Background/Purpose: Using light microscopy (LM) or immunofluorescence (IF), combined proliferative and membranous lupus nephritis (LN) is defined as an active proliferative class III/IV lesion and diffusely distributed membranous lesion (involving >50% tuft of >50% glomeruli) in ISN/RPS 2003. A mixed-type LN was reported to show poor prognosis^1,2; however, an interesting case report on corticosteroid-free treatment regimen of rituximab and mycophenolate mofetil is recently published³. We examined the renal outcome of mixed-type LN based on renal remission, end-stage renal disease (ESRD), and death.

Methods: We retrospectively evaluated 66 cases constituting class III and IV lesions, including 22 showing mixed-type LN on renal biopsy, during 2005–2014. Mixed-type LN were divided into 2 groups; membranous findings on LM + IF (LM group; n = 18) and those on IF only (IF group; n = 4). Renal remission was defined as a spot urine protein/creatinine ratio <0.5 g/g Cr and normal or near-normal eGFR (within 10% of normal eGFR) in EULAR/ERA-EDTA recommendations and KDIGO guidelines. 

Results: Clinical findings were mean age 40.6 ± 15.8 years (male:female = 6:16), disease duration 5.2 ± 5.2 years, and observation period 2.2 ± 2.0 years and concentration of urine protein 3.5 ± 2.9 g/day, serum creatinine 0.93 ± 0.49 mg/dl, dsDNA 225.2 ± 745.6 IU/ml, C3 57.6 ± 24.0 mg/dl, and C4 9.9 ± 7.0 mg/dl. Pathological findings were activity index 6.0 ± 3.1, chronicity index 2.4 ± 2.6, cellular crescents 54.6%, fibrinoid necrosis 22.7%, and chronicity of glomeruli 72.7%. Twenty of 22 cases were class IV + V and 2 cases were class III + V. Most cases received a high dose of corticosteroids (0.6–1.0 mg/kg/day) and various immunosuppressants such as cyclophosphamide, tacrolimus, azathioprine, cyclosporine, and mizoribine for remission induction and maintenance therapy. IF group cases had a tendency toward shorter disease duration than LM group cases; there were no chronic lesions. The IF group cases achieved renal remission at the last observation and no ESRD or death. The LM group cases had a statistically significant lower remission rate of 27.8%; two cases developed ESRD and death.

Conclusion: This retrospective clinico–pathological study shows that mixed-type LN, defined as per findings of LM + IF, has a poor prognosis. However, mixed-type LN determined by IF only has an unexpectedly high remission rate, probably because of early detection of membranous lesions without morphological alterations.

References:

1. Najafi CC, Korbet SM, Lewis EJ, Schwartz MM, Reichlin M, Evans J. Significance of histologic patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis. Kidney Int. 2001;59(6):2156–63.

2. Sloan RP, Schwartz MM, Korbet SM, Borok RZ, Lupus Nephritis Collaborative Study Group. Long-term outcome in systemic lupus erythematosus membranous glomerulonephritis. J Am Soc Nephrol. 1996;7(2):299–305.

3. Tedeschi B, Arnaud L, Hie M, Mathian A, Amoura Z. Successful treatment of combined proliferative and membranous lupus nephritis using a full corticosteroid-free regimen. Ann Rheum Dis. 2014;73(2):474–5.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/combined-proliferative-and-membranous-lupus-nephritis-is-the-prognosis-really-poor/