Are there special considerations when treating patients with the nephrotic syndrome?
Patients with the nephrotic syndrome may be resistant to diuretic therapy because of hypoalbuminemia and albuminuria. Because diuretics are highly protein-bound, they are confined to the vascular space and delivered rapidly to the kidney. The hypoalbuminemia in patients with the nephrotic syndrome expands the volume of distribution of the drug and slows the rate of delivery to the kidney. (In spite of this, administration of a solution of albumin to which a loop diuretic has been added does not substantially increase diuresis.) Except for the aldosterone antagonists, spironolactone and eplerenone, diuretics act on the luminal membrane. However, intraluminal binding of thiazide and loop diuretics by albumin in the tubular fluid makes them inactive. For these reasons, blocking sodium reabsorption at an additional site in the nephron may be necessary to achieve diuresis. A thiazide diuretic is typically chosen. The combination of a loop diuretic and a thiazide diuretic can precipitate severe hypokalemia; the plasma potassium concentration must be monitored carefully. Angiotensin inhibition by angiotensin-converting enzyme inhibitors or by angiotensin receptor blockers can be an important adjunct to diuretic therapy. These drugs may decrease albuminuria and increase the plasma albumin concentration, thereby enhancing the response to diuretics.