Nephrotic Syndrome

 

Nephrotic Syndrome

Pathophysiology, Causes, and Management

Nephrotic syndrome is defined by severe proteinuria (>3.5 g/day), hypoalbuminemia, generalized edema, and hyperlipidemia. It arises from increased glomerular capillary permeability, usually due to podocyte injury or basement membrane defects. Causes include primary glomerular diseases (e.g., minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy) and secondary systemic conditions (e.g., diabetes, lupus nephritis, infections, drugs, malignancies). Major complications include thrombosis, recurrent infections, malnutrition, and progression to chronic kidney disease (CKD). Early recognition and tailored management are crucial to improve outcomes.

Nephrotic syndrome and nephritic syndrome are both kidney disorders affecting the glomeruli, but they differ in their underlying pathology, clinical features, and laboratory findings. Here is a comparison in table format. 

 I. Pathophysiology

The central defect is injury to the glomerular capillary wall, leading to abnormal filtration of plasma proteins, especially albumin.

Key Clinical Features:

1. Proteinuria: >3.5 g/day in adults; >40 mg/m²/hr in children
2. Hypoalbuminemia: <2.5 g/dL
3. Edema: From reduced oncotic pressure and sodium retention
4. Hyperlipidemia & Lipiduria: Due to hepatic lipoprotein overproduction and urinary lipid loss

Pathophysiological Mechanisms:

• Proteinuria: Loss of selective GBM permeability due to podocyte effacement
• Hypoalbuminemia: Hepatic synthesis insufficient to compensate for albumin loss
• Edema: Reduced oncotic pressure with RAAS-mediated sodium/water retention
• Hyperlipidemia: Increased hepatic synthesis of LDL/VLDL
• Hypercoagulability: Urinary loss of anticoagulants (antithrombin III) and enhanced platelet activity

II. Causes

Nephrotic syndrome is classified into primary (idiopathic) and secondary forms.

A. Primary Nephrotic Syndrome

1. Minimal Change Disease (MCD):

·         Most frequent in children

·         Podocyte injury seen on EM

·         Excellent steroid response

2. Focal Segmental Glomerulosclerosis (FSGS):

·         Common in adults, higher prevalence in African descent

·         Segmental scarring; variable steroid response

·         Often progresses to ESRD

3. Membranous Nephropathy (MN):

·         Leading cause in adults

·         Immune complex deposition; often PLA2R antibody-positive

·         Variable prognosis, guided by risk stratification

4. Membranoproliferative GN (MPGN):

·         Mixed nephritic-nephrotic features

·         Immune complex deposition in mesangium and GBM

B. Secondary Nephrotic Syndrome

• Diabetic nephropathy: Most common adult cause
• Lupus nephritis: Immune complex–mediated
• Amyloidosis: Amyloid deposition in glomeruli
• Infections: Hepatitis B/C, HIV, malaria
• Drugs: NSAIDs, penicillamine, heroin
• Malignancies: Hodgkin’s lymphoma (MCD), solid tumors (MN)

III. Clinical Features

• Generalized edema (periorbital, pedal)
• Frothy urine
• Fatigue, weight gain
• Hypertension (more frequent in secondary causes)

Diagnostic Evaluation:

• Urinalysis: Proteinuria, lipiduria (Maltese crosses)
• 24-hr urine protein / protein-creatinine ratio
• Serum albumin, lipid profile, renal function tests
• Renal biopsy: Essential for diagnosis, except typical pediatric MCD
• Immunological tests: ANA, complements, anti-dsDNA for secondary causes

IV. Management

A. General Supportive Care

• Dietary sodium restriction: Control edema
• Fluid restriction: In severe edema
• Diuretics: For fluid overload
• ACE inhibitors/ARBs: Reduce proteinuria, preserve renal function
• Statins: Treat hyperlipidemia
• Anticoagulation: In patients with high thrombosis risk (albumin <2 g/dL)
• Vaccinations: Pneumococcal and influenza due to infection risk

B. Disease-Specific Treatment

• Minimal Change Disease: Steroids (prednisone), relapse may need immunosuppressants
• FSGS: Often steroid-resistant; managed with calcineurin inhibitors, mycophenolate; risk of ESRD
• Membranous Nephropathy: Guided by anti-PLA2R antibody and risk stratification; may need rituximab or cyclophosphamide
• Secondary Nephrotic Syndrome (e.g., diabetic nephropathy): Glycemic control, BP control, RAAS blockade

V. Complications

• Thromboembolism: DVT, renal vein thrombosis
• Infections: Due to loss of IgG and complement
• Hypovolemia: Especially in children with severe diuresis
• CKD/ESRD: Particularly in FSGS or uncontrolled secondary causes

VI. Prognosis

• Minimal Change Disease: Excellent prognosis in children (≈90% remission)
• FSGS: Poor prognosis, frequent relapses, ESRD risk
• Membranous Nephropathy: Variable—some remit, some persist, others progress
• Secondary NS: Outcome depends on control of underlying disease

 Conclusion

Nephrotic syndrome is a multifactorial kidney disorder with varied causes and outcomes. Prompt diagnosis, supportive measures, and disease-specific therapy significantly improve prognosis, particularly in steroid-sensitive cases. Long-term monitoring for relapse, CKD progression, thrombosis, and infection is essential for optimizing patient outcomes.

 FAQs on Nephrotic Syndrome

1. What is nephrotic syndrome in simple terms?
Nephrotic syndrome is a kidney problem where your body leaks too much protein into the urine. This causes swelling (edema), low blood protein, and high cholesterol.

2. What are the early warning signs of nephrotic syndrome?
The most common early signs are swelling around the eyes (especially in the morning), swollen feet or ankles, and foamy urine.

3. Is nephrotic syndrome a disease by itself?
No. Nephrotic syndrome is a group of symptoms caused by different kidney diseases. It can be primary (affecting only the kidneys) or secondary (caused by conditions like diabetes or lupus).

4. Can nephrotic syndrome be cured?
In some cases, yes. For example, children with minimal change disease often recover fully with steroids. In other cases, treatment controls symptoms and slows kidney damage rather than curing the condition.

5. What foods should I avoid if I have nephrotic syndrome?
Patients are usually advised to limit salt (to reduce swelling) and sometimes control protein and fluid intake, depending on kidney function. Always follow a doctor’s or dietitian’s advice.

6. What are the long-term risks of nephrotic syndrome?
If untreated, it may lead to blood clots, frequent infections, or chronic kidney disease (CKD). With proper treatment and follow-up, many patients do well.