Nephrotic Syndrome
BASICS
DESCRIPTION
- A constellation of clinical and laboratory features defined by the presence of massive proteinuria (>3.5 g/1.73 m2/24 hr), hypoalbuminemia (<2.5 g/dL), and peripheral edema, with hypercoagulability and susceptibility to infection
- In children nephrotic proteinuria is defined as >40 mg/m2/hr
- It can be due to intrinsic renal disease or caused by congenital infections, diabetes mellitus, systemic lupus erythematosus, neoplasia or certain drug use (1),(2).
EPIDEMIOLOGY
- Diabetic nephropathy
- Minimal change disease (MCD)
- Most common cause of nephrotic syndrome in children aged <10 years (90%)
- Idiopathic condition in adults associated with NSAID use or Hodgkin lymphoma
- Amyloidosis: 4–17% of idiopathic nephrotic syndrome—two renal types primary (AL) and secondary (AA)
- Lupus nephropathy (LN): Adult women are affected about 10 times more often than men.
- Focal segmental glomerulosclerosis (FSGS)
- 35% of nephrotic syndrome in adults, most common primary nephrotic syndrome in African Americans
- Has both primary (idiopathic) and secondary forms (associated with HIV, morbid obesity, reflux nephropathy, previous glomerular injury)
- Membranous nephropathy
- Most common cause of primary nephrotic syndrome in adults (40%)
- Most often primary (idiopathic) but can be secondary associated with malignancy, hepatitis B, autoimmune diseases, thyroiditis, and certain drugs including NSAIDs, penicillamine, gold and captopril
- Membranoproliferative glomerulonephritis (MGN)
- May present in the setting of a systemic viral or rheumatic illness
Incidence
- Worldwide, children have an incidence of 1.15 to 16.9 per 100,000 children, with lower incidence in Europe and North America, and higher in Southeast Asia and East Asia (1).
- Approximately 3 cases per 100,000 per year in adults. There is increased incidence and development of severe disease in African American and Hispanic population.
ETIOLOGY AND PATHOPHYSIOLOGY
- Primary renal disease (e.g., MCD, FSGS, MGN, IgA nephropathy)
- Secondary renal disease (e.g., diabetic nephropathy, amyloidosis, and paraproteinemias)
- Increased glomerular permeability to protein macromolecules, especially albumin
- Edema results primarily from renal salt retention, with arterial underfilling from decreased plasma oncotic pressure playing an additional role.
- The hypercoagulable state is likely due to loss of antithrombin III in urine.
Genetics
Mutations in genes regulating podocyte proteins identified in families with inherited nephrotic syndrome.
RISK FACTORS
- Children
- Often idiopathic, with kidney biopsy showing MCD
- Family history of nephrotic syndrome may be associated with genetic mutations.
- Viral infections, including HIV, hepatitis B, cytomegalovirus, and parvovirus B19
- Sickle cell disease (2)
- Adults
- Drug addiction (e.g., heroin [FSGS])
- Hepatitis B and C, HIV, CMV, Parvovirus B1, toxoplasmosis, other infections
- Immunosuppression
- Nephrotoxic drugs (lithium, bisphosphonates, interferon therapy, gold, bucillamine, and penicillamine)
- Vesicoureteral reflux (FSGS)
- Cancer (usually MGN, may be MCD)
- Chronic analgesic use/abuse (NSAIDs)
- Preeclampsia
- Diabetes mellitus
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Citation
Domino, Frank J., et al., editors. "Nephrotic Syndrome." 5-Minute Clinical Consult, 34th ed., Wolters Kluwer, 2026. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116404/all/Nephrotic_Syndrome.
Nephrotic Syndrome. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2026. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116404/all/Nephrotic_Syndrome. Accessed July 16, 2025.
Nephrotic Syndrome. (2026). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (34th ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116404/all/Nephrotic_Syndrome
Nephrotic Syndrome [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2026. [cited 2025 July 16]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116404/all/Nephrotic_Syndrome.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC
T1 - Nephrotic Syndrome
ID - 116404
ED - Domino,Frank J,
ED - Baldor,Robert A,
ED - Golding,Jeremy,
ED - Stephens,Mark B,
BT - 5-Minute Clinical Consult, Updating
UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116404/all/Nephrotic_Syndrome
PB - Wolters Kluwer
ET - 34
DB - Medicine Central
DP - Unbound Medicine
ER -