Patient education: The nephrotic syndrome (Beyond the Basics)

NEPHROTIC SYNDROME OVERVIEW — The term "nephrotic syndrome" refers to a group of symptoms and laboratory findings that may occur in people with certain kinds of kidney (renal) disease:

●High levels of protein (albumin) in the urine

●Low levels of the protein (albumin) in the blood

●Swelling (also called edema) of the face, legs, or ankles due to the abnormal collection of fluids in the tissues, usually accompanied by weight gain

This article will review the causes, evaluation, and treatment of nephrotic syndrome. More detailed information is available by subscription. (See "Overview of heavy proteinuria and the nephrotic syndrome".)

HOW DOES NEPHROTIC SYNDROME DEVELOP? — Nephrotic syndrome develops when there is damage to the glomeruli, the structures in the kidneys that work to filter the blood (figure 1). This damage allows proteins in the blood (such as albumin) to leak into the urine, causing increased excretion of protein (proteinuria) (see "Patient education: Protein in the urine (proteinuria) (Beyond the Basics)"). Eventually, blood levels of albumin become reduced. Accompanying abnormalities of kidney function lead to accumulation of fluid in the tissues (edema).

How are glomeruli damaged? — Many different disorders can cause damage to the glomeruli, resulting in nephrotic syndrome. In some cases, damage is confined to the kidneys alone. In other cases, organs other than the kidney are also affected (such as in diabetes mellitus or systemic lupus erythematosus):

●In children, the most common cause of glomerular damage is a condition known as minimal change disease.

●In adults, approximately 30 percent of people with nephrotic syndrome have an underlying medical problem, such as diabetes or lupus; the remaining cases are due to kidney disorders such as minimal change disease, focal segmental glomerulosclerosis (FSGS), or membranous nephropathy.

Minimal change disease — Minimal change disease is a kidney disease that can occur in both adults and children. People with minimal change disease have normal or very mild abnormalities of the glomeruli. (See "Minimal change disease: Etiology, clinical features, and diagnosis in adults".)

Focal segmental glomerulosclerosis — FSGS is the most common cause of nephrotic syndrome in adults. FSGS causes collapse and scarring of some glomeruli. The cause of primary FSGS is unknown, although some cases (usually in children or young adults) are the result of a genetic defect, an infection, or a toxic response to a drug.

Membranous nephropathy — Membranous nephropathy is a condition in which the walls of the glomerular blood vessels become thickened from the accumulation of protein deposits, causing increased "leakiness." It is not clear why membranous nephropathy develops in most people, but an "auto-immune" mechanism is suspected ("auto-immune" = reaction to oneself). (See "Membranous nephropathy: Pathogenesis and etiology".)

Diabetes mellitus — Kidney disease is common in people with diabetes who have chronically elevated blood glucose levels and/or high blood pressure (see "Patient education: Type 1 diabetes: Overview (Beyond the Basics)" and "Patient education: Type 2 diabetes: Overview (Beyond the Basics)"). Some patients with more advanced disease can develop the nephrotic syndrome.

Lupus — Lupus is a disease that can affect multiple organs of the body, including the kidney. Nephrotic syndrome is common in people with severe lupus. (See "Patient education: Systemic lupus erythematosus (Beyond the Basics)".)

NEPHROTIC SYNDROME SYMPTOMS — The most common symptoms of nephrotic syndrome are swelling, weight gain, fatigue, blood clots, and infections. Kidney failure may develop in some people. Increased excretion of protein may lead to "frothy" appearing urine in the toilet bowl.

Swelling (edema) — Swelling that occurs in people with nephrotic syndrome commonly affects the lining of the eye socket, which often causes swelling around the eyes upon waking in the morning. Swelling (edema) can also occur in the feet or ankles after sitting or standing for any period of time. (See "Patient education: Edema (swelling) (Beyond the Basics)".)

Weight gain — Weight gain can occur in people who develop swelling. Weight gain can occur rapidly.

Uncommonly, weight loss can occur in people who are losing large quantities of protein in the urine. This may be due to malnutrition or an underlying condition, such as poorly controlled diabetes mellitus, a chronic viral infection, or cancer.

Kidney failure — Some people with nephrotic syndrome have a gradual decline in kidney function, which causes no symptoms in the early stages. However, as kidney function continues to worsen, symptoms of kidney failure can develop, including shortness of breath, weakness and easy fatigability (from anemia), and loss of appetite.

Blood lipids — The concentration of lipids (cholesterol and/or triglycerides) can become greatly elevated in nephrotic syndrome. If persistent, this may increase the risk of coronary artery disease.

Blood clots — People with nephrotic syndrome are at an increased risk of blood clots in the veins or arteries. Clots in the veins can travel to the lungs. This can be dangerous, or even fatal. (See "Hypercoagulability in nephrotic syndrome".)

Infection — People with severe nephrotic syndrome are at increased risk for infections (particularly children with minimal change disease), although the reasons for this are not well understood.

NEPHROTIC SYNDROME DIAGNOSIS — Nephrotic syndrome is diagnosed based upon a number of laboratory tests, including urine and blood tests. (See "Patient education: Kidney (renal) biopsy (Beyond the Basics)".)

Urine tests — Urine tests are often done to determine the amount of protein (albumin) in the urine.

Blood tests — A number of blood tests may be recommended to help determine the underlying cause of nephrotic syndrome to assess the risk of complications and to evaluate overall kidney function. (See "Glomerular disease: Evaluation and differential diagnosis in adults".)

Kidney biopsy — Kidney biopsy is the standard procedure for determining the underlying cause of nephrotic syndrome when a cause cannot be identified by noninvasive laboratory testing. (See "Patient education: Kidney (renal) biopsy (Beyond the Basics)".)

NEPHROTIC SYNDROME TREATMENT

Treat the underlying disease — The first line of treatment in nephrotic syndrome is to treat the underlying cause, if the cause is found. In addition, almost all patients are given an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), which lower blood pressure, prevent worsening of kidney disease, and reduce the amount of protein excreted in the urine.

Diabetes mellitus — The optimal treatment for diabetic kidney disease is not well understood, although the best approach likely includes intensive management of blood sugar levels, cholesterol, and blood pressure. Use of ACE and ARB medications are first line in the treatment of diabetic kidney disease because they lower the amount of protein in the urine and protect the kidney. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists are two classes of drugs that are also being used in patients with diabetes to lower the amount of protein in the urine.

Lupus — People with lupus who have nephrotic syndrome or evidence of worsening kidney function can be treated with glucocorticoids (steroids) and other medications that suppress the immune system. Most people respond well to such a regimen.

Minimal change disease — People with minimal change disease almost always respond initially to treatment with glucocorticoids (steroids). However, relapses are common, and additional treatments are often required. (See "Minimal change disease: Treatment in adults".)

Focal segmental glomerulosclerosis — Prolonged treatment with glucocorticoids (steroids) is often recommended for people with primary focal segmental glomerulosclerosis (FSGS). Secondary FSGS is treated primarily with ACE inhibitors or ARBs. (See 'Treat the underlying disease' above.)

Membranous nephropathy — The best treatment for membranous nephropathy is a source of debate. In many people, a period of "watch and wait" is recommended initially to determine if the condition is worsening or causing complications. During this time, an ACE inhibitor or ARB is recommended, and it is important to keep blood pressure and cholesterol levels controlled. Additional treatment, including medications that suppress the immune system, may be needed if membranous nephropathy progresses.

Without immunosuppressive treatment, approximately 10 to 30 percent of people with membranous nephropathy have a complete resolution of symptoms over several years, a further 10 to 30 percent of people have a partial remission, and approximately 40 percent of people slowly lose kidney function. As a result, most people with mild symptoms are advised to delay immunosuppressive treatment until/unless symptoms worsen. (See "Membranous nephropathy: Treatment and prognosis".)

Treating the symptoms of nephrotic syndrome — In addition to treating the underlying cause of nephrotic syndrome, the signs and symptoms of nephrotic syndrome can sometimes be treated.

Proteinuria — An ACE inhibitor or ARB is often recommended to reduce the loss of protein in the urine (proteinuria). An SGLT2 inhibitor may be added to the ACE inhibitor or ARB to further lower protein in the urine. (See "Overview of heavy proteinuria and the nephrotic syndrome".)

Edema — Swelling in the lower legs (edema) and collection of fluid in the abdomen (ascites) can occur in people with nephrotic syndrome. Edema and ascites often improve in people who follow a low-sodium diet and take a "water pill" (diuretic). (See "Patient education: Low-sodium diet (Beyond the Basics)" and "Pathophysiology and treatment of edema in adults with the nephrotic syndrome".)

High cholesterol — High cholesterol levels are often seen in people with nephrotic syndrome. If nephrotic syndrome persists, treatment is needed to lower blood cholesterol. Most people are initially treated with a cholesterol-lowering medication called a statin. (See "Patient education: High cholesterol and lipids (Beyond the Basics)".)

Blood clots — If a blood clot forms in a blood vessel, treatment may include a blood thinner, such as warfarin (brand name: Jantoven), for as long as the nephrotic syndrome persists. (See "Patient education: Warfarin (Beyond the Basics)" and "Hypercoagulability in nephrotic syndrome".)

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Chronic kidney disease (The Basics)
Patient education: Lupus and kidney disease (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Protein in the urine (proteinuria) (Beyond the Basics)
Patient education: Type 1 diabetes: Overview (Beyond the Basics)
Patient education: Type 2 diabetes: Overview (Beyond the Basics)
Patient education: Systemic lupus erythematosus (Beyond the Basics)
Patient education: Edema (swelling) (Beyond the Basics)
Patient education: Kidney (renal) biopsy (Beyond the Basics)
Patient education: Low-sodium diet (Beyond the Basics)
Patient education: High cholesterol and lipids (Beyond the Basics)
Patient education: Warfarin (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up to date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Acute kidney injury (AKI) in minimal change disease and other forms of nephrotic syndrome
Membranous nephropathy: Pathogenesis and etiology
Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting
Glomerular disease: Evaluation and differential diagnosis in adults
Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults
Lipid abnormalities in nephrotic syndrome
Pathophysiology and treatment of edema in adults with the nephrotic syndrome
Overview of heavy proteinuria and the nephrotic syndrome
Hypercoagulability in nephrotic syndrome
Urinalysis in the diagnosis of kidney disease
Minimal change disease: Etiology, clinical features, and diagnosis in adults
Minimal change disease: Treatment in adults
Membranous nephropathy: Treatment and prognosis

The following organizations also provide reliable health information.

●National Library of Medicine

     (www.nlm.nih.gov/medlineplus/healthtopics.html)

●National Institute of Diabetes and Digestive and Kidney Diseases

     (www.niddk.nih.gov)

●National Kidney Foundation

     (www.kidney.org)

●American Kidney Fund

     (www.kidneyfund.org/)

●American Association of Kidney Patients

     (www.aakp.org)

[1-3]