Rapidly progressive glomerulonephritis medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Rapidly progressive glomerulonephritis}}
{{Rapidly progressive glomerulonephritis}}
{{CMG}} Accociate editor-in-Chief: Nazia Fuad, M.D  
* {{CMG}} Accociate editor-in-Chief: Nazia Fuad, M.D  


==Overview==
==Overview==
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====Immunosuppressive Therapy====
====Immunosuppressive Therapy====
'''Cyclophosphamide'''
preffered regimen(1) Cyclophosphamide:<ref name="pmid19451574">{{cite journal |vauthors=de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO |title=Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial |journal=Ann. Intern. Med. |volume=150 |issue=10 |pages=670–80 |date=May 2009 |pmid=19451574 |doi= |url=}}</ref>
* Addition of cyclophosphamide is necessary to prevent relapse  
* Addition of cyclophosphamide is necessary to prevent relapse  
* relapse is commonly seen in patients getting glucocorticoids alone
* relapse is commonly seen in patients getting glucocorticoids alone
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* Can be given intravenously or orally
* Can be given intravenously or orally


* ''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.
* ''IV'': 15 mg/kg (maximum dose: 1,200 mg) every 2 weeks for 3 doses, followed by maintenance pulses of 15 mg/kg IV (maximum dose: 1,200 mg) every 3 weeks until  after remission is achieved
* ''PO'': 2 mg/kg. Dose adjusted to a 2-week leukocyte nadir count goal 3000-4000/uL
* ''PO'':1.5- 2 mg/kg/day until remission is achieved, followed by 1.5 mg/kg/day for 3 more months.
'''Azathioprine'''<br>PO azathioprine (AZA) has been recommended by some experts to replace cyclophosphamide after an initial 3-month induction period of cyclophosphamide.
* Preffered regimen(2) Rituximab IV, 375 mg/m2 once weekly, 4 dose
*''Route'': PO
'''Maintenance of Remission'''  
*''Dose'': 2 mg/kg
* It is important to prevent relapses,
*''Duration'': 6-12 months
* Azathioprine or methotrexate is used for maintenance therapy


'''Methotrexate'''
* '''Azathioprine'''  
* Methotrexate (MTX) has been used in mild forms of granulomatosis with polyangiitis (formerly Wegener granulomatosis) as a replacement for cyclophosphamide.<ref name="pmid17873756">{{cite journal| author=Villa-Forte A, Clark TM, Gomes M, Carey J, Mascha E, Karafa MT et al.| title=Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12-year single-practice experience. | journal=Medicine (Baltimore) | year= 2007 | volume= 86 | issue= 5 | pages= 269-77 | pmid=17873756 | doi=10.1097/MD.0b013e3181568ec0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17873756 }} </ref>
* Azathioprine (AZA) is recommended after a 3-month induction period of cyclophosphamide.  
* In more severe forms, it has been used following short-term induction therapy with cyclophosphamide.<ref name="pmid17873756">{{cite journal| author=Villa-Forte A, Clark TM, Gomes M, Carey J, Mascha E, Karafa MT et al.| title=Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12-year single-practice experience. | journal=Medicine (Baltimore) | year= 2007 | volume= 86 | issue= 5 | pages= 269-77 | pmid=17873756 | doi=10.1097/MD.0b013e3181568ec0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17873756 }} </ref> 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.
''Induction of Remission for Severe Cases:''
*Cyclophosphamide
**''Route'': PO
**''Dose'': 2 mg/kg adjusted for renal function and WBC count
*Prednisone
**''Route'': PO
**''Dose'': 1 mg/kg
''Initial Treatment:''
*Methotrexate (MTX)
**''Route'': PO
**''Dose'': 15 mg/wk increased over 4-8 weeks to 25 mg/wk if tolerated and if necessary
**''Duration'': At least 2 years
*Prednisone
**''Route'': PO
**''Dose'': 1 mg/kg/d to gradually decrease as long as no documented disease recurrence


'''Rituximab'''<br>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.
*PO, 2 mg/kg for 6-12 months
''Regimen:''
Rituximab:
*''Route'': IV
*''Dose'': 375 mg/m2
*''Duration'': Once weekly 4 consecutive weeks
Cyclophosphamide
*''Route'': IV
*''Dose'': 15 mg/kg
*''Duration'': Co-administed with 1st and 3rd rituximab doses
Methylprednisolone
*''Route'': IV and PO
*''Dose'': 1g IV then followed by daily low-dose oral corticosteroids for maintenance


'''Methotrexate'''
* PO,20mg per week for 12 months.
'''Other'''<br>Some medications have never been studied. However, they have been shown to be effective based on findings in case reports. These medications include:
'''Other'''<br>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)
*IV immunoglobulins (Igs)
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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>
*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>
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.


