Minimal Change Disease
(Lipoid Nephrosis; Nil Disease)
Minimal change disease causes abrupt onset of edema and heavy proteinuria, mostly in children. Renal function is typically normal. Diagnosis is based on clinical findings or renal biopsy. Prognosis is excellent. Treatment is with corticosteroids or, in patients who do not respond, cyclophosphamide or cyclosporine.
Minimal change disease (MCD) is the most common cause of nephrotic syndrome in children 4 to 8 yr (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 NSAIDs) and hematologic cancers (especially Hodgkin lymphoma).
MCD 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 yr. Albumin is lost in the urine of patients with MCD more so than larger serum proteins probably because MCD causes changes in the charge barrier that affect albumin selectively.
In children, the following:
Renal biopsy is required in atypical cases and in adults. Electron microscopy demonstrates edema with diffuse swelling (effacement) of foot processes of the epithelial podocytes (see Figure: 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.
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 po once/day for 4 to 6 wk in children and 1 to 1.5 mg/kg po once/day for 6 to 8 wk 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 wk and change to a maintenance regimen to minimize toxicity (2 to 3 mg/kg on alternate days for 4 to 6 wk in children and for 8 to 12 wk in adults, tapering during the next 4 mo). 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 yr. However, half or more relapse, requiring treatment with the same or a different regimen.
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/day for 12 wk or chlorambucil 0.15 mg/kg once/day for 8 wk). (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 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 po bid, adjusted to obtain a whole-blood trough concentration of 50 to 150 μg/L (40 to 125 nmol/L).
Patients responsive to cyclosporine frequently relapse when the drug is stopped.
MCD accounts for most cases of nephrotic syndrome in children and is usually idiopathic.
Suspect MCD 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.