Nephrotic syndrome

Overview

Nephrotic syndrome is a kidney disorder characterized by a group of clinical signs that result from damage to the glomeruli, the tiny blood vessels in the kidneys that filter waste and excess fluids. The hallmark features of nephrotic syndrome include massive proteinuria (excretion of large amounts of protein in the urine), hypoalbuminemia (low levels of albumin in the blood), edema (swelling), and hyperlipidemia (elevated blood lipids).

This condition can occur in both children and adults and may be caused by a variety of primary kidney diseases or secondary to systemic conditions. If left untreated, nephrotic syndrome can lead to serious complications such as infections, blood clots, and progression to chronic kidney disease or end-stage renal failure.

Causes

Nephrotic syndrome results from increased permeability of the glomerular basement membrane, allowing large proteins like albumin to leak into the urine. The causes of nephrotic syndrome are generally divided into two categories: primary (idiopathic) and secondary.

Primary Causes (Intrinsic Renal Diseases)

• Minimal change disease (MCD): The most common cause in children; glomeruli appear normal under a light microscope

• Focal segmental glomerulosclerosis (FSGS): Scarring in scattered parts of some glomeruli; more common in adults

• Membranous nephropathy: Thickening of the glomerular basement membrane due to immune deposits; often seen in adults

Secondary Causes (Systemic Diseases)

• Diabetes mellitus: Diabetic nephropathy is a leading cause of nephrotic syndrome in adults

• Systemic lupus erythematosus (SLE): Autoimmune disease affecting multiple organs, including the kidneys

• Infections: Such as hepatitis B, hepatitis C, HIV, or malaria

• Certain medications: NSAIDs, gold salts, and some antibiotics

• Malignancies: Especially solid tumors or hematologic cancers like lymphoma

Symptoms

The signs and symptoms of nephrotic syndrome are a result of protein loss, fluid retention, and compensatory metabolic changes. Common clinical features include:

• Edema: Swelling around the eyes (especially in the morning), ankles, feet, and abdomen due to fluid retention

• Proteinuria: Foamy or frothy urine due to high protein content

• Hypoalbuminemia: Low serum albumin contributing to edema

• Hyperlipidemia: Elevated cholesterol and triglycerides

• Fatigue and weakness: Due to fluid imbalance and nutrient loss

• Weight gain: From fluid accumulation

• Increased susceptibility to infections: Particularly peritonitis or cellulitis due to immune protein loss

• Blood clots: Due to loss of anticoagulant proteins in urine

Diagnosis

Diagnosing nephrotic syndrome involves a combination of physical examination, laboratory tests, and sometimes a kidney biopsy to determine the underlying cause.

• Urinalysis: Detects proteinuria (usually >3.5 g/day), hematuria may be absent or minimal

• 24-hour urine collection: Quantifies the exact amount of protein lost

• Serum albumin: Usually low (<3.0 g/dL)

• Lipid profile: Shows elevated cholesterol and triglyceride levels

• Renal function tests: Serum creatinine and BUN to assess kidney function

• Blood tests: To screen for secondary causes (e.g., ANA for lupus, HbA1c for diabetes, viral markers)

• Renal ultrasound: Assesses kidney size and structure

• Kidney biopsy: Recommended in adults or steroid-resistant cases to determine specific histological subtype

Treatment

Treatment of nephrotic syndrome aims to reduce proteinuria, control symptoms, treat the underlying cause, and prevent complications. Management often requires collaboration between primary care physicians, nephrologists, and other specialists.

General Measures

• Dietary modification: Low-sodium diet to manage edema; adequate protein intake depending on renal function

• Fluid restriction: In cases of severe edema or hyponatremia

Medications

• Corticosteroids: First-line treatment in minimal change disease and sometimes effective in FSGS

• Immunosuppressive agents: Such as cyclophosphamide, cyclosporine, or tacrolimus in steroid-resistant or dependent cases

• ACE inhibitors or ARBs: Reduce proteinuria and protect kidney function

• Diuretics: To manage edema (e.g., furosemide, spironolactone)

• Statins: To manage hyperlipidemia

• Anticoagulants: In cases of thrombosis or high risk of blood clots

• Antibiotics and vaccines: To prevent and treat infections

Treatment of Underlying Cause

• Diabetes control: Intensive glycemic control in diabetic nephropathy

• Autoimmune disease management: Immunosuppressants for lupus nephritis or vasculitis

• Infection treatment: Antiviral or antimicrobial therapy if nephrotic syndrome is secondary to infection

Prognosis

The prognosis of nephrotic syndrome depends on the underlying cause, response to treatment, and age of onset. In children with minimal change disease, prognosis is generally excellent, with most achieving complete remission with corticosteroids. Adults with FSGS or membranous nephropathy may have a more variable response and a higher risk of progression to chronic kidney disease.

Potential complications include acute kidney injury, chronic kidney disease, thromboembolism, severe infections, and malnutrition. Early diagnosis, appropriate treatment, and regular follow-up are essential to improve outcomes and minimize complications.

With advances in medical therapy and supportive care, many individuals with nephrotic syndrome can manage their condition effectively and maintain a good quality of life.