November 30, 2009 Recommendations for primary care clinicians regarding the diagnosis

and treatment of nephrotic syndrome in adults are reviewed in the November 15 issue of the
American Family Physician.
"In nephrotic syndrome, a variety of disorders cause proteinuria, often resulting in marked
edema and hypoalbuminemia," write Charles Kodner, MD, from the University of Louisville
School of Medicine in Louisville, Kentucky. "Hyperlipidemia is a common associated
finding. Family physicians may encounter persons with nephrotic syndrome from primary
(idiopathic) renal disease or a number of secondary causes, and should initiate appropriate
diagnostic workup and medical management pending specialist consultation."
Nephrotic syndrome may be classified as primary (or idiopathic) renal disease, or it may be
secondary to various causes. The most common primary causes in adults are focal segmental
glomerulosclerosis and membranous nephropathy.
Focal segmental glomerulosclerosis accounts for approximately one third of cases of primary
nephrotic syndrome and for approximately 3.3% of new cases of end-stage renal disease, and
it is the leading cause of idiopathic nephrotic syndrome in adults. It is characterized by
sclerosis and hyalinosis of segments of less than 50% of all glomeruli on electron
microscopic studies. Clinical features may include hypertension, renal insufficiency, and
hematuria.
In membranous nephropathy, electron microscopic study reveals thickening of the glomerular
basement membrane, and immunofluorescent staining shows immunoglobulin G and C3
deposits. This form of nephrotic syndrome, which also accounts for approximately one third
of cases of primary nephrotic syndrome, is most often diagnosed at ages 30 to 50 years.
Patients may have microscopic hematuria, and roughly one quarter have systemic lupus
erythematosus, hepatitis B, malignant disease, drug-induced nephrotic syndrome, or other
underlying systemic disease.
Another form of primary nephrotic syndrome is minimal-change disease, which together with
immunoglobulin A nephropathy is responsible for approximately one quarter of cases of
idiopathic nephrotic syndrome. It is diagnosed from normal-appearing glomeruli on renal
biopsy microscopic examination with effacement of foot processes on electron microscopic
studies. After upper respiratory tract infection or immunization, relatively mild or benign
cases of minimal-change disease may develop.
Secondary causes of nephrotic syndrome include diabetes mellitus, which is the most
common secondary cause. Other causes are systemic lupus erythematosus, hepatitis B or C,
use of nonsteroidal anti-inflammatory drugs, minimal-change disease, amyloidosis, multiple
myeloma, HIV, or preeclampsia.
Typical presenting features of nephrotic syndrome are marked edema, proteinuria,
hypoalbuminemia, and usually hyperlipidemia.

Possible complications of nephrotic syndrome are venous thromboembolism. Although acute

renal failure and serious bacterial infection may occur, they are much less common.
To date, there are no established guidelines regarding diagnostic evaluation of patients with
nephrotic syndrome. To diagnose specific disorders, blood tests should be used selectively,
but a broad-ranging or unguided workup is not recommended. Imaging studies are seldom
necessary. In some cases, however, renal biopsy may help confirm an underlying disease or
identify idiopathic disease that has a greater probability of responding to corticosteroids.
Professional organizations have also not yet issued recommendations for treatment of
nephrotic syndrome. Most patients should be treated with fluid and sodium restriction, oral or
intravenous diuretics, and angiotensin-converting enzyme inhibitors.
"Diuretics are the mainstay of medical management; however, there is no evidence to guide
drug selection or dosage," Dr. Kodner writes. "Based on expert opinion, diuresis should aim
for a target weight loss of 1 to 2 lb (0.5 to 1 kg) per day to avoid acute renal failure or
electrolyte disorders. Loop diuretics, such as furosemide (Lasix) or bumetanide, are most
commonly used."
In persons with nephrotic syndrome, angiotensin-converting enzyme inhibitors have been
shown to decrease proteinuria and lower the risk for progression to renal disease.
Although corticosteroid treatment may benefit some adults with nephrotic syndrome,
research evidence supporting this therapy is limited. At present, intravenous albumin,
prophylactic antibiotics, and prophylactic anticoagulation are not advised.
Key Recommendations
Key clinical recommendations for practice, and their accompanying level of evidence rating,
are as follows:

To evaluate the extent of proteinuria, persons with nephrotic syndrome should

undergo measurement of random urine protein-to-creatinine ratio (level of evidence,
C).

Although renal biopsy may help guide diagnosis and management in selected patients,
it is not recommended for all persons with nephrotic syndrome (level of evidence, C).

Most persons with nephrotic syndrome should be treated with sodium and fluid
restriction and high-dose diuretic therapy (level of evidence, C).

Most persons with nephrotic syndrome should be treated with angiotensin-converting

enzyme inhibitors (level of evidence, C).

Despite the lack of evidence that corticosteroid treatment has any proven therapeutic
benefit for nephrotic syndrome, some physicians recommend it for persons who are
refractory to conservative management (level of evidence, C).

"In most cases, family physicians should consult specialists in renal medicine about the need
for renal biopsy in individual patients," Dr. Kodner concludes.
"There are no clinical guidelines and few high-quality studies on the management of
nephrotic syndrome in adults. Recommendations are based primarily on early case series,
other observational studies, and expert opinion."
Dr. Kodner has disclosed no relevant financial relationships.

Laurie Barclay, MD
November 30, 2009
http://www.medscape.com/viewarticle/713110 16/6/2015