Overview of the pathogenesis and causes of glomerulonephritis in children
- Patrick Niaudet, MD
Patrick Niaudet, MD
- Section Editor — Pediatric Nephrology
- Professor of Pediatrics
- Hôpital Necker-Enfants Malades, Paris, France
Glomerulonephritis (GN) generally presents as a constellation of findings that include hematuria, proteinuria, edema, and often hypertension. GN is caused by a number of disorders that are all characterized by glomerular injury accompanied by inflammation. In some cases, GN may progress to renal failure.
The pathogenesis and etiology of glomerulonephritis in children will be reviewed here. The approach to evaluating a child with glomerulonephritis is discussed separately. (See "Evaluation of a child with glomerular disease".)
Although the pathogenesis is not fully understood, current evidence suggests that most cases of glomerulonephritis (GN) are due to an immunologic response to a variety of different etiologic agents. The immunologic response, in turn, activates a number of biological processes (eg, complement activation, leukocyte recruitment, and release of growth factors and cytokines) that result in glomerular inflammation and injury [1,2]. GN may be isolated to the kidney (primary glomerulonephritis) or be a component of a systemic disorder (secondary glomerulonephritis) (table 1).
The immunologic mechanisms involved in the pathogenesis of GN are briefly reviewed here and are discussed in greater detail separately. (See "Mechanisms of immune injury of the glomerulus".)
Immunologic damage — Humoral (also referred to T helper cell 2-regulated) immune response to a variety of inciting agents results in immunoglobulin deposition and complement activation within the glomeruli. In most of these disorders, immune complex deposition is an active process caused by in situ binding of antibodies to antigens localized within the glomeruli. The antigens may be structural glomeruli components, such as the Goodpasture antigen in the non-collagenous domain of the alpha-3 chain of type IV collagen in the glomerular basement membrane (GBM). Alternatively, the antigens may be trapped or deposited within the glomerulus, including self antigens such as DNA in the form of nucleosomes in lupus nephritis, or exogenous antigens due to infectious agents such as bacteria (Streptococcus, Staphylococcus) or viruses (hepatitis B). Another possible mechanism for immune complex deposition is the passive process of trapping circulating immune complexes within the glomeruli. Although this process has been studied in animal models (serum sickness disease), it appears to be less commonly seen in human GN than in situ glomerular immune complex formation.
- Chadban SJ, Atkins RC. Glomerulonephritis. Lancet 2005; 365:1797.
- Couser WG. Pathogenesis of glomerulonephritis. Kidney Int Suppl 1993; 42:S19.
- Rodriguez-Iturbe B. Postinfectious glomerulonephritis. Am J Kidney Dis 2000; 35:XLVI.
- Zhang Y, Shen Y, Feld LG, Stapleton FB. Changing pattern of glomerular disease at Beijing Children's Hospital. Clin Pediatr (Phila) 1994; 33:542.
- Sanjad S, Tolaymat A, Whitworth J, Levin S. Acute glomerulonephritis in children: a review of 153 cases. South Med J 1977; 70:1202.
- Immunologic damage
- Secondary processes
- ETIOLOGIC CLASSIFICATION
- Clinical presentation
- - Acute GN
- - Rapidly progressive GN
- - Recurrent macroscopic hematuria
- - Chronic GN
- - Light microscopy
- - Immunofluorescence microscopy
- - Electron microscopy
- SPECIFIC DISORDERS
- Primary GN
- Secondary GN
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS