A. SYMPTOMS AND SIGNS
Edema may appear insidiously and increase slowly or can appear suddenly and accumulate rapidly. Symptoms other than those related to the mechanical effects of edema are not remarkable.
On physical examination, massive peripheral edema is apparent. Signs of hydrothorax and ascites are common.
Pallor is often accentuated by the edema, and striae commonly appear.
B. LABORATORY FINDINGS
The urine contains large amounts of protein, 4-10 g/24 h or more. There is a good correlation between the urine protein to creatinine ratio (from a “spot” AM urine) and the 24-hour. proteinuria. For example, a ratio in excess of 3:1 in the spot urine usually correlates to a 24-hour proteinuria of 3 g. The sediment contains casts, including the characteristic fatty and waxy varieties; renal tubular cells, some of which contain fatty droplets (oval fat bodies); and variable numbers of erythrocytes. A mild normochromic anemia is common, but anemia may be more severe if renal damage is great. Nitrogen retention varies with the severity of impairment of renal function.
The plasma is often lipemic, and the blood cholesterol is usually greatly elevated. Plasma protein is greatly reduced. The albumin fraction may fall to less than 2 g/dL. Serum complement is usually low in active disease. The serum electrolyte concentrations are often normal, although the serum sodium may be slightly low; total serum calcium may be low, in keeping with the degree of hypoalbuminemia and decrease in the protein-bound calcium moiety. During edema-forming periods, urinary sodium excretion is very low and urinary aldosterone excretion is elevated. If renal insufficiency (see preceding discussion) is present, the blood and urine findings are usually altered accordingly.
Renal biopsy is often essential to establish the diagnosis between the various conditions and to indicate prognosis.
C. DIFFERENTIAL DIAGNOSIS
The nephrotic syndrome (nephrosis) may be associated with a variety of primary renal diseases or may be secondary to a systemic process: collagen-vascular diseases (eg, disseminated lupus erythematosus, polyarteritis), diabetic nephropathy, amyloid disease, thrombosis of the renal vein, myxedema, multiple myeloma, malaria, syphilis, reaction to toxins or heavy metals, reactions to drugs, and constrictive pericarditis.
An adequate diet with restricted sodium intake (0.5-1 g/d) and prompt treatment of intercurrent infection are the basis of therapy. Diuretics may be given but are often only partially effective. Salt-free albumin and other oncotic agents are of little help, and their effects are transient. The corticosteroids have been shown to be of value in treating nephrotic syndrome when the underlying disease is of minimal change-focal segmental glomerulosclerosis, systemic lupus erythematosus, or proliferative and crescentic glomerulonephritis.
Steroids are often less effective in the treatment of membranous disease and membranoproliferative lesions of the glomerulus.
Alkylating agents, azathioprine, mycophenolate mofetil, cyclosporine, and tacrolimus, have been used in the treatment of nephrotic syndrome. Encouraging early results have been reported in children and adults with proliferative or membranous lesions and with systemic lupus erythematosus. It is not known what percentage of patients can be expected to benefit from these drugs.
Both corticosteroids and cytotoxic agents are commonly associated with serious side effects. At present, this form of therapy should be employed only in patients in whom the disease has proved refractory to well-established treatment regimens.
Reduction in proteinuria and improvement in nephrotic edema have been reported using low-protein diets and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Most recently, studies have shown some improvements with lipid-lowering drugs.
The course and prognosis depend on the basic disease responsible for nephrotic syndrome. In most children with nephrosis (usually secondary to minimal change nephropathy), the disease appears to run a rather benign course when properly treated and to leave insignificant sequelae.
Of the remaining children, most go inexorably into renal insufficiency. Adults with nephrosis fare less well. Hypertension, heavy proteinuria, and renal dysfunction are poor prognosticators.