Thursday, May 21, 2015

Glomerular Diseases

Everyone has a different approach to this problem and categorizes diseases in different ways. It is important to choose one classification system and stick with it. What can be confusing about the Nephritic vs Nephrotic diseases is that there is significant overlap in their presentations, including the degree of proteinuria seen in disease.
Here is a helpful and simple approach to the problem:

Now I will elaborate on these diseases using the above approach:


1. Immune Complex (Granular IF)
Pearl: IgA nephropathy is synpharangyitic (occurs at the time of pharyngitis) whereas post-strep GN is postpharyngitic (occurs 2 weeks after pharyngitis)

Low Complement
  • Post-Streptococcal Glomerulonephritis
    • Usually exhibit low amount of urinary protein
    • Present with hematuria with or without RBC casts.
    • Low C3, Normal C4; ASOT+; Anti-DNAse B+
    • Treatment is supportive – usually resolves in 3-4 weeks
  • Membranoproliferative
o    Type I - HCV/HBV/SLE/IE/Cancer/Sjogrens
    • C3 may be normal; C4 low
  • Cryoglobulinemia - Type II
o    Low C4; C4 normal
    • Treatment: Rituximab and cyclophosphamide
  • SLE
    • C3 and C4 low
    • Class III/IV
    • There are 6 stages of Lupus nephritis – Stage III and IV (focal proliferative and diffuse proliferative) are categorized here. This stage is treated with steroids, MMF, and cyclophosphamide
    • In general, biopsy is indicated in lupus nephritis when complements are low, active urinary sediment, and with a positive anti-dsDNA
    • All patients should be on ACE inhibitors to target proteinuria of less than 1g per day, and a BP of less than 130/80 and have dyslipidemia management.
  • Infective Endocarditis
  • Cholesterol Emboli
    • Rarely spontaneous, usually occurs following a procedure manipulating large vessels
    • Other manifestations include purple toe syndrome and livedo reticularis.
Normal Complement
  • IgA Nephropathy
    • Gross hematuria 1-3 days after URTI.
    • First line therapy is non-immunosuppressive therapy:
      • ACE inhibitors
      • +/- fish oils
    • Starts systemic steroids if:
  1. Increasing creatinine (not for stable, elevated creatinine)
  2. Protein >1g/day
  3. Active kidney disease on biopsy
  • HSP – Henoch-Schรถnlein Purpura
    • Associated with IgA nephropathy
    • Associated with palpable purpuric rash
    • May also present with mononeuritis multiplex
    • Generally seen in younger patients
    • Occurs in older patients as a paraneoplastic syndrome in MDS
    • Treatment generally supportive, may include steroids
2. Anti-GBM (linear IF)
  • Presents with RPGN (Rapidly progressive GN)
  • 40% of patients have ANCA positivity as well
  • Goodpasture’s Disease is the term used when GN is associated with lung hemorrhage – occurs in 50% of patients. Anti-GBM Disease means there is no lung involvement.
  • Treatment:
    • Pulse steroids, cyclophosphamide, plasma exchange therapy
    • Who to treat:
      • All patients with pulmonary hemorrhage
      • All patients with kidney involvement who do not require dialysis
      • Selected patients on dialysis: those with lung involvement or with systemic vasculitis (ANCA)
    • Duration depends on disappearance of anti-GBM
    • Taper medications over 3-6 months 
    • Patients on dialysis are often not treated – their kidneys are too damaged and therapy will not benefit them

3. ANCA (Pauci Immune)

All three of these diseases affect both the lungs and the kidneys and therefore may present with hematuria and hemoptysis
  • GPA (Granulomatosis with Polyangiitis)
    • Anti-PR3 (cANCA) positive
    • Present with saddle nose deformities, nasal polyps
    • May also have salivary gland involvement
    • Treat with pulse steroids, cyclophosphamide, maybe PLEX
  • EGPA (Eosinophilic Granulomatosis with Polyangiitis)
    • antiMPO (pANCA) positive
    • Also presents with neuropathies and may occur with asthma
  • MPA (Microscopic Polyangiitis)
    • antiMPO (pANCA) positive
    • Open lung biopsy is the best way to diagnose MPA

  • Each cause of nephrotic syndrome may be primary or secondary to an underlying disease process
  • Generally, the treatment for these diseases includes ACE inhibitors/ARBs  and  treating the underlying cause of the disease
  • If primary disease (and therefore no underlying cause) - use steroids for treatment.
  • Complications:
    • Thrombosis – this is due loss of ATIII and Protein C/S in the urine
    • Infection - this is due loss of immunoglobulins in the urine; leads to infection by encapsulated organisms
    • Dyslipidemia – due to overproduction of LDL and VLDL
    • Edema – due to low oncotic pressure (loss of protein) and subsequent activation of the RAAS system

1. Minimal Change Disease 
o   Most common cause of nephrotic syndrome in children
o   Most cases are idiopathic
o   Secondary causes include NSAIDs, Hodgkins/lymphoproliferative disorders, and leukemias.

2. Focal Segmental Glomerulosclerosis (FSGS)
o   Most common cause of nephrotic syndrome in adults
o   Can be thought of as a more severe form of Minimal Change Disease
o   Often asymptomatic except for hypertension
o   Secondary causes include HIV, lupus, sickle cell disease, heroin, urinary reflux, and obesity
o   FSGS is slowly progressive
o   Notable variant is HIV associated nephropathy (HIVAN) – this is a collapsing variant of FSGS. It is treated with HAART and ACE inhibitors; may transplant

3. Membranous Nephropathy
o   Second most common cause of nephrotic syndrome in adults
o   Most cases are idiopathic (>80%)
o   Immune complex mediated diseases
o   Rule of thirds with prognosis – one third will resolve, one third will worsen, and one third will have chronic changes
o   Treated with ACE inhibitors
o   Secondary causes:
o   Hepatitis B, Hepatitis C, Syphilis
o   Malignancy – lung and colon
o   Drugs used to treat RA (Gold, Penicillamine, NSAIDs, etc.)
o   SLE Stage V. Indications for immune suppression (steroids + cyclophosphamide or cyclosporine):
    • Persistent severe and symptomatic nephrotic syndrome (proteinuria persists >3.5g/d)
    • Increased or rising serum creatinine
    • Mixed membranous and proliferative lesions on biopsy
4. Nodular Disease
o   Diabetic Nephropathy – the most common cause for end-stage renal disease and dialysis in North America
o   Amyloidosis – In AA disease (secondary to an inflammatory disorder, such as Rheumatoid Arthritis), the kidneys are involved in nearly in all patients.

Sorry for the long post. Here's a potato: