• Clinical science

Nephritic syndrome

Summary

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.

Definition

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

NephrItic syndrome indicates glomerular Inflammation.

Overview

Diseases associated with nephritic syndrome
Epidemiology Clinical features Diagnostics
Poststreptococcal glomerulonephritis
  • Usually affects children 3–12 years of age [2]

IgA nephropathy (Berger disease)

  • Most common type of idiopathic glomerulonephritis worldwide
  • Incidence: > [3]
  • Peak incidence: 2nd to 3rd decade of life [4]
  • Asymptomatic microhematuria with intermittent gross hematuria during or directly after one or more of the following:
    • Upper respiratory tract
    • Gastrointestinal infections
    • Strenuous exercise
  • 25–30% of patients progress to end-stage renal disease (ESRD) within 20 years of diagnosis. [5]
Small vessel vasculitis

Granulomatosis with polyangiitis (formerly Wegener granulomatosis)

  • Slightly more common in men
  • Peak incidence: 65–74 years [6]

Microscopic polyangiitis

  • Slightly more common in men
  • Peak incidence: 50–60 years [7]

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Goodpasture syndrome (anti–GBM antibody disease)

  • Two peaks of occurrence [9]
    • 20–30 years ( > )
    • 60–70 years ( > )

Thin basement membrane nephropathy (benign familial hematuria)

  • Estimated to affect 5–10% of the general population [10]
  • Hereditary disorder
  • Persistent microhematuria and episodic gross hematuria (e.g., following an upper respiratory tract infection or exercise)
  • Good prognosis

Alport syndrome

  • Persistent microhematuria with intermittent gross hematuria
  • EM: splitting and alternating thickening and thinning of the glomerular basement membrane (lamellated and basket-weave appearance)

Diffuse proliferative glomerulonephritis (DPGN)

Rapidly progressive glomerulonephritis (RPGN)

  • Occurrence: =
  • Peak incidence: 60–85 years [12]
  • Renal function declines rapidly over days to weeks
  • Not a disease entity itself but a possible manifestation of glomerulonephritis
  • Poor prognosis: can progress to ESRD within weeks to months

Membranoproliferative glomerulonephritis (MPGN)

  • Primary disease occurs mainly in children
  • Most commonly nephritic, but severe forms can also be nephrotic
  • Immunoglobulin (IG)-mediated membranoproliferative glomerulonephritis (type 1 MPGN)
    • Associated with SLE, monoclonal gammopathy
    • Can also be idiopathic
  • Complement-mediated membranoproliferative glomerulonephritis (type 2 MPGN: associated with dense deposit disease (IgG antibodies that stabilize C3 convertase, i.e., C3 nephritic factor, cause a persistent complement activation, leading to a depletion of C3)
  • Both associated with HBV, HCV, and cryoglobulinemia
  • May manisfest with concomitant nephrotic-range proteinuria (nephritic-nephrotic syndrome)
  • IG-mediated (type 1)
    • IF: subendothelial and mesangial IgG immune complex deposits with granular appearance
    • ↓ Serum C3 complement levels
  • Complement-mediated (type 2)
    • Intramembranous C3 deposits (dense deposit disease) on basement membrane
    • ↓ Serum C3 complement levels
  • Both types: LM with H&E or PAS stain shows mesangial ingrowth, which leads to thickening and splitting of the glomerular basement membrane (tram-track appearance)
LM = light microscopy, IM = immunofluorescent microscopy, EM = electron microscopy


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

Pathophysiology

Clinical features

Diagnostics

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.

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment