The nephrotic syndrome is characterized by albuminuria, edema, hypoalbuminemia and
hypercholesterolemia; frequently, it is accompanied by a depression of the basal metabolic
rate. It occurs most often in the course of chronic glomerulonephritis but may exist
independently, as in lipoid nephrosis. Rarely, it is associated with secondary syphilis,
leptospiral infections, amyloid disease, Kimmelstiel-Wilson syndrome or nephrotoxic
The term “nephrosis” was originally applied by Müller to degenerative lesions of the
kidney primarily involving the renal tubules. The nephrotic state, however, occurs
also with inflammatory diseases of the kidney. Furthermore, the significance of the
tubular lesion in the etiology of the syndrome is open to question for it has been
quite clearly shown that, in some instances at least, the tubular change may be the
result and not the cause of albuminuria. It is obvious that some disturbance of the
glomerular filter or in the serum proteins must be predicated to allow for the increased
supply of protein presented to the tubules.
It was originally suggested by Epstein that the low serum albumin in the nephrotic
state might result solely from urinary loss of serum proteins and that edema formation
could be adequately explained on the basis of the Starling hypothesis of lowered osmotic
pressure in hypoalbuminemia. But there is evidence that the Epstein hypothesis does
not afford a complete explanation for the formation of edema. Thus diuresis may occur
spontaneously without any increase in the low serum albumin levels. Excess protein
intake usually does not restore the blood level of albumin even when positive nitrogen
balance is established and body protein is stored.
It is now plain that leakage of albumin through the kidneys does not alone explain
the manifestations of the nephrotic state, which evidently involves much more profound
metabolic disturbances. Other factors evidently are at work. There is a renal defeet
in the handling of the sodium ion by the kidnev. Adrenal cortical hormones conceivably
might play a part in water and sodium balance; and the role of the anti-diuretic hormone
of the posterior pituitary gland has yet to be properly evaluated. The significance
of hypercholcsterolcmia and lowered basal metabolic rate in the nephrotic state is
not known, nor is it understood why the alpha globulins apparently are increased and
the gamma globulins decreased in the blood.
Measures directed against the clinical abnormalities present in the nephrotic syndrome
include diet high enough in protein to assure nitrogen balance; excessive feeding
of protein accomplishes nothing more than restoration of body protein and may actually
injure the renal tubules, Sodium intake is kept to less than 0.5 Gm. daily because
more tends to promote edema. At this level, water may be taken freely; otherwise it.
too, should be restricted. Of the diuretics, urea and mercurials are most often effective,
but neither can be relied upon. Efforts to promote diuresis by increasing the osmotic
pressure of the circulating plasma have been unsatisfactory. Therapy with hypertonic
glucose, acacia, human plasma or serum fall into this category. Salt-tree for human
albumin may be highly effective hut has serious limitations. Thyroid extract rarely
produces diuresis. In children, intercurrent infections, particularly pneumococcic
peritonitis, respond promptly to penicillin. Syphilitic nephrosis also yields rapidly
to treatment with penicillin.
Prognosis depends on the underlying disease. In lipoid nephrosis and chronic glomerulonephritis
the duration of the nephrotic state cannot be predicted. In the former, however, the
outcome is almost uniformlv good today since formerly fatal infectious complications
may now be adequately handled. Patients in the nephrotic phase of chronic glomerulonephritis.
however, (and these comprise by far the largest proportion of cases) still face the
ultimate fate of patients with the underlying disease.