KDIGO 2021- ANCA vasculitis management

 Check out the latest update in 2021 of treatment of ANCA vasculitis at KDIGO

1. Kidney biopsy is highly recommended in most cases

2. For induction- they recommend that steroids in combination with cyclophosphamide or rituximab be used for new onset AAV. 

3. For patients with GFR that is declining of crt >4.0mg/dl, there is limited data for rituximab based treatment. The combination of cyclo+ ritux can be used in that setting - RITUXIVAS protocol.

 

    4. When to do cytoxan vs rituxan?

5. Reduced dose steroids have shown similar results as high dose steroids( PEXIVAS trial)

6. Dosing for Rituxan and cyclophosphamide

7. Consider plasma exchange with crt >5.7 requiring dialysis or with rapid rise in crt and diffuse alveolar hemorrhage with hypoxemia or overlap syndrome with Anti GBM

8. Maintenance therapy

KDIGO 2021- GN Management Guidelines: MPGN

 The recent KDIGO guidelines are here

One of the most important changes is getting rid of the MPGN1, 2 and 3 classification and using the novel pathophysiology based classification and recognizing that MPGN is a pattern of injury

The diagnosis of the C3GN and DDD is tough and requires the extensive assays and testing on complement cascade.

Treatment really depends on the cause.

For idiopathic causes of MPGN pattern of injury, consider a limited course of steroids
For RPGN of idiopathic cause, steroids + cyclophosphamide
For MPGN with low GFR< 30, supportive treatment only

For C3GN, and no signs of MGRS, and failed MMF and steroids, eculizumab should be considered
 

KDIGO 2021- GN Management Guidelines: Infection associated GN

The recent KDIGO update 2021

Bacterial infection associated GN- 4 main types

Post infectious GN
Shunt nephritis
Endocarditis associated GN
IgA dominant infection related GN

All 4 of them usually have low complement levels.  No RCT for treatment
Antibiotics or surgical treatment for respective infections

Viral infection associated GN- 

Hep B- Hep B DNA >2000 IU/ml, need treatment with anti Hep B agent and no avoid immunosuppressive agents as can accelerate the viral infection.

HIV disease: HAART therapy is recommended for all HIVAN and HIVICK diseases.

Hep C associated GN:  A kidney biopsy should be performed in HCV-positive patients with clinical evidence of glomerular disease. Patients with mild or moderate forms of HCV-associated GN with stable kidney function and/or non-nephrotic proteinuria should be managed first with a DAA regimen. Patients with severe cryoglobulinemia or severe glomerular disease induced by HCV (i.e., nephrotic proteinuria or rapidly progressive kidney failure) should be treated with immunosuppressive agents (generally with rituximab as the first-line agent) and/or plasma exchange in addition to DAA therapies. Patients with HCV-related glomerular disease who do not respond to or are intolerant of antiviral treatment should also be treated with immunosuppressive agents.

KDIGO 2021- GN Management Guidelines: FSGS

 FSGS has been the waste basket diagnosis for years. KDIGO finally has adopted the primary vs secondary FSGS way of thinking to make it easier to treat FSGS and diagnose the 99% of the secondary causes. Check out these amazing figures from the supplement

Treatment wise:  If primary FSGS- steroids 1mg/kg dosing for 4 weeks and then taper over 6 months

If not, then try CNI( cyclosporine vs tacrolimus)- goal 100-175 or 5-10 range for each drug
After 6 months, no response- considering MMF, anti cd20 agents but data on both is small. 

If secondary cause- treat the secondary cause or conservative management. SGLT2i may make it there next iteration. 

KDIGO 2021: GN Management Guidelines: Membranous Nephropathy

MN management has changed in 2020 onwards thanks to two trials published in 2020-2021 that showed that cyclophosphamide/steroids is superior and rituximab is not the main player yet. 
The figures below summarize the main points of the GN 2021 KDIGO update 

KDIGO 2021: GN Management Guidelines: IgA nephropathy

 

The three figures from the recent KI GN update 2021 summarizes IgA nephropathy.

