Rapidly progressive glomerulonephritis medical therapy: Difference between revisions

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==Overview==
==Overview==
Treatment for rapidly progressive glomerulonephritis include supportive treatment and specific treatment. Supportive treatment is to treat the infection if there is one, correct the volume status with dialysis if required and smoking cessation. Specific therapy focuses on induction and maintenance of [[Remission (medicine)|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 focuses on to induce and then maintain the remissio
Treatment for rapidly progressive glomerulonephritis include supportive treatment and specific treatment. Supportive treatment is to treat the infection if there is one, correct the volume status with dialysis if required and smoking cessation. Specific therapy focuses on induction and maintenance of [[Remission (medicine)|remission]]. Medical therapy focuses on to induce and then maintain the [[Remission (medicine)|remission]]. Two pharmacologic agents used for induction of [[Remission (medicine)|remission]] in patients with rapidly progressive glomerulonephritis are [[glucocorticoids]] (high dose) and [[cyclophosphamide]]. [[Cyclophosphamide]] is necessary to prevent [[relapse]]. [[Azathioprine]] or [[methotrexate]] is used for maintenance therapy. [[Azathioprine]] (AZA) is recommended after a 3-month induction period of [[cyclophosphamide]].Indications of plasma exchange include, anti-GBM antibody disease, antineutrophil cytoplasmic antibody ([[Anti-neutrophil cytoplasmic antibody|ANCA]])-associated rapidly progressive glomerulonephritis, patients with high risk of [[renal failure]], patients with serum [[creatinine]] > 2.3 mg/dL, those patients who do not respond to pharmacologic therapy, and patients diagnosed with pauci-immune crescenteric glomerulonephriits with [[end stage renal disease]] and need [[dialysis]]. Risk and complications of plasma exchange are transient fall in blood-clotting factors, mild prolongation of prothrombin and activated partial thromboplastin times. Clinically significant bleeding is rare but a coagulation screen should be undertaken before surgery or organ biopsy is performed. Other risks include haematomas at venepuncture/line insertion sites, vasovagal episodes with fainting, fluid overload or under-replacement, and allergic or anaphylactic reactions due to plasma infusion.
* Addition of cyclophosphamide is necessary to prevent relapse  
* Relapse is commonly seen in patients getting glucocorticoids aloneIt is important to prevent relapses,
* Azathioprine or methotrexate is used for maintenance therapy  
* Azathioprine (AZA) is recommended after a 3-month induction period of cyclophosphamide.  
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==Medical therapy==
==Medical therapy==
Medical therapy focuses on  to induce and then maintain the remission.
Medical therapy focuses on  to induce and then maintain the [[Remission (medicine)|remission]]


===Pharmacologic Therapy===
===Pharmacologic Therapy===
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=== Induction of remission ===
=== Induction of remission ===
Two pharmacologic agents that are used for induction of remission in patients with rapidly progressive glomerulonephritis are;
Two pharmacologic agents that are used for induction of remission in patients with rapidly progressive glomerulonephritis are;
* Glucocorticoids (high dose)
* [[Glucocorticoids]] (high dose)
* Cyclophosphamide
* [[Cyclophosphamide]]


======Glucocorticoids<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>======
======Glucocorticoids<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>======
<blockquote>Preffered regimen (1) : Methylprednisone, 7 mg/kg/d,  Intravenous at a maximum dose of 1 g for 3 days</blockquote><blockquote>preffered regimen (2) :Prednisone, 1 mg/kg/d ,PO at a maximum dose of 80 mg for 3 weeks.</blockquote><blockquote>Then 2 mg/kg/d, PO at a maximum dose of 120 mg for 3 months'''.'''</blockquote><blockquote>Then taper patient off steroids by deceasing 25% of prednisone dose every 4 weeks until patient stops</blockquote>
* Preffered regimen (1) : [[Methylprednisolone]], 7 mg/kg/d,  Intravenous at a maximum dose of 1 g for 3 days
 
* preffered regimen (2) :[[Prednisone]], 1 mg/kg/d ,PO at a maximum dose of 80 mg for 3 weeks.
<blockquote>Then 2 mg/kg/d, PO at a maximum dose of 120 mg for 3 months'''.'''</blockquote><blockquote>Then taper patient off steroids by deceasing 25% of [[prednisone]] dose every 4 weeks until patient stops</blockquote>


======Immunosuppressive Therapy======
======Immunosuppressive Therapy======
* Preffered regimen(1) : Cyclophosphamide:''IV'': 15 mg/kg (maximum dose: 1,200 mg) every 2 weeks for 3 doses,
* Preffered regimen(1) : [[Cyclophosphamide]]:''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<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>
** followed by maintenance pulses of 15 mg/kg IV (maximum dose: 1,200 mg) every 3 weeks until  after remission is achieved<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>
* Preffered regimen(2) :Cyclophosphamide ''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) :[[Cyclophosphamide]] ''PO'':1.5- 2 mg/kg/day until remission is achieved, followed by 1.5 mg/kg/day for 3 more months.
* Preffered regimen(3) :Rituximab IV, 375 mg/m2 once weekly, 4 dose  
* Preffered regimen(3) [[:Rituximab]] IV, 375 mg/m2 once weekly, 4 dose  
'''Maintenance of Remission'''
'''Maintenance of Remission'''
*Preffered regimen (1) , Azathioprine, PO, 2 mg/kg for 6-12 months
*Preffered regimen (1) , [[Azathioprine]], PO, 2 mg/kg for 6-12 months


