig
- Patients with both diffuse proliferative and membranous LN
- Patients with both proliferative lupus nephritis and a thrombotic microangiopathy
- MAINTENANCE IMMUNOSUPPRESSION
- Choice of maintenance agent
- - Azathioprine versus mycophenolate mofetil
- Initiation of maintenance therapy
- Glucocorticoid therapy
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS
- Nonimmunosuppressive therapy
- Immunosuppressive therapy
- - Induction
- - Maintenance