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| {{Infobox_Disease
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| | DiseasesDB = 3165
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| | ICD10 = N00-N08 with .7 suffix
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| | eMedicine_mult = {{eMedicine2|med|890}} |
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| {{Rapidly progressive glomerulonephritis}} | | {{Rapidly progressive glomerulonephritis}} |
| | '''For patient information, click [[Rapidly progressive glomerulonephritis (patient information)|here]]''' |
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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
| | {{CMG}}; {{AE}} {{AEL}} {{JSS}} {{SAH}} |
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| {{CMG}} | | {{SK}} Acute cresent glomerulonephritis, RPGN |
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| {{SK}}: Crescentic glomerulonephritis; RPGN
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| ==[[Rapidly progressive glomerulonephritis overview|Overview]]== | | ==[[Rapidly progressive glomerulonephritis overview|Overview]]== |
| Rapidly progressive glomerulonephritis (RPGN) is one of the few nephrological emergency. However, it fortunately only affects 1-4% of all cases of glomerulonephritis. It is a clinical syndrome that includes signs and symptoms of glomerulonephritis, including hematuria, proteinuria, and edema with signs of renal failure and diffuse crescent formation on histopathology. Without appropriate treatment, RPGN progresses into end-stage renal disease within several days to only a few months yielding a very poor prognosis and renal outcome. RPGN is classified based on the presence of absence of anti-neutrophil cytoplasmic antibody (ANCA) and anti-GBM antibodies. Due to its rarity, the pathogenesis of RPGN is poorly understood and most probably is related to the type of RPGN and the circulating antibodies associated with each type. Evidence on treatment options for RPGN is poor; but the use of glucocorticoids and cyclophosphamide is currently recommended. Basic research and clinical data are currently emerging to better understand the disease pathogenesis and optimal therapeutic options.
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| ==[[Rapidly progressive glomerulonephritis classification|Definition]]== | | ==[[Rapidly progressive glomerulonephritis historical perspective|Historical Perspective]]== |
| Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterized by features of glomerulonephritis associated with renal impairment that rapidly worsens over a very short duration - from weeks to a few months – into end-stage renal disease (ESRD).
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| In RPGN, renal failure is the rapid loss of renal function beyond 50% over a short span ranging to a maximum of 3 months. RPGN is thus one of several causes of rapidly progressive renal failure (RPRF).
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| ==[[Rapidly progressive glomerulonephritis classification|Classification]]== | | ==[[Rapidly progressive glomerulonephritis classification|Classification]]== |
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| ===Old Classification===
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| Following its initial description in 1914, crescenteric glomerulonephritis was first classified by Couser in 1988 based on features of immunofluorescence.<ref name="pmid3287904">{{cite journal| author=Couser WG|title=Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy. |journal=Am J Kidney Dis | year= 1988 | volume= 11 | issue= 6 | pages= 449-64 | pmid=3287904 | doi= | pmc=| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3287904 }} </ref>
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| ====Type I: Anti-GBM Glomerulonephritis====
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| 20% of patients <br>
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| Presence of linear staining of glomerular basement membrane (GBM)
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| ====Type II: Pauci-Immune Glomerulonephritis====
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| 50% of patients <br>
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| Absent or minimal immune deposits
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| ====Type III: Immune Complex-Mediated Glomerulonephritis====
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| 30% of patients <br>
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| Presence of granular patterns of immune deposits within the glomerulus. Immune deposition may be associated with any of the following conditions:
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| *Infections
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| *Systemic illnesses
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| *Other primary glomerular diseases
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| ===New Classification===
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| Upon the detection of new serological markers such as anti-GBM antibodies and anti-neutrophil cytoplasmic antibodies (ANCA)<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR| title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 | pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref>, the classification of RPGN has changed to involve several types of primary glomerulonephritis that correspond to the quantity and quality of such findings in patients’ sera. ANCA and anti-GBM may co-exist in approximately 20% of the patients.<ref name="pmid7544065">{{cite journal| author=Short AK, Esnault VL, Lockwood CM| title=Anti-neutrophil cytoplasm antibodies and anti-glomerular basement membrane antibodies: two coexisting distinct autoreactivities detectable in patients with rapidly progressive glomerulonephritis. | journal=Am J Kidney Dis | year= 1995 | volume= 26 | issue= 3 | pages= 439-45 | pmid=7544065 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7544065 }} </ref>
