What is nephrotic syndrome?

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Last updated: June 19, 2025View editorial policy

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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. It occurs when the kidneys' filtering units (glomeruli) are damaged, allowing proteins that should remain in the blood to leak into the urine 1. 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, and membranous nephropathy, or secondary to conditions such as diabetes, lupus, or certain medications.

Key Characteristics

  • Heavy proteinuria (≥ 1.0 g m−2 day−1 in children)
  • Hypoalbuminemia (< 3.0 g dl−1 in adults)
  • Edema
  • Hypercholesterolemia is commonly present

Treatment and Management

Treatment typically involves addressing the underlying cause, along with medications like corticosteroids (prednisone, often starting at 1mg/kg/day for adults), diuretics to reduce swelling (such as furosemide 20-80mg daily), ACE inhibitors or ARBs to reduce protein leakage, and statins to manage high cholesterol 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 and infections, as the loss of certain blood proteins can affect immune function and blood clotting.

Complications and Prognosis

The duration and severity of proteinuria are known to be surrogate markers of the progression of glomerular disease 1. Patients with nephrotic syndrome have an increased risk of thromboembolism, and the risk of developing coronary heart disease is four times greater in nephrotic patients than in sex- and age-matched controls. The main factor predicting the prognosis in all the histologic variants of INS is the response of proteinuria to therapy. Therefore, the objectives of treatment are threefold: (1) to lower proteinuria, (2) to reduce the frequency of relapses of nephrotic syndrome, and (3) to protect the kidney and prevent progression to renal failure.

Recent Guidelines and Recommendations

Recent studies and guidelines suggest that cyclosporine can be effective in treating steroid-resistant FSGS, with a significant reduction in proteinuria and improvement in renal function 1. However, the use of cyclosporine should be cautious due to its potential nephrotoxicity. Other therapeutic options include mycophenolate mofetil (MMF), dexamethasone, and rituximab, which may be considered in patients with steroid-resistant or steroid-dependent nephrotic syndrome.

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 syndrome is defined by proteinuria, hypoalbuminemia, edema, and hypercholesterolemia 3.
  • NS is characterized by proteinuria >3.5 g/24h, edema, hypoalbuminemia, and hyperlipidemia 4.

Causes and Risk Factors

  • The majority of NS episodes are classified as unexplained or primary; the most prevalent histopathological subgroups of primary NS in people are focal segmental glomerulosclerosis and membranous nephropathy 2.
  • 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.
  • Dysregulated coagulation state, promoted by the breakdown of permselectivity barrier of the glomerular capillary wall, resulting in the leakage of high-molecular-mass proteins, is a typical feature in the clinical course of NS 5.

Diagnosis and Treatment

  • NS can be diagnosed with characteristic medical symptoms and evidence of hypoalbuminemia and severe proteinuria 2.
  • Renal biopsy is often mandatory, except in diabetes, for the diagnosis of NS 4.
  • Corticosteroids are frequently used as the initial line of defense in NS treatment 2.
  • 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.
  • Statins may confer tissue protection through lipid-independent mechanisms, which can be triggered by other mediators, such as angiotensin receptor blockers 6.

Complications

  • Urinary protein loss leads to several complications: water and sodium retention, hyperlipidemia, increased risk of thromboembolism and infection, anemia, and alteration of mineral metabolism 4.
  • Hyperlipidemia can affect renal function, increase proteinuria, and speed glomerulosclerosis, thus determining a higher risk of progression to dialysis 6.
  • Thrombotic events affect the venous system rather than arterial vessels with different features and frequencies, and deep venous system of the lower extremities and renal veins are the most frequent source of pulmonary embolism, the most dangerous NS complication 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Nephrotic Syndrome: A Review.

Cureus, 2024

Research

Management of patients with nephrotic syndrome.

Swiss medical weekly, 2009

Research

Thrombosis in nephrotic syndrome.

Seminars in thrombosis and hemostasis, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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