- What is a diffuse process?
- What is a focal process
- What is a global disease?
- What is a segmental disease?
- All of the glomeruli
- Some of the glomeruli
- The entirety of a glomeruli
- Only part of a glomeruli
How does glomerular disease present? (3)
Loss of GFR - Temporal change
Hematuria - Quality
Proteinuria - Quantity
What is a nephrotic syndrome?
Proteinuria > 3.5 g/day
Hypercoaguability (Loss proteins C and S)
What is nephritis?
What are causes of acute glomerulonephritis?
- IgA nephropathy
- Post-infectious GN
- Anti-GBM dz/Goodpasture's
- Small vessel vasculitis
- Lupus nephritis
- Membranoproliferative GN
What are mainly nephrotic: dz?
\What are mainly nephritic dz?
Which ones have crossover?
Nephrotic: Minimal change, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy
Nephritic: Crescentic (ANCA), Acute post-infectious,, Membranoproliferative GNs
Crossover: Membranoproliferative GN, IgA nephropathy
What is IgA nephropathy?
What is the common age range for patients?
What is the most prominent feature?
Is proteinuria present?
Most common GN worldwide
Most patients between age of 10-50
Hematuria is most prominent feature: 50-60% episodic gross hematuria, 30% persistent microhematuria, 10% acute GN or nephrotic syndrome
Proteinuria, if present, is generally mild
Many cases are subclinical
What are other complications that accompany IgA nephropathy?
Dysuria and loin pain with hematuria
Hematuria frequently occurs in conjunction with a URI (synpharyngitic hematuria)
HTN may be present in patients with more advanced dz
How does IgA nephropathy appear on LM, IF, and EM?
LM: Variable mesangial hypercellularity
IF: Mesangial IgA deposition
EM: Mesangial ectrone dense deposits
What is IgA nephropathy's prognosis?
What are treatment' options?
Prognosis: Based on serum creatinine, BP, proteinuria
40% will slowly develop CKD
Tx: Fish oil can slow progression
ACEi to control BP
Corticosteroids/immunosuppressants used in progressive dz
What is Henoch-Schonlein Purprua?
How can it manifest?
Systemic disorder haracterized by IgA deposition in multiple organs
Skin - Characteristic non-blanching purpura or legs and buttocks
Joints - Transient arthralgias
GI - Abdominal pain, vomiting, melena, hematochezia
Kidney - Hematuria, proteinuria, rarely with progressive renal dz
What is post-infectious GN and its standard course?
Often post-streptooccal GN
What are the symptoms of post-strep GN?
What are the laboratory studies for post-strep GN?
Sudden onset HTN, azotemia, oliguria, edema and cola- or tea-colored urine
Low C3 level, ASO elevated, urinalysis reveals RBC casts, mild proteinuria
Morphologic features of post-infectious GN (LM, IF, EM)
LM: Enlarged, hypercellular, glomeruli, diffuse mesangial and endocapillary proliferation with neutrophils. May see crescents
IF: Granular capillary wall and mesangial IgG and C3
EM: Mesangial and large subepithelial "hump-like" deposits
What is the prognosis of post-strep GN
95% of children will recover with conservative management (1% progress to renal failure)
60% of adults will recover promptly
What is rapidly progressive GN?
What are the causes?
What are the characteristics on LM?
Classic nephritic syndrome with rapid progression (days to weeks) to renal failure
Causes: Anti-GBM/Goodpasture's, immune complex GN (lupus, post-infectious, cryoglobulinemia), ANCA associated (Pauci immune)
Segmental necrosis and cellular crescent
What is Anti-GBM/Goodpasture's syndrome gender predisposition?
How does it present
What is the cause?
More often in males than females
Presents as a pulmonary-renal failure syndrome: hemoptysis, pulmonary infiltrates, glomerulonephritis
Due to circulating anti-GBM Ab
Antigen is alpha-3-chain of type IV collagen
What is the diagnostic criteria for Anti-GBM/Goodpasture's Syndrome?
What is treatment?
1. Anti-GBM antibody in blood, linear IgG and C3 on kidney biopsy IF
2. Treatment with plasmapheresis, prednisone, cytoxan
What is pauci-immune GN?
What causes it?
Crescenteric GN with little deposition of immune reactants
Idiopathic or ANCA
What small vessel vasculitis are associated with nephritis?
Microscopic polyangiitis - No granulomatous inflammation and no asthma
Wegner's granulomatosis - Necrotizing granulomatous inflammation; no asthma
- c-ANCA in 80%
- URT symptoms, mononeuritis multiplex, purpura, nephritis
- Renal biopsy: cresenteric GN without immune deposits
Curg-Strauss syndrome: Necrotizing granulomatous, inflammation, asthma, eosinophilia
What are secondary causes of nephrotic syndrome?
What is used for diagnosis?
