Solange Moll

Abstract

Membranous glomerulonephritis and crescents

A 45-year-old Swiss female was diagnosed in 1992 for a seropositive rheumatoid arthritis and

treated with different regimens including NSAIDs, gold therapy, methotrexate and anti-TNF

antibodies. Since 2006, she decided to take only homeopathic therapy. On August 2009, she

was admitted to our hospital with complaints of asthenia, legs swelling and increased body

weight (6 kg in 3 months). Physical examination revealed edema of the lower extremities and

hypertension (160/90mmHg). Initial laboratory data showed high CRP value (62mg/l),

anemia (hemoglobin: 93g/l) and rapidly progressive renal failure (serum creatinine:

313µmol/l on admission, 500µmol/l ten days later). Proteinuria (6.3g/l) with glomerular

microhematuria and pyuria was detected on urinalysis. Other laboratory data revealed positive

antinuclear antibody (1/320) and pANCA (1/640, MPO) tests. A renal biopsy was performed,

which consisted of two cores containing 10 glomerules. Three of them showed foci of

fibrinoid necrosis with GBM rupture and extracapillary fibrin, and seven showed cellular

crescents. A diffuse moderate-to-severe interstitial inflammation composed of a mixed

infiltrate of lymphocytes, histiocytes and plasmocytes was observed. Immunofluorescence

revealed granular, global glomerular capillary wall positivity for IgG and weaker staining for

C3 and C5b-9. Electron microscopy showed subepithelial electron dense deposits, often

accompanied by GBM spikes and overlying neomembrane formation. The diagnosis of

membranous glomerulonephritis stage I-II and ANCA-associated necrotizing and crescentic

glomerulonephritis was done. Methylprednisolone and cyclophosphamide iv therapy was

begun, in association with plasmapheresis and transient hemodialysis. Treatment led to rapid

improvement in renal function (serum creatinine:120µmol/l at one month) and to a significant

decline in the degree of proteinuria. Mycophenolate mofetyl was substituted for

cyclophospamide and doses of prednisone were progressively reduced. Renal function was

stable during the next following 6 months.

Only rare cases of concurrent membranous glomerulonephritis (MGN) and antineutrophil

cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis

(NCGN) have been reported in the literature (1). Recently, Snar et al. reported the clinical and

pathologic findings in 14 patients with MGN and ANCA-associated NCGN (2). Clinical

presentation included heavy proteinuria (mean 24-hr urine protein 6.5 g/d), hematuria, and

acute renal failure (mean creatinine 400µmol/l), as observed in our case. Pathologic

evaluation revealed MGN and NCGN, with crescents involving a mean of 32% of glomeruli.

Follow-up (mean of 24.3 months) was available for 13 patients, 12 of whom were treated with

steroids and cyclophosphamide. Five patients progressed to ESRD, seven had stabilization or

improvement in renal function, and one had worsening renal function. The only independent

predictor of progression to ESRD was serum creatinine at biopsy.

In conclusion, MGN with ANCA-associated NCGN is a rare dual glomerulopathy, and

prognosis is variable.

References

1. Tse WY, Howie AJ, Adu D, Savage CO, Richards NT, Wheeler DC, Michael J:

Association of vasculitic glomerulonephritis with membranous nephropathy: A report of 10

cases. Nephrol Dial Transplant 1997 12:1017 –1027.

2. Nasr SH, Said SM, Valeri AM, Stokes MB, Masani NN, D'Agati VD, Markowitz GS.

Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic

glomerulonephritis. Clin J Am Soc Nephrol. 2009 Feb;4(2):299-308

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