Snapshot A 6-year-old boy is brought to the emergency department by his mother due to swelling around his eyes and legs. The mother reports that the patient recently recovered from an upper respiratory tract infection. Physical exam is significant for periorbital and lower extremity edema. Laboratory testing is significant for hypoalbuminemia and normal complement levels. Urinalysis demonstrates 4+ protein. A presumptive diagnosis of minimal change disease is made and the patient is started on steroid therapy. Introduction Clinical definition a type of kidney disease that results in proteinuria, peripheral edema, hyperlipidemia, and hypoalbuminemia Associated conditions chronic kidney disease HBV membranous nephropathy Epidemiology Incidence annually there are 3 cases per 100,000 adults Etiology Primary glomerular disease focal segmental glomerulosclerosis most common cause of nephrotic syndrome in adults membranous nephropathy minimal change disease Secondary causes diabetic nephropathy systemic lupus erythematosus amyloidosis Pathogenesis the glomerulus becomes permeable to large molecules (e.g., albumin) this loss of albumin (proteinuria) results in hypoalbuminemia and edema associated with a hypercoagulable state pathophysiology unclear but may be due to loss of antithrombin and plasminogen proteins increased lipid synthesis secondary to proteinuria this in turn results in hypercholesterolemia and hyperlipidemia Presentation Symptoms edema periorbital, lower extremity, and genital edema frothy urine ascites weight gain fatigue shortness of breath Physical exam hypertension edema leukonychia suggestive of a low albumin state and presents as white streaking on the fingernails Studies Labs hypoalbuminemia (serum albumin of < 2.5 g/dL) hyperlipidemia Urine studies rule out transient / orthostatic proteinuria if no symptoms or signs are present other than proteinuria proteinuria > 3-3.5 g/day or > 300-350 mg/mmol on spot urine protein to creatinine ratio fatty casts with "maltese cross" sign Nephrotic SyndromeTypePathophysiologyRenal BiopsyTreatment and NotesFocal segmental glomerulosclerosis <ul><li>Podocyte injury or decreased glomerular filtration barrier integrity</li></ul><ul><li>Light microscopy<ul><li>segmental scarring</li></ul></li></ul><ul><li>Treat underlying etiology in secondary causes</li><li>Steroid therapy</li><li>Can be secondary to<ul><li>HIV<a title="question" href="#104497" link-extracted="true"><img src="/images/question.png" alt=""></a><a title="question" href="#214547" link-extracted="true"><img src="/images/question.png" alt=""></a></li><li>sickle cell disease</li><li>heroin abuse</li><li>interferon treatment</li></ul></li></ul>Minimal change disease<a title="question" href="#106080" link-extracted="true"><img src="/images/question.png" alt=""></a><ul><li>Unclear but may be due to an immune-related mechanism</li></ul><ul><li>Light microscopy<ul><li>normal appearing</li></ul></li><li>Electron microscopy<ul><li>effacement of the foot processes</li></ul></li></ul><ul><li>Steroid therapy<a title="question" href="#105566" link-extracted="true"><img src="/images/question.png" alt=""></a></li><li>Most common in children</li><li>May follow recent infection, immunizations, or may be idiopathic</li><li>Can be associated with Hodgkin lymphoma<a title="question" href="#104622" link-extracted="true"><img src="/images/question_step_2.png" alt=""></a><a title="question" href="#106281" link-extracted="true"><img src="/images/question_step_2.png" alt=""></a><a title="question" href="#104622" link-extracted="true"></a></li></ul>Membranous nephropathy<ul><li>Antibody-immune complex deposition<ul><li>IgG antibodies target podocyte antigens<ul><li>or antigens in close proximity to the podocytes</li></ul></li></ul></li><li>Complement-mediated podocyte injury</li></ul><ul><li>Light microscopy<ul><li>glomerular basement membrane thickening</li></ul></li><li>Immunofluoresence<ul><li>immune complex deposition leading to granular appearance</li></ul></li><li>Electron microscopy<ul><li>"spike and dome"</li><li>subepithelial deposits</li></ul></li></ul><ul><li>Immunosuppressive therapy in primary cases<ul><li>steroids and cyclophosphamide</li></ul></li><li>Most common cause of primary nephrotic syndrome in Caucasian adults</li><li>Primary causes<ul><li>antibodies targeting phospholipase A2 receptors</li></ul></li><li>Secondary causes<ul><li>medications</li><li>systemic lupus erythematosus</li><li>nonsteroidal anti-inflammatory drugs</li><li>gold</li><li>penicillamine</li><li>hepatitis B and C infection</li></ul></li></ul>Amyloidosis<ul><li>Amyloid deposits in the mesangium</li></ul><ul><li>Electronmicroscopy<ul><li>apple-green birefringence on Congo red stain under polarized light<a title="question" href="#213222" link-extracted="true"><img src="/images/question.png" alt=""></a></li></ul></li></ul><ul><li>Associated with multiple myeloma and chronic inflammatory conditions (i.e., rheumatoid arthritis)</li><li>Treatment involves addressing the plasma cell dyscrasia or management of the underlying inflammatory condition</li></ul>Diabetic glomerulonephropathy<ul><li>Glomerular hyperperfusion and hyperfiltration result in albumin leaking<ul><li>under these conditions the glomerulus responds via<ul><li>glomerular basement membrane thickening<ul><li>due to non-enzymetic glycosylation</li></ul></li><li>hypertrophy</li><li>sclerosing</li><li>podocyte injury</li></ul></li></ul></li></ul><ul><li>Light microscopy<ul><li>expansion of the mesangium</li><li>Kimmelstiel-Wilson lesions</li></ul></li></ul><ul><li>Angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)</li><li>Adequately controlling diabetes</li></ul> Prognosis Depends on the underlying cause e.g., patients with minimal change disease typically respond well to steroid therapy