Glomerular disease Flashcards
What is glomerular disease?
Abnormal glomerular function from damage to components of glomeruli
Damage to glomeruli can be caused by what?
Overwork (CKD), inflammation, hereditary disease
What is often necessary to diagnose the underlying etiology of glomerular disease?
Kidney biopsy
Exceptions to kidney biopsy being done for glomerular disease?
Risk>benefit (pt. refusal, definitive dx from serology, classic presentation dx)
Glomerular disease classifications?
Nephritic or Nephrotic
What is nephritic glomerular disease?
Immune mediated process causing glomerular damage
Is nephritic glomerular disease acute or chronic (with progressive scarring)?
Can be either
Signs of nephritic glomerular disease?
HTN, gross hematuria (coca-cola), RBC casts, oliguria, proteinuria (mild-mod), edema (dec. GFR –> salt/H2O retention)
What is nephrotic glomerular disease?
Glomerular damage from podocyte injury (failure of podocytes to hold protein/leakage of plasma protein)
Primary cause of nephrotic glomerular disease?
Idiopathic
Most common cause of secondary nephrotic glomerular disease?
DM
Signs of nephrotic glomerular disease?
Heavy proteinuria, hypoalbuminemia, hyperlipidemia, edema (generalized severe from loss of albumin), thrombosis (DVT/PE)
Function of a normal capillary in the glomerulus?
Keeps RBC, WBC, most proteins in blood/only lets watery fluid into urine
What happens when glomerular capillaries are diseased/damaged in nephritic and nephrotic syndrome?
Nephritic syndrome: let protein/RBCs into urine
Nephrotic syndrome: let protein into urine
What are the conditions on the nephritic spectrum (hematuria, proteinuria)?
Post-infectious GN, IgA nephropathy (Berger Disease), Henoch-Schonlein Purpura, Pauci immune GN, Anti-GBM GN, Goodpasture Syndrome, Cryoglobulin associated GN
What are the primary disorders on the nephrotic spectrum (proteinuria)?
Minimal change disease, FSGS, Membranous nephropathy
What are the secondary disorders on the nephrotic spectrum (proteinuria)?
DM (MC), Autoimmune diseases, infections, malignancy, meds
Glomerulonephritis is the ________ component of nephritic syndrome
inflammatory
Nephritic syndrome presentation depends on what?
Severity of underlying inflammation & pattern of injury
Symptoms of Nephritic syndrome?
Fever, abd/flank pain, edema, oliguria (<400mL/day), azotemia (inc. BUN/Cr), hematuria (coca-cola), HTN
Diagnostics for Nephritic syndrome?
CBC, CMP, serology testing
Urinalysis for Nephritic syndrome?
Dipstick: proteinuria (<3.5g/day), hematuria
Microscopy: RBC casts
Renal biopsy for Nephritic syndrome (given no C/I)?
Inc. WBCs, mesangial cells, immune complex disposition
Crescent shaped glomerulus on renal biopsy indicates what?
Rapidly progressing glomerulonephritis (RPGN)
Nephritic syndrome is treated by who?
Nephrologist
Treatment/management of nephritic syndrome?
Address HTN/fluid overload, immunosuppressive agents if required
What may be considered in treatment of nephritic syndrome in patients without AKI?
Antiproteinuric therapy w/ ACEi or ARB
What may be indicated in treatment of Nephritic syndrome w/ profound AKI?
Dialysis
Post-infectious glomerulonephritis is most often caused by what?
Nephritogenic group A beta-hemolytic strep (pharyngitis or impetigo)
Onset of post-infectious glomerulonephritis?
1-3 weeks after infection
What infections can cause infection-related glomerulonephritis (glomerular injury during active infection)?
Bacterial pneumonia, infectious mono, syphilis
S/Sx of post-infectious glomerulonephritis?
Hematuria (smoky/coca-cola color), proteinuria, edema, HTN, severe oliguria
Lab indicators of post-infectious glomerulonephritis?
Increased ASO titers
Urinalysis: hematuria, RBC casts, proteinuria
Renal biopsy for post-infectious glomerulonephritis?
Diffuse proliferative pattern of injury on light microscopy
Treatment for post-infectious glomerulonephritis?
-Identify/tx underlying infection
-Supportive care: control BP/fluid overload (BP meds, diuretics, salt restriction)
Prognosis for post-infectious glomerulonephritis?
Depends on severity & age
Children: usual full recovery
Adults: more prone to severe dz/CKD progression
What is IgA Nephropathy aka Berger Disease (nephritic)?
IgA deposited in glomerulus
Cause of IgA Nephropathy aka Berger Disease (nephritic)?
Unknown, possibly preceding URI
Primary IgA Nephropathy aka Berger Disease (nephritic) is ________
inherited
IgA Nephropathy aka Berger Disease (nephritic) can be secondary to which infections/conditions?
HIV, CMV, celiac, cirrhosis
Prevalence of IgA Nephropathy aka Berger Disease (nephritic)?
- MC in children/young adults
- Males
-MC primary glomerular dz in western world (esp. Asia)
Classic presentation of IgA Nephropathy aka Berger Disease (nephritic)?
Gross hematuria associated w/ URI, red/smoky urine 1-2 days after onset, possible proteinuria, HTN, or other nephritic sx
Is there any helpful serology testing for IgA Nephropathy aka Berger Disease (nephritic)?
no
Renal biopsy for IgA Nephropathy aka Berger Disease (nephritic)?
Focal glomerulonephritis w/ mesangial proliferation, if rapidly progressive: crescent formation (rare)
Treatment approach for IgA Nephropathy aka Berger Disease (nephritic) is tailored to what?
Risk of progression
Low risk: no HTN, normal GFR, minimal proteinuria
High risk: proteinuria >1g/day, dec. GFR, or HTN
Treatment for IgA Nephropathy aka Berger Disease (nephritic) with low risk of progression?
Low risk of progression: Monitor annually
High risk of progression: ACEi or ARB for BP/proteinuria control
+/- corticosteroids, kidney transplant in ESRD
Recurrence of IgA Nephropathy aka Berger Disease (nephritic) after kidney transplant?
30% recurrence 5-10 years post-transplant (rarely leads to failure)
What amount of patients IgA Nephropathy aka Berger Disease (nephritic) have spontaneous remission?
1/3 of pts
What is Henoch-Schonlein Purpura (HSP) (nephritic)?
Systemic small vessel leukocytoclastic vasculitis w/ IgA depositing on glomerular vessel walls
“IgA vasculitis”
Prevalence of Henoch-Schonlein Purpura (HSP) (nephritic)?
MC in children, males w/ inciting infection (group A strep)
Cause of Henoch-Schonlein Purpura (HSP) (nephritic)?
Preceding URI/GI infection, (?) exposure to allergen
S/Sx of Henoch-Schonlein Purpura (HSP) (nephritic)?
Prodrome: headache, fever, anorexia
Sx: Arthralgia, hematuria, colicky abd pain, nausea, palpable purpura of LE (HALLMARK)
What % of patients with Henoch-Schonlein Purpura (HSP) (nephritic) have kidney involvement?
20-50%
Treatment of Henoch-Schonlein Purpura (HSP) (nephritic)?
Usually self-limiting, supportive care
If severe: Immunosuppressants, plasma exchange
What may occur from severe Henoch-Schonlein Purpura (HSP) (nephritic)?
CKD, ESRD
Monitoring of Henoch-Schonlein Purpura (HSP) (nephritic)?
Urinalysis and BP 6 months after initial presentation
What causes Pauci-Immune Glomerulonephritis (nephritic)?
Various systemic ANCA-associated small vessel vasculitides or may present as primary renal lesion w/ no systemic involvement
Pauci-Immune Glomerulonephritis (nephritic) is considered to be ______ ______
Rapidly progressive
S/Sx of Pauci-Immune Glomerulonephritis (nephritic)?
Systemic inflammation (fever, malaise, wt. loss), hematuria, proteinuria, purpura
Is serology used for the dx of Pauci-Immune Glomerulonephritis (nephritic)?
Often used
Biopsy for Pauci-Immune Glomerulonephritis (nephritic) is required and should to be done when?