Basically, At this point, given negative studies for steroids, only thing we have that has strong evidence is conservative management. Interestingly, SGLT2i did not make it to the guidelines.  ACEI/ARB+ SGLT2i might be the best treatment options we have for IgA Nephropathy. 

The one place where immunosuppressive meds will help is Crescentic IgA nephropathy and IgA with MCD. 

Here is the final table on all meds and their data from KDIGO

Does immunosuppressive meds help IgA nephropathy? Do we await the budesonide directed therapy approval, do we await more supportive agents such as ET1 antagonists or Aldo antagonists? Time will tell. Till then, IgA nephropathy is still the hardest GN to treat as we don't have clear options for treating the pathophysiology of the disease. 

KDIGO Guidelines for Glomerular Diseases: ANTI GBM disease

ANTI GBM disease based GN
KDIGO guidelines from Kidney International

1. Initiating cyclophos + steroids + plasmapheresis in all anti GBM GN except those who are on dialysis at presentation and have 100% crescents in a good sample and do not have pulmonary hemorrhage( 1B)
2. No maintenance therapy is needed for anti GBM GN( 1 D)
3. Defer kidney transplantation after anti GBM GN until anti GBM antibodies have been undetected for minimum of 6 months ( not graded)

For full details see: http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201227a.pdf

KDIGO Glomerular Disease Guidelines: ANCA vasculitis

Pauci immune focal and segmental necrotizing GN guidelines by KDIGO

1. Initial treatment( cyclophosphamide and steroids) ( Grade 1A)
2. Rituximab and steroisd be used as alternative when above is contraindicated ( Grade 1B)
3. Plasmapheresis be added if there is rapid rise in crt or on dialysis (Grade 1C)
4. Plasmapheresis be added for pulmonary hemorrhage( Grade 2C)
5. Overlap diseases of ANCA and anti GBM - use plasmapheresis (Grade 2D).
6. If dialysis dependent for 3 months, stop cyclophosphamide if no extra renal manifestations( Grade 2C).
7. Maintenance therapy should be used if achieved remission ( Grade 1B)
8. Continue maintenance therapy for 18 months who achieved remission ( Grade 2D).
9. No maintenance in dialysis dependence and no extra renal manifestations ( Grade 1C)
10. Azathioprine is first choice at 1-2mg/kg/day orally as maintenance therapy ( Grade 1B)
11. MMF up to 1mg BID if above not possible( Grade 2C)
12. Bactrim use as adjunct( Grade 2B)
13. Methotrexate for maintenance  if intolerant to azathioprine and MMF if GFR >60 ( Grade 1C)
14. Etanercept should not be used as adjunct therapy ( Grade 1A).
15. Severe Relapse should be treated just like initial disease ( Grade 1C)
16. Other relapses should mean to re starting maintenance therapy ( Grade 2C)
17. Resistant disease:- Rituximab should be used ( 1C), IVIG( 2C) and plasmapheresis (2D)
18. ANCA titer alone should not change therapy ( Grade 2D)
19. Delaying transplantation till complete extrarenal manifestations have been in remission for 12 months( Grade 1C)
20. Not delaying transplantation for those in complete remission but still ANCA positive( Grade 1C).

For full details: http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201226a.pdf
Image source: UNC kidney center website

KDIGO Guidelines for Glomerular Diseases: LUPUS NEPHRITIS

KDIGO is publishing guidelines in Glomerular Diseases in Kidney International

Topic: Lupus Nephritis


1. Class I LN be treated by extra renal manifestations rather than renal ( 2D)
2. Class II LN - No specific renal treatment if <1gm of proteinuria( 2D)
3. Class II LN- Proteinuria >3gm be treated with steroids or CNI like a minimal change disease (2D)
4. Class III LN- Steroids (1A) + either cyclophosphamide or MMF (1B)
5. Class III LN- if first option is not working to change to the alternative option above in 3 months (2D)
6. Class III Maintenance - Imuran or MMF ( 1B) and low dose steroids for one year (2D)
7. Class IV - same as Class III as above
8. Class V- If normal kidney function, and non nephrotic range proteinuria, conservative management and treatment dictated by extra renal manifestations( 2D)
9. Class V- persistent proteinuria:- steroids + cyclophosphamide and or CNI or MMF or Imuran ( 2D)
10. All patients should be on hydroxycholoroquine (2C)

For other detailed recommendations look at http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201225a.pdf

KDIGO Guidelines for Glomerular Diseases: HSP

KDIGO released guidelines for glomerular diseases in Kidney International this year.