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| ====Type I: Anti-GBM Disease====
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| *Anti-GBM antibody-mediated without pulmonary involvement
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| *Goodpasture’s disease: Anti-GBM antibody-mediated with pulmonary hemorrhage
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| ====Type II: Immune Complex-Mediated Disease====
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| ====Type III: Pauci-Immune Disease====
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| ANCA positive
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| *Idiopathic renal-limited vasculitis / renal-limited necrotizing crescenteric glomerulonephritis (NCGN)
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| *Granulomatosis with polyangiitis (formerly “Wegener’s granulomatosis")
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| *Microscopic polyangiitis
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| *Churg-Strauss syndrome
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| ====Type IV: Mixed Anti-GBM and ANCA Associated Disease====
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| ====Type V: Pauci-Immune====
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| ANCA negative
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| ==[[Rapidly progressive glomerulonephritis pathophysiology|Pathophysiology]]== | | ==[[Rapidly progressive glomerulonephritis pathophysiology|Pathophysiology]]== |
| The pathogenesis of RPGN is unclear and is poorly understood. Nonetheless, circulating factors are thought to play a significant role in the disease and its progression.<ref name="pmid2161532">{{cite journal| author=Falk RJ, Terrell RS, Charles LA, Jennette JC| title=Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. | journal=Proc Natl Acad Sci U S A | year= 1990 | volume= 87 | issue= 11 | pages= 4115-9 | pmid=2161532 | doi= | pmc=PMC54058 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2161532 }} </ref> RPGN, as an outcome, seems to be actually related to the type of RPGN. As such, there does not seem to be a unifying pathophysiology, but rather a combination of pathways that lead to a similar renal outcome. Genetic susceptibility has been shown to be associated with elevated levels of circulating antibodies, such as anti-GBM and ANCA, but little has been elaborated.<ref name="pmid7544065">{{cite journal| author=Short AK, Esnault VL, Lockwood CM| title=Anti-neutrophil cytoplasm antibodies and anti-glomerular basement membrane antibodies: two coexisting distinct autoreactivities detectable in patients with rapidly progressive glomerulonephritis. | journal=Am J Kidney Dis | year= 1995 | volume= 26 | issue= 3 | pages= 439-45 | pmid=7544065 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7544065 }} </ref>
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| In type I anti-GBM glomerulonephritis, antibodies against the non-collagenous domain of alpha-3 chain of type IV collagen of the glomerular basement membrane with a linear pattern on immunofluorescence are responsible for renal involvement.<ref name="pmid18590526">{{cite journal| author=Ramaswami A, Kandaswamy T, Rajendran T, Aung H, Jacob CK, Zinna HS et al.| title=Goodpasture's syndrome with positive C-ANCA and normal renal function: a case report. | journal=J Med Case Rep | year= 2008 | volume= 2 | issue= | pages= 223 | pmid=18590526 | doi=10.1186/1752-1947-2-223 | pmc=PMC2475522 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18590526 }} </ref><ref name="pmid4937848">{{cite journal| author=Lewis EJ, Cavallo T, Harrington JT, Cotran RS| title=An immunopathologic study of rapidly progressive glomerulonephritis in the adult. | journal=Hum Pathol | year= 1971 | volume= 2 | issue= 2 | pages= 185-208 | pmid=4937848 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4937848 }} </ref><ref name="pmid7360526">{{cite journal| author=Cunningham RJ, Gilfoil M, Cavallo T, Brouhard BH, Travis LB, Berger M et al.| title=Rapidly progressive glomerulonephritis in children: a report of thirteen cases and a review of the literature. | journal=Pediatr Res | year= 1980 | volume= 14 | issue= 2 | pages= 128-32 | pmid=7360526 | doi=10.1203/00006450-198002000-00012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7360526 }} </ref> The granular distribution along the GBM exhibit IgG and C3 deposits. Crescent formation is predominantly due to the formation of fibrin/fibrinogen.<ref name="pmid7360526">{{cite journal| author=Cunningham RJ, Gilfoil M, Cavallo T, Brouhard BH, Travis LB, Berger M et al.| title=Rapidly progressive glomerulonephritis in children: a report of thirteen cases and a review of the literature. | journal=Pediatr Res | year= 1980 | volume= 14 | issue= 2 | pages= 128-32 | pmid=7360526 | doi=10.1203/00006450-198002000-00012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7360526 }} </ref>
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| In Type II pauci-immune glomerulonephritis, such as in polyangittis with granulomatosis (formerly Wegener granulomatosis) and polyarteritis nodosa, findings of p-ANCA and c-ANCA in patients are considered landmarks in understanding these diseases; but their true significance has not yet been delineated.<ref name="pmid2161532">{{cite journal| author=Falk RJ, Terrell RS, Charles LA, Jennette JC| title=Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. | journal=Proc Natl Acad Sci U S A | year= 1990 | volume= 87 | issue= 11 | pages= 4115-9 | pmid=2161532 | doi= | pmc=PMC54058 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2161532 }} </ref><ref name="pmid6297657">{{cite journal| author=Davies DJ, Moran JE, Niall JF, Ryan GB| title=Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? | journal=Br Med J (Clin Res Ed) | year= 1982 | volume= 285 | issue= 6342 | pages= 606 | pmid=6297657 | doi= | pmc=PMC1499415 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6297657 }} </ref> Studies have shown that ANCA may in fact interact with neutrophils due to the presence of myeloperixoidases on the surface of neutrophils. The interaction drives neutrophils to undergo activation via oxidative burst that finally leads to their “dose-dependent” degranulation and release of toxic oxygen radicals.