1.

Typical idiopathic nephrotic syndrome (nephrosis) of childhood and the other forms of the nephrotic syndrome discussed in this report are not morphologically distinguishable from one another, except for those infants showing unusual renal tubular dilatation.

2.

Progressive morphologic renal abnormalities occur during the clinical expression of the nephrotic syndrome over many months and years.

3.

The severity of the microscopic pathology in patients who fail to respond to treatment is related to the duration of the disease. The rate of progression of the pathology is highly variable from patient to patient, and the factors which determine the rate of progression in an individual patient are unknown.

4.

Patients with idiopathic nephrotic syndrome (nephrosis) in whom renal biopsy specimens reveal minimal glomerular abnormalities usually respond to treatment with adrenocortical steroids.

5.

Cessation of proteinuria followingadrenocortical steroid therapy is accompanied by improvement in the morphology of renal biopsy specimens.

6.

Response to therapy with adrenocortical steroid hormones is usually associated with preservation of normal microscopic renal morphology, even though the nephrotic syndrome recurs for a number of years.

7.

Patients in whom renal biopsies showmore severe glomerular pathology often fail to respond to treatment with adrenocortical steroids. Morphologic alterations in the kidney are not, however, the only factors explaining the refractory state, since some patients with minimal lesions fail to respond to treatment, while a few patients with moderately severe pathology have obtained clinical remissions after therapy.

8.

Predictions of the outcome of the idiopathicnephrotic syndrome, based on the severity of the morphologic changes in a renal biopsy, are generally reliable, but exceptions occur frequently enough to make the application of this method of prediction of doubtful value in individual cases. Such predictions are not valid in patients with either the familial or infantile forms of the nephrotic syndrome.

9.

Electron microscopy of renal glomerulireveals an abnormality of structure of the epithelial cell foot processes in all forms of the nephrotic syndrome which have been studied.

10.

Similar abnormalities have beendemonstrated in several forms of experimental nephrotic syndrome produced in laboratory animals.

11.

The severity of the epithelial cell foot process lesion appears to be related to the severity of the proteinuria. The epithelial cell foot process abnormalities are also reversible, and normal structure is found in patients responding to therapy.

12.

The epithelial cell foot process lesionis the first pathologic change recognizable in the idiopathic nephrotic syndrome (nephrosis) and is present when renal glomeruli appear to be normal by light microscopy. Abnormality of structure of the endothelial cells and lamina densa are visible by electron microscopy of renal biopsy specimens obtained later in the course of the nephrotic syndrome and are correlated with the proliferative and membranous changes recognized by light microscopy.

13.

Hypotheses concerning the mechanisms of proteinuria and the possible relationship of glomerular structure to the nephrotic syndrome are discussed.