Systemic diseases, Diabetes mellitus, SLE, amyloidosis, infections (HIV, HBV, HCV, syphilis), drugs (NSAIDs, gold penicillamine)
2ndary causes: ANA, anti-dsDNA, complement, serum and urine protein electrophoreses, HBV/HCV serologies, cryoglobulins, syphilis serology
Also renal biopsy generally indicated
ACEi/ARB (reduce intraglomerular pressure and proteinuria), statins (lipids), diuretics, salt restriction (edema)
What is minimal change disease?
What is the course with children?
What are the causes with adults?
Most common cause of nephrotic syndrome in children
Peak incidence ages 2-6, 5% progress to ESRD, spontaneous remissions can occur, treatment with steroids often induces remission although relapses occur in about 75%, fewer relapses after puberty
In adults can be idiopathic or associated with drugs (NSAIDs), neoplasms (Hodgkin's lymphoma, other cancers), infections (syphilis, HIV)
What is observed for Minimal Change Disease on LM, IF, EM?
What is treatment?
LM: Glomeruli, interstitium and tubules appear normal
IF: Negative or mesangial IgM
EM: Podocyte foot process effacement
Children respond well to corticosteroids, majority of adults also respond to steroid (longer than in children, partial remissions)
What is membranous nephropathy?
What are the secondary causes?
Most common cause of nephrotic syndrome in Caucasian adults
Secondary causes account for 15-20% of cases
Infections - HBV
Connective tissue diseases - SLE
Neoplasms - Carcinoma of lung, colon, stomach, breast, non-Hodgkin's lymphoma
Drugs - Gold, penicillamine, Hg, NSAIDs, captopril
What is the course of membranous nephropathy?
What is the prognosis?
Onset is generally insidious
Patients usually present with heavy proteinuria & nephrotic syndrome
HTN & Azotemia later
Occult malignancies and infections may become evident later
Renal vein thrombosis occurs in 20%
Rule of thirds
1/3rd spontaneous remission
1/3rd partial remission with stable function
1/3rd slowly progressive loss of renal function
What is Membranous Nephropathy appearance on LM, IF, EM?
What is the treatment?
LM: Diffuse thickening of GBM, GBM "spikes" on silver stain
IF: Granular GBM deposits of IgG
EM: Subepithelial deposits
Treatment: ACEi/ARB for those without poor prognostic factors, otherwise steroids/immunosupressants
What is focal segmental glomerulosclerosis?
What are the sequelae?
What are the types of FSGS?
Most common cause of idiopathic nephrotic syndrome in African-Americans
More agressive than minimal change disease: HTN, hematuria more common, renal dysfunction is commonly progressive, ESRD occurs 5-20 years after presentation
Primary - Usually presents with acute onset of nephrotic syndrome
Secondary - Usually manifests with slow increasing renal insufficiency and proteinuria
Hereditary - Mutations in proteins that make up the glomerular slit diaphragm
What are secondary causes of FSGS?
Drugs - NSAIDs, heroin
Infections - HIV
Healed previous glomerular injury
Loss of functioning renal mass - unilateral agenesis, reflux nephropathy
How does FSGS appear on LM, IF, EM?
What is prognosis?
What is treatment?
LM: Focal and segmental glomerular sclerosis with capillary collapse, hyaline and lipid deposition and adhesion to Bowman's capsule
IF: Negative or IgM and C3 in mesangium or in segmental scars
EM: Podocyte foot prcess effacement, may see segmental sclerosis
Prognosis correlates with degree of proteinuria, progression in 50% at 10 years, trreatment for steroid-resistant/relapsing patients is problematic
Treat with ACEi to reduce proteinuria, corticosteroids or other immunosuppressive
What is the sequelae of Membranoproliferative Glomerulo-nephritis (MPGN)?
What are the causes of MPGN?
Proteinuria & hematuria commonly coexisting with HTN in 1/3
Low C3 complement is a prominent feature
Variable presentation: 50% nephrotic syndrome, 30% asymptomatic proteinuria w/w/o hematuria, 20% acute GN
Primary or Secondary (SLE, connective tissue diseases, cryoglobulinemia, infections - HCV, HBV, endocarditis, abscesses, neoplasms)
What is MPGN findings in LM, IF, EM?
LM: Hypercellular glomeruli, endocapillary cell proliferation, lobular appearing glomeruli
IF: Granular C3 deposition
EM: Subendothelial deposits
What is SLE?
What is lupus nephritis?
What iare the sequelae?
What is treatment for SLE?
Multi-system auto-immune disorder (abnormal autoantibody production, immune complex deposition, inflammatory cell infiltration)
Common cause of diffuse proliferative GN with many of the different clinical syndromes of renal disease can occur in the setting of SLE (renal biopsy needed to clarify lesion)
40% of the patients develop overt nephritis (follow U/A in SLE patients, HTN suggests the presence of renal disease)
General principles: Aggressive BP control, lipid control, appropriate treatment of extrarenal involvement
Classes III-V: Usually treated with corticosteroids + cytotoxic therapy; Class IV: Renal failure rate 25% by 5-10 years