ASAP
Biopsy results for Pauci-Immune Glomerulonephritis (nephritic)?
Necrotizing lesions and crescents on light microscopy, lack of antibody deposition
Treatment of Pauci-Immune Glomerulonephritis (nephritic)?
High dose steroids & cytotoxic agents
Prognosis of Pauci-Immune Glomerulonephritis (nephritic)?
Extremely poor if not treated, complete remission in 75% if aggressively treated
Antiglomerular basement membrane GN and Goodpasture Syndrome (nephritic) are considered to be ______ _________
Rapidly progressive
What happens in Antiglomerular basement membrane GN (nephritic)?
Autoantibodies are directed against the glomerular BM causing GN
What causes Goodpasture Syndrome (nephritic)?
Concomitant immune attack on alveolar BM results in pulmonary hemorrhage as well as GN from Antiglomerular basement membrane
(GN + pulmonary hemorrhage)
The onset of Antiglomerular basement membrane GN and Goodpasture Syndrome (nephritic) is often preceded by what?
URI
S/Sx of Antiglomerular basement membrane GN and Goodpasture Syndrome (nephritic)?
Hemoptysis, dyspnea, possible respiratory failure, hematuria, proteinuria
CXR for Antiglomerular basement membrane GN and Goodpasture Syndrome (nephritic) may show what?
Pulmonary infiltrates if pulm hemorrhage present
Are serology & urinalysis helpful in the dx of Antiglomerular basement membrane GN and Goodpasture Syndrome (nephritic)?
Yes (+anti-GBM antibodies serology)
Urinalysis helpful
Renal Biopsy for Antiglomerular basement membrane GN and Goodpasture Syndrome (nephritic)?
Crescent formation on light microscopy
Treatment for Antiglomerular basement membrane GN and Goodpasture Syndrome (nephritic)?
*Emergent tx if pulm hemorrhage & strong suspicion for Goodpastures
Plasma exchange & corticosteroids
What med has been used for refractory cases of Antiglomerular basement membrane GN and Goodpasture Syndrome (nephritic)?
Rituximab
Prognosis of Antiglomerular basement membrane GN and Goodpasture Syndrome (nephritic)?
If oliguric AKI or require dialysis: poor
What is Cryoglobulin-Associated GN (nephritic)?
Vasculitis caused by cold-precipitable immunoglobulins (cryoglobulins) –> Immune complexes deposit in vessels/cause inflammation
Most common underlying infection in Cryoglobulin-Associated GN (nephritic)?
HCV
S/Sx of Cryoglobulin-Associated GN (nephritic)?
Purpuric necrotizing skin lesions in dependent areas, fever, hepatosplenomegaly, arthralgias
What would be elevated in Cryoglobulin-Associated GN (nephritic)?
Rheumatoid factor & cryoglobulin (+)
Treatment for Cryoglobulin-Associated GN (nephritic)?
Tx underlying cause (ex. viral suppression)
What is Nephrotic Syndrome characterized by?
Proteinuria, hypoalbuminemia, hyperlipidemia, edema
Primary causes of Nephrotic Syndrome?
Minimal change disease, Focal segmental glomerulosclerosis (FSGS), Membranous neuropathy
Secondary causes of Nephrotic Syndrome?
DM (MC), autoimmune disease, infections, malignancy, meds
S/Sx of Nephrotic Syndrome?
Edema (peripheral or generalized, periorbital), proteinuria (>3.5g/day), Frothy urine, DVT, dyspnea
Diagnostics for Nephrotic Syndrome?
CBC, CMP, lipid panel, serology, Urinalysis, Renal bx
Urinalysis for Nephrotic Syndrome?
Spot urine protein:Cr ratio or 24hr protein excretion (>3.5g/day), Proteinuria (foamy), often bland microscopy (few elements, fatty casts, oval fat bodies in HLD)
Treatment for Nephrotic Syndrome?
Address: protein, edema, hyperlipidemia, hypercoagulable states (Low serum albumin <2g/dL)
Often includes immunosuppressive therapy (steroids)
Nephrotic syndrome requires immediate referral to where?
