(See also Overview of Nephrotic Syndrome Overview of Nephrotic Syndrome Nephrotic syndrome is urinary excretion of > 3 g of protein/day due to a glomerular disorder plus edema and hypoalbuminemia. It is more common among children and has both primary and secondary... read more .)
Minimal change disease is the most common cause of nephrotic syndrome in children 4 to 8 years (80 to 90% of childhood nephrotic syndrome), but it also occurs in adults (10 to 20% of adult nephrotic syndrome). The cause is almost always unknown, although rare cases may occur secondary to drug use (especially nonsteroidal anti-inflammatory drugs [NSAIDs]) and hematologic cancers (especially Hodgkin lymphoma Hodgkin Lymphoma Hodgkin lymphoma is a localized or disseminated malignant proliferation of cells of the lymphoreticular system, primarily involving lymph node tissue, spleen, liver, and bone marrow. Symptoms... read more ).
Symptoms and Signs
Minimal change disease causes nephrotic syndrome, usually without hypertension or azotemia; microscopic hematuria occurs in about 20% of patients, mainly adults. Azotemia can occur in secondary cases and in patients > 60 years. Albumin is lost in the urine of patients with minimal change disease more so than larger serum proteins, probably because the disease causes changes in the charge barrier that affect albumin selectively.
In adults with idiopathic nephrotic syndrome, renal biopsy
In children, the diagnosis can be suspected (and treatment begun) based on the following typical characteristics:
Sudden onset of unexplained nephrotic-range proteinuria that is mainly albumin
Normal renal function
Non-nephritic urine sediment
Renal biopsy is required in adults and in children with atypical presentations. Electron microscopy demonstrates edema with diffuse swelling (effacement) of foot processes of the epithelial podocytes (see figure Electron microscopic features in immunologic glomerular disorders Electron microscopic features in immunologic glomerular disorders ). Complement and Ig deposits are absent on immunofluorescence. Although effacement is not observed in the absence of proteinuria, heavy proteinuria may occur with normal foot processes.
Electron microscopic features in immunologic glomerular disorders
Sometimes cyclophosphamide or cyclosporine
Spontaneous remissions occur in 40% of cases, but most patients are given corticosteroids. About 80 to 90% of patients respond to initial corticosteroid therapy (eg, prednisone 60 mg/m2 orally once a day for 4 to 6 weeks in children and 1 to 1.5 mg/kg orally once a day for 6 to 8 weeks in adults), but 40 to 73% of responders relapse. Patients who respond (ie, have cessation of proteinuria or a diuresis if edema is present) should continue prednisone for another 2 weeks and change to a maintenance regimen to minimize toxicity (2 to 3 mg/kg on alternate days for 4 to 6 weeks in children and for 8 to 12 weeks in adults, tapering during the next 4 months). More prolonged initial therapy and slower tapering of prednisone lower relapse rates. Nonresponsiveness may be due to underlying focal sclerosis that was missed on biopsy due to sampling error.
Complete remission occurs in > 80% of patients treated with corticosteroids, and treatment is usually continued for 1 to 2 years. However, half or more relapse, requiring treatment with the same or a different regimen.
Oral cytotoxic drugs
In corticosteroid nonresponders (< 5% of children and > 10% of adults), frequent relapsers, and corticosteroid-dependent patients, prolonged remission may be achieved with an oral cytotoxic drug (usually cyclophosphamide 2 to 3 mg/kg once a day for 12 weeks or chlorambucil 0.15 mg/kg once a day for 8 weeks). (See the Cochrane abstract review Non-corticosteroid treatment for nephrotic syndrome in children.) However, these drugs may suppress gonadal function (most serious in prepubertal adolescents), cause hemorrhagic cystitis, have mutagenic potential, and suppress bone marrow and lymphocyte function. Dosage should be monitored with frequent complete blood counts (CBCs), and hemorrhagic cystitis should be sought by urinalysis. Adults, particularly if older or hypertensive, are more prone to adverse effects from these cytotoxic drugs. Another alternative is cyclosporine 3 mg/kg orally twice a day, adjusted to obtain a whole-blood trough concentration of 50 to 150 mcg/L (40 to 125 nmol/L). Patients responsive to cyclosporine frequently relapse when the drug is stopped.
Most patients who are unresponsive to these interventions respond to alternative therapies, including angiotensin-converting enzyme (ACE) inhibitors, azathioprine, and mycophenolate mofetil; < 5% progress to renal failure.
Minimal change disease accounts for most cases of nephrotic syndrome in children and is usually idiopathic.
Suspect minimal change disease in children who have sudden onset of nephrotic-range proteinuria with normal renal function and a non-nephritic urine sediment.
Confirm the diagnosis by renal biopsy in adults and atypical childhood cases.
Treatment with corticosteroids is usually sufficient.
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