Minimal Change Nephropathy



This glomerulopathy is the most common cause of childhood nephrotic syndrome, is most prev­alent in children aged 2 to 6 years, and displays a 3:1 male predominance. Up to 25 per cent of cases of adult nephrotic syndrome may be mini­mal change. Edema in an otherwise healthy in­dividual is the mode of clinical presentation in over 75 per cent of cases. Up to one third of child­hood cases appear to follow an upper respiratory infection.

Proteinuria over 50 mg/kg/day with a serum al­bumin <2.0 gm/dl and a serum cholesterol >300 mg/dl are typical findings. The proteinuria is highly selective in children, being mostly albu­minuria, but is less selective in adults. Lipiduria, seen as lipid droplets or “Maltese crosses” under polarized light, is characteristic. Microscopic hematuria occurs in a minority of patients. Serum complement levels are normal. IgG levels may be severely depressed, especially in patients with heavy proteinuria.

Renal insufficiency and azotemia do not occur unless caused by severe vascular volume con­traction. Postural hypotension and circulatory collapse may occur in the face of severe reduc­tions of serum oncotic pressure. An increased sus­ceptibility to infection by encapsulated organisms (Pneumococcus, Haemophilus, Klebsiella) is no­table when proteinuria is great and may relate to an acquired IgG deficiency. Thrombosis of renal and peripheral veins, associated with a hyper-coagulable state, is not uncommon.
The term minimal change or nil lesion refers to the fact that the glomeruli appear normal on light microscopy . There is no significant or consistent staining for immune reactants. Elec­tron microscopy reveals nothing more than the “fusion” of epithelial cell foot processes, a non­specific finding that likely reflects the loss of the anionic charge of the glomerulus and subsequent collapse of the epithelial cell onto the basement membrane. While glomerular deposits are absent, circulating immune complexes of unknown origin have been reported in both children and adults with this disorder. No regular etiological associ­ation is known for the disease in children, but some adults with the minimal change lesion are found to have Hodgkin’s disease.

The natural course of minimal change nephro­pathy is that of spontaneous remission and re­lapse, with eventual disappearance of proteinuria. However, because of the exquisite sensitivity of the proteinuria to corticosteroids, current prog­nostic categories are based on the response of the nephrotic syndrome to steroids. Steroids are given at an initial dose of about 60 mg/sq m/day of pred­nisone for 4 weeks, then tapered over 8 to 12 weeks, and discontinued only after the patient has remained free of proteinuria for about 4 weeks.

About two thirds of patients will have complete remission of proteinuria with this regimen. An­other 25 per cent of patients will experience re­mission of the nephrotic syndrome but will con­tinue to have mild proteinuria. However, almost two thirds of the initial responders will ultimately relapse and require subsequent courses of steroids to return to remission.

Of the fewer than 10 per cent who do not re­spond to the initial course of steroids, some will remit with either prolonged therapy or an in­creased dose of prednisone. Failure to respond to steroids or persistent steroid dependency has been used as an indication for concomitant ther­apy with an alkylating agent such as cyclophos­phamide. However, the considerable risk of this drug, including the danger of gonadal injury or carcinogenesis in children, makes its use highly controversial in the treatment of a disease with a naturally favorable outcome.

About three fourths of individuals will be free of proteinuria, off treatment, at 10 years. The mor­tality rate in children is less than 5 per cent and is usually related to vascular complications and ~*r occasionally to infections but not to renal insuf­ficiency. Adults have a response to steroids and an eventual outcome similar to that described for children. Nonresponders to steroids will often be found to have a glomerulopathy other than min­imal change, often focal sclerosis.