A. 37 Nephrotic Syndrome Flashcards
A. 37 Nephrotic Syndrome
define
Nephrotic syndrome is a collection of signs and symptoms indicating damage to the glomerular filtration barrier. It is characterized by massive proteinuria (> 3.5 g/24 hours), hypoalbuminemia, and edema.
A. 37 Nephrotic Syndrome
Name the nephrotic diseases
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Diabetic nephropathy
Amyloid nephropathy
Membranoproliferative glomerulonephriti
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General Pathophysiology
Damage of glomerular filtration barrier
Sequelae of glomerular filter damage
- Structural damage of glomerular filtration barrier → massive renal loss of protein (hyperproteinuria) → reactively increased hepatic protein synthesis
- Loss of negative charge of glomerular basement membrane → loss of selectivity of barrier (especially for negatively charged albumin)
- Podocyte damage and fusion → nonselective proteinuria (except in minimal change disease, which manifests with selective glomerular proteinuria) [7]
If protein loss exceeds hepatic synthesis (usually with a loss of protein > 3.5 g/24 hours) → hypoproteinemia/hypoalbuminemia, initially with both normal GFR and creatinine
- ↓ Serum albumin → ↓ colloid osmotic pressure → edema (especially if albumin levels are < 2.5 g/dL)
Loss of antithrombin III, protein C, and protein S, increased synthesis of fibrinogen, and loss of fluid into the extravascular space → hypercoagulability
Loss of transport proteins
- Loss of thyroglobulin transport protein → thyroxin deficiency
Vitamin D binding protein → vitamin D deficiency
- Loss of plasma proteins → ↓ plasma protein binding → increase in free plasma drug concentration, but drug toxicity is usually not increased [18][19][20]
↑ Plasma levels of cholesterol, LDL, triglycerides, and lipoproteins (mainly LPA) to compensate for the loss of albumin → lipiduria (fatty casts) [21]
Loss of immunoglobulins → increased risk of infection, especially Streptococcus pneumoniae infection (pulmonary edema also increases the risk for S. pneumoniae infection)
Sodium retention → possible hypertension
A. 37 Nephrotic Syndrome
Clinical Features
- Massive proteinuria > 3.5 g/24 hours
- Edema
Typically starts with periorbital edema
Peripheral edema (pitting)
Pleural effusion
Pericardial effusion
Ascites
In severe cases, anasarca - Hypoalbuminemia
- Hyperlipidemia
- Hypercoagulable state with increased risk of thrombosis and embolic events (e.g., pulmonary embolism, renal vein thrombosis)
- Increased susceptibility to infection
A. 37 Nephrotic Syndrome
DX
- Confirm nephrotic-range proteinuria.
- Assess for potential concomitant and underlying conditions.
- Assess for nephrotic syndrome complications.
- Consider kidney biopsy to determine renal pathology.
A. 37 Nephrotic Syndrome
urinanalysis
Urine sediment microscopy
- Nephrotic sediment
- Lipiduria, fatty casts with Maltese cross appearance under polarized light
- Renal tubular epithelial cell casts
A. 37 Nephrotic Syndrome
Labs
CBC: ↑ Hb/Hct may indicate hemoconcentration
BMP: ↑ Cr and/or ↑ BUN may be seen; ↓ Na is commonly seen. Serum protein: ↓ total protein, ↓ albumin (< 3 g/dL)
Coagulation factors: ↓ ATIII, ↓ protein S, ↓ plasminogen ; ↑ fibrinogen, ↑ D-dimer
Lipid profile: Hyperlipidemia (↑ LDL, ↑ triglycerides) may be present.
Vitamin D levels: ↓ 25-OH Vit-D
Inflammatory markers: ↑ ESR, ↑ CRP may suggest underlying infection, inflammatory condition, or vasculitis.
A. 37 Nephrotic Syndrome
TX
Edema
Dietary sodium restriction: < 3 g/day (usually 1.5–2 g/day) [1][12]
Fluid restriction: < 1.5 liters/day
First-line: oral loop diuretic e.g., furosemide
Proteinuria
RAAS inhibitor: ACEI e.g., ramipril or ARB e.g., losartan
Dyslipidemia
Lipid-lowering therapy (e.g., atorvastatin
Hypercoagulability
Prophylactic anticoagulation: UFH
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Minimal Change Disease
Most common cause of nephrotic syndrome in children
Often idiopathic
Secondary causes (rare)
Immune stimulus (e.g., infection, immunization)
Tumors (e.g., Hodgkin lymphoma)
Certain drugs (e.g., NSAIDs)
effacement of podocyte foot processes
Selective glomerular proteinuria
TX - Predinsone
A. 37 Nephrotic Syndrome
Focal segmental glomeruloscleros
Most common cause of nephrotic syndrome in adults,
Can be idiopathic
Heroin use
HIV infection
Sickle cell disease
Massive obesity
Interferon treatment
Congenital malformations (e.g., Charcot-Marie-Tooth syndrome) [8][9]
NPHS1 and NHPS2 mutations
Possibly IgM, C1, and C3 deposits inside the sclerotic regions
EM: effacement of podocyte foot processes
TX
Prednisone (often shows poor response)
If necessary, PLUS other immunosuppressants (e.g., cyclosporine, tacrolimus)
RAAS inhibitors
A. 37 Nephrotic Syndrome
Membranous nephropathy
Primary: anti-PLA2R antibodies
Secondary:
Infections (HBV, HCV, malaria, syphilis)
Autoimmune diseases (e.g., SLE)
Tumors (e.g., lung cancer, prostate cancer)
Medications (e.g., NSAIDs, penicillamine, gold)
Granular subepithelial deposits of IgG and C3 (dense deposits) → spike and dome appearance
TX
RAAS inhibitors
Prednisone (often shows poor response)
PLUS other immunosuppressants (e.g., cyclophosphamide) in severe disease
Usually leads to ESRD if left untreated
A. 37 Nephrotic Syndrome
Diabetic nephropathy
Leading cause of ESRD in high-income countries
Eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson nodules)
Mesangial matrix expansion
TX
Stringent glycemic control
RAAS inhibitors
A. 37 Nephrotic Syndrome
Amyloid nephropathy
More commonly seen in elderly patients
The kidney is the most commonly affected organ in systemic amyloidosis.
Multiple myeloma(AL amyloidosis)
Chronic inflammatory disease, e.g., tuberculosis, rheumatoid arthritis (AA amyloidosis)
Congo red stain: amyloid deposition in the mesangium showing apple-green birefringence under polarized light
Nodular glomerulosclerosis
IM: positive for AA protein (AA amyloidosis), positive for kappa and lambda light chains (AL amyloidosis)
EM: amyloid fibrils
TX
Melphalan, corticosteroids
Treatment of underlying disease (e.g., bone marrow transplantation may be used for multiple myeloma)
A. 37 Nephrotic Syndrome
Membranoproliferative glomerulonephritis
Usually manifests with nephritic sediment, which can indicate:
Nephritic-nephrotic syndrome: if there is concomitant nephrotic-range proteinuria (> 3.5 g/24 hours)
Pure nephritic syndrome: if there is no proteinuria or proteinuria is below nephrotic range (< 3.5 g/24 hours)
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Complications
Thrombotic complications
Venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism)
Arterial thromboembolism
Renal vein thrombosis: thrombus formation in the renal veins or their branches
Athersclerosis
CKD
Increased risk of infections
vit D deficiency
anemia
