Glomerulonephritis - Yagil Flashcards
Which diseases are categorized as nephritic and which are nephrotic?
Nephritic:
– Acute proliferative glomerulonephritis
– Crescentic glomerulonephritis
– Anti-GBM Disease
PSGN
RPGN
Goodpasture syndrome
Pauci-immune
IgA nephropathy
Alport syndrome
Thin membrane disease
Nephrotic:
– Minimal change disease
– Focal segmental glomerulosclerosis
– Membranous glomerulonephritis
– Membranoproliferative
–SLE GN
–Microangiopathies
Causes of Post-Infectious and non-infectious Glomerulonephritis
Classically Strep but also hepatitis, HIV
Non-infectious: SLE, Henoch-Schonlein purpura, Necrotizing vasculitis, Goodpasture Syndrome
What are the differential diagnoses for low complement?
SLE, membranoproliferative GN type I, PIGN (associated with endocarditis, shunt nephritis or hepatitis B).
How does PSGN develop? After how long? What is the clinical presentation?
Caused by GAS: Usually after skin infection (impetigo) after 3-6 weeks
Or after pharyngitis after 1-3 weeks.
Most common in children 4-6yo (10% over 14). In elderly can happen when immigrate to new strain site.
Generalized symptoms of systemic infection at first
Later:
– Hematuria (not reddish like IgA nephropathy, lot of casts and all elements and cells that could possibly enter becoming coca-cola colored) - 100% (ALL)
– macrohematuria 30%
– Proteinuria (usually not nephrotic but could also be)
– Mild oliguria (<500cc/day) and azotemia
– Edema (sodium and water retention, kidney inflamed)
– HTN (from hypovolemia, can be severe enough to cause:
– CHF
• Volume overload
– edema 85%
– hypertension 60-80% - causes low aldosterone and hyperkalemia
– CHF 20% (not uncommon considering these are young people)
• CNS 10%
• GFR < 50% common
Need a low complement: C3 will be low-important for clinical differentiation of kidney diseases, normal C4
Serology supports strep infection but doesn’t predict severity of GN. ASO elevated in 75% in any PIGN
Anti-DNAse B elevated in 90%
Urine shows high RBCs, WBCs and renal tubular epithelial cells (RTEs), red cell casts, hemoglobin casts, granular casts (important to confirm with peers).
LM: cell proliferation
IF: IgG and C3 complexes along capillary wallsEM: EM: subePithelial deposits-humPs (P-P-P)-between BM and podocyte
Therapy, Prognosis of PSGN/PIGN
Supportive/symptomatic: give diuretics with hypertension. Furosemide and not thiazides because in renal failure won’t work.
Prognosis:
Most recover, 1-2% progress rapidly, 1-2% progress to chronic.
Worse prognosis for endemic than epidemic. Younger patients have better prognosis.
Azotemia bad prognosis for elderly
– Children: 90% complete in a few days
– Adults: 50% complete in a few days
35% complete in a few weeks
5% progress to RPGN
10% progress to CGN (different numbers in different series)-follow up
2-5% mortality (rare)
Antibiotics do not reduce opportunity for PSGN but good epidemiologically
What is the clinical presentation and differential diagnosis for rapidly progressive GN
Causitive factors of RPGN (Types)
Treatment
Normal kidney function one day and a week later nephritic urine and failing creatinine
DDx: Acute GN with or without crescents, Crescentic glomerulonephritis with or without vasculitis, etc.
Rapidly worsening GFR, End Stage Renal Disease (ESRD) in weeks-months), usually nephritic syndrome
Extracapillary proliferation beyond Bowman’s space along glomerulus, crescents
Treatment: steroids and cytotoxic agents
- Type 1: Anti-GBM (renal-pulmonary disorders)
- Type 2: Immune complex
- Type 3: Pauci-immune
- Type 4: Double-antibody positive disease
- Type 5: Idiopathic
Type I RPGN: Anti-Glomerular Basement Membrane (GBM) Disease
Goodpasture’s Syndrome (Prognosis, etc.)
Circulating anti-GBM Ab
IF linear staining of IgG and C3 along GBM-defining factor
Without lung hemorrhage referred to as idiopathic anti-GBM disease but with lung hemorrhage referred to as Goodpasture’s Syndrome
Goodpasture’s Syndrome
Can get recovery of renal function if disease is detected early enough (many detected late).
