Nephrotic Syndrome Flashcards
What is the definition of nephrotic syndrome?
Proteinuria >3.5g/24 hours plus Hypoalbuminemia and oedema
What is the aetiology of nephrotic syndrome?
Primary glomertular disorders (80-90% of cases) and or systemic diseases and toxic exposures (10-20% of cases)
Primary (idiopathic) forms - often associated with other conditions - minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis
Secondary forms - diabetic nephropathy, amyloid nephropathy, lupus nephritis
What is nephrotic syndrome?
Collection of symptoms and signs indicating damage to the glomerular filtration barrier. Characterised by massive proteinuria, Hypoalbuminemia and oedema
What are the clinical features of nephrotic syndrome?
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
Other clinical features
Hypercoagulable state with increased risk of thrombosis and embolic events (e.g., pulmonary embolism, renal vein thrombosis)
Increased susceptibility to infection
Hypertension in some cases
Possibly frothy urine
Symptoms of hypocalcemia (e.g., tetany, paresthesia, muscle spasms)
Symptoms of the underlying disease (e.g., malar rash in lupus nephritis)
See also “Nephrotic vs. nephritic syndrome.”
What are the diagnostics for nephrotic syndrome?
Initial evaluation - confirmation of nephrotic range proteinuria - qualitative assessment by urine dipstick - usually shows > 3+ proteins. Hematuria may indicate concomitant glomerulonephritis
Quantitative assessments of urine protein excretion - 24 hour urine protein - >3.5g/24 hours. Spot urine protein/creatinine ratio >3.5g/g
Urine sediment microscopy - nephrotic sediment - lipiduria, renal tubular epithelial cell casts. Hematuria with acanthocytes and or RBC casts
What are the additional lab studies for nephrotic syndrome?
CBC - increased Hb/Hct
BMP - increased creatinine and or BUN, decreased sodium is commonly seen
Serum protein - decreased total protein, decreased albumin (<3g/dl)
Coagulation factors - decreased Antithrombin 3, decreased protein S (cofactor of protein C), decreased plasminogen, increased fibrinogen, increased D dimer
Lipid profile - hyperlipidemia
Vitamin D levels - decreased
Inflammatory markers - increased ESR, increased CRP may indicate underlying infection
Ultrasound to assess kidney size and shape to rule out obstruction
When is a renal biopsy recommended?
To confirm the diagnosis when the aetiology of nephrotic syndrome is unclear and or to guide management
What is the management for symptoms and complications of nephrotic syndrome?
Oedema - dietary sodium restriction <3g/day
Fluids restriction - <1.5L/day
Diuretic therapy - first line - oral loop diuretic, second line - add oral thiazide or thiazide like diuretic and or switch to IV loop diuretic. Consider adjunctive IV albumin
Proteinuria - antiproteinuric therapy - indicated in most patients. RAAS inhibitor - ACE inhibitor or ARB are most commonly used - effects - reduces proteinuria, treats hypertension, may slow progression of any underlying renal diseases. Also can administer low sodium diet, thiazide diuretic, mineralocorticoid receptor antagonist. Dietary protein - avoid high protein diet
Dyslipidemia - lipid lowering therapy
Hypercoagulability - prophylactic anticoagulation eg heparin or warfarin
Infectious risk - pneumococcal vaccination, annual vaccination for influenza
What is the treatment plan for primary forms of nephrotic glomerulopathies?
Immunosuppressive therapies eg glucocorticoids
Primary membranous nephropathy - initial management - conservative therapy including RAAS inhibitor. Can consider immunosuppressive therapy eg prednisone AND cyclophosphamide
Primary focal segmental glomerulosclerosis - initial management - supportive therapy including RAAS inhibitor. Consider immunosuppressive therapy eg prednisone AND cyclophosphamide
Primary minimal change disease - initial - immunosuppressive therapy eg prednisone
Diabetic nephropathy - Strict glycemic control
RAAS inhibition (e.g., ACEI or ARB)
Optimization of blood pressure control
Close surveillance and timely referral to renal replacement therapy if ESRD (end stage renal disease) is anticipated
Amyloid nephropathy - treatment of the underlying disease
Lupus nephritis - pharmacological management - IV glucocorticoids, plus other immunosuppressants eg cyclophosphamide
What are the complications of nephrotic syndrome?
Thrombotic complications [45]
Venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism)
Arterial thromboembolism
Renal vein thrombosis: thrombus formation in the renal veins or their branches [46]
Cause: hypercoagulable state (e.g., malignancies, antiphospholipid syndrome, nephrotic syndrome)
Manifestations: flank pain, hematuria, ↑ LDH, anuria/renal failure in bilateral thrombosis
Diagnostics
CT angiography or MR venography (preferred modality in patients with renal injury or failure)
Doppler ultrasonography if no other diagnostic modality is available
Treatment
Anticoagulation
Thrombolysis or thrombectomy in selected patients
Complications: rupture of renal capsule, pulmonary embolism, kidney injury
Atherosclerotic complications [45][47]
Abnormal lipid metabolism in combination with a hypercoagulable state leads to an increased risk of atherosclerotic complications
Manifestation: myocardial infarction, stroke
Chronic kidney disease: FSGS and membranous nephropathy in particular may progress to chronic kidney disease and ESRD.
What is the DD for nephrotic syndrome?
Nephritic syndrome
Lupus nephritis
What is the prognosis for nephrotic syndrome?
Minimal change disease - usually excellent
