Anti-GBM Disease & Goodpasture Syndrome: Overview & Treatment

Terminologies Associated with Anti-Glomerular Basement Membrane Disease and Goodpasture Syndrome

Goodpasture syndrome

• It is any condition in which there is rapidly progressive glomerulonephritis (RPGN) and alveolar hemorrhage (Blood in the alveoli) 
• It has several causes
  • Anti-GBM disease 
  • Vasculitis 

Anti-GBM disease

• Part of Goodpasture syndrome 
• Anti-GBM disease means the presence of antibodies against GBM 
• Antibodies can be against any component. 
• Alpha 3 component of collagen type IV of the glomerular basement membrane, In Goodpasture disease 
• If antibodies against the Alpha 5 component Alport are produced, it causes syndrome (post-transplant anti-GBM disease) 
• In Alport syndrome, the Alpha 5 gene is mutated
• Donor kidney transplanted has Alpha 5 genes normal
• Body produces antibodies against normal alpha 5 genes of the donor's kidney

Also read: Overview of Histiocytic and Dendritic Cell Disorders

Goodpasture disease

• Autoantibodies directed against the Alpha 3 component of type 4 collagen 
• Include RPGN, lung hemorrhage or both 
• It happens because of autoimmunity to alpha 3

Alport syndrome post-transplant anti-GBM disease

• If the antibodies are against Alpha 5, then it is called a posttransplant anti-GBM disease 
• Post-transplant anti-GBM disease is seen in conditions like Alport syndrome 
• In Alport syndrome, the alpha 5 gene is mutated 
• Generally, alpha 5 is not expressed in these patients 
• The donor kidney will have normal alpha 5, recipient body produces antibodies against alpha 5

Etiology and Pathogenesis

• Type 4 collagen is present in almost all basement membranes 
• Type of alpha-chain-forming type 4 collagen varies in each structure
• Autoimmunity to a component of the Glomerular Basement Membrane
  • Type IV collagen 
  • Carboxyl terminal of the NC1 domain of type IV collagen of alpha 3 chain (Goodpasture antigen) 
• Against Goodpasture antigen antibodies are produced

Predisposing factors

• Genetic factors
  • Association: HLA class II alleles, DRB1*1501 and DR4 (high risk alleles) 
  • Protection: -DR1 and Dr7 
• Precipitating factors 
• Anything exposing the alpha-3 chain of the glomerular basement membrane or alveolar basement membrane can precipitate disease in people at high risk of anti-GBM disease.
  • Hydrocarbon exposure 
  • Cigarette smoking 
  • Renal trauma/inflammation 
  • Small vessel vasculitis 
  • Membranous nephropathy

Also read: Feeding & Eating Disorders in Infants: Types & Management

Predisposing events

Predisposing Events Associated with the Presentation of Goodpasture Disease 

• Possibly induce autoimmune response and disease
  • Systemic small-vessel affecting glomeruli vasculitis 
  • Membranous nephropathy
  • Lithotripsy of renal stones
  • Urinary obstruction
  • Alemtuzumab therapy for multiple sclerosis
• Precipitate pulmonary hemorrhage (toxic to lungs)
  • Cigarette smoke 
  • Hydrocarbon exposure 
  • Pulmonary infection 
  • Fluid overload

PYQ

Q. Which is the protective allele? 

Ans. DR1 and DR7 are protective alleles.

PYQ 

Q. What is the diagnosis for a 25-year-old male presenting with glomerulonephritis with breathing difficulties and a history of smoking? 

Ans. Anti-GBM disease

PYQ 

Q. What is the most sensitive technique to detect alveolar hemorrhage?

Ans. Increased uptake of inhaled carbon dioxide (DLCO) 

Also read: Membranous Nephropathy : Types, Epidemiology and Investigation

Patients with Anti-GBM and other diseases

• ANCA vasculitis
  • Double-positive disease: low titers of anti-GBM antibodies 
  • ANCA specific for MPO
  • Antibodies to vasculitic glomerular damage
  • Course and response similar to vasculitis 
• Membrane Nephropathy 
• Alemtuzumab therapy

Factors in the decision to treat Goodpasture disease aggressively 

• Plasma exchange and Immunosuppression are done even if creatinine is >5.5 in
  • If the patient is ANCA positive (Double positive),
  • lung hemorrhage

