- Author: Malvinder S Parmar, MB, MS; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Rapidly progressive glomerulonephritis (RPGN) is defined as any glomerular disease characterized by extensive crescents (usually >50%) as the principal histologic finding and by a rapid loss of renal function (usually a 50% decline in the glomerular filtration rate [GFR] within 3 mo) as the clinical correlate.
The image shown below depicts the histologic findings observed in patients with severe types of RPGN.
Some patients have acute glomerulonephritis and present with rapidly progressive renal failure that develops within weeks to months and displays little tendency for spontaneous or complete recovery. Glomerular crescents can complicate any glomerulopathy, even noninflammatory glomerulopathy. In patients with noninflammatory glomerulopathies, the crescents tend to be fibrotic rather than cellular. Cellular crescents are a manifestation of a severe inflammatory process.
Idiopathic or primary crescentic glomerulonephritis is classified into the following types:
Type I with linear deposits of immunoglobulin G (IgG) (anti–glomerular basement membrane [GBM] disease)
Type II with granular deposits of immunoglobulin (immune-complex mediated)
Type III with few or no immune deposits (pauci-immune) - Antineutrophil cytoplasmic antibody (ANCA–associated is related to small vessel vasculitis (SVV) and may be renal-limited or part of a systemic disease, like granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis or microscopic polyangiitis (MPA)
Type IV combinations of types I and III
Type V ANCA-negative pauci-immune renal vasculitis (5-10%)
RPGN can develop in any of the following clinical settings:
Complication of acute or subacute infectious process
Renal complication of multisystem disease: Secondary forms comprise more than 40% of cases.
In association with use of certain drugs: A review of published data on an association between hydrocarbon exposure and anti-GBM antibody-mediated disease suggests the possibility of a casual relationship.
Primary glomerular disease in which the kidney is the sole organ involved and in which extrarenal manifestations are caused by renal function disturbances
Acute RPGN is mediated by antibody or cellular immunity or by interaction of the two arms of the immune system. Deposition of antibody along the basement membrane and/or glomerular deposition of preformed soluble immune complexes can result in glomerulonephritis. Lymphocytes and macrophages, along with deposited antibody, are important in the production of proliferation and proteinuria. The involved lymphocytes are identified as T cells; most are helper T cells with some suppressor T cells. Antibody- and cell-mediated immunity are together responsible for many lesions observed in patients with acute RPGN, and cell-mediated immunity without antibody may produce crescentic glomerulonephritis.
Crescents are defined as the presence of 2 or more layers of cells in the Bowman space. The presence of crescents in glomeruli is a marker of severe injury, and this may be seen with any form of severe glomerular injury.
The initiating event is the development of a physical disruption in the GBM. The lesions are mediated by processes involving macrophages and cell-mediated immunity. Following disruption of the glomerular capillary, circulating cells, inflammatory mediators, and plasma proteins pass through the capillary wall into the Bowman space. Cells and mediators from the interstitium enter the Bowman space with disruption of the Bowman capsule, which leads to development of crescents.
The major participants in crescent formation are coagulation proteins, macrophages, T cells, fibroblasts, and parietal epithelial cells. Activated macrophages contribute to the crescents by proliferating and releasing procoagulant tissue factor, interleukin-1 (IL-1) and tumor necrosis factor (TNF). T cells are not prominent components, but they play an important role in glomerular injury by antigen recognition and macrophage recruitment.
The crescents may be circumferential or noncircumferential, and the presence of circumferential crescents in over 80% of glomeruli portends a poor prognosis and often manifests as advanced kidney disease.
The reversibility of crescents correlates with relative predominance of cellular components. Whether crescents progress or resolve may depend upon the integrity of the Bowman capsule and resulting cellular composition of the crescent. Progression to fibrous crescents is more common when capsular rupture occurs and fibroblasts along with macrophages are prominent in the Bowman space. The presence of fibrous crescents usually correlates with glomerular sclerosis or irreversibility.
Idiopathic crescentic glomerulonephritis accounts for fewer than 10% of all patients presenting with primary glomerulopathy. RPGN type III is more common than RPGN types I or II. More than 50% of patients with crescentic glomerulonephritis present with acute nephritic syndrome and rapidly deteriorating renal function; however, other modes do occur (eg, asymptomatic, 15%; nephrotic, 10%; chronic renal failure, 15%).
Peak incidence of anti-GBM disease occurs in spring and early summer. No seasonal predilection is observed in patients with non–anti-GBM disease.
Renal failure at presentation carries an increased risk for end-stage renal disease and death despite immunosuppressive therapy. Death or dialysis occurs in 73% of patients who are treated with conventional therapy and in 88% of patients if they are oligoanuric at time of presentation.
No racial predilection exists.
For RPGN types I and III, a predilection for males exists.
RPGN has a broad age distribution, as follows:
RPGN type I generally occurs in young adults.
RPGN types II and III generally occur in older adults; the peak incidence occurs in the fourth to sixth decades of life.
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