Topic: Henoch Schonlein Purpura Nephritis


1. HSP nephritis and persistant proteinuria of 0.5-1g/d be treated with ACEI or ARB( Grade 2D)
2. If proteinuria is >1gm, to be treated just like IgA nephropathy with steroids for 6 months
3. Steroids should not be used to prevent HSP Nephritis ( Grade 1B)
4. Crescentic HSP Nephritis should be treated with Steroids and alkylatic agents( Grade 2D)

For full article , look at
http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201224a.pdf

KDIGO Glomerular Diseases Guidelines: IgA Nephropathy

KDIGO just released guidelines for GN in a supplement in KI

Topic: IgA Nephropathy


1. Long term ACEI or ARB for proteinuria >1gm( Grade 1B)
2. ACEI or ARB treatment if proteinuria between 0.5gm to 1gm ( Grade 2D)
3. Patients with persistent proteinuria >1g/d despite 3-6 months of conservative management, and GFR >50ml/min get 6 month course of steroids (Grade 2C)
4. Not use cyclophosphamide or aza in IgA unless there is RPGN with crescents ( Grade 2D)
5. Not use cytotoxic agents for GFR< 30ml/min unless there is RPGN ( Grade 2C)
6. Fish oil is recommended if proteinuria is >1gm/d ( Grade 2D).
7. Not using antiplatelet agents in IgA( Grade 2C).
8. Minimal change with IgA:- treat like minimal change ( Grade 2B)
9. AKI associated with MCD:- perform a kidney biopsy in AKI with macroscopic hematuria if no change in renal function for 5 days
10. General supportive care for AKI in IgA for biopsy showing ATN( Grade 2C)
11. Steroids and cyclophosphamide in crescentic IgA( Grade 2D).
12. Tonsillectomy is not recommended ( Grade 2C)

For full recs see http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201223a.pdf

KDIGO Guidelines for Glomerular diseases: Infection related GN

KDIGO guidelines published this year in KI supplement.
TOPIC: Infection related GN

1. Treat the underlying infectious disease for the following: Post streptococal GN, infective endocarditis related GN and shunt nephritis.
2. For Hep C related GN, and CKD stage 1 and 2, combined treatment with anti virals ( Grade 2C).
3. For Hep C related GN, CKD stage 3,4,5- suggest monotherapy with pegylated interferon with dose adjustment ( Grade 2D).
4. For Hep C with mixed cryo with nephrotic proteinuria or progressive renal disease: plasmapheresis, rituximab or cyclophosphamide  in conjunction with IV steroids and antiviral therapy( Grade 2D).
5. For Hep B related GN, treatment of Hep B with interferon alpha ( Grade 1C).
6. For HIV associated GN, anti retro virals are the most important regardless of CD4 count ( Grade 1B).

http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201222a.pdf

KDIGO Guidelines for Glomerular Diseases: MPGN

  KDIGO guidelines are proposed this year in recent Kidney International on glomerular disease.

Topic: MPGN

1. It is very important to evaluate for secondary causes

2. Conditions to consider are: Infections like Hepatitis C,  autoimmune diseases, MGUS, complement dysregulation and chronic thrombotic microangiopathy and to treat those underlying conditions.

3. Adults and children with idiopathic MPGN with nephrotic syndrome and progressive decline in renal function receive oral cyclophosphamide or MMF with low dose alternating steroid for 6 months( Grade 2D).

