What is the pathophysiology and management of nephritic syndrome?

Pathophysiology and Management of Nephritic Syndrome

Nephritic syndrome is characterized by a constellation of hematuria, proteinuria, hypertension, and in some cases acute kidney injury and fluid retention due to acute glomerular inflammation, requiring prompt diagnosis and management to prevent progression to chronic kidney disease. 1

Pathophysiology

• Nephritic syndrome develops following pathological injury to renal glomeruli, which may be primary (kidney-specific disease) or secondary to systemic disorders 2
• The syndrome is characterized by inflammation of the glomeruli, leading to disruption of the glomerular filtration barrier 1
• This inflammation causes increased permeability of the glomerular capillaries, resulting in hematuria and moderate proteinuria (typically less than nephrotic range) 3
• Immunological mechanisms play a key role in the injury of the glomerular capillary in most forms of nephritic syndrome 4
• The inflammatory process leads to decreased glomerular filtration rate, resulting in sodium and water retention, which contributes to hypertension and edema 1

Common Causes

• Post-infectious glomerulonephritis (most commonly following streptococcal infection) 3
• IgA nephropathy (Berger's disease) 1
• Lupus nephritis 1
• Membranoproliferative glomerulonephritis 1
• ANCA-associated vasculitis 1

Clinical Presentation

• Hematuria (microscopic or macroscopic) is the hallmark finding 3
• Moderate proteinuria (typically non-nephrotic range) 3
• Hypertension due to volume expansion and activation of the renin-angiotensin-aldosterone system 1
• Edema (less prominent than in nephrotic syndrome) 1
• Acute kidney injury with varying degrees of renal insufficiency 1
• Oliguria may be present in severe cases 1

Diagnostic Evaluation

• Urinalysis showing dysmorphic red blood cells, red cell casts, and protein 1
• Quantitative measurement of proteinuria using urine protein:creatinine ratio (PCR) or albumin:creatinine ratio (ACR) 2
• Complete blood count, serum electrolytes, kidney function tests, and serum albumin 5
• Complement levels (C3, C4) - often decreased in post-infectious GN and lupus nephritis 4
• Serological tests based on clinical suspicion (anti-streptolysin O, anti-DNase B, ANA, anti-dsDNA, ANCA) 1
• Renal ultrasound to assess kidney size and echogenicity 5
• Kidney biopsy is often necessary for definitive diagnosis and to guide treatment 2

Management Approach

General Measures

• Prompt referral to a nephrologist (ideally within 2 weeks) for evaluation and management 2
• Maintenance of intravascular euvolemia and adequate nutrition 6
• Prevention of complications and preservation of kidney function 6

Specific Treatments

• Treatment of the underlying cause when possible 1
• Management of hypertension using appropriate antihypertensive medications 3
  • ACE inhibitors or ARBs are often preferred due to their antiproteinuric effects 3
• Diuretics (primarily furosemide 0.5-2 mg/kg per dose) for patients with fluid overload and preserved kidney function 6
  • Avoid diuretics in patients with evidence of intravascular hypovolemia 6
• Immunosuppressive therapy based on the specific cause and severity:
  • Corticosteroids are often the first-line therapy for many forms of nephritic syndrome 7
  • For steroid-resistant cases, calcineurin inhibitors (cyclosporine, tacrolimus) may be considered 7
  • Other options include mycophenolate mofetil, rituximab, or cyclophosphamide depending on the underlying cause 7

Prevention and Management of Complications

• Infection prophylaxis measures, especially in severe cases 6
• Adequate nutrition to prevent malnutrition 6
• Monitoring for thromboembolism, especially with significant hypoalbuminemia 5

Monitoring and Follow-up

• Regular monitoring of kidney function, proteinuria, and blood pressure 1
• Adjustment of therapy based on clinical response 7
• Long-term follow-up to monitor for progression to chronic kidney disease 1

Pitfalls and Caveats

• Avoid immunosuppressive agents for genetic forms of glomerular disease as they are unlikely to respond 6
• Be cautious with diuretic dosing; excessive doses can lead to intravascular volume depletion 6
• Distinguish between nephritic and nephrotic syndrome, as management approaches differ 3
• Consider the potential side effects of immunosuppressive therapy, especially in patients with comorbidities 7
• Watch for worsening of proteinuria and kidney function to avoid missing the opportunity to provide appropriate immunosuppressive therapy 7