Nephrology
When to admit pts w/ Nephrotic Syndrome?
Refractory edema and rapidly worsening kidney function
How to address protein in Nephrotic Syndrome treatment?
Limit in mild dz, replace in severe dz, ACEi or ARBs lower urine protein excretion
Monitor for: AKI & hyperkalemia (do not use both meds together d/t risk of hyperkalemia)
How to address edema in Nephrotic Syndrome treatment?
Dietary salt restriction, diuretics
How to address hyperlipidemia in Nephrotic Syndrome treatment?
Diet & exercise, pharmacotherapy
What causes hypercoagulable states (Low serum albumin <2g/dL) in Nephrotic Syndrome treatment?
Urinary loss of anti-thrombin proteins c & s —> increased platelet activation
Management of hypercoagulable states (Low serum albumin <2g/dL) in Nephrotic Syndrome treatment?
Warfarin for at least 3-6 months if evidence of thrombosis
If PE, renal vein thrombosis, recurrent thromboemboli: may require indefinite anticoagulation
What is the most common cause of proteinuric renal disease in children (80%)?
Minimal change disease
S/Sx of Minimal change disease (nephrotic)?
Full nephrotic syndrome sx
Is serology helpful in the dx of Minimal change disease (nephrotic)?
No
Bx for Minimal change disease (nephrotic) is reserved for which patients?
refractory disease or unusual presentation (systemic sx)
*usually appears normal on microscopy
Treatment of Minimal change disease (nephrotic)?
Empiric tx and often has remission in 4-8wks w/ oral corticosteroids
Is relapse with Minimal change disease (nephrotic) common?
Yes (but progression to ESRD is rare)
Complications of Minimal change disease (nephrotic) are usually related to what?
Prolonged corticosteroid use
What is Focal segmental glomerulosclerosis (FSGS) (nephrotic)?
Renal injury from damage to podocytes: primary (inherited) or secondary (obesity, HTN, HIV, renal overwork)
S/Sx of Focal segmental glomerulosclerosis (FSGS) (nephrotic)?
Proteinuria, dec. GFR, nephrotic sx in primary dz
Is serology helpful in dx of Focal segmental glomerulosclerosis (FSGS) (nephrotic)?
No
Dx of Focal segmental glomerulosclerosis (FSGS) (nephrotic) requires what?
Renal bx
Treatment for all forms of Focal segmental glomerulosclerosis (FSGS) (nephrotic)?
Diuretics (edema), ACEi or ARB (HTN, proteinuria), Statin or Niacin (hyperlipidemia)
Reserve what meds for primary Focal segmental glomerulosclerosis (FSGS) (nephrotic)?
Immunosuppressants (steroids)
Treatment for secondary Focal segmental glomerulosclerosis (FSGS) (nephrotic)?
Tx underlying cause (obesity, HTN, etc.)
Most common cause of primary nephrotic syndrome in adults?
Membranous nephropathy
Causes of Membranous nephropathy (nephrotic)?
Autoimmune (complex deposited in glomerular capillary walls)
Secondary causes: Cancer, Hep B/C, Syphilis, SLE, NSAIDs
S/Sx of Membranous nephropathy (nephrotic)?
May be asx or have edema, frothy urine, DVT (may be initial sign)
Diagnostics for Membranous nephropathy (nephrotic)?
Serology (for underlying illness), cancer screening
Treatment for Membranous nephropathy (nephrotic)?
Tx underlying illness/cause
Conservative tx - (ACEi, ARBs for antiproteinuric)
Immunosuppressant tx is reserved for what patients with Membranous nephropathy (nephrotic)?
Those w/ increased risk of progression to ESRD or refractory to conservative treatment
Disease course of Membranous nephropathy (nephrotic)?
Vairable: 50% progress to ESRD, some spontaneously resolve
*excellent transplant candidates
Renal biopsy for Minimal change disease (nephrotic)?
Normal light microscopy
Loss of podocytes on electron microscopy
Renal biopsy for FSGS (nephrotic)?
Sclerosis of some glomeruli segments on light microscopy
Renal biopsy for Membranous nephropathy (nephrotic)?
Thick basement membrane