Patients with nephrotic syndrome (NS) present with edema, proteinuria, hypoalbuminemia, and hyperlipidemia. In children, the most common causes are idiopathic minimal change disease and focal segmental glomerulosclerosis (FSGS). In adults, FSGS and membranous nephropathy (MN) are the most common primary causes. There are numerous secondary causes, including diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections. In addition to confirming the diagnosis of NS by measuring proteinuria and serum albumin and lipid levels, evaluation should assess for secondary causes. In children, most cases are due to minimal change disease, which is responsive to steroid treatment. A glucocorticoid should be prescribed for children younger than 12 years. If the patient improves with steroid treatment, no biopsy is needed. If the patient does not improve, genetic testing and kidney biopsy are warranted to determine the diagnosis. In adults, biopsy typically is indicated for diagnosis, except in patients with positive test results for serum anti-phospholipase A2 receptor antibodies. This is diagnostic of MN. For patients with NS, management of initial and infrequent recurrences involves reduction of proteinuria with glucocorticoids. Frequent recurrences and/or the inability to discontinue glucocorticoids requires alternative therapies. Steroid-resistant NS also requires use of alternative therapies. Long-term NS management includes dietary sodium restriction, edema management, and blood pressure control. Thromboembolism prophylaxis should be considered for patients with NS and high risk of thromboembolism, particularly those with MN.
Case 3. LM is a 6-year-old patient who is brought to your office by her parents with 2 weeks of progressively worsening edema. Her mother reports LM has experienced no fever, chills, rhinorrhea, cough, dyspnea, nausea, vomiting, hematuria, diarrhea, hematochezia, or melena. On physical examination, LM has mild periorbital edema and 2+ pitting edema over the abdomen and ankles. Urinalysis shows 3+ protein with no blood and the spot urine protein level is greater than 2 g/dL. The urine protein to creatinine ratio is greater than 12 mg/mg and blood tests reveal hypoalbuminemia and hyperlipidemia.
Nephrotic syndrome (NS) is a kidney condition resulting from disruption of the glomerular filtration barrier. Defining characteristics are proteinuria along with hypoalbuminemia (often resulting in edema) and hyperlipidemia.91,92
Etiology and Epidemiology
Primary and secondary causes of NS are listed in Table 5.
Table 5 Causes of Nephrotic Syndrome
| Primary Causes (Intrinsic Kidney Disorders) Minimal change disease Focal segmental glomerulosclerosis Primary membranous nephropathy Secondary Causes Allergic Antitoxins (eg, rabies, botulism, venom) Insect stings Toxicodendron (eg, poison ivy/oak) Venomous snake bites Drugs Captopril Heroin Interferon alfa Lithium Nonsteroidal anti-inflammatory drugs Pamidronate Penicillamine | Secondary Causes (continued) Genetic Focal segmental glomerulosclerosis Hereditary nephritis (Alport syndrome) Congenital nephrotic syndrome (Finnish type) Pierson syndrome Nail-patella syndrome Denys-Drash syndrome Immunologic Cryoglobulinemia Erythema multiforme Henoch-Schönlein purpura Polyarteritis nodosa Sjögren syndrome Systemic lupus erythematosus Infections Bacterial infection (eg, syphilis, leprosy, infective endocarditis) Protozoal infection (eg, filariasis, helminthiasis, malaria, schistosomiasis) Viral infection (eg, hepatitis B or C, HIV, Epstein-Barr virus, herpes zoster) | Secondary Causes (continued) Malignancies Carcinoma (eg, breast, lung, colon, stomach, kidney, prostate) Hematologic malignancy (eg, multiple myeloma, leukemia, lymphoma) Melanoma Metabolic Diabetes Other Conditions Amyloidosis Castleman disease Chronic allography nephropathy Preeclampsia Sarcoidosis |
Information from various sources.
CHILDREN
In children, the most common causes of NS are minimal change disease and focal segmental glomerulosclerosis (FSGS).93 Minimal change disease accounts for 77% of cases with a median age of 3 years, whereas FSGS accounts for 7% to 10% of cases with a median age of 6 years.93–95 These conditions are considered idiopathic NS, which is male-predominant, with a male to female ratio of 3.8:1.95 In older children and adolescents, the most common causes of NS are FSGS, membranous nephropathy (MN), and membranoproliferative glomerulonephritis.91
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