Type III Collagen Glomerulopathy

Helen Liapis, MD

Joseph Gaut, MD, PhD

Key Facts

Terminology

Idiopathic glomerular disease defined by accumulation of mesangial and subendothelial type III collagen

Clinical Issues

Rare (< 0.1% of biopsies)
Presents with hematuria or proteinuria
Hemolytic uremic syndrome, children
Variable disease course
Increased serum and urine procollagen III peptide

Microscopic Pathology

Lobular glomeruli without inflammation
Thickened capillary walls
Mesangial and capillary wall expansion with eosinophilic, silver-positive material
Electron microscopy
- Mesangial and subendothelial curvilinear fibrils
- Fibers tend to be frayed and curved, ˜ 60 nm periodicity
Immunohistochemical staining for type III collagen positive in mesangium and GBM

Top Differential Diagnoses

Nail-patella syndrome
Hereditary multiple exostoses
Fibronectin glomerulopathy
Fibrillary glomerulopathy

Diagnostic Checklist

Diagnosis made by demonstration of collagen III in glomeruli

Type III collagen glomerulopathy has a varied glomerular pathology. In this particular case, the glomeruli are hypercellular with a lobular appearance. (Courtesy G. Herrera, MD.)

Immunohistochemical stain for collagen III shows deposits of collagen III in the GBM and mesangium in a case of type III collagen glomerulopathy. Normal glomeruli have no detectable collagen III.

TERMINOLOGY

Synonyms

Collagenofibrotic glomerulopathy

Definitions

Idiopathic glomerular disease defined by accumulation of mesangial and subendothelial type III collagen
Initially described by Arakawa and colleagues in 1979

ETIOLOGY/PATHOGENESIS

Proposed Etiologies

Probably systemic disease of collagen metabolism
- Increased level of N-terminal procollagen type III in blood
  - Indicative of increased synthesis/catabolism
  - Deposit in glomeruli
  - Excreted in urine
Occasional cases in siblings suggest a genetic component, as yet unidentified
Some believe this is a primary disease of the glomerulus

CLINICAL ISSUES

Epidemiology

Incidence
- Rare (˜ 0.1% of biopsies)
Age
- All ages
Gender
- M:F = 1:1
Ethnicity
- Majority of reported cases are Japanese
- Cases also reported in USA, Europe, India, South America, China

Presentation

Microhematuria
Hypertension
Edema
Proteinuria, nephrotic range in 60%
Anemia
- Adults typically have anemia of chronic disease
- Children occasionally present with thrombotic microangiopathy
Hemolytic uremic syndrome, children

Laboratory Tests

10-100x increase in serum and urine N-terminal procollagen type III peptide (PIIINP)

Treatment

Drugs
- No specific treatment
- Steroid therapy is reported to slow disease progression

Prognosis

Variable disease course, limited data
- ˜ 35% of adults and ˜ 90% of children progress to end-stage renal failure

MICROSCOPIC PATHOLOGY

Histologic Features

Glomeruli
- Lobular or mesangial hypercellularity, variable
  - Nodular pattern at times resembles diabetic glomerulopathy
- Expansion of mesangium with eosinophilic, silver-positive material
- Thickening of GBM
  - Occasional double contours
- Closure of capillary loops
- No inflammation
No specific changes in tubules, interstitium, or vessels