<ref name="pmid2161532">{{cite journal| author=Falk RJ, Terrell RS, Charles LA, Jennette JC| title=Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. | journal=Proc Natl Acad Sci U S A | year= 1990 | volume= 87 | issue= 11 | pages= 4115-9 | pmid=2161532 | doi= | pmc=PMC54058 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2161532 }} </ref> TNF priming also seems to play an important role in the ANCA-induced degranulation of neutrophils.<ref name="pmid3009619">{{cite journal| author=Klebanoff SJ, Vadas MA, Harlan JM, Sparks LH, Gamble JR, Agosti JM et al.| title=Stimulation of neutrophils by tumor necrosis factor. | journal=J Immunol | year= 1986 | volume= 136 | issue= 11 | pages= 4220-5 | pmid=3009619 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3009619 }} </ref><ref name="pmid7044447">{{cite journal| author=Gallin JI, Fletcher MP, Seligmann BE, Hoffstein S, Cehrs K, Mounessa N| title=Human neutrophil-specific granule deficiency: a model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response. | journal=Blood | year= 1982 | volume= 59 | issue= 6 | pages= 1317-29 | pmid=7044447 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7044447 }} </ref> As such, it is perhaps that TNF production during infections and inflammatory diseases in vivo may prime neutrophils in ANCA-positive patients to facilitate neutrophilic activation and subsequent pro-inflammatory cascade of RPGN disease.<ref name="pmid2161532">{{cite journal| author=Falk RJ, Terrell RS, Charles LA, Jennette JC| title=Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. | journal=Proc Natl Acad Sci U S A | year= 1990 | volume= 87 | issue= 11 | pages= 4115-9 | pmid=2161532 | doi= | pmc=PMC54058 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2161532 }} </ref><ref name="pmid3009619">{{cite journal| author=Klebanoff SJ, Vadas MA, Harlan JM, Sparks LH, Gamble JR, Agosti JM et al.| title=Stimulation of neutrophils by tumor necrosis factor. | journal=J Immunol | year= 1986 | volume= 136 | issue= 11 | pages= 4220-5 | pmid=3009619 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3009619 }} </ref><ref name="pmid7044447">{{cite journal| author=Gallin JI, Fletcher MP, Seligmann BE, Hoffstein S, Cehrs K, Mounessa N| title=Human neutrophil-specific granule deficiency: a model to assess the role of neutrophil-specific granules in the evolution of the inflammatory response. | journal=Blood | year= 1982 | volume= 59 | issue= 6 | pages= 1317-29 | pmid=7044447 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7044447 }} </ref>
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| While the majority of patients with pauci-immune RPGN indeed have elevated levels of ANCA, the remaining 20% of patients with the same disease do not. Interestingly, 30% of patients in remission continue to have elevated levels of ANCA. Both these problematic findings raise the question of the actual importance of ANCA in the pathogenesis of RPGN.<ref name="pmid11007827">{{cite journal| author=Hedger N, Stevens J, Drey N, Walker S, Roderick P| title=Incidence and outcome of pauci-immune rapidly progressive glomerulonephritis in Wessex, UK: a 10-year retrospective study. | journal=Nephrol Dial Transplant | year= 2000 | volume= 15 | issue= 10 | pages= 1593-9 | pmid=11007827 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11007827 }} </ref> A novel hypothesis currently suggests that RPGN is in fact a podocytopathy, defined as an intrinsic disease of the podocytes that normally maintains glomerular capillary membranes.( 16906157) As such, it is thought that the CXCR4 and VHL-HIF pathway target gene expression in renal biopsies, based on experimental studies on mice.<ref name="pmid16906157">{{cite journal| author=Ding M, Cui S, Li C, Jothy S, Haase V, Steer BM et al.| title=Loss of the tumor suppressor Vhlh leads to upregulation of Cxcr4 and rapidly progressive glomerulonephritis in mice. | journal=Nat Med | year= 2006 | volume= 12 | issue= 9 | pages= 1081-7 | pmid=16906157 | doi=10.1038/nm1460 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16906157 }} </ref>
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| ==[[Rapidly progressive glomerulonephritis causes|Causes]]== | | ==[[Rapidly progressive glomerulonephritis causes|Causes]]== |
| ===Primary RPGN===
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| RPGN may be a primary condition. The diagnosis of primary glomerulonephritis is made when the clinical syndrome of the disease complies with the new classification of RPGN based on the 5 types of disease.
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| Nonetheless, ruling out other causes of RPGN is necessary before the diagnosis of primary RPGN is made.
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| The cause of ANCA levels in patients with ANCA-associated glomerulonephritis is not known. Environmental and genetic factors have been postulated. It is believed that infectious etiologies, such as arboviruses, may be contributory. These findings are based only on observations and small studies that patients with ANCA-associated glomerulonephritis are more commonly diagnosed during “flu season”, flu-like prodrome is usually the most common presenting symptoms of these patients, and presence of serological proof of previous arbovirus infection. Further disease progression in ANCA-associated diseases into clinical syndromes of polyarteritis nodosa and Wegener granulomatosis has been postulated to be caused by activation of autoantibody-induced leukocytes.<ref name="pmid2221646">{{cite journal| author=Falk RJ, Hogan S, Carey TS, Jennette JC| title=Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. | journal=Ann Intern Med | year= 1990 | volume= 113 | issue= 9 | pages= 656-63 | pmid=2221646 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2221646 }} </ref> However, no consistent validation of such claims has been made.
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| ===Secondary RPGN===
| | ==[[Rapidly progressive glomerulonephritis differential diagnosis|Differentiating Rapidly progressive glomerulonephritis from other Diseases]]== |
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| ====Infections====
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| *Infective endocarditis
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| *Sepsis
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| *HBV infection with vasculitis or cryoglobulinemia
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| *HCV infection with vasculitis or cryoglobulinemia
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| ====Drugs====
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| *Allopurinol
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| *D-penicillamine
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| *Hydralazine
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| *Rifampin
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| ====Multi-Organ Disease====
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| *Systemic lupus erythematosus
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| *Henoch-Schonlein purpura
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| *Systemic necrotizing vasculitis
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| *Relapsing polychondritis
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| *Cryoglobulinemia
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| *Other vasculitides
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| ====Malignancies====
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| *Colon cancer
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| *Pulmonary cancer
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| *Lymphoma
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| ====Other Conditions====
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| *Behcet’s disease
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| *Membranoproliferative glomerulonephritis
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| *IgA nephropathy
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| *Poststreptococcal glomerulonephritis
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| *Hereditary nephritis
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| ==[[Rapidly progressive glomerulonephritis differential diagnosis|Differential Diagnosis]]== | |
| During the evaluation of RPGN, the differential diagnosis of RPGN must first include secondary causes of RPGN and other forms of primary glomerulonephritis before the diagnosis of primary RPGN is to be made and before considering other differential diagnoses.
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| Other diseases that need that to be considered as differential diagnoses include:
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| *Amyloidosis
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| *Antiphospholipid syndrome
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| *Malignant hypertension
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| *Multiple myeloma
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| *Polyarteritis nodosa
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| ==[[Rapidly progressive glomerulonephritis epidemiology and demographics|Epidemiology and Demographics]]== | | ==[[Rapidly progressive glomerulonephritis epidemiology and demographics|Epidemiology and Demographics]]== |
| RPGN accounts for a small minority of all cases of glomerulonephritis. Only 1-4% of kidney biopsies are RPGN. The prevalence and predominance of RPGN among different ethnicities and geographical locations is currently not known.
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| ==[[Rapidly progressive glomerulonephritis risk factors|Clinical Presentation]]==
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| RPGN is a difficult diagnosis because of its presenting insidious non-specific symptoms, especially when uncomplicated by other diseases or associated with secondary etiologies.<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR| title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 | pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref> Perhaps the most common presenting symptom of RPGN is just fatigue.<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR| title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 | pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref> Other constitutive symptoms, such as nausea, vomiting, unintentional weight loss, loss of appetite, and diffuse nonspecific abdominal and musculoskeletal pain, are also common. This nonspecific “flu-like” prodrome has raised the suspicion of whether RPGN is a rare unfortunate complication of an infectious etiology.<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR| title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 | pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref>
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| Renal symptoms, such as azotemia, oliguria, and nephritic syndrome, with gross hematuria are frequently seen in patients with RPGN.<ref name="pmid7360526">{{cite journal| author=Cunningham RJ, Gilfoil M, Cavallo T, Brouhard BH, Travis LB, Berger M et al.| title=Rapidly progressive glomerulonephritis in children: a report of thirteen cases and a review of the literature. | journal=Pediatr Res | year= 1980 | volume= 14 | issue= 2 | pages= 128-32 | pmid=7360526 | doi=10.1203/00006450-198002000-00012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7360526 }} </ref> Patients might present with several chief complaints, such as symptoms associated with hypertension, such as headache or blurry vision, symptoms of renal insufficiency, or even symptoms of associated diseases such as hemoptysis, sinusitis, cough, and dyspnea in those who that have pulmonary involvement. It has been noted that adult population is less likely to experience hypertension in RPGN as compared to the pediatric population.<ref name="pmid7360526">{{cite journal| author=Cunningham RJ, Gilfoil M, Cavallo T, Brouhard BH, Travis LB, Berger M et al.| title=Rapidly progressive glomerulonephritis in children: a report of thirteen cases and a review of the literature. | journal=Pediatr Res | year= 1980 | volume= 14 | issue= 2 | pages= 128-32 | pmid=7360526 | doi=10.1203/00006450-198002000-00012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7360526 }} </ref> As such, the presenting symptoms might vary significantly depending on the type of RPGN.
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| Most findings on physical examination are related to diseases that are associated with RPGN, such as skin lesions in vasculitis, or those associated with renal failure.
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| ==[[Rapidly progressive glomerulonephritis natural history, complications and prognosis|Prognosis]]==
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| The prognosis of RPGN is poor due to the rapid deterioration of kidney function into end-stage renal disease (ESRD) within a few weeks or months. Early diagnosis and management are both important factors to improve prognosis and avoid progression into ESRD.<ref name="pmid8808106">{{cite journal| author=Hogan SL, Nachman PH, Wilkman AS, Jennette JC, Falk RJ| title=Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. | journal=J Am Soc Nephrol | year= 1996 | volume= 7 | issue= 1 | pages= 23-32 | pmid=8808106 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8808106 }} </ref><ref name="pmid8944617">{{cite journal| author=Lal DP, O'Donoghue DJ, Haeney M| title=Effect of diagnostic delay on disease severity and outcome in glomerulonephritis caused by anti-neutrophil cytoplasmic antibodies. | journal=J Clin Pathol | year= 1996 | volume= 49 | issue= 11 | pages= 942-4 | pmid=8944617 | doi= | pmc=PMC500837 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8944617 }} </ref><ref name="pmid3826068">{{cite journal| author=Heilman RL, Offord KP, Holley KE, Velosa JA| title=Analysis of risk factors for patient and renal survival in crescentic glomerulonephritis. | journal=Am J Kidney Dis | year= 1987 | volume= 9 | issue= 2 | pages= 98-107 | pmid=3826068 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3826068 }} </ref> Histopathologically, the extent of fibrous crescents is associated with poorer renal survival.<ref name="pmid1244562">{{cite journal| author=Whitworth JA, Morel-Maroger L, Mignon F, Richet G| title=The significance of extracapillary proliferation. Clinicopathological review of 60 patients. | journal=Nephron | year= 1976 | volume= 16 | issue= 1 | pages= 1-19 | pmid=1244562 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1244562 }} </ref> The degree of renal impairment at diagnosis is also a significant prognostic factor. Serum creatinine > 6 mg/dL is associated with very poor renal outcomes in patients with anti-GBM disease.<ref name="pmid8203364">{{cite journal| author=Mokrzycki MH, Kaplan AA| title=Therapeutic plasma exchange: complications and management. | journal=Am J Kidney Dis | year= 1994 | volume= 23 | issue= 6 | pages= 817-27 | pmid=8203364 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8203364 }} </ref>
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| The prognosis of RPGN also depends on the exact diagnosis within subtypes of RPGN. The amount of studies that studied the natural history and prognosis of RPGN and its subtypes are very rare, especially because the disease itself is uncommon. Appropriate therapy in patients with anti-GBM disease and Goodpasture’s disease was shown to significantly alter prognosis, with survival rates reaching as high as 70-90%; but only 40% of patients do not require dialysis after 1 year.<ref name="pmid9241619">{{cite journal| author=Levy JB, Pusey CD| title=Still a role for plasma exchange in rapidly progressive glomerulonephritis? | journal=J Nephrol | year= 1997 | volume= 10 | issue= 1 | pages= 7-13 | pmid=9241619 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9241619 }} </ref>
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|
| |
| Another study that enrolled patients with microscopic polyangiitis and glomerulonephritis and positive ANCA.<ref name="pmid8808107">{{cite journal| author=Nachman PH, Hogan SL, Jennette JC, Falk RJ| title=Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. | journal=J Am Soc Nephrol | year= 1996 | volume= 7 | issue= 1 | pages= 33-9 | pmid=8808107 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8808107 }} </ref> Following appropriate therapy, more than 70% of the patients were in remission; almost half of which continued to be disease-free after 4 years. Similarly, renal function at diagnosis is associated with renal outcome in patients with positive ANCA.<ref name="pmid8808107">{{cite journal| author=Nachman PH, Hogan SL, Jennette JC, Falk RJ| title=Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. | journal=J Am Soc Nephrol | year= 1996 | volume= 7 | issue= 1 | pages= 33-9 | pmid=8808107 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8808107 }} </ref>
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|
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| Patients with poststreptococcal RPGN generally have better outcomes compared to those with primary RPGN. But these findings were observed in the adult population, and may not be true for pediatric patients.<ref name="pmid5476201">{{cite journal| author=Leonard CD, Nagle RB, Striker GE, Cutler RE, Scribner BH| title=Acute glomerulonephritis with prolonged oliguria. An analysis of 29 cases. | journal=Ann Intern Med | year= 1970 | volume= 73 | issue= 5 | pages= 703-11 | pmid=5476201 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5476201 }} </ref><ref name="pmid7360526">{{cite journal| author=Cunningham RJ, Gilfoil M, Cavallo T, Brouhard BH, Travis LB, Berger M et al.| title=Rapidly progressive glomerulonephritis in children: a report of thirteen cases and a review of the literature. | journal=Pediatr Res | year= 1980 | volume= 14 | issue= 2 | pages= 128-32 | pmid=7360526 | doi=10.1203/00006450-198002000-00012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7360526 }} </ref>
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| ==[[Rapidly progressive glomerulonephritis diagnostic criteria|Diagnosis]]==
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|
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| ===Blood Work-Up===
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| * Complete blood count (CBC) differential and platelet count
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|
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| * Serum electrolytes
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|
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| * Creatinine and blood urea nitrogen (BUN)
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|
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| * Lactate dehydrogenase (LDH)
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|
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| * Creatine phosphokinase (CPK)
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|
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| * Liver function tests
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|
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| * Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
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|
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| * Antinuclear antibody (ANA)
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|
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| * Anti-GBM antibodies
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|
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| * ANCA
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|
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| * Cryoglobulins
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|
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| * HBV and HCV titers
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|
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| * Complement C3 and C4 levels
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|
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| * Serum protein electrophoresis
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|
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| Anemia is common among patient with RPGN, mostly due to renally impaired production of erythropoietin or GI bleeding. Eosinophilia may be seen in a subset of patients with Churg-Strauss disease.
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|
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| Patients with RPGN may show formation of immune complexes and cryoglobulins. Complement C3 levels is usually low in immune-complex mediated RPGN. The presence of ANCA and anti-GBM is variable; their presence is important for classification of disease and further management planning. Anti-GBM levels is However, anti-GBM antibody level is not prognostic and is not associated with disease activity.<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR| title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 | pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref> On the contrary, literature regarding ANCA-associated glomerulonephritis suggests that levels of ANCA is associated with disease activity and may be used as an index for such purposes.<ref name="pmid2857806">{{cite journal| author=van der Woude FJ, Rasmussen N, Lobatto S, Wiik A, Permin H, van Es LA et al.| title=Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. | journal=Lancet | year= 1985 | volume= 1 | issue= 8426 | pages= 425-9 | pmid=2857806 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2857806 }} </ref><ref name="pmid2684074">{{cite journal| author=Tervaert JW, van der Woude FJ, Fauci AS, Ambrus JL, Velosa J, Keane WF et al.| title=Association between active Wegener's granulomatosis and anticytoplasmic antibodies. | journal=Arch Intern Med | year= 1989 | volume= 149 | issue= 11 | pages= 2461-5 | pmid=2684074 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2684074 }} </ref><ref name="pmid2221646">{{cite journal| author=Falk RJ, Hogan S, Carey TS, Jennette JC| title=Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. | journal=Ann Intern Med | year= 1990 | volume= 113 | issue= 9 | pages= 656-63 | pmid=2221646 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2221646 }} </ref>
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|
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| ESR and CRP may be elevated and are correlated with the level of inflammation and thus activity of the disease.