==References==
==References==

Revision as of 15:27, 20 July 2018

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Overview

Rapidly progressive glomerulonephritis as obvious from its name is a syndrome that rapidly progresses to acute renal failure so early diagnosis by renal biopsy and serology is very important. The treatment should be initiated as soon as possible to minimize the irreversible renal injury. treatment include supportive treatment and specific treatment. supportive treatment is to treat the infection if there is one, correct the volume status with dislysis if required and smoking cessation . Specific therapy focuses on induction and maintenance of remission . Emperic therapy should be started immediatly if the disease is very severe or if renal biopsy result is delayed. After the diagnosis is established, specific therapy can be started according to subtype of the disease.

Medical therapy

Medical therapy focuses to induce and then maintain the remission.

Pharmacologic Therapy

Induction of remission

Two pharmacologic agents that are used for induction of remission in patients with rapidly progressive glomerulonephritis are;

  • Corticosteroids(high dose)
  • Cyclophosphamide

Glucocorticoids[1]

1. Methylprednisone

  • Intravenous (IV) 7 mg/kg/d at a maximum dose of 1 g for

2. Prednisone

  • 1 mg/kg/d ,PO at a maximum dose of 80 mg for 3 weeks
  • 2 mg/kg/d at a maximum dose of 120 mg for 3 months.
  • Taper patient off steroids by deceasing 25% of prednisone dose every 4 weeks until patient stops

Immunosuppressive Therapy

preffered regimen(1) Cyclophosphamide:[2]

  • Addition of cyclophosphamide is necessary to prevent relapse
  • relapse is commonly seen in patients getting glucocorticoids alone
  • Can be given intravenously or orally
  • IV: 15 mg/kg (maximum dose: 1,200 mg) every 2 weeks for 3 doses, followed by maintenance pulses of 15 mg/kg IV (maximum dose: 1,200 mg) every 3 weeks until after remission is achieved
  • PO:1.5- 2 mg/kg/day until remission is achieved, followed by 1.5 mg/kg/day for 3 more months.
  • Preffered regimen(2) Rituximab IV, 375 mg/m2 once weekly, 4 dose

Maintenance of Remission

  • It is important to prevent relapses,
  • Azathioprine or methotrexate is used for maintenance therapy
  • Azathioprine
  • Azathioprine (AZA) is recommended after a 3-month induction period of cyclophosphamide.
  • PO, 2 mg/kg for 6-12 months

Methotrexate

  • PO,20mg per week for 12 months.

Other
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)
  • Antithymocyte antibody
  • Monoclonal antibodies to CD4
  • Monoclonal antibodies to CD25

Plasma Exchange

Indications of plasma exchange:

  • Removal of circulating auto-antibodies in patients with anti-GBM antibody disease
  • Patients with high risk of renal failure
  • Patients with serum creatinine > 2.3 mg/dL[3]
  • Patients who do not respond to pharmacologic therapy
  • Patients diagnosed with pauci-immune crescenteric glomerulonephriits with ESRD and need dialysis[3]

References

  1. Nachman PH, Hogan SL, Jennette JC, Falk RJ (1996). "Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis". J Am Soc Nephrol. 7 (1): 33–9. PMID 8808107.
  2. de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO (May 2009). "Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial". Ann. Intern. Med. 150 (10): 670–80. PMID 19451574.
  3. 3.0 3.1 Levy JB, Pusey CD (1997). "Still a role for plasma exchange in rapidly progressive glomerulonephritis?". J Nephrol. 10 (1): 7–13. PMID 9241619.

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