Glomerulonephritis

Glomerulonephritis is a group of diseases characterized by inflammation and immune-mediated injury of the glomeruli, the filtering units of the kidney. It typically produces a nephritic picture of hematuria, variable proteinuria, hypertension, and declining filtration, and its many forms are distinguished by the renal biopsy and by the pattern of immune deposits seen on immunofluorescence and electron microscopy.

Definition

Glomerulonephritis is inflammatory injury of the renal glomeruli, frequently immune-mediated, that disrupts the glomerular filtration barrier and commonly presents with hematuria, proteinuria, hypertension, and reduced glomerular filtration.

Scope

This entry covers glomerulonephritis as a pathologic and syndromic category: the inflammatory glomerular lesions, their classification by light, immunofluorescence, and electron microscopy, and the clinical syndromes they produce. It treats representative entities such as IgA nephropathy and focal segmental glomerulosclerosis as illustrations rather than providing management guidance.

Core questions

• Is the glomerular injury proliferative (nephritic) or predominantly a barrier defect (nephrotic), and where do overlaps occur?
• What does the immunofluorescence pattern of immune deposits reveal about the underlying disease?
• Is the process primary (confined to the kidney) or secondary to systemic disease?
• How much active inflammation versus chronic glomerulosclerosis is present?

Key concepts

• Nephritic syndrome: hematuria, hypertension, reduced filtration
• Immune-complex deposition and complement activation
• Immunofluorescence patterns (granular versus linear versus pauci-immune)
• Proliferative versus non-proliferative lesions
• IgA nephropathy
• Focal segmental glomerulosclerosis
• Crescent formation and rapidly progressive glomerulonephritis
• Glomerular basement membrane and podocyte injury

Mechanisms

Most forms of glomerulonephritis arise from immune-mediated injury. Circulating immune complexes may deposit in the glomerulus or form in situ, activating complement and recruiting inflammatory cells that damage the capillary wall and mesangium; immunofluorescence reveals granular deposits in these immune-complex diseases and linear staining in anti-glomerular basement membrane disease. In IgA nephropathy, abnormally glycosylated IgA1 and its immune complexes deposit in the mesangium. Severe inflammatory injury can rupture the capillary wall and provoke crescent formation, the hallmark of rapidly progressive glomerulonephritis. In contrast, focal segmental glomerulosclerosis reflects podocyte injury and scarring rather than primary inflammation. Persistent injury of any cause converges on glomerulosclerosis.

Clinical relevance

Glomerulonephritis is a leading category of glomerular disease and a frequent reason for renal biopsy, and recognizing the nephritic pattern is part of evidence appraisal in nephrology and pathology. This entry explains how these diseases are classified and studied and is not a source of diagnostic or treatment recommendations for individual patients.

Epidemiology

IgA nephropathy is among the most common primary glomerulonephritides worldwide, with notably higher reported frequency in parts of Asia, while the relative frequency of other patterns varies with age, geography, and biopsy practice. Focal segmental glomerulosclerosis is an important cause of nephrotic-range proteinuria in adults.

History

The classification of glomerulonephritis advanced through the twentieth century with the renal biopsy and the introduction of immunofluorescence and electron microscopy, which allowed glomerular diseases to be defined by their immune deposits and ultrastructure. IgA nephropathy was delineated as a distinct entity in the late 1960s, and focal segmental glomerulosclerosis was progressively characterized as both a primary podocytopathy and a secondary pattern.

Debates

Is focal segmental glomerulosclerosis one disease or a shared lesion?

Focal segmental glomerulosclerosis is increasingly viewed as a histologic pattern with primary (podocytopathic), genetic, and secondary (adaptive) causes rather than a single disease, which complicates classification and interpretation of biopsies.

Seminal works

• donadio-2002
• dagati-2011
• benzing-2021

Frequently asked questions

What distinguishes glomerulonephritis from nephrotic syndrome?

Glomerulonephritis emphasizes inflammatory glomerular injury and a nephritic picture (hematuria, hypertension, reduced filtration), whereas nephrotic syndrome is defined by heavy proteinuria, hypoalbuminemia, and edema. Some glomerular diseases produce features of both.

Why is immunofluorescence important in glomerulonephritis?

The pattern of immune deposits — granular, linear, or pauci-immune — helps separate immune-complex diseases, anti-glomerular basement membrane disease, and ANCA-associated forms, which look similar on light microscopy but differ in mechanism.