Renal Biopsy

Brian McNally, M.D.

Specimen Type:

Kidney

History:

A 20 year old female presented with fever, anemia, nephritic syndrome, and acute renal failure. Her past medical history included recurrent urinary tract infections. Her serum creatinine was 2.1 mg/dL. Complements were normal and serologies were all negative. No previous significant clinical history.

Pathologic Features:

Light Microscopy

Sections of the tissue submitted for light microscopic examination consist of renal cortex. At least thirty (30) glomeruli are present, and approximately 25% of the glomeruli are globally sclerosed. Most viable glomeruli contain necrotizing areas and adjacent fibrocellular crescents (figures 1 and 2). Some crescents are circumferential. Red blood cell casts are present, and there is focal tubulitis with significant tubular damage. An intense interstitial inflammatory infiltrate is present, and the infiltrate is composed predominantly of lymphocytes and plasma cells (figure 3). The interstitium is edematous, but significant interstitial fibrosis is not present. There is mild eccentric intimal fibrous thickening of the medium size arteries, but the arterioles are unremarkable. Vasculitis is not present.

Immunofluorescence

Sections of the tissue submitted for immunofluorescence microscopic examination contain up to eleven (11) glomeruli. Four (4) are globally sclerosed. Findings are as follows:

  • Albumin: Linear staining along glomerular capillary loop walls and tubular basement membranes (1+). No vascular staining.
  • IgG: Linear staining along glomerular capillary loop walls (2+ (figures 4 and 5)). No interstitial or vascular staining.
  • IgM: Focal, segmental, granular, mesangial staining (1+). No interstitial or vascular staining.
  • IgA: No staining in glomerular, interstitial or vascular compartments.
  • C1q: No staining in glomerular, interstitial or vascular compartments.
  • C3: Focal, segmental, granular, mesangial staining (2+). No interstitial or vascular staining.
  • Fibrinogen: Granular staining in glomeruli adjacent to crescents (2+). No interstitial or vascular staining.
  • Kappa: Linear staining along glomerular capillary loop walls (1-2+). No interstitial or vascular staining.
  • Lambda: Linear staining along glomerular capillary loop walls (1-2+). No interstitial or vascular staining.
Electron Microscopy

Sections of the tissue submitted for electron microscopic examination contain up to five (5) glomeruli. One glomerulus is globally sclerosed and the four additional glomeruli have cellular crescents. Fibrin deposition is also present within the crescent. The crescents partially displace the adjacent glomeruli. Effacement of the visceral epithelial cell foot processes is present. Immune complexes are not present along the peripheral capillary walls. There is segmental wrinkling of the capillary loop walls, as well as mild subendothelial expansion. The glomerular basement membranes are of normal thickness (figure 6). An occasional gap is present along a peripheral capillary loop wall. The mesangial areas are slightly expanded, but are otherwise unremarkable. Mesangial immune complexes are not present (figure 7). Interstitial fibrosis and edema is present. Immune complexes are not present along tubular basement membranes. An interstitial inflammatory infiltrate associated with focal tubulitis is present.

Differential Diagnosis:

Not applicable for this case, please continue to the Diagnosis.

Diagnosis:

Kidney, biopsy—Crescentic glomerulonephritis (approximately 90% of viable glomeruli with crescents), consistent with anti-glomerular basement membrane (anti-GBM) antibody disease.
Glomerular sclerosis (approximately 25% globally sclerosed glomeruli) with mild vascular sclerosis.

This case is an example of anti-GBM antibody disease, one of the causes of rapidly progressive glomerulonephritis (RPGN). Anti-GBM antibody disease, as in this case, generally presents as a diffuse extracapillary proliferative or crescentic GN. Crescentic GN is characterized by an accumulation of cells in the extracapillary portion of the glomerulus (the urinary or Bowman space). Per WHO criteria, the cells must form a layer at least two cells thick with the appearance of a crescent. Crescentic GN represents a nonspecific pattern, and may be observed in a variety of conditions. In addition to anti-GBM antibody disease, glomerular crescents may be seen in cases of post infectious GN, lupus nephritis (LN), IgA nephropathy (IgAN), and others. ANCA-associated GN’s without or with small vessel vasculitis (i.e. Wegener granulomatosis, Churg Strauss syndrome, and microscopic polyangiitis) also may present as a crescentic GN. There is no universally accepted definition of crescentic GN in terms of the proportion of glomeruli that must have crescents. Some authors require crescents in at least 30% of the glomeruli, while others require crescents in at least 50%.

Crescentic GN may occur in patients of almost any age, but there are two age peaks. One peak represents adolescents to young adults, predominantly males. The other peak represents middle-aged to older adults, with an equal incidence in men and women. The clinical onset of disease is usually abrupt, but may be insidious. Most patients present with severe oliguria or anuria. Crescentic transformation of primary membranous nephropathy (MN) associated with the development of anti-GBM antibody is a rare cause of acute renal failure in patients with MN (1). Goodpasture’s syndrome, the combination of anti-GBM antibody disease with pulmonary hemorrhage, is rare. Even thought the classical presentation of Goodpasture’s syndrome is that of RPGN, pulmonary hemorrhage, and anti-GBM antibodies in the circulation, in rare cases it can present with repeated pulmonary hemorrhage and minor urinary abnormalities (2). In all cases of repeated pulmonary hemorrhage, the possibility of Goodpasture’s syndrome should be considered and investigated further.

Patients with Crescentic GN may have a variety of abnormal laboratory findings. Serum urea nitrogen and creatinine levels are elevated (3). Urinalysis discloses hematuria with dysmorphic red cells, often with erythrocyte casts. Proteinuria is common, but is usually modest in amount. Anti-GBM antibodies are present in 2% to 20% of cases and should be tested for in all cases of crescentic GN, with or without pulmonary hemorrhage.

The prognosis of Crescentic GN depends in part on the primary disease; historically, cases associated with infection had a slightly more favorable prognosis than other cases, which almost universally progressed to complete renal failure. Immunosuppressive therapy, usually combining corticosteroids in relatively high doses with cytotoxic agents such as cyclophosphamide, have had a beneficial effect in a substantial number of cases when started early in the disease. Plasmapheresis combined with immunosuppressive therapy has been found to have a beneficial effect in cases of anti-GBM antibody disease, particularly when started early in the disease. Rapamycin also has the potential to significantly reduce the B and T cell responses and thereby protect from glomerulonephritis when administered early in the disease (4). Once disease is established though, rapamycin seems to worsen glomerulonephritis by disturbing the endothelial cell/vascular endothelial growth factor system in the kidney.

References:

  1. Nayak SG, Satish R: Crescentic transformation in primary membranous glomerulopathy: association with anti-GBM antibody. Saudi J Kidney Dis Transpl. 2007 Nov; 18(4):599-602.
  2. Ramaswami A, Kandaswamy T, Rajendran T, Aung H, Jacob CK, Zinna HS, Telesinge PU: Goodpasture’s syndrome with positive C-ANCA and normal renal function: A case report. J Med Case Reports. 2008 Jun 30; 2: 223.
  3. Atlas of Renal Pathology. Kern, Silva, Laszik, Bane, Nadasdy, Pitha, editors. Philadelphia: W. B. Saunders Company.
  4. Hochegger K, Jansky GL, Soleiman A, Wolf AM, Tagwerker A, Seger C, Griesmacher A, Mayer G, Rosenkranz AR: Differential effects of rapamycin in anti-GBM glomerulonephritis. J Am Soc Nephrol. 2008 Aug; 19(8): 1520-9. Epub 2008 May 14.