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. Treatment is with corticosteroids or, in patients who do not respond, cyclophosphamide or cyclosporine. Prognosis is excellent.
(See also Overview of Nephrotic Syndrome.)
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).
Symptoms and Signs of Minimal Change Disease
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.
Diagnosis of Minimal Change Disease
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
Image provided by Agnes Fogo, MD, and the American Journal of Kidney Diseases' Atlas of Renal Pathology (see www.ajkd.org).
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 ). 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.
Електронно-мікроскопічні особливості імунологічних захворювань ниркових клубочків
Treatment of Minimal Change Disease
Corticosteroids
Sometimes cyclophosphamide, calcineurin inhibitors (eg, cyclosporine or tacrolimus), mycophenolate mofetil, or rituximab
Кортикостероїди
Spontaneous remissions occur in 40% of cases, but most patients are given corticosteroids. About 80 to 90% of patients respond to initial high-dose 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.
Treatment is usually continued for 1 to 2 years. However, half or more relapse, requiring treatment with the same or a different regimen.
Інші імунодепресанти
In corticosteroid nonresponders (< 5% of children and > 10% of adults), frequent relapsers, and corticosteroid-dependent patients, prolonged remission may be achieved with the addition of another immunosuppressive agent (1, 2). These agents include cyclophosphamide, a calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and possibly rituximab. The choice of agent is influenced by clinician and patient preferences, drug availability and cost, tolerability, and potential toxicity.
Довідкові матеріали щодо лікування
1. Larkins NG, Liu ID, Willis NS, et al: Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev 4(4):CD002290, 2020. doi: 10.1002/14651858.CD002290.pub
2. Azukaitis K, Palmer SC, Strippoli GF, et al: Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst Rev 3(3):CD001537, 2022. doi: 10.1002/14651858.CD001537.pub5
Prognosis for Minimal Change Disease
The prognosis for patients with minimal change disease who receive treatment is favorable, and > 80% of patients achieve remission. Progression to renal failure occurs in < 5 % of patients and is more common among those who do not initially respond to corticosteroids (1).
Довідковий матеріал щодо прогнозу
1. Tarshish P, Tobin JN, Bernstein J, et al: Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol 8(5):769-776, 1997 doi: 10.1681/ASN.V85769
Ключові моменти
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.
Treat initially with corticosteroids.
The prognosis is favorable, and the majority of patients achieve remission with initial treatment.