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|
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| ===Urine Work-Up===
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| *Urinalysis
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| *Urinary protein electrophoresis
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|
| |
| Patients with RPGN do not usually have a full-blown picture of nephrotic syndrome; Nephrotic syndrome only occurs in less than 30% of cases.<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR| title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 | pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref> Proteinuria, if present, is usually mild to moderate. Hematuria of glomerular type with dysmorphic red blood cells is usually present on urinalysis and associated with red cell casts. Mild to moderate leukocyturia may be seen and other casts, such as epithelial cell leukocyte, or fatty casts. Urinary findings in RPGN are important features that not only favor diagnostic work-up, but also follow-up and therapeutic effectiveness.
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|
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| ===Kidney Ultrasound===
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| Kidney ultrasound is usually done during diagnostic biopsy. Due to its rapid progression, renal biopsy usually shows normal-sized kidneys. Although the test is not diagnostic, its non-invastive nature and the necessity to rule out other etiologies of renal impairment are both in favor of performing a renal ultrasound.
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|
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| ===Kidney Biopsy===
| |
| An ultrasound or CT-guided kidney biopsy is the only gold standard to diagnose RPGN and determine prognosis of the disease. The pathological hallmark of RPGN is presence of epithelial crescents in the Bowman’s capsule with or without endocapillary proliferation.<ref name="pmid7360526">{{cite journal| author=Cunningham RJ, Gilfoil M, Cavallo T, Brouhard BH, Travis LB, Berger M et al.| title=Rapidly progressive glomerulonephritis in children: a report of thirteen cases and a review of the literature. | journal=Pediatr Res | year= 1980 | volume= 14 | issue= 2 | pages= 128-32 | pmid=7360526 | doi=10.1203/00006450-198002000-00012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7360526 }} </ref> The extent of fibrous crescents along the glomerulus are considered a poor prognostic element.
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|
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| [[Rapidly progressive glomerulonephritis medical therapy|Management]]
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| Treatment of RPGN must be very aggressive due to its generally poor prognosis if left unmanaged. Hence, treatment must not await the results of the kidney biopsy; but must be initiated as soon as possible because fibrosis may start very early during the course of the disease. Presence of fibrosis marks irreversible damage.
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|
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| In some studies, patients already on dialysis were also responsive to therapy and treatment should not be delayed for these patients either.<ref name="pmid8808107">{{cite journal| author=Nachman PH, Hogan SL, Jennette JC, Falk RJ| title=Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. | journal=J Am Soc Nephrol | year= 1996 | volume= 7 | issue= 1 | pages= 33-9 | pmid=8808107 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8808107 }} </ref> Nonetheless, the true response among this specific sub-population and their associated risks and outcomes are poorly understood.<ref name="pmid8808107">{{cite journal| author=Nachman PH, Hogan SL, Jennette JC, Falk RJ| title=Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. | journal=J Am Soc Nephrol | year= 1996 | volume= 7 | issue= 1 | pages= 33-9 | pmid=8808107 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8808107 }} </ref>
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|
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| ===Pharmacologic Therapy===
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|
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| In 1990, the Glomerular Disease Collaborative Network published its findings after a 24-month follow-up of 70 patients with ANCA and pauci-immune necrotizing and crescentic glomerulonephritis.<ref name="pmid2221646">{{cite journal| author=Falk RJ, Hogan S, Carey TS, Jennette JC| title=Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. | journal=Ann Intern Med | year= 1990 | volume= 113 | issue= 9 | pages= 656-63 | pmid=2221646 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2221646 }} </ref> In the cohort trial, 14 patients were treated with corticosteroids, 30 patients received both corticosteroids and oral cyclophosphamide, 15 patients received both corticosteroids and intravenous cyclophosphamide, and 11 patients received no treatment.<ref name="pmid2221646">{{cite journal| author=Falk RJ, Hogan S, Carey TS, Jennette JC| title=Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. | journal=Ann Intern Med | year= 1990 | volume= 113 | issue= 9 | pages= 656-63 | pmid=2221646 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2221646 }} </ref> The authors concluded that oral corticosteroids with either oral or intravenous cyclophosphamide regimens are equally effective treatment options for patients with ANCA-associated glomerulonephritis for patients with renal-limited disease, glomerulonephritis, and alveolar hemorrhage.<ref name="pmid2221646">{{cite journal| author=Falk RJ, Hogan S, Carey TS, Jennette JC| title=Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. | journal=Ann Intern Med | year= 1990 | volume= 113 | issue= 9 | pages= 656-63 | pmid=2221646 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2221646 }} </ref>
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|
