Nephritic syndrome

Nephritic syndrome is characterized by glomerular capillary damage leading to hematuria, pyuria, water retention, and subsequent hypertension and edema. It can be caused by a variety of conditions including autoimmune, hereditary, and infectious diseases. Nephritic diseases can manifest with varying degrees of severity, ranging from asymptomatic hematuria to systemic involvement, as in rapidly progressive glomerulonephritis. The urine sediment is typically characterized by red blood cell casts, mild to moderate proteinuria (< 3.5 g/day), and sterile pyuria. Diagnosis of the underlying disease is often based on presentation and laboratory values, although renal biopsy may be indicated for confirmation.

Nephritic syndrome is an inflammatory process that is defined as the presence of one or more of the following: ^[1]

• Hematuria with acanthocytes
• RBC casts in urine
• Proteinuria (< 3.5 g/24 h)
• Hypertension
• Mild to moderate edema
• Sterile pyuria
• Oliguria
• Azotemia

NephrItic syndrome indicates glomerular Inflammation.

Low serum C3 levels are seen in poststreptococcal glomerulonephritis, lupus nephritis, and membranoproliferative glomerulonephritis.

• General pathophysiology
  • Inflammation → cytokine release → glomerular capillary damage
    • Porous glomerular basement membrane → leakage of proteins and RBCs → nephritic sediment (all blood components are detectable on urinalysis)
      • Proteinuria (< 3.5 g/24h): leakage of proteins
      • Hematuria: leakage of RBCs, which stick together and form red blood cell casts in the renal tubules
    • Oliguria: inflammatory infiltrates reduce fluid movement across the membrane (↓ GFR)
    • Azotemia: inflammation prevents sufficient filtering and excretion of urea
    • Salt retention → intravascular volume expansion → hypertension and edema
• Membranoproliferative glomerulonephritis: characterized by deposition of antibodies between podocytes and the basal membrane
  • Membranoproliferative glomerulonephritis type 1: subendothelial immune complex deposits → activation of the classical complement pathway → cell injury, mesangial proliferation, and matrix expansion
  • Membranoproliferative glomerulonephritis type 2 (dense deposit disease): intramembranous deposition of complement C3 (C3 nephritic factor, an IgG autoantibody that stabilizes C3 convertase and continuously activates C3, leading to its depletion) → activation of the alternative complement pathway

• Intermittent gross hematuria (red or brown urine, i.e., cola-colored urine)
• Hypertension
• Pitting edema
• In ↓ GFR: oliguria and uremic symptoms (see “Uremia”)
• For a comparison of nephrotic and nephritic syndrome see “Nephrotic vs. nephritic syndrome”

• Urinalysis: nephritic sediment ^[14]
  • Hematuria (either microhematuria or intermittent macrohematuria)
  • Acanthocytes
  • Red blood cell casts: RBC casts form through the congregation of proteins and RBCs inside the tubules.
  • Mild to moderate proteinuria of > 150 mg/24 h but < 3.5 g/24 h (nonselective glomerular proteinuria)
  • Sterile pyuria and sometimes WBC casts
• Blood tests
  • ↑ Creatinine, ↓ GFR
  • Azotemia with ↑ BUN
  • Complement, ANA, ANCA, and anti-GBM antibodies
• Renal biopsy: sometimes indicated in patients with a nonspecific disease pattern to confirm diagnosis

Glomerular hematuria is a typical finding in nephritic syndrome. It is characterized by acanthocytes, RBC casts, and mild to moderate proteinuria. Nonglomerular hematuria is characterized by bright red or pink urine, the occurrence of blood clots, normal RBC morphology, and the absence of RBC casts.

• See “Nephrotic vs. nephritic syndrome.”

The differential diagnoses listed here are not exhaustive.

• Supportive therapy
  • Low-sodium diet
  • Water restriction
• Medical therapy
  • If proteinuria and/or hypertension: angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers
  • If severe hypertension and/or edema: diuretics
  • Sometimes immunosuppressive therapy is indicated (e.g., in lupus nephritis).
  • If RPGN from anti-GBM antibody disease: plasmapheresis
• In the case of:
  • Severe renal insufficiency or kidney failure: renal replacement therapy (e.g., hemodialysis, possibly transplantation)
  • Membranoproliferative glomerulonephritis (type 1 and type 2 MPGN)
    • RAAS inhibitors are often added to treatment
    • Prednisone alone or in combination with other immunosuppressants (cyclosporine OR tacrolimus)