Membranous glomerulonephritis with monoclonal immune deposits and crescents

Sir,

Membranous glomerulonephritis is most often idiopathic. However, membranous nephropathy can be secondary to other conditions. In this report, we present an unusual cause of secondary membranous glomerulonephritis. The pattern of injury was unusual in that the membranous nephropathy was associated with crescents. The primary disease was detected following the renal biopsy.

A 29-year-old man presented with generalized malaise, shortness of breath and oedema. At admission, the patient had the following laboratory values: serum creatinine 4.4 mg/dl, blood urea nitrogen 110 mg/dl, white blood cell count 4 x 109/l, haemoglobin 7.6 gm/dl, haematocrit 26%, platelet count 367 x 109/l, total protein 6.1 mg/dl, serum calcium 8.8 mg/dl. Complements were within normal range. ANA and ANCA titers were negative. Urinalysis was positive for 3+ albumin, 3+ red blood cells and protein: creatinine ratio was 8. Renal biopsy was done to determine the cause of renal failure.

Renal biopsy showed glomeruli with thickened peripheral capillary walls and fine spike like projections. Eleven out of 21 glomeruli were sclerosed. Three glomeruli showed cellular crescents (Figure 1A). Fibrinoid necrosis, inflammatory cells or proliferative features were not present. The interstitium showed moderate interstitial fibrosis and tubular atrophy. On immunofluorescence microscopy, there was diffuse granular deposition of IgA (4+/4+) (Figure 1B) and C3 (3+/4+) along the peripheral capillary walls. The deposits were positive for {kappa} light chains (Figure 1C), but negative for IgG, IgM and {lambda} light chains. On electron microscopy, the glomerular capillary walls showed subepithelial deposits that were separated by basement membrane spikes (Figure 1D). The deposits showed fine tubular substructures. Subendothelial and mesangial deposits were not seen.



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Fig. 1. The glomeruli show (A) thickened glomerular basement membranes and a cellular crescent, granular capillary wall staining for (B) IgA and (C) {kappa} light chains, and (D) subepithelial electron dense deposits.

 
The renal biopsy diagnosis was: (i) membranous glomerulonephritis, secondary to monoclonal paraprotein deposition; and (ii) crescentic glomerulonephritis.

Follow up was as follows: serum IFE showed monoclonal IgA {kappa} with depressed IgM and IgG. Bone marrow biopsy showed <5% plasma cells. Treatment with prednisone, antihypertensive and diuretic agents was initiated. However, the renal function continued to decline and after 1 year the serum creatinine was 6.4 mg/dl. Two small lytic lesions were noted on skeletal survey. Six cycles of chemotherapy were given.

The patient continues to have monoclonal IgA {kappa} on serum IFE. At present, the patient is on dialysis and is being considered for transplant.

Typically patients with lymphoproliferative diseases that present with severe proteinuria have underlying renal amyloidosis. Review of literature revealed one report of membranous nephropathy associated with B-cell lymphoma [1] and one with polycythaemia [2].

In most cases of secondary membranous glomerulonephritis, the relationship to the associated disease is tentative and etiologic implication unproven. However, in this case the deposits were clearly monoclonal and are thus related to the underlying monoclonal gammopathy. Furthermore, the deposits show a fine tubular substructure that is often seen in paraproteins.

This case was also complicated by cellular crescents. Typically, membranous nephropathy with crescents occurs in one of two settings: (i) underlying autoimmune disease [3], or (ii) associated ANCA positive vasculitis [4]. In our case, ANA and ANCA titers were negative.

As a speculation to the underlying etiology, it is possible that the circulating monoclonal immunoglobulin recognizes an epitope on the visceral epithelial cells, and forms immune complexes in the subepithelial location leading to membranous glomerulonephritis.

Sanjeev Sethi

Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN Email: sethi.sanjeev{at}mayo.edu

References

  1. Evans DJ, Macanovic M, Dunn MJ, Pusey CD. Membranous glomerulonephritis associated with follicular B-cell lymphoma and subepithelial deposition of IgG1-{kappa} paraprotein. Nephron Clin Pract 2003, 93: 112–118[CrossRef]
  2. Lim CS, Jung KH, Kim YS et al. Secondary polycythemia associated with idiopathic membranous nephropathy. Am J Nephrol 2000, 20: 344–346[CrossRef][ISI][Medline]
  3. Dohi KSH, Kawano T, Kanauchi M, Ishikawa H, Watanabe T. Membranous nephropathy with crescents in rheumatoid arthritis: a case report. Nippon Jinzo Gakkai Shi 1991, 33: 523–527[Medline]
  4. Taniguchi YYN, Kumagai J, Ito T, Yamakido M, Taguchi T. Myeloperoxidase antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis and membranous glomerulonephropathy. Clin Nephrol 1999, 52: 253–255[ISI][Medline]




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