Despite treatment, many progress to chronic renal failure.
(Other pulmonary-renal syndrome: Wegener’s)
Type II RPGN: Immune Complex Type
Complicated of any immune complex GN
Granular pattern by immunofluorescence
Course related to underlying disease (if malignant will be malignant)
Quite common: 40-50% of all RPGN
Prompt diagnosis and treatment to save renal function
Type III RPGN Pauciimune Syndrome
Pathogenesis, Clinical presentation, treatment
Pauci is a form of vasculitis with little IF hypersensitivity, associated with ANCA.
40-50% of RPGN
Usually have systemic systems: weakness, fatigue, pulmonary infiltrates, sinusitis (red flag for pulm/renal: Wegener syndrome)
Usually in 5th decade or later
• Nephritic
• Most common is crescentic glomerulonephritis
– Pauci-immune type (no anti-GBM Ab nor Ag-Ab)
• Pathogenesis:– Idiopathic
• Microscopically:
– Severe glomerular injury, crescents w/in Bowman’s
Spaces
90% either C-ANCA or P-ANCA +
• Clinical P-ANCA associated with polyarteritis nodosa;
– C-ANCA associated Wegener’s granulomatosis
(ANCA-negative most likely Goodpasture’s if pulmonary)
• Treat : plasmapheresis, corticosteroids, other immunosuppressive drugs
If early, recovery may follow tx
IgA Nephropathy, Berger Syndrome
aka Mesangioproliferative Glomerular Nephritis
Pathophysiology
Identification
Prognostic signs
Treatment
Most common cause of primary GN disease in 15-30 year olds
IgA (or IgM less often) deposition on the kidney after exposure to antigen. DDx: PSGN.
If recurrent do biopsy:
Idiopathic, no underlying disease identified except secondary associated diseases identified where they show hematuria and IgA complexes in mesangium (but not pathognomonic)
40% asymptomatic microscopic hematuria
Dipstick positive for heme (grossly looks normal) though totally asymptomatic. Child grows perfectly happily: incidental finding commonly.
40% had macroscopic hematuria (reddish urine- ddx: eating beets, few drugs can cause it, compression, rhabdomyolosis-myoglobinuria or hemoglobinuria, hematuria) following URI or GI infection of less than a week (if a week make sure not PIGN)
10% nephrotic syndrome, no proteinuria
10% renal failure
30% can get chronic immune disease
May have fever
“Recurrent Hematuria Syndrome”
Mean age 30 (but discovered often in younger people)
Family history (11%, not usually, if there is FH think more of Familial nephritis or thin membrane disease)
Microscopic and macroscopic hematuria are major factors, also male gender and smoking
Infection related exacerbations high
Proteinuria low
Hypertension unless develops or progresses (not from benign cause)
Reduced GFR
In the east 30% progress to kidney failure but not in the west, progresses differently, may be different disease.
There is treatment but no cure
Prognostic signs: proteinuria, HTN, renal impairment (do CrCl not just PCr)
If moderate proteinuria give ACEi
If severe give immunosuppressive agent, ACEi, Corticosteroids and any treatment possible to delay dialysis
Tonsillectomy
Immunosuppressors
Cyclosporine A
Fish Oil
ACEi
The rest not used or experimental
Consensus: with advanced disease should aggressively treat patient. Otherwise will lose kidneys. Transplant will have recurrence.
Thin Membrane Disease
Pathogenesis
Reduced thickness of basement membrane
• The abnormality is traced to gene encoding collagen Type IV.
• Most of the patients are heterozygous for the defective gene. Genetically transmitted in some families. Not sure whether or not it is generally.
• Heterozygous Renal function is normal with an excellent prognosis.
• Few are homozygotes and may progress to chronic
renal failure.
If family history, do follow up and make sure nothing develops. No biopsy necessary.
If additional findings (proteinuria, rising creatinine) and unsure of diagnosis do biopsy.
Familial Nephritis - Alport Syndrome
Pathogenesis
• This syndrome is characterized by
glomerulonephritis, nerve deafness and eye
disorders (lenticonus) and is more frequent and more severe in
males.
Proteinuria and hematuria
• Inheritance is heterogeneous, most are x-Iinked
dominant, although some cases are autosomal
recessive or autosomal dominant.
