SM 205a/208a/209a/212a - Renal Syndromes, Nephrosis, Nephritis Flashcards
Characteristic of nephritic or nephrotic syndrome?
WBC casts
Neither
Interstitial cause likely
Kimmelsteiel-Wilson nodules are pathopneumonic for which renal syndrome?
Diabetic nephropathy
What conditions might FSGS be secondary to?
HIV + Heroine use
Reduced renal mass
Hyperfiltration injury
Obesity
What pathologic findings are present?
Focal segmental glomerulosclerosis
Not all glomeruli show sclerosis (focal)
Only parts of the affected glomeruli are affected (segmental)
How does sepsis affect glomerular macromolecule handling?
Sepsis -> Podocyte dysfunction
- Alters slit diaphragm structure and function
- More proteinuria
What is the treatment for minimal change disease?
What should you consider if there is no response?
Steroids
If no response, consider FSGS
If initial response but frequent relapse, try steroid-sparing immunosuppressive agents
Characteristic of nephritis or nephrosis?
Low serium albumin
Nephrosis
What are the differences in the presentation of IgA nephropathy and PIGN?
-
Timing
- IgA nephropathy is synpharyngitic and recurrent
- Occurs at the same time or soon after URI or sore throat
- Patient may report that they have had other episodes of hematuria throughout their lives
- PIGN occurs after infection (7-14 days), and is not recurrent
- IgA nephropathy is synpharyngitic and recurrent
-
Biopsy
- IgA nephropathy shows mesangial deposits
- LM: Mesangial proliferation
- FM: Granular mesangial deposits
- EM: Mesangial deposits
- PIGN shows granular deposits
- LM: Hypercellularity
- FM: Starry sky
- EM: Sub-epithelial humps
- IgA nephropathy shows mesangial deposits
What levels of proteinuria qualify as “nephrotic range?”
- Adults: 3 gm/day
- Children: 50 mg/kg/day
- Urine Prot: Urine Creatinine > 2
What is “nephrotic-range proteinuria?”
Proteinuria >2.5 - 3 grams/day
Can use (urine protein / urine creatinine) = grams of protein/day
as a proxy for 24h urine collection
Which patients with suspected nephrotic syndrome are not routinely biopsied?
Children
If suspicion is high for minimal change disease, treat empirically with corticosteroids
If the patient recovers, it was likely MCD and you avoided doing an invasive procedure :)
Which renal syndromes result from primary glomerular disease?
Membranous nephropathy (nephrotic)
Membranoproliferative glomerulonephritis (nephritic)
What is the classic finding for Pauci-Immune Glomerulonephritis?
ANCA
Pauci-Immune = microscopic polyangiitis (p-ANCA) or
granulomatosis with polyangiitis (c-ANCA)
Glomerular handling of macromolecule is dependent on…
Size and charge
Which renal syndrome will show linear IgG deposits on FM?
Anti-GBM disease
(aka RPGN Type I)
A nephritic syndrome
Why is important to identify and treat membranous nephropathy quickly?
To avoid potential complications
- Renal vein thrombosis
- Pulmonary embolism due to hypercoagulability
What renal syndrome shows this pattern on immunofluorescence?
What would you expect from the patient’s history?
- IgA Neprhopathy (nephritic)
- Deposits in the mesangium instead of the basement membane
- We would expect them to be IgA
- History
- Recurrent hematuria (tea/cola colored urine) associated with URI or pharyngitis
- Synpharyngitic - occurs during or very soon after infection
What is the mechanism of hyperlipidemia in nephrotic syndrome?
Multiple potential causes
- Increased hepatic lipoprotein synthesis
- Oncotic/viscosity signal
- May be overlap with albumin synthesis pathway and lipid synthesis pathway
- Defective lipid transport
- HDL lost in urine
- Decreased LPL and LCAT activity
- Albumin binds to the products of cholesterol breakdown
- Loss of albumin = cannot bind to products = le chaltlier towards the reactants
- Decreaed cholesterol breakdown
What is the treatment for lupus nephritis?
Depends on the level of inflammation
- Minimal inflammation
- Focus on treatment of lupus
- Active inflammation
- High-dose steroids + immune-modulating drugs
(important to control inflammation to protect the kidney)
- High-dose steroids + immune-modulating drugs
Which renal syndromes are associated with a history of Hep B and Hep C?
- Nephrotic
- Membranous nephropathy
- Nephriti
- MPGN
Apple-green birefringensce in polarized light on a congo-red stain is characteristic of what pathologic finding?
