What is nephrotic syndrome?

From the Guidelines

Nephrotic syndrome is a kidney disorder characterized by excessive protein loss in the urine, low blood protein levels, high cholesterol, and swelling in the body, defined as presence of heavy proteinuria (≥ 1.0 g m−2 day−1 in children), hypoalbuminemia (< 3.0 g dl−1 in adults), and edema, as stated in the study by 1.

Definition and Causes

Nephrotic syndrome occurs when the kidney's filtering units (glomeruli) are damaged, allowing proteins that should remain in the blood to leak into the urine. The main symptoms include edema (swelling) particularly in the legs, ankles, and around the eyes; foamy urine due to protein content; and fatigue.

• Nephrotic syndrome can be caused by primary kidney diseases like minimal change disease, focal segmental glomerulosclerosis, or membranous nephropathy, as mentioned in the study by 1.
• It can also develop secondary to conditions such as diabetes, lupus, or certain infections.

Diagnosis and Treatment

Treatment typically involves addressing the underlying cause, along with medications like corticosteroids, diuretics to reduce swelling, ACE inhibitors or ARBs to reduce protein leakage, and statins to manage high cholesterol, as recommended in the guideline by 1.

• Dietary modifications including sodium restriction and moderate protein intake are also important.
• The condition requires monitoring of kidney function, protein levels, and potential complications like blood clots or infections, as the immune system may be compromised due to protein loss.

Management and Recommendations

The KDIGO 2021 clinical practice guideline for the management of glomerular diseases, as stated in the study by 1, provides recommendations for the management of nephrotic syndrome, including the use of immunosuppressive therapy in patients with severe, disabling, or life-threatening symptoms related to the nephrotic syndrome.

• The guideline also recommends monitoring of urinary protein excretion and renal function to determine the need for immunosuppressive therapy, as mentioned in the study by 1.
• The management of nephrotic syndrome should be individualized, taking into account the underlying cause, severity of symptoms, and potential complications, as recommended in the study by 1.

From the Research

Definition and Characteristics of Nephrotic Syndrome

• Nephrotic syndrome (NS) is characterized by edema, proteinuria, hypoalbuminemia, and hyperlipidemia 2, 3, 4, 5.
• The syndrome is defined by increased permeability to proteins at the level of the glomerulus, allowing for passage of albumin and other proteins into the urine 4.
• Proteinuria leads to a cascade of clinical complications, including fluid accumulation, kidney inflammation, and dysregulation of coagulation and immunity 4.

Causes and Classification of Nephrotic Syndrome

• The most common causes of NS in children are idiopathic minimal change disease and focal segmental glomerulosclerosis (FSGS) 2.
• In adults, FSGS and membranous nephropathy (MN) are the most common primary causes 2.
• There are numerous secondary causes, including diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections 2.
• NS can be classified as primary (idiopathic) or secondary, with primary NS being further divided into histopathological subgroups such as FSGS and MN 3.

Diagnosis and Evaluation of Nephrotic Syndrome

• Diagnosis of NS is based on characteristic medical symptoms and evidence of hypoalbuminemia and severe proteinuria 3.
• Evaluation should assess for secondary causes, and may involve genetic testing and kidney biopsy 2.
• In children, most cases are due to minimal change disease, which is responsive to steroid treatment, and a glucocorticoid should be prescribed for children younger than 12 years 2.

Complications and Management of Nephrotic Syndrome

• NS is associated with several complications, including thrombosis, acute renal damage, and infection 3.
• Management of NS involves reduction of proteinuria with glucocorticoids, and alternative therapies such as calcineurin inhibitors, mycophenolate mofetil, and rituximab may be necessary for frequent recurrences or steroid-resistant NS 2, 3.
• Long-term management includes dietary sodium restriction, edema management, and blood pressure control, as well as thromboembolism prophylaxis for patients with high risk of thromboembolism 2.