Glomerulonephritis: the main patterns
How the main glomerular diseases differ in which part of the glomerulus they injure and where immune deposits sit, why that decides a nephrotic or nephritic picture, and how three kinds of microscopy tell them apart on a biopsy.
By the end, you can
- Relate where an immune deposit sits (mesangial, subendothelial, subepithelial or along the basement membrane) to whether a disease is nephrotic or nephritic.
- Distinguish minimal change disease, FSGS and membranous nephropathy by cause and by their light, immunofluorescence and electron microscopy.
- Explain how IgA nephropathy, post-infectious glomerulonephritis and the membranoproliferative pattern place immune complexes or complement close to the blood.
- Classify crescentic glomerulonephritis by its three immunofluorescence types and link each to its blood test.
- Recognise the classic biopsy features and tests of each pattern, and explain how the main treatments act on the mechanism.
What it is
Glomerulonephritis, in the broad sense used here, covers the diseases that injure the glomeruli. Strictly, those without inflammation, such as minimal change disease, are glomerulopathies, but they are taught alongside. Each disease has a characteristic pattern: which cell or layer is injured, whether immune deposits are present and where they sit, and how the glomerulus responds. Read on a kidney biopsy with three kinds of microscopy, the pattern predicts whether the disease presents as nephrotic syndrome, nephritic syndrome or a mixture.
5 types to tell apart
- Podocyte diseases (no immune deposits)
- Minimal change disease and FSGS: the podocyte is injured by a circulating factor, a faulty gene, a virus, a drug or overload. Nephrotic.
- Subepithelial immune deposits
- Membranous nephropathy: complexes form outside the basement membrane, away from the blood, and injure podocytes through complement. Nephrotic.
- Mesangial and subendothelial immune complexes
- IgA nephropathy, post-infectious glomerulonephritis, immune-complex MPGN and lupus nephritis: complexes face the blood and recruit inflammatory cells. Nephritic or mixed.
- Complement-driven disease (C3 glomerulopathy)
- The alternative complement pathway runs out of control and C3 is deposited with little or no immunoglobulin. Often mixed.
- Crescentic (rapidly progressive) glomerulonephritis
- Severe injury from anti-GBM antibodies, immune complexes or ANCA, with crescents in most glomeruli and loss of function over weeks.
US spelling: haematoxylin → hematoxylin.
Normal function
The compartments of a glomerulus, and how a biopsy reads them
A glomerular capillary loop has distinct compartments, and diseases are told apart by which one they strike. Blood in the touches the . Outside it lies the (GBM), and outside that the , whose face the . The loops hang from a stalk of and matrix, which lies on the blood side of the GBM, separated from the blood only by endothelium.
Where an immune deposit sits largely decides what follows. In the usual explanation, deposits in the mesangium or under the endothelium (subendothelial) are on the blood side of the GBM, so the complement fragments and antibody stems (Fc regions) they display recruit neutrophils and monocytes from the blood: the glomerulus inflames and a nephritic picture follows. Deposits under the podocytes (subepithelial) lie outside the GBM, away from the blood: complement injures the podocytes, but few inflammatory cells reach them, so protein leaks with little inflammation, a nephrotic picture. Antibody bound to the GBM itself, or neutrophils activated without deposits (ANCA), cause the most violent injury.
A kidney biopsy is read with three microscopes. Light microscopy, with haematoxylin and eosin, periodic acid–Schiff (PAS) and silver stains, shows cell numbers, the thickness of capillary walls, scars and crescents. Immunofluorescence on frozen tissue stains IgG, IgA, IgM, C3 and C1q, which may lie in a smooth line along the GBM, in lumps (granular) or not at all. Electron microscopy shows the podocyte foot processes and the exact position of electron-dense deposits.
| Feature | Examples | Usual picture |
|---|---|---|
| Podocyte, no deposits | Minimal change disease, FSGS | Nephrotic; bland urine |
| Subepithelial (outside the GBM) | Membranous nephropathy | Nephrotic: the GBM keeps inflammatory cells away from the deposits |
| Mesangial | IgA nephropathy, IgA vasculitis, mild lupus nephritis | Haematuria and mild proteinuria; nephritic when active |
| Subendothelial (inside the GBM) | Post-infectious disease, MPGN, proliferative lupus nephritis | Nephritic or mixed: the complexes face the blood |
| Within the GBM | Dense deposit disease (C3 glomerulopathy) | Mixed nephritic and nephrotic |
| Antibody to the GBM itself | Anti-GBM disease | Nephritic, often crescentic |
| No deposits; ANCA-activated neutrophils | Granulomatosis with polyangiitis, microscopic polyangiitis | Nephritic, often crescentic, with necrosis |
Simplified; many diseases deposit in more than one site (post-infectious humps are subepithelial but come with subendothelial deposits), and the picture also depends on how active the injury is.
Underlying change · Step 1 of 5
Podocyte diseases: minimal change and FSGS
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 2 of 5
Deposits under the podocytes: membranous nephropathy
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Complexes near the blood: IgA and post-infectious disease
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
The membranoproliferative pattern and C3 glomerulopathy
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Crescentic glomerulonephritis: three immunofluorescence types
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .