Therapy of diffuse or focal proliferative lupus nephritis
- Ronald J Falk, MD
Ronald J Falk, MD
- Nan and Hugh Cullman Eminent Professor of Nephrology
- Chair, Department of Medicine
- Director, UNC Kidney Center
- University of North Carolina-Chapel Hill
- Maria Dall'Era, MD
Maria Dall'Era, MD
- Associate Professor of Medicine
- University of California, San Francisco
- 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 patients with diffuse or focal proliferative LN (class III or IV LN) [1-3]. Immunosuppressive therapy is usually not indicated for minimal mesangial and mesangial proliferative LN. Treatment of patients with lupus membranous nephropathy (class V LN) is presented elsewhere. (See "Diagnosis and classification of renal disease in systemic lupus erythematosus", section on 'Classification' and "Clinical features and therapy of lupus membranous nephropathy".)
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 response of proteinuria, hematuria, and the severity of azotemia) (see 'Failure to achieve a clinical response' below). A complete renal response based upon these clinical criteria may or may not correspond to a histologic complete remission.
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- RISK FACTORS FOR PROGRESSION
- Delayed therapy
- Failure to achieve a clinical response
- - Relapses
- Class of lupus nephritis
- Race and ethnicity
- NONIMMUNOSUPPRESSIVE THERAPY
- PRINCIPLES OF IMMUNOSUPPRESSIVE THERAPY
- Goal of immunosuppressive therapy
- - Complete response versus complete remission
- Pregnant patients
- INITIAL (INDUCTION) THERAPY
- Approach to initial (induction) therapy
- Preferred therapy: Glucocorticoids plus either cyclophosphamide or mycophenolate mofetil
- - Glucocorticoids
- Dosing of glucocorticoids
- - Choosing between cyclophosphamide and mycophenolate mofetil
- - Efficacy of cyclophosphamide
- - Dosing of cyclophosphamide
- Mycophenolate mofetil
- - Efficacy of mycophenolate mofetil
- - Dosing of mycophenolate mofetil
- - Monitoring patients during initial (induction) therapy
- - Preventing toxicity
- Patients who are resistant to initial therapy
- Less preferred therapies
- - Tacrolimus
- - Rituximab
- - Costimulatory blockade with CTLA4-Ig
- Patients with both diffuse proliferative LN and lupus membranous nephropathy
- EXTENDED (MAINTENANCE) THERAPY
- Choice of agent for extended (maintenance) therapy
- - Preference for mycophenolate mofetil
- Approach to extended (maintenance) therapy
- Dosing and duration of extended (maintenance) therapy
- Glucocorticoid therapy during extended (maintenance) therapy
- Monitoring patients during extended (maintenance) therapy
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS