Type III RPGN (Pauci-Immune)

ANCA associated

Idiopathic

Wegener granulomatosis

Microscopic polyarteritis nodosa/microscopic polyangiitis

previously described.[48] In some of these patients, the anti-GBM antibodies cross-react with pulmonary alveolar basement membranes to produce the clinical picture of pulmonary

hemorrhage associated with renal failure (Goodpasture syndrome). Plasmapheresis to remove the pathogenic circulating antibodies is usually part of the treatment, which also includes

therapy to suppress the underlying immune response.

The Goodpasture antigen, as was noted earlier, is a peptide within the noncollagenous portion of the a3 -chain of collagen type IV. [27] What triggers the formation of these antibodies is

unclear in most patients. Exposure to viruses or hydrocarbon solvents (found in paints and dyes) has been implicated in some patients, as have various drugs and cancers. There is a high

prevalence of certain HLA subtypes and haplotypes (e.g., HLA-DRB1) in affected patients, a finding consistent with the genetic predisposition to autoimmunity.[49]

The second type of RPGN is the result of immune complex-mediated disease. It can be a complication of any of the immune complex nephritides, including postinfectious

glomerulonephritis, SLE, IgA nephropathy, and Henoch-Schönlein purpura. In all of these cases, immunofluorescence studies reveal the granular pattern of staining characteristic of

immune complex deposition. These patients cannot usually be helped by plasmapheresis, and they require treatment for the underlying disease.

The third type of RPGN, also called pauci-immune type, is defined by the lack of anti-GBM antibodies or immune complexes by immunofluorescence and electron microscopy. Most

patients with this type of RPGN have antineutrophil cytoplasmic antibodies (ANCA), of cytoplasmic (C) or perinuclear (P) patterns, in the serum, which, as we have seen ( Chapter 11 ),

play a role in some vasculitides. Hence, in some cases, this type of RPGN is a component of a systemic vasculitis such as Wegener granulomatosis or microscopic polyarteritis. In many

cases, however, pauci-immune crescentic glomerulonephritis is isolated and hence idiopathic. More than 90% of such idiopathic cases have c-ANCA or p-ANCA in the sera.[50] The

presence of circulating ANCAs in both idiopathic RPGN and cases of RPGN that occur as a component of systemic vasculitis, and the similar pathologic features in either setting, have led

to the idea that these disorders are pathogenetically related. According to this concept, all cases of RPGN of the pauci-immune type are manifestations of small vessel vasculitis or

polyangiitis, which is limited to glomerular and perhaps peritubular capillaries in cases of idiopathic crescentic glomerulonephritis. [51] The clinical distinction between systemic vasculitis

with pauci-immune renal involvement and idiopathic crescentic glomerulonephritis accordingly has become deemphasized, as these entities are viewed as part of a spectrum of vasculitic

disease. ANCAs have proved to be invaluable as a highly sensitive diagnostic marker for pauci-immune RPGN, but proof of their role as a direct cause of RPGN has been elusive. Recent

strong evidence of their pathogenic potential has been obtained by studies in which antibodies against myeloperoxidase (the target antigen of most p-ANCAs) are transferred into mice.[52]

To summarize, all three types of RPGN may be associated with a well-defined renal or extrarenal disease, but in many cases (approximately 50%), the disorder is idiopathic. Of the patients

with this syndrome, about one fifth have anti-GBM antibody-induced disease without lung involvement; another one fourth have immune complex-mediated disease RPGN; and the

remainder are of the pauci-immune type. The common denominator in all types of RPGN is severe glomerular injury.

Morphology.

The kidneys are enlarged and pale, often with petechial hemorrhages on the cortical surfaces. Depending on the underlying cause, the glomeruli may show focal necrosis, diffuse or focal

endothelial proliferation, and mesangial proliferation. The histologic picture, however, is dominated by the formation of distinctive crescents( Fig. 20-17 ). Crescents are formed by

proliferation of parietal cells and by migration of monocytes and macrophages into the urinary space. Neutrophils and lymphocytes may be present. The crescents eventually obliterate

Bowman space and compress the glomerular tuft. Fibrin strands are prominent between the cellular layers in the crescents;indeed, as discussed earlier, the escape of fibrin into

Bowman space is an important

Figure 20-17Crescentic glomerulonephritis (PAS stain). Note the collapsed glomerular tufts and the crescent-shaped mass of proliferating cells and leukocytes internal to Bowman

capsule. (Courtesy of Dr. M.A. Venkatachalam, University of Texas Health Sciences Center, San Antonio, TX.)

Figure 20-18Rapidly progressive glomerulonephritis. Electron micrograph showing characteristic wrinkling of GBM with focal disruptions in its continuity (arrows).

TABLE 20-8-- Causes of Nephrotic Syndrome

Prevalence (%) *

Children Adults

Date: 2016-04-22; view: 1297