8 y/o with three weeks of progressive edema of face, legs, and abdomen
Patient will present as → a 6-year-old boy who 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 and fatty casts with a "maltese cross" sign.
Nephrotic syndrome ⇒ patient has peripheral or periorbital edema, ascites, pleural effusions and hypertension. Proteinuria is > 3.5 grams per day (on a 24-hour urine) and lab tests show hypoalbuminemia and hyperlipidemia
"Compare this to nephritic syndromewhich is where there’s peripheral or periorbital edema, hypertension, oliguria, hematuria and proteinuria between 1 and 3 grams per day"
Proteinuria occurs because of changes to capillary endothelial cells, the glomerular basement membrane (GBM), or podocytes, which normally filter serum protein selectively by size and charge.
- The disorder results in urinary loss of macromolecular proteins, primarily albumin (protein) but also opsonins, immunoglobulins, erythropoietin, transferrin, hormone-binding proteins, and antithrombin III.
The most common primary causes are:
Membranous nephropathy: most common in non-diabetic adults associated with malignancies.
- Caused by immune complex formation in the glomerulus - basement membrane becomes damaged
Minimal change disease: the most common cause in kids. Assume minimal change disease if a child with idiopathic nephrotic syndrome improves after treatment with corticosteroids.
- The cause and pathogenesis of minimal change disease is unclear and it is currently considered idiopathic.
Focal segmental glomerulosclerosis (FSGS): obese patients, heroin, and HIV+ black males.
- Primary, when no underlying cause is found
- Secondary, when an underlying cause is identified
- Toxins and drugs such as heroin and pamidronate
- Familial forms
- Secondary to nephron loss and hyperfiltration, such as with chronic pyelonephritis and reflux, morbid obesity, diabetes mellitus
The most common secondary causes are:
- Lupus: both nephritic and nephrotic
- Diabetes: a common cause of nephrotic syndrome and subsequent renal failure
Diagnosis is suspected in patients with edema and proteinuria on urinalysis and confirmed by random (spot) urine protein and creatinine levels or 24-h measurement of urinary protein. The cause may be suggested by clinical findings (eg, SLE, preeclampsia, cancer); when the cause is unclear, additional (eg, serologic) testing and renal biopsy are indicated.
- A 24-hour protein collection demonstrating proteinuria above 3.5 grams per day (24-h urine collection) is diagnostic
- Serologic testing and renal biopsy is indicated unless the cause is clinically obvious
- Besides proteinuria, urinalysis may demonstrate casts (hyaline, granular, fatty, waxy, or epithelial cell)
- Lipiduria, the presence of free lipid or lipid within tubular cells (oval fat bodies), within casts (fatty casts), or as free globules, suggests a glomerular disorder causing nephrotic syndrome
- Hypoalbuminemia - serum albumin often is < 3.5 g/dL
- Hyperlipidemia - levels of low-density lipoprotein or LDL above 130 milligrams per deciliter and levels of triglycerides above 150 milligrams per deciliter
Treat the causative disorder and with angiotensin inhibition, Na restriction, and often diuretics and/or statins.
- Minimal change disease: Prednisone 1 mg/kg (up to 80 mg every day) × 4-8 weeks; gradually taper if a response is noted. ACE-Is may also be used as an adjunct to therapy (to reduce proteinuria), or as sole therapy in mild cases.
- Frequent relapsers: Prolonged treatment with immunosuppressants chlorambucil, cyclosporine, or cyclophosphamide should be considered.
- Membranous nephropathy: Depends on the risk of progression to ESRD; judged by the amount of proteinuria and the degree of renal insufficiency. Patients at moderate to high risk should be treated with a combination of glucocorticoids and cytotoxic therapy (cyclophosphamide). Those at low risk can be treated with ACE-Is. Lipid-lowering agents should be used in cases of persistent nephrotic syndrome.
- Focal segmental glomerulosclerosis: ACE-I should be used for reduction of proteinuria. Immunosuppression with prednisone is the first-line therapy.
- Steroid-resistant cases may benefit from the addition of cyclosporine. Relapses require reinitiation of steroids.
congestive heart failure
Dependent edema is the most typical finding with CHF. Laboratory findings do not generally include proteinuria or hypoalbuminemia.
end-stage liver disease
Symptoms of end-stage liver disease usually include increased abdominal girth indicating ascites. Hypoalbuminemia can occur as a result of malnutrition or concurrently with nephrotic syndrome.
Malnutrition is marked by physical wasting, not edema. Hypoalbuminemia may be seen, but hyperlipidemia is not typical.
Renal ultrasound may identify hydronephrosis from a stone or other source of obstruction.
Cystoscopy can be used in the evaluation of hematuria to assess for bladder or urethral neoplasm, benign prostatic hyperplasia, and radiation or chemical cystitis.
Computed tomography scan
CT scanning may identify neoplasms of the kidney or ureter as well as benign conditions such as urolithiasis.
- Minimal-change nephropathy
- Focal glomerulosclerosis
- Membranous nephropathy
- Hereditary nephropathies
- Diabetes mellitus
- Lupus erythematosus
- Viral infections (eg, hepatitis B, hepatitis C, HIV)
- Amyloidosis and paraproteinemias
- Preeclampsia Alloantibodies from enzyme replacement therapy
Hematuria is among the most common presenting symptoms in adults with nephrotic syndrome
The first sign of nephrotic syndrome in children is usually swelling of the face
The presence of deep venous thrombosis or pulmonary embolism suggests a diagnosis other than nephrotic syndrome
Weight loss and hypotension are frequently present in adults with nephrotic syndrome