What is nephrotic syndrome?

From the Guidelines

Nephrotic syndrome is a kidney disorder characterized by excessive protein loss in the urine, leading to low blood protein levels, high cholesterol, and swelling throughout the body. It occurs when the kidney's filtering units (glomeruli) are damaged, allowing proteins that should remain in the blood to leak into the urine 1. The hallmark symptoms include severe edema (swelling) particularly in the legs, feet, and around the eyes; foamy urine due to protein content; and fatigue. Common causes include diabetes, lupus, certain medications, infections, and primary kidney diseases like minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy 1.

Key Characteristics and Treatment

• The syndrome is defined by a set of clinical features and laboratory findings, including heavy proteinuria (excess protein in the urine), hypoalbuminemia (low albumin in the blood), hyperlipidemia (elevated lipids in the blood), and edema 1.
• Treatment typically involves addressing the underlying cause while managing symptoms with medications such as corticosteroids (prednisone, often 1mg/kg/day for 4-16 weeks depending on response), diuretics like furosemide to reduce swelling, ACE inhibitors or ARBs to reduce protein leakage, and statins to control cholesterol.
• Dietary modifications including sodium restriction (less than 2g daily) and moderate protein intake are also important, as they help in managing the condition and preventing further kidney damage 1.
• Patients should monitor their weight daily, watch for increasing swelling, and seek immediate medical attention if they develop shortness of breath, chest pain, or severe abdominal pain, as complications like blood clots and infections can occur due to protein loss and altered immune function.

Definitions and Response to Treatment

• Relapse is defined as proteinuria > 3.5 g/day occurring after complete remission has been obtained for > 1 month, and frequently relapsing is considered as 2+ relapses within 6 months 1.
• Complete remission is achieved when proteinuria is reduced to < 0.20 g/day and serum albumin is > 35 g/L, while partial remission is defined as a reduction of proteinuria to between 0.21 g/day and 3.4 g/day & a decrease in proteinuria of > 50% from baseline.
• The response to treatment, such as corticosteroids and cytotoxic agents, varies among patients, with some achieving complete or partial remission, while others may be steroid-resistant or dependent 1.

Prognosis and Management

• The prognosis and management of nephrotic syndrome depend on the underlying cause, the severity of the disease, and the response to treatment, with the goal of achieving remission, preventing progression to end-stage renal disease (ESRD), and managing complications 1.
• Recent studies, such as those published in Kidney International 1, provide insights into the treatment recommendations and outcomes for patients with nephrotic syndrome, emphasizing the importance of individualized care and close monitoring.

From the Research

Definition and Characteristics of Nephrotic Syndrome

• Nephrotic syndrome (NS) is characterized by hypoalbuminemia, severe proteinuria, and peripheral edema, frequently in conjunction with hyperlipidemia 2.
• Individuals with NS usually show symptoms of weariness and swelling, but no signs of serious liver damage or cardiac failure 2.
• The majority of NS episodes are classified as unexplained or primary, with the most prevalent histopathological subgroups of primary NS in people being focal segmental glomerulosclerosis and membranous nephropathy 2.

Diagnosis and Pathobiochemistry

• NS can be diagnosed with characteristic medical symptoms and evidence of hypoalbuminemia and severe proteinuria 2.
• The pathobiochemistry of NS involves alterations in genes that affect the selectivity of the kidneys and abnormalities in proteins related to podocytes 2.
• Understanding the molecular mechanisms that influence these processes is crucial to developing specific and targeted therapeutic approaches 2.

Complications and Risks

• Thrombosis of the veins with high cholesterol levels is a significant NS risk 2.
• Acute renal damage and infection are further possible side effects of NS 2.
• Proteinuria may lead to the formation of cellular or fibrous crescents with reciprocal development of rapidly progressive glomerulonephritis or focal glomerulosclerosis 3.
• Hypoalbuminemia is usually associated with increased risk of mortality and kidney dysfunction 3.

Treatment Options

• Corticosteroids are frequently used as the initial line of defense in NS treatment 2, 4, 5.
• The use of calcineurin inhibitors, mycophenolate mofetil, and rituximab is mentioned in the text, along with current research to identify safer and more efficient therapeutic choices 2, 4, 6.
• General treatment includes administering an appropriate diet, use of diuretics and lipid-lowering drugs, and initiation of anticoagulant treatment, if required 4.
• Special treatment involves the administration of immunosuppressive and cytostatic drugs, which can be initiated only after the evaluation of renal histology and the overall risk status of the patient 4.