Nephritic syndrome

Nephritic syndrome is an inflammatory process that is defined as the presence of one or more of the following:

• Hematuria – patients complain of tea coloured urine
• Red blood cell casts in urine
• Proteinuria of less than 3.5g/24 hours
• Oliguria – urinary output less than 400 ml per day or less than 20 ml per hour
• Sterile pyuria
• Hypertension
• Mild to moderate edema
• Azotemia – buildup of nitrogenous products (BUN-usually ranging 7 to 21 mg/dL), creatinine in the blood, and other secondary waste products within the body

Causes can be divided into infectious and non-infectious causes. Non-infectious causes can be further classified into primary causes and secondary causes.

Causes of nephritic glomerulonephritis

• Pathophysiology of glomerulonephritis
  • Pathophysiology depends on the underlying cause of the nephritic syndrome.
  • Damage is at the glomerular filtration barrier through the following mechanisms:
    • Direct damage to the endothelial cell layer
    • Deposition of immune complex in subendothelial, subepithelial, and mesangial space
    • Disruption of glomerular basement membrane by primary renal or secondary systemic diseases
    • Damage to the podocytes’ cellular layer
  • The disruption of the glomerular filtration barrier in nephritic syndrome allows leakage of proteins and red blood cells in the urine resulting in reduced renal function.
  • The dysmorphic RBCs (a feature of glomerular hematuria – acanthocytes and RBC casts) are pathognomonic of glomerulonephritis.
  • RBC casts are formed when deformed, and distorted RBCs and white blood cells are encased by the Tamm-Horsfall protein (THP).
  • THP is secreted by renal tubular cells and excreted in urine normally.
• Patient history
  • Recent upper respiratory tract or skin infection – post-strep glomerulonephritis
  • Ulcers and rash on the extremities – vasculitis
  • Hemoptysis and dyspnea may be present – Goodpasture syndrome
  • Features of underlying infection – mentioned under etiology
• Signs and symptoms
  • Periorbital and pedal edema
  • Hematuria with red or cola-colored urine
  • Proteinuria in non-nephrotic (i.e., less than 3.5 gm/day) range and may cause foamy urine when protein content is high
  • Hypertension or poorly controlled blood pressure (BP) in patients with previously controlled BP
  • Renal insufficiency characterized by oliguria (reduced urine output), and azotemia, due to decreased glomerular filtration rate (GFR)
• Physical examination
  • Features of fluid overload
    • Pedal and periorbital edema
    • Basal lung crackles – pulmonary edema
    • JVP distention
  • Features of underlying disease
• Differenitals
  • Nephrotic syndrome
  • Familial nephritis
  • Idiopathic hematuria
  • Anaphylaxis
• Investigations
  • Urinalysis
    • Hematuria – micro and macro
    • Red blood cell casts
    • Acanthocytes
    • Sterile pyuria – WBCs present, no bacteria
  • U/E/Cs:
    • elevated urea and creatinine with electrolyte derangement common
  • Blood cultures: indicated with high fevers, suspected chronic infection
  • ANA: Anti-nuclear antibodies to rule out autoimmune disorders
  • Serum C3 and C4 Complement Levels: The complement levels are low in diseases in which there is an activation of the inflammatory cascade resulting in deposition of immune complexes in the glomerulus. The conditions include post-streptococcal glomerulonephritis, infective endocarditis, and SLE.
  • ASO Titers: High levels of anti-streptolysin O, anti-DNase B antibody titers indicate a recent streptococcal infection
  • ANCA: Both cytoplasmic and peripheral anti-neutrophil cytoplasmic antibodies (ANCA) levels are assessed to rule out systemic vasculitis (i.e., granulomatosis with polyangiitis, microscopic polyangiitis)
  • Anti-dsDNA Antibodies: Highly sensitive for the diagnosis of systemic lupus erythematosus
  • Anti-glomerular Basement Membrane Antibodies: To rule out Goodpasture syndrome
  • Hepatitis B Surface Antigen and HCV Antibodies: To rule out hepatitis B and C infection
  • Renal biopsy: definitive diagnosis
• Supportive treatment
  • Low sodium diet
  • Water restriction
• Medical treatment
  • RAAS inhibitors to control proteinuria and hypertension
  • Loop diuretics to control hypertension and edema
  • Immunosuppressive therapy with corticosteroids or cyclophosphamide
  • Antibiotics for underlying infection
  • Treatment of other underlying causes
  Renal replacement therapy may be needed in severe cases where renal failure has occurred. In the case of Goodpasture syndrome – plasma exchange + immunosuppression
• Complications of nephritic glomerulonephritis
  • Acute renal failure and progression to RPGN
  • Uncontrolled hypertension
  • Azotemia
  • Electrolyte imbalances
    • Hyperkalemia
    • Hyperphosphatemia
    • Hypocalcemia
  • Heart failure