* Preffered regimen (2) :Methotrexate, PO,20mg per week for 12 months.
* Preffered regimen (2) :[[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)
*Antithymocyte antibody
*Antithymocyte antibody
*Monoclonal antibodies to CD4
*[[Monoclonal antibodies]] to CD4
*Monoclonal antibodies to CD25
*[[Monoclonal antibodies|Monoclonal antibodies to CD25]]


===Plasma Exchange===
===Plasma Exchange===


Indications of plasma exchange:
Indications of plasma exchange<ref name="pmid29503131">{{cite journal |vauthors=Apaydin S |title=The treatment of ANCA-associated rapidly-progressive glomerulonephritis and Goodpasture syndrome with therapeutic apheresis |journal=Transfus. Apher. Sci. |volume=57 |issue=1 |pages=8–12 |date=February 2018 |pmid=29503131 |doi=10.1016/j.transci.2018.02.007 |url=}}</ref>:


*Removal of circulating auto-antibodies in patients with anti-GBM antibody disease
*Anti-GBM antibody disease
*Antineutrophil cytoplasmic antibody ([[Anti-neutrophil cytoplasmic antibody|ANCA]])-associated rapidly progressive glomerulonephritis


*Patients with high risk of renal failure
*Patients with high risk of [[renal failure]]


*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>
*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>
*Patients who do not respond to pharmacologic therapy
*Patients who do not respond to pharmacologic therapy


*Patients diagnosed with pauci-immune crescenteric glomerulonephriits with end stage renal disease 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 [[end stage renal disease]] 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>
 
Risk and complications of plasma exchange
*Transient fall in [[Clotting factors|blood-clotting factors]]
*Mild prolongation of [[prothrombin time]] and [[Partial thromboplastin time|activated partial thromboplastin times]].
*[[Hematoma|Haematomas]] at venepuncture/line insertion sites
*[[Vasovagal syncope|Vasovagal]] episodes with fainting
*Fluid overload or under-replacement
*[[Allergy|Allergic]] or [[Anaphylaxis|anaphylactic]] reactions due to plasma infusion.


==References==
==References==

Latest revision as of 19:41, 31 July 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Accociate editor-in-Chief: Nazia Fuad M.D.

Overview

Treatment for rapidly progressive glomerulonephritis include supportive treatment and specific treatment. Supportive treatment is to treat the infection if there is one, correct the volume status with dialysis if required and smoking cessation. Specific therapy focuses on induction and maintenance of remission. Medical therapy focuses on to induce and then maintain the remission. Two pharmacologic agents used for induction of remission in patients with rapidly progressive glomerulonephritis are glucocorticoids (high dose) and cyclophosphamide. Cyclophosphamide is necessary to prevent relapse. Azathioprine or methotrexate is used for maintenance therapy. Azathioprine (AZA) is recommended after a 3-month induction period of cyclophosphamide.Indications of plasma exchange include, anti-GBM antibody disease, antineutrophil cytoplasmic antibody (ANCA)-associated rapidly progressive glomerulonephritis, patients with high risk of renal failure, patients with serum creatinine > 2.3 mg/dL, those patients who do not respond to pharmacologic therapy, and patients diagnosed with pauci-immune crescenteric glomerulonephriits with end stage renal disease and need dialysis. Risk and complications of plasma exchange are transient fall in blood-clotting factors, mild prolongation of prothrombin and activated partial thromboplastin times. Clinically significant bleeding is rare but a coagulation screen should be undertaken before surgery or organ biopsy is performed. Other risks include haematomas at venepuncture/line insertion sites, vasovagal episodes with fainting, fluid overload or under-replacement, and allergic or anaphylactic reactions due to plasma infusion.

.

Medical therapy

Medical therapy focuses on 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;

Glucocorticoids[1]
  • Preffered regimen (1) : Methylprednisolone, 7 mg/kg/d, Intravenous at a maximum dose of 1 g for 3 days
  • preffered regimen (2) :Prednisone, 1 mg/kg/d ,PO at a maximum dose of 80 mg for 3 weeks.

Then 2 mg/kg/d, PO at a maximum dose of 120 mg for 3 months.

Then taper patient off steroids by deceasing 25% of prednisone dose every 4 weeks until patient stops

Immunosuppressive Therapy
  • Preffered regimen(1) : Cyclophosphamide: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[2]
  • Preffered regimen(2) :Cyclophosphamide PO:1.5- 2 mg/kg/day until remission is achieved, followed by 1.5 mg/kg/day for 3 more months.
  • Preffered regimen(3) Rituximab IV, 375 mg/m2 once weekly, 4 dose

Maintenance of Remission

  • Preffered regimen (1) , Azathioprine, PO, 2 mg/kg for 6-12 months
  • Preffered regimen (2) :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:

Plasma Exchange

Indications of plasma exchange[3]:

  • Anti-GBM antibody disease
  • Antineutrophil cytoplasmic antibody (ANCA)-associated rapidly progressive glomerulonephritis
  • Patients with serum creatinine > 2.3 mg/dL[4]
  • Patients who do not respond to pharmacologic therapy

Risk and complications of plasma exchange

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. ↑ Apaydin S (February 2018). "The treatment of ANCA-associated rapidly-progressive glomerulonephritis and Goodpasture syndrome with therapeutic apheresis". Transfus. Apher. Sci. 57 (1): 8–12. doi:10.1016/j.transci.2018.02.007. PMID 29503131.
  4. ↑ 4.0 4.1 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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