| In 1996, Nachman and colleagues outlined a protocol for therapeutic management of patients with microscopic polyangiitis and necrotizing and crescentic glomerulonephritis associated with ANCA. In the trial, 107 patients were enrolled. 25 patients received only corticosteroids, 72 received cyclophosphamide and corticosteroids, and 10 patients did not receive cyclophosphamide or corticosteroids. The authors concluded that 77.3% of those receiving therapy remitted, and 67% of those who were not in remission following the first regimen were in remission after a second course of the same regimen.<ref name="pmid8808107">{{cite journal| author=Nachman PH, Hogan SL, Jennette JC, Falk RJ| title=Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. | journal=J Am Soc Nephrol | year= 1996 | volume= 7 | issue= 1 | pages= 33-9 | pmid=8808107 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8808107 }} </ref>
| | ==[[Rapidly progressive glomerulonephritis risk factors|Risk Factors]]== |
|
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| ====Glucocorticoids==== | | ==[[Rapidly progressive glomerulonephritis screening|Screening]]== |
|
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|
| =====Regimen===== | | ==[[Rapidly progressive glomerulonephritis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| ''Follow step 1, then 2, then 3''<br>
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| '''1. Methylprednisone'''
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| *''Route'': Intravenous (IV)
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| *''Dose'': 7 mg/kg/d at a maximum dose of 1 g
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| *''Duration'': 3 days
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| '''2. Prednisone'''
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| *''Route'': Per Os (PO)
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| *''First Dose'': 1 mg/kg/d at a maximum dose of 80 mg for 3 weeks
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| *''Second Dose'': 2 mg/kg/d at a maximum dose of 120 mg for 3 months
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| '''3. Taper'''
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| *Taper patient off steroids by deceasing 25% of prednisone dose every 4 weeks until patient stops
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|
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|
| ====Immunosuppressive Therapy==== | | ==Diagnosis== |
| | [[Rapidly progressive glomerulonephritis diagnostic study of choice|Diagnostic study of choice]] | [[Rapidly progressive glomerulonephritis history and symptoms|History and Symptoms]] | [[Rapidly progressive glomerulonephritis physical examination|Physical Examination]] | [[Rapidly progressive glomerulonephritis laboratory findings|Laboratory Findings]] | [[Rapidly progressive glomerulonephritis electrocardiogram|Electrocardiogram]] | [[Rapidly progressive glomerulonephritis x ray|X-Ray Findings]] | [[Rapidly progressive glomerulonephritis echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Rapidly progressive glomerulonephritis CT scan|CT-Scan Findings]] | [[Rapidly progressive glomerulonephritis MRI|MRI Findings]] | [[Rapidly progressive glomerulonephritis other imaging findings|Other Imaging Findings]] | [[Rapidly progressive glomerulonephritis other diagnostic studies|Other Diagnostic Studies]] |
|
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|
| =====Regimen===== | | ==Treatment== |
| | | [[Rapidly progressive glomerulonephritis medical therapy|Medical Therapy]] | [[Rapidly progressive glomerulonephritis surgery|Surgery]] | [[Rapidly progressive glomerulonephritis primary prevention|Primary Prevention]] | [[Rapidly progressive glomerulonephritis secondary prevention|Secondary Prevention]] | [[Rapidly progressive glomerulonephritis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Rapidly progressive glomerulonephritis future or investigational therapies|Future or Investigational Therapies]] |
| #Cyclophosphamide
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| | |
| ##Route: IV or PO
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| ##Dose
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| ###IV: 0.5 g/m2, at a maximum dose of 1g/m2. Dose adjusted to a 2-week leukocyte nadir count goal 3000-4000/uL.
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| ###PO: 2 mg/kg. Dose adjusted to a 2-week leukocyte nadir count goal 3000-4000/uL
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| Normal 0 false false false EN-US JA X-NONE Addition of cyclophosphamides for patients with RPGN is necessary to prevent relapse, which is commonly seen in patients receiving glucocorticoids alone and leads to remission in more than 80% of the cases.<ref name="pmid8808107">{{cite journal| author=Nachman PH, Hogan SL, Jennette JC, Falk RJ| title=Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. | journal=J Am Soc Nephrol | year= 1996 | volume= 7 | issue= 1 | pages= 33-9 | pmid=8808107 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8808107 }} </ref>
| |
| The studies excluded patients with granulomatosis with polyangiitis (formerly Wegener granulomatosis). In cases of granulomatosis with polyangiitis (formerly Wegener granulomatosis), oral therapy has been preferred by some experts. IV cyclophosphamide generally have less total dose and thus less toxicity than its oral counterpart.
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| | |
| #Azathioprine
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| | |
| PO azathioprine (AZA) has been recommended by some experts to replace cyclophosphamide after an initial 3-month induction period of cyclophosphamide.
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| | |
| ##Route: PO
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| ##Dose: 2 mg/kg 1 tablet
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| ##Duration: 6-12 months
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| #Methotrexate
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| | |
| Methotrexate (MTX) has been used in mild forms of granulomatosis with polyangiitis (formerly Wegener granulomatosis) as a replacement for cyclophosphamide. (17873756) In more severe forms, it has been used following short-term induction therapy with cyclophosphamide.(17873756). Villa-Forte and colleagues enrolled 82 patients in 2007; 70% of those had severe disease on admission and required cyclophosphamide for remission induction. Severity was based on clinical and histopathological findings: pulmonary hemorrhage, neurological abnormalities, need for dialysis, serum creatinine > 2 mg/dL, and RPGN. 72% of patients were in remission after 1 year, and 91% reached remission at any duration. Relapse rates were as high as 66% within 2 years, most of which responded to reinitiation of therapy.
