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| __NOTOC__ | | __NOTOC__ |
| {{Infobox_Disease
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| | Name = {{PAGENAME}}
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| | DiseasesDB = 3165
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| | ICD10 = N00-N08 with .7 suffix
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| | ICD9 =
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| | ICDO =
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| | OMIM =
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| | MedlinePlus =
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| | eMedicine_mult = {{eMedicine2|med|890}} |
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| | MeshID =
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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. | | |
| | ==[[Rapidly progressive glomerulonephritis historical perspective|Historical Perspective]]== |
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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]]== |
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| ==[[Rapidly progressive glomerulonephritis risk factors|Risk Factors]]== | | ==[[Rapidly progressive glomerulonephritis risk factors|Risk Factors]]== |
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| | ==[[Rapidly progressive glomerulonephritis screening|Screening]]== |
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| ==[[Rapidly progressive glomerulonephritis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== | | ==[[Rapidly progressive glomerulonephritis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| ==Diagnosis== | | ==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]] |
| [[Rapidly progressive glomerulonephritis diagnostic criteria|Diagnostic Criteria]] | [[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 CT|CT]] | [[Rapidly progressive glomerulonephritis MRI|MRI]] | [[Rapidly progressive glomerulonephritis ultrasound|Ultrasound]] | [[Rapidly progressive glomerulonephritis other imaging findings|Other Imaging Findings]] | [[Rapidly progressive glomerulonephritis other diagnostic studies|Other Diagnostic Studies]] | |
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| ==Treatment== | | ==Treatment== |
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| [[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]] | | [[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]] |
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| [[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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