Last updated on April 13, 2019 at 18:30
IgA nephropathy, also known as Berger disease is the most common cause of glomerulonephritis worldwide. As the name suggests it’s caused by immune complexes of IgA. It usually occurs after or during an upper respiratory tract or gastrointestinal infection. Children and young adults are most commonly affected. IgA nephropathy usually causes nephritic syndrome, but it can occasionally cause nephrotic syndrome as well. It may cause rapidly progressing glomerulonephritis.
IgA is the main immunoglobulin in mucosal secretions. Mucosal infections trigger increased IgA production by plasma cells. These antibodies form immune complexes that deposit in the kidney and cause the regular hypersensitivity type III reaction. The disease involves some genetic defects that predispose to the deposition of immune complexes. Genetic defects in the complement system may also be involved.
Diseases with mucosal defects like coeliac disease can also lead to the development of IgA nephropathy. The same goes for liver diseases, as the liver is involved in clearance of the IgA immune complexes. In these cases it’s called secondary IgA nephropathy. Mesangial deposition of IgA and C3 can be seen on immunofluorescence.
Patients usually present with gross haematuria. It usually lasts for several days and then subsides, only to return every few months. Many patients maintain normal renal function for decades. 25-50% of cases develop into chronic renal failure.
Nearly all forms of acute glomerulonephritis can progress to chronic glomerulonephritis. In these cases there is irreversible and progressive glomerular fibrosis, which causes a progressive reduction in GFR. This will eventually cause chronic renal failure and uraemia.
The mechanism of action is similar to that of all chronic renal failures – if enough nephrons are lost during the acute GN will the remaining nephrons hyperfiltrate, which damages them in the long run.
Chronic GN can develop in:
- Poststreptococcal GN – rarely
- Rapidly progressing GN – usually
- Membranoproliferative GN
- Membranous nephropathy
- IgA nephropathy
- Focal segmental glomerulosclerosis
The major histological morphology of end-stage glomerulonephritis, which is commonly seen in chronic glomerulonephritis, is hyalinization of the glomeruli. The surface of the kidney also becomes granular and the cortex is thinned. The kidneys are usually smaller as well.
The uraemia that accompanies chronic renal failure can lead to:
- Fibrinous pericarditis
- Secondary hyperparathyroidism
- Left ventricular hypertrophy
- Loss of appetite
Lupus nephritis is the renal involvement in patients with SLE. About half of all people with SLE develop some form of lupus nephritis. Renal failure is the most common cause of death in people with SLE. Lupus nephritis can cause both nephritic and nephrotic syndrome.
SLE is a condition where the bodies produce antibodies against molecules that are in the nucleus, like DNA and histones. These antibodies are called anti-nuclear antibodies (ANAs). When cells die from apoptosis DNA and histones will be released. The antibodies form immune complexes with these nuclear molecules, which then deposit in the glomeruli and cause a type III hypersensitivity reaction.
The kidney appears normal under light microscopy in 30% of cases, however immunofluorescence and electron microscopy show abnormalities in the glomeruli in almost all patients with SLE.
There are six different types of lupus nephritis, where each form is more serious than the last:
|Number||Name||Morphology of glomerulus|
|Class I||Minimal mesangial lupus nephritis||No structural abnormalities|
|Class II||Mesangial proliferative lupus nephritis||A mild increase in mesangial matrix|
|Class III||Focal lupus nephritis||Focal lesions with swelling, proliferation, neutrophils and fibrinoid deposits|
|Class IV||Diffuse lupus nephritis||Diffuse lesions with swelling, proliferation, neutrophils and fibrinoid necrosis|
|Class V||Membranous lupus nephritis||Thickened capillary walls due to deposition of immune complex|
|Class VI||Advanced sclerosing lupus nephritis||Complete sclerosis of more than 90% of glomeruli|
The lecture doesn’t mention all these details, so not all of it is important to know.
Class IV and onward is characterised by a segmental thickening of the capillary wall, which causes a “wire loop” morphology on light microscopy. Haematuria and proteinuria begin at class III and become progressively worse. At class VI is there end-stage renal failure.
Henoch-Schönlein purpura (HSP) is an acute immune-complex mediated small vessel vasculitis. It commonly affects children. The disease is characterized by purpuric skin lesions, abdominal pain, vomiting, intestinal bleeding, arthralgia and renal abnormalities. Its kidney manifestation is very similar to IgA nephropathy, in that it causes nephritic syndrome.
HSP commonly begins after an upper respiratory tract infection. It’s self-limiting and usually resolves within one month.
The pathogenesis of HSP involves deposition of IgA immune complexes in the vascular walls of the skin, GI tract, joints and kidneys. This elicits a type III hypersensitivity reaction by activating the complement system.
Granulomatosis with polyangiitis
Also called Wegener’s granulomatosis, this systemic disease affects the ENT (ear, nose, throat), lower respiratory tract, kidney, skin, eyes and heart. There is renal involvement in 80% of cases.
Granulomatosis with polyangiitis can range from mild focal necrotizing glomerulonephritis to pauci-immune rapidly progressing glomerulonephritis with potential renal failure.
Amyloidosis of the kidney is the most common and most serious feature of amyloidosis. The kidney may appear normal or it can be large, pale, grey and firm. Amyloids deposit mostly in the glomeruli but also in the interstitial peritubular tissue.
Inside the glomeruli amyloids can deposit in the mesangium, in the subendothelial space or rarely in the subepithelial space. In the beginning is there nephrotic syndrome, but as the deposition progresses may amyloids completely obliterate the glomerular tuft and render the whole glomerulus lost. As more and more glomeruli are lost will the chronic renal failure progress until there is uraemia.
21. Nephritic syndrome (acute poststreptococcal glomerulonephritis). Rapidly progressive glomerulonephritis. Diabetic nephropathy.
23. Acute tubular necrosis (ischaemic and toxic). Drug-induced (hypersensitive) interstitial nephritis, analgetic nephropathy, urate nephropathy. Acute and chronic pyelonephritis (pathogenesis, morphology, consequences and clinical course)