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| | |
| ''Induction of Remission for Severe Cases:''
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| *Cyclophosphamide
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| **Route: PO
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| **Dose: 2 mg/kg adjusted for renal function and WBC count
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| *Prednisone
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| **Route: PO
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| **Dose: 1 mg/kg
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| ''Initial Treatment:''
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| *Methotrexate (MTX)
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| **Route: PO
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| **Dose: 15 mg/wk increased over 4-8 weeks to 25 mg/wk if tolerated and if necessary
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| **Duration: At least 2 years
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| *Prednisone
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| **Route: PO
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| **Dose: 1 mg/kg/d to gradually decrease as long as no documented disease recurrence
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| #Rituximab
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| The RITUXVAS (Randomized trial of Rituximab vs. Cyclophosphamide in ANCA-Associated Vasculitis) and RAVE (Rituximab in ANCA-Associated Vasculitis Trial) trials<ref name="pmid22095945">{{cite journal| author=Berden AE, Jones RB, Erasmus DD, Walsh M, Noël LH, Ferrario F et al.| title=Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody-associated glomerulonephritis after rituximab therapy. | journal=J Am Soc Nephrol | year= 2012 | volume= 23 | issue= 2 | pages= 313-21 | pmid=22095945 | doi=10.1681/ASN.2011040330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22095945 }} </ref> showed in 2012 that anti-B therapy by rituximab, a chimeric anti-human CD20 monoclonal antibody, may improve renal survival in patients with vasculitis and positive ANCA and had renal impairment, including patients with granulomatosis with polyangiitis (formerly Wegener granulomatosis).<ref name="pmid22095945">{{cite journal| author=Berden AE, Jones RB, Erasmus DD, Walsh M, Noël LH, Ferrario F et al.| title=Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody-associated glomerulonephritis after rituximab therapy. | journal=J Am Soc Nephrol | year= 2012 | volume= 23 | issue= 2 | pages= 313-21 | pmid=22095945 | doi=10.1681/ASN.2011040330 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22095945 }} </ref> The findings were based on earlier reports of improved outcome using rituximab.
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| ''Regimen:''
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| *Rituximab:
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| **Route: IV
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| **Dose: 375 mg/m2
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| **Duration: Once weekly 4 consecutive weeks
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| *Cyclophosphamide
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| **Route: IV
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| **Dose: 15 mg/kg
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| **Duration: Co-administed with 1st and 3rd rituximab doses
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| *Methylprednisolone
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| **Route: IV and PO
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| **Dose: 1g IV then followed by daily low-dose oral corticosteroids for maintenance
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| #Other
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| | |
| Normal 0 false false false EN-US JA X-NONE Some medications have never been studied. However, they have been shown to be effective based on findings in case reports. These medications include:
| |
| | |
| ##IV immunoglobulins (Igs)
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| ##Antithymocyte antibody
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| ##Monoclonal antibodies to CD4
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| ##Monoclonal antibodies to CD25
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| ===Plasma Exchange===
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| | |
| Indications of plasma exchange:
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| | |
| *Removal of circulating auto-antibodies in patients with anti-GBM antibody disease
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| | |
| *Patients with high risk of renal failure
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| *Patients with serum creatinine > 2.3 mg/dL<ref name="pmid9241619">{{cite journal| author=Levy JB, Pusey CD| title=Still a role for plasma exchange in rapidly progressive glomerulonephritis? | journal=J Nephrol | year= 1997 | volume= 10 | issue= 1 | pages= 7-13 | pmid=9241619 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9241619 }} </ref>
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| *Patients who do not respond to pharmacologic therapy
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| *Patients diagnosed with pauci-immune crescenteric glomerulonephriits with ESRD and need dialysis<ref name="pmid9241619">{{cite journal| author=Levy JB, Pusey CD| title=Still a role for plasma exchange in rapidly progressive glomerulonephritis? | journal=J Nephrol | year= 1997 | volume= 10 | issue= 1 | pages= 7-13 | pmid=9241619 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9241619 }} </ref>
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| The true value of plasma exchange has been demonstrated by a few small trials in secondary analysis.<ref name="pmid9744974">{{cite journal| author=Hricik DE, Chung-Park M, Sedor JR| title=Glomerulonephritis. | journal=N Engl J Med | year= 1998 | volume= 339 | issue= 13 | pages= 888-99 | pmid=9744974 | doi=10.1056/NEJM199809243391306 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9744974 }} </ref> The real indications and benefit to risk ratio of plasma exchange are yet to be elucidated.
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| ==Case Studies== | | ==Case Studies== |
| [[Rapidly progressive glomerulonephritis case study one|Case #1]] | | [[Rapidly progressive glomerulonephritis case study one|Case #1]] |
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| ==References==
| | [[Category: (name of the system)]] |
| <references/>
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| {{Nephrology}}
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| [[Category:Kidney diseases]] | |
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| [[de:Rasch progressive Glomerulonephritis]]
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| {{WH}}
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| {{WS}}
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