Amyloidosis
The most critical determinant of whether or not a molecule of effective Stokes radius = 40 Å is filtered by the glomerulus is:
a. Blood pressure
b. Hydration status
c. The endothelial glycocalyx
d. The lamina densa of the glomerular basement membrane
e. The epithelial slit pore
e. The epithelial slit pore
40 Å is on the larger side of proteins that can be filtered - the large size of this protein matters more than any charge hindrance or hydrostatic forces that typically affect smaller proteins
What are the characteristics of IgA nephropathy on…
LM
FM
EM
IgA nephropathy = nephritic
- LM
- Mesangial proliferation (hypercellularity)
- FM
- Granular IgA deposits in the mesangium
- EM
- Mesangial deposits
How is membranous nephropathy treated?
- Secondary: treat underlying cause (if presnt)
- Solid tumor cancer treatment
- Stop medication exposure
- Treat Hep B or Hep C
- Treat Lupus
- Primary: Depends on degree of proteinuria
- Low-level: RAAs blockade, Na+ restriction, diuresis
- High-level: Immune modulation
Characteristic of nephritic or nephrotic syndrome?
Proteinuria >3 grams/day
Neprotic
What defines nephrotic syndrome?
(Classic tetrad)
- Proteinuria
- Hypoalbuminemia
- Edema
- Hypercholesterolemia
What is required for a diagnosis of lupus nephritis?
Kidney biopsy + History of lupus
What are the major nephritic syndromes?
- Immune Complex
- IgA
- PIGN
- Lupus Nephritis
- Pauci-Immune
- ANCA-Associated GN (vasculitis, +P-ANCA, +C-ANCA)
- Anti-GBM
What tubular dysfunctions can cause proteinuria?
- Dent disease
- Disorder of chloride transport, cannot reabsorb protien
- Fanconi syndrome
- Nephropathic cystinosis
- Tubulointerstitial nephritis
- Nephrotoxins
What are the 3 major primary nephrotic syndromes?
Minimal Change Diseae
Focal Segmental Glomerular Sclerosis
Membranous Nephropathy
What are the characteristics of diabetic nephropathy on light microscopy?
Diffuse GBM thickening (leads to proteinuria)
Nodular sclerosis: Kimmelstiel-Wilson nodules
What is the most common cause of nephrotic syndrome in Caucasian adults?
Membranous nephropathy
Which renal syndrome is associated with APOL1 mutation?
FSGS-nephrotic syndrome
(FSGS is a pattern of injury, not a renal syndrome, I just didn’t know how else to phrase the question)
What are the characteristics of Membranous Nepropathy on..
LM:
FM:
EM:
Membranous nephropathy = nephrotic
- LM
- Thickened capillary wall (Wire-Loop)
- Thickened GBM
- Spikes and holes on silver stain
- FM
- Granular IgG and C3 deposits in the basement membrane
- EM
- Sub-epithelial immune deposits
- Spike and dome pattern
Match the image to the correct renal syndrome:
IgA Nephropathy
Anti-GBM Disease
A = Anti-GBM disease
- Linear deposits along the GBM
- Expect these to be IgG
B = IgA nephropathy
- Granular dposits in the mesangium
- Expect these to be IgA
Both are nephritic syndromes
How does podocyte effacement affect filtration of larger macromolecules?
Effacement decreases the available filtration surface area
This leads to decreased filtration of larger marcomolecules
Note: Loss of negative charges = more albumin gets through
(But less of other proteins due to decreased surface area)
Which glomerular nephritis is most common worldwide?
IgA Nephropathy
Which nephrotic syndromes result from primary podocytopathy?
Minimal change disease (MCD)
Focal Segmental Glomerulosclerosis (FSGS)
What are the characteristics of RPGN on light microscopy?
Diffuse, crescenteric glomererulonephritis affecting >50% of all glomeruli
Describe the key differences betwee Class IV Lupus Nephritis and Class V Lupus Nephritis
- Class IV
- Nephritic
- Low serum complement
- Cell proliferation, wire loops
- Class V
- Nephrotic (Yes, very confusing)
- Normal serum complement
- Thickened GBM, spike and dome pattern
- Like membranous nephropathy
What are the characteristics of FSGS on..