Also read: Minimal Change Disease

C. Supportive Treatment 

Avoid Precipitation of Lung Hemorrhages like

• Fluid overload
• Smoking and other respiratory irritants
• High FiO2
• Local or distant infection
• Anticoagulants used during PLEX/Dialysis
• Depletion of clotting factors

Monitoring Effect of Treatment

• Renal disease: serum creatinine 
• Lung
  • Hb 
  • Cxray
  • DLCO (increased CO absorption) 
• Anti-GBM antibodies disappear within 8 weeks →14 months

Duration of Treatment and Relapses

• 3 months (cyclophosphamide), 6 months (steroid) 
• Double positive: Longer time of treatment 
• Relapse: Rare

Double Positive Disease 

• Prognosis is better than just anti-GBM alone 
• Prolonged treatment 

Also read: Hematuria, Pyuria, Urinary Tract Infection And Treatment In Pregnancy

Transplantation

• 6 months of undetectable anti-GBM antibody levels 
• Alport's syndrome
  • Mutation of alpha 5 
  • 2% develop RPGN-graft loss; duration varies over subsequent transplants
  • Anti-Alpha 5 (IV) NC1 antibodies

KDIGO Guidelines

• Treat all patients except
  • Requiring dialysis (creatinine: >5.5-6.5)
  • 100% crescents on biopsy
  • >50% glomerulosclerosis (Chronic)
• However, pulmonary hemorrhage has to be treated
• Start treatment even before the diagnosis is confirmed 
• Plasma exchange should be continued till anti-GBM titers are no longer detected
• Cyclophosphamide for 3 months 
• Steroids for 6 months 
• No maintenance therapy for anti-GBM 
• Double positive should be treated like ANCA vasculitis 
• Refractory cases- Rituximab 
• Kidney transplantation for 6 months of negative titers of antibody

Also read: Hypertension In Pregnancy

Rapidly Progressive Glomerulonephritis (RPGN)

• Glomerular injury, which is acute and severe → Renal function deterioration over days to weeks 
• Histologic counterpart is crescentic GN 
• Acute deterioration of renal function with crescents
• In AKI, the patient can present because of
  • glomerular involvement (RPGN) 
  • Interstitial involvement (AIN) 
  • Tubular involvement (ATN) 
  • Vascular involvement (TNA)

Conditions Presenting as RPGN

Treatment algorithm in RPGN

• When a patient presents with RPGN, do not waste time
  • Immediately get a CT to vascular hemorrhage diagnose 
  • Rule out infection; don't heavily immunosuppress the patient

Also read: Renal Physiology In Pregnancy

Quick Revision

• Goodpasture syndrome, any cause of RPGN and vascular hemorrhage
  • Anti-GBM 
  • Vasculitis 
• Goodpasture disease, an antibody directed against the alpha 3 chain of collagen type IV, NC1 domain 
• Pulmonary renal syndrome, mostly non-immune. 
• Immune causes are Goodpasture disease 
• Anti-GBM has
  • Goodpasture disease, against alpha 3 
  • Alport syndrome post-transplant anti-GBM disease, against alpha 5
• Goodpasture antigen, NC1 domain of carboxyl terminal of alpha 3 chain of type 4 collagen 
• Most sensitive technique to identify alveolar hemorrhage is increased diffusion on carbon monoxide, DLCO 
• Precipitants of alveolar hemorrhage
  • Smoking 
  • Hydrocarbon exposure 
  • Fluid overload
  • Infection 
• Conditions causing non-specific binding to GBM
  • DM
  • Cadaveric kidney
  • LCDD (Light chain deposition disease)
  • Fibrillary GN
• Double-positive disease
  • ANCA (MPO) 
  • Treatment and prognosis are like vasculitis 
  • Prognosis: Double positive>anti-GBM
• Factors against aggressive treatment
  • Creatinine>5.5-6.5 
  • Exception: if the patient has lung hemorrhage or renal biopsy shows less severe kidney disease, no 100% crescents
  • Patient requires early transplantation 
• Transplantation, done after 6 months of negative anti-GBM antibodies 

Also read: Tropical Acute Kidney Injury

Hope you found this blog helpful for your NEET SS Nephrology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs. 

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