24.7: Nephrotic Syndrome I : Introduction

Nephrotic Syndrome is a chronic kidney disorder defined by clinical findings such as severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema. These symptoms result from damage to the glomeruli, the kidney’s filtering units, increasing their permeability to proteins.

Definition and Meaning:

Proteinuria, defined as the loss of more than 3.5 grams of protein per day in adults, is a crucial feature of nephrotic syndrome. This condition is often accompanied by edema, the accumulation of fluid that causes swelling, and hyperlipidemia, characterized by increased levels of cholesterol and triglycerides. It is important to note that nephrotic syndrome is not a specific disease; instead, it is a collection of symptoms resulting from various underlying kidney diseases that affect the filtering function of the glomeruli.

Common Causes:

Primary Glomerular Diseases:

• Minimal Change Disease (MCD): The most common cause in children, with no significant structural changes visible on light microscopy.
• Focal Segmental Glomerulosclerosis (FSGS): Often found in adults and characterized by scarring in some parts of the glomeruli.
• Membranous Nephropathy: More prevalent in adults, involving a thickening of glomerular capillary walls.

Secondary Causes:

• Systemic Diseases: The most common secondary cause in adults is diabetes mellitus, with lupus nephritis (from systemic lupus erythematosus) and amyloidosis also contributing.
• Infections: HIV (human immunodeficiency virus), hepatitis B, and hepatitis C.
• Medications: Including NSAIDs [Nonsteroidal anti-inflammatory drugs], certain antibiotics, and some cancer treatments.
• Toxins: Exposure to heavy metals like mercury and certain recreational drugs.

Clinical Manifestations:

• Edema: Often initially appears around the eyes (periorbital) and ankles but can become generalized (anasarca) as the condition progresses.
• Proteinuria: Results in frothy or foamy urine due to the excess protein being excreted.
• Hypoalbuminemia Causes decreased blood oncotic pressure, worsening fluid retention, and edema.
• Hyperlipidemia: Elevated cholesterol and triglycerides occur as the liver compensates for protein loss.
• Additional Complications: Individuals may experience an increased risk of infections, thromboembolic events, and malnutrition.

Pathophysiology:

• Glomerular Injury: Damage to the glomerular filtration barrier, especially to podocytes—cells lining the glomeruli—increases protein permeability.
• Protein Loss: Large proteins like albumin leak into the urine, leading to hypoalbuminemia. This drop in albumin levels causes fluid to shift from the bloodstream into tissues, resulting in edema.
• Liver Compensation: In response to hypoalbuminemia, the liver increases lipoprotein synthesis, leading to hyperlipidemia.
• Increased Clotting Risk: Loss of anticoagulant proteins and hyperlipidemia raises the risk for thromboembolism.
• Immune System Alterations: The loss of immunoglobulin G (IgG) in the urine weakens immune defenses, making infections more likely

Summary:

Nephrotic syndrome is a significant clinical syndrome often resulting from underlying kidney damage. It leads to severe protein loss, generalized edema, and complications such as hyperlipidemia, infection susceptibility, and a heightened risk of blood clots. Early diagnosis and treatment of nephrotic syndrome are important to avoid complications and help patients improve their health.