Take a look at the full article at: http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201221a.pdf

KDIGO Guidelines for Glomerular Diseases: Membranous Nephropathy

KDIGO guidelines have been now published on glomerular diseases in KI this year
(image source: kidneypathology.com)
Topic: Membranous Nephropathy

1. Initial therapy should only be started on patients with nephrotic syndrome and one of the following: more than 4g/day of proteinuria AND remains over 50% of the baseline value, AND does not show progressive decline, during anti hypertensive and proteinuric therapy with 6 months of observation( Grade 1B) or presence of disabling or severe complication of nephrotic syndrome( clot, significant edema)( Grade 1C) or rise in creatinine by 30% or more in 6-12 months from time of diagnosis (Grade 2C).

2. Immunosuppresive therapy to be not used if chronic disease found with small kidneys on sonogram.
3. 6 months of modified Pontecelli regimen ( oral or IV cyclophosphamide and steroids) for 6 months( Grade 1B) as initial therapy. Steroid month starts with IV steroids (1gm) for 3 days followed by oral steroids( 0.5mg/kg/day) for 27 days. The cyclo month starts and finishes with 2.0mg/kg/day of oral for 30 days.
4. CNI can be used for 6 months if cannot use above Pontecelli regimen( Grade 1C). CNI dose be reduced by month 2 to a level of about 50% of starting dose provided remission is maintained and no treatment related nephrotoxicity is develping( Grade 2C).
5. For resistant cases, suggesting switching from alkylating regimen based to CNI based and vice versa.
6. Relapses should be treated with the same therapy that worked ( Grade 2D).
7. If an alkylating therapy was used initially, then that regimen should only be used one more time again. (Grade 2B).
8. Nephrotic syndrome with albumin <2.5g/dl and additional risks for thrombosis,may benefit from warfarin ( 2C).

For full paper see: http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201220a.pdf

KDIGO Guidelines for Glomerular Diseases: FSGS in adults

KDIGO released guidelines in glomerular diseases in a Kidney International supplement this year.( image source: RFN)

Topic: FSGS in Adults

1. Exclude secondary causes of FSGS , genetic testing not required routinely
2. Steroids at 1mg/kg daily as initial treatment ( 2C) if idiopathic
3. Minimum 4 week course but up to 16 weeks if not responding in 4 weeks
4. Taper over 6 months after response( Grade 2D)
5. Contraindication to steroids: use CNI( Grade 2D)
6. Relapsing FSGS should be treated just like relapsing MCD( with cyclosporine instead) for 4-6 months
7. If there is partial or complete remission, continue CNI till 12 months( 2D)
8. If cannot tolerate CNI, use combination of MMF with steroids ( 2C)

For full recommendations see: http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201219a.pdf

KDIGO Guidelines for Glomerular Diseases 2012: Minimal Change Disease

KDIGO Kidney International supplementary material released the guidelines for management of glomerular diseases. ( image source: http://library.med.utah.edu/WebPath/RENAHTML/RENAL102.html)

Topic: Minimal change disease in Adults

1. Initial treatment - Steroids ( Grade 1C) 1mg/kg or alternating 2mg/kg QOD for 4 weeks minimum if complete remission achieved and 16weeks if complete remission not achieved (2C)
2. Taper after remission over 6 months( Grade 2D)
3. If cannot tolerate steroids, oral cyclophosphamide or CNIs can be used( Grade 2D)
4. For relapses, use the same steroid protocols
5. For frequently relapsing and or steroid dependent minimal change, oral cylcophosphamide can be used at 2-2.5mg/kg.day  for 8 weeks( 2C)
6. For frequently relapsing and or steroid dependent minimal change, oral cyclosporine can be used at 3-5mg/kg.day or tacrolimus 0.05-0.1mg/kg/day in divided doses for 1-2 years (2C)
7. MMF 500-1000mg BID for 1-2 years for intolerance also to 5,6 ( 2D)
8. Re-evaluate patients with resistant minimal changes for secondary causes.
9. For initial episode of nephrotic syndrome associated with MCD, statins and ACEI/ARBS not be used in normotensive individuals for proteinuria ( 2D).
10. MCD with AKI, treat with renal repalcement therapy if need be but with steroids.

take a look at full recommendations at http://www.nature.com/kisup/journal/v2/n2/pdf/kisup201218a.pdf