7 - Glomerular Disease 1 Flashcards
What are three mechanisms of glomerular disease?
- Immune complex deposition: circulate and deposit in the glomerulus; activates complement causing PMN chemotaxis
- Antibodies against the glomerular basement membrane (GBM) or glomerular antigens
- Cytokine production by inflammatory cells
Describe diffuse, focal, global, and segmental in terms of glomerular disease?
Diffuse is when it impacts many glomeruli.
Focal is when it impacts less than 50% of the glomeruli.
Global means it impacts the entire glomerulus.
Segmental means it impacts a segment of a glomerulus.
How does glomerular disease present?
Any of these things at any time:
- loss of GFR
- hematuria - quality
- proteinuria - quantity
NephrOtic syndrome is a constellation of what things?
- Proteinuria >3.5 g/day
- Hypoalbuminemia
- Edema
- Hyperlipidemia
- Lipidemia
- Hypercoagulability
Nephritis is a constellation of what things?
- Mild proteinuria
- Hematuria
- Hypertension
- Edema
What are the three primary diseases that cause nephrotic syndrome?
- Minimal change disease
- Focal segmental glomerulosclerosis
- Membranous nephropathy
What are some causes of acute glomerulonephritis?
- IgA nephropathy
- Post-infectious GN
- Anti-GBM disease/Goodpasture’s
- Small vessel vasculitis
- Lupus nephritis
- Membranoproliferative GN
What is IgA nephropathy? What age group gets it? What is seen?
Most common glomerulonephritis WORLDWIDE.
Most pts between 10 and 50
Hematuria, frequently in conjunction with a URI (Synpharyngitic hematuria) ; if proteinuria present it’s generally mild.
Many cases are subclinical.
What is seem on immunofluorescence in IgA nephropathy? What is seen on light micropscopy?
IF: Mesegangial IgA deposition
LM: variable mesangial hypercellularity
What is the prognosis in IgA nephropathy based on? How can it be treated?
Prognosis based on serum creatinine, BP, and degree of proteinuria - 40% develope chronic kidney disease.
Fish oil may slow progression.
ACE inhibitors to control high BP
Corticosteroids and other immunosuppressants may be used in progressive disease.
What is Henoch-Shonlein purpura? What are the manifestations?
Systemic disorder characterized by IgA deposition in multiple organs:
- skin - non-blanching purpura on legs/buttocks
- joints: transient arthralgias
- GI: abd. pain, vomitting, melena
- Kidney: hematuria (ie this is a nephritis!); rarely progresses to renal failure
What is post-infectious glomerulonephritis? When does it occur?
Post-strep GN is a classic example.
Follows infection of group A beta-hemolytic streptococcus. 7-14 days after after pharyngitis or 14-28 days after skin infection.
Sudden onset HTN, azotemia, oliguria (decreased urine), edema, and cola-colored urine.
What do lab tests show in post-strep GN?
- Low C3 copmlement
- Anti-streptolysin O (ASO) can be elevated
- Urinalysis: RBCs, mild proteinuria
What is seen on IF and EM in post-strep GN?
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% will progress to renal failure)
60% of adults will recover promptly.
What is rapidly progressive glomerulonephritis? What are some causes?
Classic nephritis syndrome with rapid progression (days to weeks) to renal failure.
Somtimes referred to as “crescent GN”
What are some causes of rapidly progressive glomerulonephritis?
- Anti-GBM/Goodpasture’s
- Immune complex GN: lupus nephritis, post-infectious, cryoglobulinemia
- ANCA associated GN (Pauci immune)
How does goodpasture’s syndrome present? Who gets it?
Males > females
May present as pulmonary-renal syndrome with hemoptysis, pulmonary infiltrates, and glomerulonephritis.
Due to circulating anti-GBM antibody an antigen in the apha3 chain of type IV collagen.
How would you diagnose goodpastures syndrome (anti-GBM)? How do you treat it?
+ anti-GBM antibody in the blood
LINEAR IgG and C3 on kidney biopsy
EMERGENT treatment with plasmapheresis, prednisone, and cytoxan (immunosuppressant).
What causes pauci-immuno GN?
Crescenteric GN with little (pauci means little) deposition of immune reactants
Idiopathic OR associated with antineutrophil cytoplasmic antibody (ANCA) vasculitis.
What are examples of small vessel vasculitis that cause pauci-immune GN?
- Microscopic polyangitis - no granulomatous inflammation and no asthma
- Granulomatosis with polyangitis - necrotizing granulomatous inflammation; no asthma
- Eosinophilic granulomatosis with polyangiitis - necrotizing granulomatous inflammation, asthma, eosinophilia
What is granulomatous with polyangiitis (GPA)? How does it present and what does a biopsy show?
Granulomatous vasculitis of medium to small arterioles.
c-ANCA + in 80%
Presents with upper resp tract symptoms (sinusitis), mononeuritis multiplex, purpura, and nephritis.
Renal biopsy shows cresenteric GN without immune deposits.
What is the seen clinically, on light microscopy, and on IF with Anti-GBM/goodpastures?
Clinically: +anti-GBM antibody in blood
LM: crescenteric GN
IF: Linear IgG and C3
What is the seen clinically, on light microscopy, and on IF with rapidly progressive GN from immune complexes?
Clinically: lupus or post-strep
LM: crescenteric GN
IF: variable deposition of IC and cmoplement
What is the seen clinically, on light microscopy, and on IF with pauci-immune rapidly progressive GN?
Clinically: ANCA+
LM: crescenteric GN
IF: negative
What primary renal diseases can cause nephrotic syndrome? Which most commonly occurs in children?