– The lesion in Alport Syndrome is characterized by
defective GBM synthesis
In x-linked cases mutation in gene encoding collagen type IV
GBM is split, layers one on top of the other. Typical and pathognemonic.
Can also do kidney biopsy and if see not intact membrane (not tramtracks)
In light microscopy see focal segmental proliferation and glomerulosclerosis, progressing to diffuse global
glomerulosclerosis.
• Immunofluorescence studies are negative.
Electron microscopy shows splitting and lamellation of the glomerular basement membrane, imparting to
the basement membrane a basket-woven appearance
Some live long, some end up on dialysis at age 40
• Symptoms usually start between the ages of 5 to 20 years with chronic renal failure occurring between the ages of 20 and 50 years.
Chronic renal failure does develop
Minimal Change Disease
Pathophysiology
Factors associated
Clinical presentation
Remission and relapse
Global effacement of foot processes by EM (Looks normal by LM and IF)
Pathogenesis not completely understood but includes IL-13 which affects the composition of podocyte cell membrane (nephrin and podocin). NSAIDs complicate pathology.
Peak incidence is 2-6 y/o
65% of nephrotic syndrome in children and 15% in adults
Proteinuria but usually no hematuria or HTN
Lipid drops in urine as sediment or on top = lipoid nephrosis
Presents with edema d/t decreased oncotic pressure hypoalbuminemia, hemoconcentration, sodium retention and hyperaldosteronemia. Eyelid swelling up to anasarca (generalized fluid retention in all spaces), pleural effusion, scrotal or labial edema and pitting edema of the legs.
If doesn’t fit clinical context, investigate other disorders (like a paraneoplastic feature of a tumor), otherwise no biopsy
Maybe on a spectrum with Focal Segmental GN
Responds to steroids and immunosuppressives (if not may need to add cytotoxic agent), immunologically mediated through lymphocytes, symptoms respond to aldosterone antagonist. With measles went into remission.
For first attack, give prednisone.
Remission is if urinary excretion of protein <4mg/m2/hr or albustix is trace for 3 days.
Relapse is returning at all. Frequent relapse is 2 or more within 6 months. Steroid dependence is 2 consecutive relapses within treatment time or within 14 days of cessation. Steroid resistance: Failure to achieve response in spite of 4 weeks (4 months for adults) of corticosteroid treatment. give cyclophosphamide or cyclosporine.
Focal Segmental Glomerulosclerosis
Pathophysiology
Causes
Clinical presentation
Nephrotic syndrome (in 70% of children and 50% of adults) All glomeruli affected but at different levels. May not see all in one cut.
Idiopathic most common.
Secondary causes:
Reflux Nephropathy
Morbid obesity- large problem
HIV
Heroin associated is classical
Minimal change disease may be a more benign version
End stage renal disease within 5-20 years (sooner if more protein loss because indicates interstitial inflammation and if HIV associated)
- Hematuria
- Hypertension
- Decreased glomerular filtration rate and nonselective proteinuria
Biopsy for significant proteinuria, may be inconclusive
Unresponsive to corticosteroids and immunosuppressive therapy (unlike MCD) but try anyway, add cyclosporine.
Primary disease will recur in transplant kidney.
Plasmapheresis can help.
Worse prognosis in African Americans. Minority of patients have spontaneous remission
Membranous Nephropathy
Pathophysiology
Clinical presentation
Prognosis
Treatment
25% of GN
Basement membrane is thickened
LM: widening of capillary walls. Involvement of mesangium.
EM: Subepithelial deposits (like PSGN)
If membranous, r/o diseases, can’t determine without ruling out secondary causes. Secondary causes: SLE, Elderly: tumors, drugs, systemic disease and hep B (and C, treat hepatitis and nephropathy will resolve).
Renal vein thrombosis is a common complication with pulmonary embolism
Uncommon: renal insufficiency, HTN.
Microhematuria common. Proteinuria minimal.
1/3 of cases will have spontaneous remission without remission, 1/3 persistent proteinuria and 1/3 progressive renal failure. Literary treatment recommendations mixed. Wait up to 6 months to see if proteinuria improves and if not treat.
Prognosis worse for males and elderly
Treatment:
Difficult to determine if spontaneous or treatment related recovery.
Non-specific therapy: ACEi if nephrotic for HTN (to decrease PGC and hopefully proteinuria).
Sudden and acute deterioration could be from acute renal vein thrombosis from hypercoaguability.
