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 "maltese cross" sign.
Nephrotic syndrome is defined as urinary excretion of > 3 g of protein on a 24 hour urine due to a glomerular disorder plus edema and hypoalbuminemia
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.
- Minimal change disease: most common cause in kids. Assume minimal change disease if a child with idiopathic nephrotic syndrome improves after treatment with corticosteroids.
- Focal segmental glomerulosclerosis: obese patients, heroin and HIV black males.
The most common secondary causes are:
- Lupus: both nephritic and nephrotic.
- Diabetes: 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.
- Urine random (spot) protein/creatinine ratio ≥ 3 or significant proteinuria (3 g protein in a 24-h urine collection) is diagnostic (normal excretion is <150 mg/day).
- Serologic testing and renal biopsy 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.
- Serum albumin often is < 2.5 g/dL
- Total cholesterol and triglyceride levels are typically increased.
Treat the causative disorder and with angiotensin inhibition, Na restriction, and often diuretics and/or statins.
- Steroids in Minimal Change Disease and FGS
|Nephrotic syndrome is a group of symptoms including massive proteinuria defined as a daily loss of 3.5 gm or more of protein, hyperlipidemia, generalized edema, and hypoalbuminemia which results from renal pathology. Nephrotic syndrome is caused by several diseases including membranous glomerulonephritis, minimal change disease, and focal segmental glomerulosclerosis. Nephrotic syndrome is usually initially related to a derangement in the glomerular capillary walls that result in increased permeability to plasma proteins. Loss of protein leads to hypoalbuminemia beyond the compensatory rate of synthesis in the liver, which contributes to generalized edema due to decreased colloid osmotic pressure in the blood. Additionally, nephrotic syndromes are often characterized by immunodeficiency due to loss of immunoglobulins and thrombotic complications due to loss of anticoagulants like antithrombin, protein C and protein S in the urine.|
|Minimal change disease is a relatively benign disorder that is the most common cause of nephrotic syndrome in children. This disease is characterized by diffuse effacement of foot processes called podocytes of visceral epithelial cells. This podocyte effacement is visible with examination by electron microscopy while the glomeruli appear virtually normal by light microscopy. In minimal change disease, the glomerular basement membrane loses its negative charge which makes it unable to repel the negatively charged albumin. Therefore, this form of nephrotic syndrome is characterized by selective loss of albumin with minimal loss of immunoglobulins. This disease is typically triggered by a recent infection or immune stimulus like a prophylactic immunization and has dramatic response to corticosteroid therapy.|
|Membranous glomerulonephritis, also commonly called membranous nephropathy, is the second most common cause of nephrotic syndrome in adults behind focal segmental glomerulosclerosis. This renal disorder is characterized by diffuse capillary and glomerular basement membrane thickening due to the accumulation of electron dense, immunoglobulin containing deposits along the subepithelial side of the basement membrane. This cause of nephrotic syndrome can manifest independently or in association with other systemic diseases and several other identifiable etiologic agents. The most notable associations include drugs like gold, underlying malignant tumors, particularly solid tumors including carcinomas of the lung and colon and melanoma, systemic illnesses like lupus and infections including chronic hepatitis B and hepatitis C. However, it is important to note that approximately 85% of patients have no associated conditions and the disease is considered to be idiopathic. On light microscopy, the glomeruli typically exhibit uniform, diffuse thickening of the capillaries and glomerular basement membrane. On electron microscopy, the thickening is seen to be caused by irregular dense immune complex deposition between the basement membrane and epithelial cells. The basement membrane between the deposits appear as irregular spikes and over time, the spikes thicken to produce dome-like protrusions over the immune deposits. This is commonly described as having a spike and dome appearance with subepithelial deposits. Immunofluorescence demonstrates a granular pattern.|
|Focal segmental glomerulosclerosis (FSGS) is the most common adult cause of nephrotic syndrome. As the name implies, these lesions are characterized by sclerosis of some but not all of the glomeruli, making the inflammation focal as opposed to diffuse. Additionally, the lesions within the glomeruli only affect a section of the capillary making the damage segmental. This disease can occur as primary disease but also occurs in association with other conditions including HIV infection and heroine addiction. Clinically, FSGS typically has a high incidence of microscopic hematuria, reduced GFR, hypertension, nonselective proteinuria, and poor response to corticosteroid therapy. This disease has relatively poor prognosis with many individuals progressing to chronic kidney disease and more than half of the patients developing end stage kidney disease in 10 years. On light microscopy, the glomeruli that are affected demonstrate segmental sclerosis and hyalinosis while the unaffected glomeruli appear relatively normal. Electron microscopy demonstrates focal damage of visceral epithelial cells while immunofluorescence staining is usually negative.|
|Membranoproliferative glomerulonephritis (MPGN) is a type of nephritic-nephrotic kidney disorder characterized by alterations in the glomerular basement membrane, proliferation of glomerular cells, and leukocyte infiltration. MPGN accounts for approximately 10 to 20% of cases of nephrotic syndrome in both children and young adults and is divided into two major categories on the basis of distinct immunofluorescent and pathologic differences called type I and type II MPGN. In type I MPGN, there is evidence of immune complex deposition in the glomerulus with activation of both the classical and alternative complement pathways. In many cases, the antigens involved in MPGN are thought to be derived from infectious agents such as hepatitis C and hepatitis B viruses. By light microscopy, both types of MPGN demonstrate enlarged hypercellular glomerular caused by proliferation of cells in the mesangium. Electron microscopy shows a glomerular basement membrane that is thickened and the glomerular capillary wall often shows a tram-track appearance caused by duplication, commonly called splitting, of the basement membrane by ingrowth of the mesangium. Specifically, type I MPGN is characterized by the presence of discrete subendothelial immune complexes. Immunofluorescence demonstrates a granular pattern of C3 deposition. Type II MPGN, also called dense deposit disease, has abnormalities that suggest activation of the alternative pathway. More than 70% of patients have a circulating antibody called C3 nephritic factor, which is an autoantibody that binds to the C3 convertase in the alternative pathway. C3 nephritic factor binding causes stabilization of the convertase, protecting it from enzymatic degradation and therefore favors persistent C3 activation and hypocomplementemia. It is called dense deposit disease due to deposition of dense material of unknown composition in the glomerular basement membrane.|
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