- Membranous nephropathy
- Focal segmental glomerulosclerosis (FSGS)
- Minimal change disease
In children ~80% will have minimal change disease
What are secondary causes of nephrotic syndrome?
Systemic disease:
- diabetes mellitus
- SLE
- amyloidosis
- Infections: HIV, HepB, HepB, syphilis
- Drugs: NSAIDs, gold, penicillamine
How do you diagnose nephrotic syndrome?
Helpful lab studies for the secnodary causes.
Renal biopsy generally indicated.
What is the treatment for all causes of nephrotic syndrome?
ACE inhibitor or ARB to lower intraglomerular pressure and reduce proteinuria.
Lipid lowering therapy (statins)
Diuretics and salt restriction to improve edema
What is the most common cause of nephrotic syndrome in children? What is the peak incidence? What is the treatment and prognosis?
Minimal change disease
Peak incidence ages 2-6, 5% progress to ESRD.
Spontaneous remissions can occur; treat with steroids often induces remission but 75% relapse (fewer relapses after puberty).
What can cause minimal change disease in adults?
Idiopathic or associated with:
- Drugs: NSAIDs
- Neoplasms such as Hodgkin’s lymphoma
- Infections such as syphilis or HIV
What is seem on LM and EM in minimal change disease?
LM: glomeruli, interstitium and tubules appear normal
EM: podocyte foot process effacement (fusion)
What is the treatment of minimal change disease in adults and children?
Children respond well to corticosteroids
Majority of adults respond to steroids: usually takes longer than in children; partial remission may occur.
Who gets membranous nephropathy and what is it caused by?
Most common cause of nephrotic syndrome in caucasion adults.
Caused by antibodies to the podocyte antigens phospholipase A2 receptor (70%) or thrombospondin type-1 domain containing 7A (10%).
What are secondary causes of membranous nephropathy?
HepB infection
SLE
Neoplasms: consider age-appropriate cancer screening
Drugs: gold, NSAIDs, murcury, captopril, penicilliamine
Describe the onset and symptoms seen in membranous nephropathy?
Onset is generally insidious.
Pts usually present with heavy proteinuria and nephrotic syndrome.
Renal vein thrombosis occurs in ~20%.
What is seem on LM, IF, and EM in membranous nephropathy?
LM: diffuse thickening of the GBM, and GBM “spikes” on silver stain
IF: granular GBM deposits of IgG
EM: subepithelial deposits
What is the outcome of membranous nephropathy?
How are pts managed?
Rule of thirds:
- 1/3 spontaneous remission
- 1/3 partial remissions with stable function
- 1/3 slowly progressive loss of renal function
Pts without poor prognostic factors managed conservatively with ACE-I or ARBs and followed closely. Otherwise +/- immunosuppressive drugs.
What is focal segmental glomerulosclerosis (FSGS)? How does it compare to minimal change disease?
Most common cause of idiopathic nephrotic syndrome in african americans.
More aggressive than minimal change disease:
- HTN, hematuria more common
- renal dysfunction commonly progressive
- ESRD occurs 5-20 yrs post-presentation
What are primary, secondary, and hereditary focal segmental glomeruloscleoris (FSGS)?
Primary: usually presents with acute onset of nephrotic syndrome
Secondary: slowly increasing renal insufficiency and proteinuria
Hereditary: mutations in proteins that make up the glomerular slit diaphragm
What are secondary causes of FSGS?
HIV
Obesity
Drugs: NSAIDs, herion
What is seen on LM, IF, and EM in focal segmental glomerulosclerosis (FSGS)?
FM: focal and segmental glomerular sclerosis with capillary collapse
IF: negative or IgM and C3 in mesangium
EM: podocyte foot process effacement
What does the prognosis of focal segmental glomerulosclerosis correlate with? What is the treatment? How often does it progress to ESRD?
Prognosis correlates with the degree of proteinuria
ACE inhibitors reduce the proteinurea
Corticosteroids can induce remission in some; difficult to treat steroid-resistant pts who relapse (immunosuppresives used)
Progression to ESRD in 50% at 10 yrs.
What dglomerular diseases can cause nephrotic and nephritic features?
Membranoproliferative glomerulo-nephritis (MPGN)
Systemic lupus erythematous (SLE)
What is the presentation of someone with membranoproliferative glomerulo-nephritis (MPGN)?
Proteinuria and hematuria commonly coexist
HTN occurs in 1/3
Low C3 complement is prominent feature
Variable clinical presentation
- half have nephrotic syndrome
- 30% asymptomatic proteinuria +/- hematuria
- 20% acute GN
What are some causes of secondary membranoproliferative glomerulo-nephritis (MPGN)?
Hepatitis C virus
SLE
Cryoglobulinemia
Neoplasms
What is seen on IF and EM in membranoproliferative glomerulo-nephritis (MPGN)?
IF: granular C3 deposition
EM: subendothelial deposits
What are characteristics in systemic lupus erythematosus (SLE)?
Multi-system autoimmune disorder
- abnormal autoantibody production
- immune complex deposition
- inflammatory cell infiltration
What is lupus nephritis and who gets it? How do you diagnose lupus nephritis?
Common cause of diffuse proliferative GN
40% of pts develop overt nephritis
Many of the clinical syndromes of renal disease can occur in the setting of SLE.
Renal biopsy important to classify the lesion in SLE (there’s 6 different classifications).
What is the treatment for lupus nephritis?
General principal to manage any class:
- aggressive BP control
- control of lipid levels
- appropriate treatment of extrarenal involvement
How would you treat lupus nephritis classes III-IV? How common is renal failure in class IV?
Usually treated with corticosteroids + cytotoxic therapy
Class IV: renal failure rate 25% by 5-10 yrs.
