Clinical features and therapy of lupus membranous nephropathy
- 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 classification of the morphological findings present on renal biopsy. Ten to 20 percent of patients with LN have pure membranous (class V) LN [1-3], although some reports suggest a higher percentage among African-American populations . Treatment is indicated for patients with lupus membranous nephropathy, especially those with a severe (symptomatic) nephrotic syndrome, an elevated or rising serum creatinine, and/or concomitant focal or diffuse proliferative changes on renal biopsy.
The clinical features and treatment of lupus membranous nephropathy will be reviewed here. The various types of LN, the treatment of focal and diffuse proliferative LN, and management of the patient with end-stage renal disease are presented separately. (See "Diagnosis and classification of renal disease in systemic lupus erythematosus" and "Therapy of diffuse or focal proliferative lupus nephritis" and "End-stage renal disease due to lupus nephritis".)
Lupus membranous nephropathy is present in 10 to 20 percent of patients with lupus nephritis (LN) [5-7]. Affected patients typically present with proteinuria (often but not always in the nephrotic range) and a normal or only slightly elevated serum creatinine [8-10]. In addition, patients with lupus membranous nephropathy frequently have microscopic hematuria, and some may have nephrotic syndrome (with hypoalbuminemia and edema) and hypertension.
The presence of significant hematuria and cellular casts with or without an elevated serum creatinine suggests concurrent proliferative disease, which is not uncommon and is associated with a much worse prognosis than class V alone. In a review of 79 patients with lupus membranous nephropathy, 36 had pure membranous lesions, 15 had endocapillary proliferation and/or necrosis in less than 50 percent of glomeruli, and 28 had endocapillary proliferation and/or necrosis in more than 50 percent of glomeruli . (See 'Prognosis' below and 'Pathology' below.)
Extrarenal or serologic manifestations of systemic lupus erythematosus (SLE) frequently precede but can occasionally develop after the onset of kidney disease. Lupus membranous nephropathy is the one form of LN that may present with few or no other clinical or serologic manifestations of SLE (eg, complement levels may be normal, and anti-double-stranded DNA antibodies, which are highly specific for SLE, may not be elevated) [6,8,11-13]. In a randomized trial of 42 patients with lupus membranous nephropathy described below, low C3, low C4, and anti-double-stranded DNA antibodies were present in 3, 3, and 9 patients, respectively (7, 7, and 21 percent, respectively) . Thus, patients without extrarenal or serologic manifestations of SLE who have a renal biopsy suggesting lupus membranous nephropathy (including mesangial deposits and tubuloreticular inclusions) should be regarded as having LN and are at risk of subsequently developing SLE. (See "Overview of the clinical manifestations of systemic lupus erythematosus in adults" and "Diagnosis and differential diagnosis of systemic lupus erythematosus in adults".)
- Lupus nephritis: prognostic factors and probability of maintaining life-supporting renal function 10 years after the diagnosis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). Am J Kidney Dis 1992; 19:473.
- Huong DL, Papo T, Beaufils H, et al. Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center. Medicine (Baltimore) 1999; 78:148.
- Neumann K, Wallace DJ, Azen C, et al. Lupus in the 1980s: III. Influence of clinical variables, biopsy, and treatment on the outcome in 150 patients with lupus nephritis seen at a single center. Semin Arthritis Rheum 1995; 25:47.
- Bhinder S, Singh A, Majithia V. Membranous (class V) renal disease in systemic lupus erythematosus may be more common than previously reported: results of a 6-year retrospective analysis. Am J Med Sci 2010; 339:230.
- Cameron JS. Lupus nephritis. J Am Soc Nephrol 1999; 10:413.
- Donadio JV Jr, Burgess JH, Holley KE. Membranous lupus nephropathy: a clinicopathologic study. Medicine (Baltimore) 1977; 56:527.
- Appel GB, Silva FG, Pirani CL, et al. Renal involvement in systemic lupud erythematosus (SLE): a study of 56 patients emphasizing histologic classification. Medicine (Baltimore) 1978; 57:371.
- Austin HA 3rd, Illei GG, Braun MJ, Balow JE. Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. J Am Soc Nephrol 2009; 20:901.
- Sloan RP, Schwartz MM, Korbet SM, Borok RZ. Long-term outcome in systemic lupus erythematosus membranous glomerulonephritis. Lupus Nephritis Collaborative Study Group. J Am Soc Nephrol 1996; 7:299.
- Mercadal L, Montcel ST, Nochy D, et al. Factors affecting outcome and prognosis in membranous lupus nephropathy. Nephrol Dial Transplant 2002; 17:1771.
- Adu D, Williams DG, Taube D, et al. Late onset systemic lupus erythematosus and lupus-like disease in patients with apparent idiopathic glomerulonephritis. Q J Med 1983; 52:471.
- Sun HO, Hu WX, Xie HL, et al. Long-term outcome of Chinese patients with membranous lupus nephropathy. Lupus 2008; 17:56.
- Beck LH Jr, Salant DJ. Treatment of membranous lupus nephritis: where are we now? J Am Soc Nephrol 2009; 20:690.
- Jennette JC, Iskandar SS, Dalldorf FG. Pathologic differentiation between lupus and nonlupus membranous glomerulopathy. Kidney Int 1983; 24:377.
- Pasquali S, Banfi G, Zucchelli A, et al. Lupus membranous nephropathy: long-term outcome. Clin Nephrol 1993; 39:175.
- Waldman M, Appel GB. Update on the treatment of lupus nephritis. Kidney Int 2006; 70:1403.
- Adler SG, Johnson K, Louie JS, et al. Lupus membranous glomerulonephritis: different prognostic subgroups obscured by imprecise histologic classifications. Mod Pathol 1990; 3:186.
- Schwartz MM, Kawala K, Roberts JL, et al. Clinical and pathological features of membranous glomerulonephritis of systemic lupus erythematosus. Am J Nephrol 1984; 4:301.
- Kanda H, Kubo K, Tateishi S, et al. Antiproteinuric effect of ARB in lupus nephritis patients with persistent proteinuria despite immunosuppressive therapy. Lupus 2005; 14:288.
- Karim MY, Pisoni CN, Ferro L, et al. Reduction of proteinuria with mycophenolate mofetil in predominantly membranous lupus nephropathy. Rheumatology (Oxford) 2005; 44:1317.
- Spetie DN, Tang Y, Rovin BH, et al. Mycophenolate therapy of SLE membranous nephropathy. Kidney Int 2004; 66:2411.
- Kasitanon N, Petri M, Haas M, et al. Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with and without concurrent proliferative disease: a retrospective study of 29 cases. Lupus 2008; 17:40.
- Mok CC, Tong KH, To CH, et al. Risk and predictors of arterial thrombosis in lupus and non-lupus primary glomerulonephritis: a comparative study. Medicine (Baltimore) 2007; 86:203.
- Branten AJ, Vervoort G, Wetzels JF. Serum creatinine is a poor marker of GFR in nephrotic syndrome. Nephrol Dial Transplant 2005; 20:707.
- Myers BD, Chagnac A, Golbetz H, et al. Extent of glomerular injury in active and resolving lupus nephritis: a theoretical analysis. Am J Physiol 1991; 260:F717.
- KDIGO. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl 2012; 2:209. http://www.kdigo.org/clinical_practice_guidelines/pdf/KDIGO-GN-Guideline.pdf (Accessed on December 23, 2013).
- Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 2012; 71:1771.
- Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 2009; 20:1103.
- Ginzler EM, Dooley MA, Aranow C, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005; 353:2219.
- Moroni G, Maccario M, Banfi G, et al. Treatment of membranous lupus nephritis. Am J Kidney Dis 1998; 31:681.
- Mok CC, Ying KY, Lau CS, et al. Treatment of pure membranous lupus nephropathy with prednisone and azathioprine: an open-label trial. Am J Kidney Dis 2004; 43:269.
- Radhakrishnan J, Moutzouris DA, Ginzler EM, et al. Mycophenolate mofetil and intravenous cyclophosphamide are similar as induction therapy for class V lupus nephritis. Kidney Int 2010; 77:152.
- Touma Z, Urowitz MB, Ibañez D, Gladman DD. Time to recovery from proteinuria in patients with lupus nephritis receiving standard treatment. J Rheumatol 2014; 41:688.
- Bao H, Liu ZH, Xie HL, et al. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol 2008; 19:2001.
- CLINICAL PRESENTATION
- NONIMMUNOSUPPRESSIVE THERAPY
- Angiotensin inhibition
- Goal blood pressure
- Lipid lowering
- IMMUNOSUPPRESSIVE THERAPY
- Indications for immunosuppressive therapy
- - Nephrotic syndrome
- - Increased serum creatinine
- - Concurrent proliferative lupus nephritis
- - Other patients
- Choice of immunosuppressive therapy
- Monitoring and follow-up
- - Repeat renal biopsy
- Nonresponders and relapsing disease
- Combined membranous and diffuse proliferative lupus nephritis
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS