Renal glomeruli excrete urinary substances and excess water as an ultrafiltrate into the urine by selectively filtering the blood. Any damage to the glomeruli disrupts the filtration process and results in the appearance of blood components (proteins and red blood cells) in the urine. Glomerular damage is commonly caused by immune-mediated processes, which often lead to glomerulonephritis. Non-inflammatory causes, such as metabolic disease (e.g., diabetes, amyloidosis), can also result in significant damage to the glomeruli. The pathophysiology of glomerular diseases is complex; most patients present with either nephritic syndrome (low-level proteinuria, microhematuria, oliguria, and hypertension) or nephrotic syndrome (high-level proteinuria and generalized edema). All glomerular diseases can progress to acute or chronic renal failure. Thus, quick diagnosis and immediate initiation of therapy are required to prevent irreversible kidney damage.
Terminology of glomerular diseases
- Primary: a kidney disease specifically affecting the glomeruli (e.g., minimal change glomerulonephritis)
- Secondary: a disease affecting the glomeruli in the context of a systemic disease (e.g., lupus nephritis in SLE) or a disease affecting another organ (e.g., diabetic nephropathy)
- Diffuse: > 50% of glomeruli affected (e.g., diffuse proliferative glomerulonephritis)
- Focal: < 50% of glomeruli affected (e.g., focal segmental glomerulosclerosis)
- Global: entire glomerulus is affected
- Segmental: only part of the glomerulus is affected
- Proliferative: an increased number of cells in the glomerulus
- Membranous: thickening of the glomerular basement membrane (e.g., membranous nephropathy)
- Sclerosing: scarring of the glomerulus
- Necrotizing: cell death within the glomerulus
- Crescentic: accumulation of cells such as macrophages, fibroblasts, and epithelial cells in Bowman space
- The glomerular filtration barrier consists of 3 parts
- Initial segment: Fenestrated glomerular capillary endothelium prevents large proteins from passing through.
- Second segment: The glomerular basement membrane (GBM) contains a negative charge produced by heparan sulfate.
- Final segment: Visceral epithelial cells produce/maintain the GBM and contain intercellular junctions created by podocytes that prevent further protein loss.
Damage to the glomeruli → disruption of the glomerular filtration barrier → can lead to nephritic or nephrotic syndrome
- See “Pathophysiology” in “Nephritic syndrome.“
- See “Pathophysiology” in “Nephrotic syndrome.“
Overview glomerular diseases
Nephrotic vs. nephritic syndrome 
- Nephritic syndrome and nephrotic syndrome are both common clinical manifestations of glomerular diseases.
- Both syndromes are composed of characteristic clinical (e.g., edema, hypertension) and laboratory findings (e.g., glomerular hematuria, massive proteinuria), which result from damage to the glomeruli.
- Glomerular diseases are usually categorized by the syndrome they cause, which is either nephritic or nephrotic.
- Some diseases that manifest with nephritic syndrome can simultaneously cause nephrotic-range proteinuria (> 3.5 g/day), the main feature of nephrotic syndrome. When the criteria for both syndromes are fulfilled, the findings are referred to as mixed nephritic-nephrotic syndrome.
- Classifying the patient's presentation as nephritic, nephrotic, or mixed nephritic-nephrotic can help narrow down the list of likely differential diagnoses.
All glomerular diseases can lead to acute and chronic kidney failure.