LM:
FM:
EM:
FSGS = nephrotic
- LM
- 1 or more lesions of segmental sclerosis
- Not all glomeruli involved
- Only a portion of each involved glomerulus is affected
- FM: nonspecific
- EM
- Podocyte effacement
Note: FSGS is a pattern of injury
May be idiopathic, drug induced, or a complication of other diseaes
How can nephrotic syndrome lead to hypercoagulability?
- Possible loss of anticoagulants in the urine
- Increased platelet aggregation: albumin is a carrier protein
- Altered fibrinolysis
- Glycoprotein charge on platelet and vessel wall
- Hemoconcentration, dehydration, steroids
Class V Lupus Nephritis presents like which renal syndrome?
Membranous nephropathy (nephrotic)
- LM
- Thickened GBM
- Spike and hole pattern on silver stain
- FM
- Full House
- EM
- Sub-epithelial immune deposits
- Spike and dome pattern
- Normal serum complement
Which proteins are necessary for reabsorbing protein in the kidney tubule?
Megalin
Cubulin
Amnnionless (in clathrin-coated pits)
Failure of these proteins -> Proteinuria
What is ANCA?
What are the relevant types?
Anti-neutrophil cytoplasmic antibodies
An autoimmune phenomenon
Present in Pauci-immune disease, a nephritic syndrome
(RPGN Type III)
- p-ANCA = antibody against myeloperoxidase
- c-ANCA = antibody against proteinase 3
- X-ANCA = atypical ANCA
Describe the characteristics of MPGN on…
LM
FM
EM
MPGN = Nephritic
- LM
- Lobular glomerulus (shown in picture)
- Hypercellular
- Tram-Tracking on silver stain
- FM
- Granular C3 deposits (+/- IgG) in the Basement Membrane
- EM
- Variable
Characteristic of nephritic or nephrotic syndrome?
Edema, hyperlipidemia, and hypoalbuminemia
Nephrotic syndrome
Characteristic of nephritis or nephrosis?
Normal heart and pleural fluid
Nephrosis
How does nephrosis affect protein homeostasis?
- Loss of plasma protein in the urine ->
- -> Decreased levels of plasma proteins
- -> peripheral edema, metabolic abnormalities
Which two renal syndromes cause foot process effacement?
Both nephrotic
- Minimal change disease
- More likely in children than adults
- No changes on LM or FM
- Focal segmental glomerulosclerosis
- More likely in adults than children
- Focal segmental sclerosis on LM
- 1 or more lesions
- FM shows non-specific staining
Whch renal syndrome shows “tram tracking” on silver stain?
MPGN (Nephritic)
What are the characteristics of Minimal Change Disease on..
LM:
FM:
EM:
Minimal change disease = Nephrotic
- LM: No changes
- FM: No changes
- EM: Podocyte effacement
Usually responds well to steroid treatment
How is FSGS treated?
Challenging
Start with steroids - Usuallly not responsive, use calcineurin inhibitor or Cellcept next
Treat secondary cause if possible
How does fluid overload affect glomerular macromolecule handling?
Increased proteinuria
Filtration equilibrium is not yet reached - Increaed overall filtration, drags proteins across the filtration barrier
How can you use serum and urinary levels of beta2-Microglobulin to differentiate between tubular and glomerular dysfunction?
Note - beta2-Microglobulin is usually freely filtered by the glomerulus and reabsorbed in the proximal tubule
- If glomerular dysfunction
- High serum beta2-Microglobulin
- Low urinary beta2-Microglobulin
- If tubular dysfunction
- Low serum beta2-Microglobulin
- High urinary beta2-Microglobulin
What are the characteristics fo Pauci-Immune disease on…
LM
FM
EM
Pauci-Immune disease = RPGN Type III - Nephritic
ANCA will show up on labs
- LM
- Fibrinoid necrosis (necrotizing vasculidities)
- Diffuse, crescenteric glomerulonephritis affecting >50% of glomeruli
- FM
- No depositis
- EM
- No deposits
A 12 year old patient presents with sudden-onset edema and 4 g/day proteinuria.
Renal biopsy shows no findings on LM or FM, but their EM is shown below:
What is the most likely diagnosis?
Minimal change disease
Which renal syndrome is characterized by a “spike and dome” pattern on EM?
Membranous nephropathy (nephrotic syndrome)
What is the best correlation for hypercoagulability in nephrotic syndrome?
Decreased circulating free protein S
Less free protein S = more hypercoagulable
What are the characteristics of Anti-GBM disease on…
LM:
FM:
EM:
Anti-GBM = RPGN Type I = Nephritic
- LM
- Diffuse, crescenteric GN affecting >50% of glomeruli
- FM
- Linear IgG deposits
- EM
- No distinct deposits - evenly distributed
Characteristic of nephritis or nephrosis?
Increased intravsascular volume
Nephritis
What are the characteristics of Post-Infectious Glomerulonephritis on…
LM
FM
EM
PIGN = Nephritic syndrome
- LM
- Hypercellularity - Neutrophils, lymphocytes
- FM
- Granular
- IgG and complement
- EM
- Sub-epithelial humps
Characteristic of nephritis or nephrosis?
Hypertension
Nephritis (usually)
(Nephrosis sometimes)
Nephritic syndrome is a clinical sequalae of __________
Nephritic syndrome is a clinical sequalae of glomerular inflammation
Why is plasmapheresis used to treated Anti-GBM Disease?
Remove immune complexes from the blood to prevent further damage to the GBM
(Plasmapheresis = remove patient’s plasma, replace it with other plasma)
Why are vomiting and diarrhea especially worrisome in nephrotic syndrome?
Can lead to low effective blood volume, which is easily missed in the setting of edema
What causes tubulointerstitial nephritis?
- Infections
- Acute pyelonephritis
- Chronic pyelonephritis and reflux nephropathy
- Drug-induced
- Analgesics
- Caffeine
- Ischemia
- Metabolic derangements
- Physical damage
Characteristic of nephritis or nephrosis?
Decreased GFR
Nephritis
Characteristic of nephritic or nephrotic syndrome?
RBCs, RBC casts
Nephritic
What are the requirements for diagnosis of FSGS?
Kidney biopsy showing…
-
Focal segmental sclerosis
- Focal = not all glomeruli are involved
- Segmental = only a portion of the involved glomeruli are affected
- 1 or more lesions of segmental sclerosis on light microscopy
- Foot process effacement on electron microscopy
What are the two proposed mechanisms for edema formation in nephrotic syndrome?
- Underfilling (traditional) model - Driven by Starling forces
- Loss of serum proteins
- -> Decreased oncotic force in the capillaries
- -> Increased movement of fluid from capillaries -> interstitium
- -> Vascular volume contraction (they are underfilled)
- -> Decreaed glomerular perfusion
- -> Increased renin secretion
- -> Thirst, aldosterone, increased Na+ reabsorption
- Overfilling model
- Primary Na+ retention drives edema
- In this case, aldosterone and renin would be low
How does dehydration affect glomerular macromolecule handling?
Increaesd proteinuria due to increased concentration of proteins in the filtrate
Characteristic of nephritis or nephrosis?
Renal inflammation
Nephritis
A patient presents with purpura, ulcers, and flu-like symptoms.
Urinalysis shows RBCs and RBC casts
LM shows fibrinoid necrosis and crescenteric glomerulonephritis affecting >50% of glomeruli
FM and EM are unremarkable
Which renal syndrome is most likely?
Nephritic
Pauci-Immune disease (RPGN Type III)
What is the treatment for Anti-GBM disease?
Aggressive treatment!
Steroids + Cyclophosphamide + Plasmapheresis
An extremely edematous child is seen in the emergency ward for relapse of known minimal change nephrotic syndrome.
What are the benefits and problems in treating the edema with furosemide?
-
Benefits
- Furosemide will effetively diurese the patient
- Interrupt the viscious cycle of nephrotic Na+ retention
-
Potential problems
- Less effective if renal perfusion in is poor
- If low EBV is missed and furosemide is given, further volume depletion could cause death
- May exacerbate hemoconcentration
- -> Thrombosis
- Wastes total body K+ stores
How does nephrotic syndrome affect bone metabolism?
Loss of Vitamin D binding protein and Vitamin D metabolites in the urine
- Usually reabsorbed by megalin, but it is busy trying to reabsorb albumin
- -> Decreased Ca2+ absorption
- -> Increased PTH (due to low Ca2+)
What is the pathologic finding assoicated with diabetic nephropathy?
Kimmelstiel-Wilson Nodules
(Nodular sclerosis)
Which renal syndrome will have ANCAs?
Pauci-Immune Disease (aka RPGN Type III)
- Neprhitic
- ANCA = Anti-neutrophil cytoplasmic antibody
- p-ANCA = antibody against myeloperoxidase
- c-ANCA = antibody against proteinase 3
Characteristic of nephritis or nephrosis?
Cardiomegaly + pulmonary edema
Nephritis
