A Young Woman with Diffuse Proliferative Glomerulonephritis - Renal and Urology News

A Young Woman with Diffuse Proliferative Glomerulonephritis

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  • Light micrographs of a biopsy specimen revealed glomeruli with endocapillary proliferation with some degree of mesangial expansion and proliferation. Wire loops are evident in image B and immunofluorescent stains for C1q are shown in image C.

    A.

    Light micrographs of a biopsy specimen revealed glomeruli with endocapillary proliferation with some degree of mesangial expansion and proliferation. Wire loops are evident in image B and immunofluorescent stains for C1q are shown in image C.

  • Light micrographs of a biopsy specimen revealed glomeruli with endocapillary proliferation with some degree of mesangial expansion and proliferation. Wire loops are evident in image B and immunofluorescent stains for C1q are shown in image C.

    B.

    Light micrographs of a biopsy specimen revealed glomeruli with endocapillary proliferation with some degree of mesangial expansion and proliferation. Wire loops are evident in image B and immunofluorescent stains for C1q are shown in image C.

  • Light micrographs of a biopsy specimen revealed glomeruli with endocapillary proliferation with some degree of mesangial expansion and proliferation. Wire loops are evident in image B and immunofluorescent stains for C1q are shown in image C.

    C.

    Light micrographs of a biopsy specimen revealed glomeruli with endocapillary proliferation with some degree of mesangial expansion and proliferation. Wire loops are evident in image B and immunofluorescent stains for C1q are shown in image C.

A 23-year-old Asian-American woman was diagnosed with systemic lupus erythematosus (SLE) a few months earlier. Her lupus symptoms at time of diagnosis included a malar rash, mild alopecia, and intermittent arthralgias in the hands. On exam, she had a blood pressure of 140/90 mm Hg, a faint erythematous facial rash with nasolabial sparing, evident mild alopecia, and no oral ulcers. Her lungs were clear, there was no heart murmur, no hepatosplenomegaly, and no significant leg edema or other rash. There was mild, occasional synovitis in the PIPS and MCPs in both hands. Other findings included a serum creatinine of 0.9 mg/dL, a positive ANA (titer > 320), ds DNA Ab (titer 2560), + SSA, + SSB, hypocomplementemia, leucopenia, and lymphopenia. Lupus anticoagulant serology was negative. Recently, she was noted to have an active urine sediment with over 180 mostly dysmorphic red blood cells/hpf, over 70 white blood cells/hpf, and urine protein quantified to over 3 grams by random ratios. A renal biopsy was performed and representative light micrographs are shown below. Immunofluorescence studies were positive for IgG, IgM, IgA, C3, and c1q (shown below) in variable intensity. A diagnosis of class 4 lupus nephritis, or diffuse proliferative glomerulonephritis was made. She was started on low-dose ACE inhibitor therapy, hydroxychloroquine, and an additional immunosuppressive regimen.

This case was prepared by Kevin T. Harley, MD, Assistant Clinical Professor of Medicine, Division of Nephrology & Hypertension, at the University of California in Irvine.References:1.      Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction...

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This case was prepared by Kevin T. Harley, MD, Assistant Clinical Professor of Medicine, Division of Nephrology & Hypertension, at the University of California in Irvine.

References:

1.      Appel GB, Contreras G, Dooley MA, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20:1103-1112.

2.      Liu Z, Zhang H, Liu Z, et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Intern Med. 2015;162:18-26.

3.       Rovin BH, Furie R, Appel G, et al.  Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012;;64:1215-1226.


Answer: E

Standard induction therapy for diffuse proliferative glomerulonephritis generally includes prednisone starting at around 60 mg/day (or IV solumedrol) combined with either IV cyclophosphamide 1g/m2 monthly (or lower doses in shorter intervals), or mycophenolate mofetil (MMF) orally titrated up to 2-3 grams per day, given over 6 months. The ALMS trial was an international randomized, controlled trial that demonstrated no superiority of MMF over IV cyclophosphamide for induction therapy of proliferative lupus nephritis.  In women of childbearing age, mycophenolate-based treatments are usually preferred given the potential long-term effects of cyclophosphamide on fertility.

Rituxamab is frequently given to SLE patients including those with nephritis.  However, randomized controlled trials have not demonstrated significant difference in renal outcomes when it is added to steroids and mycophenolate compared with placebo.  In refractory cases of lupus nephritis, where desired remission in proteinuria has not been achieved by induction with steroids and either MMF or cyclophosphamide, addition of rituximab may be useful.

A number of relatively recent studies has examined the use of induction regimens that include the calcineurin inhibitor tacrolimus. One multicenter study in China compared a regimen of tacrolimus, MMF, and steroids to monthly IV cyclophosphamide and steroids. After 6 months, there were significantly higher rates of remission and time to remission noted in the former group. Similar findings have not yet been demonstrated in other countries and ethnic groups. 

Belimumab is a human monoclonal antibody to B cell stimulating factor used in the treatment of SLE.  However, there are no available randomized controlled trials to support its use as an induction agent in treatment of lupus nephritis.

Our patient was started on an induction regimen of prednisone and MMF. She was counseled to avoid conception while on mycophenolate and ACE inhibitors. 

 


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