I know this is actually topic 22 but I thought it made more sense for this topic to be before topic 21, so I switched them.
Nephritic syndrome is a clinical syndrome that includes:
- Haematuria with dysmorphic RBCs
- Oliguria and azotaemia
- Proteinuria – less than 3.5g per day
Common for all conditions that cause nephritic syndrome is that there is a proliferation of cells within the glomeruli, often with inflammatory leukocytic infiltrate. The inflammatory reaction injures the capillary walls, which allows blood to pass into the filtrate. The inflammation also decreases the GFR, which is what causes the oliguria and azotaemia. Hypertension occurs due to fluid retention and increased renin release from the kidneys.
Several disorders can cause nephritic syndrome:
- Poststreptococcal glomerulonephritis
- IgA nephropathy (Berger’s disease)
- Granulomatosis with polyangiitis (Wegener’s)
- Rapidly progressive glomerulonephritis
- Henoch-Schönlein purpura
- Alport syndrome
Also called PSGN, this condition refers to acute glomerular inflammation that results from a preceding infection with “nephritogenic” group A β-haemolytic streptococci. The bacterium is considered nephritogenic if it carries the virulence factor “M protein”. PSGN mostly occurs in children between 6 and 10.
It follows after the patient recovers from a pharyngeal infection or skin infection called impetigo caused by that bacterium. These infections themselves are usually mild and spontaneously resolve themselves. 1-4 weeks after the infections have cleared and the patient has recovered is when PSGN may occur.
It’s an immune complex-mediated disease. Antibodies bind streptococcal antigens in the circulation (or in situ). The resulting immune complexes deposit in the glomerulus and cause tissue injury, mostly by activating the complement system.
Under light microscopy the glomeruli are enlarged and hypercellular. Electron microscopy shows subepithelial deposits in the glomerular basement membrane. These deposits produce “humps”, a morphology that is characteristic for PSGN. Under immunofluorescence there are granular deposits of IgG and complement in the capillary walls.
It usually presents in children with abrupt development of fever, nausea, oliguria and haematuria. The latter is usually seen as cola-coloured urine. Lab tests show increased levels of antibodies against streptococcus, and decreased level of complement factors.
PSGN is usually mild. 95% of children recover completely, while the remaining 5% develop renal failure. Adults with PSGN have worse prognosis. They have a higher risk of developing renal failure. PSGN may develop into rapidly progressing GN or into chronic glomerulonephritis.
PSGN can be caused by other infective agents as well (which is why it should be called postinfectious) like staphylococcus endocarditis, pneumococcus pneumonia, HBV, HCV, HIV and malaria.
Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome and not a specific form of GN. It’s characterised by rapid, progressive loss of renal function, nephritic syndrome and severe oliguria. There is usually a 50% decline in GFR within 3 months, which is why it’s “rapidly progressive”. If untreated will it lead to acute renal failure within weeks or months.
Three types of RPGN exist:
- Type I – due to anti-glomerular basement membrane antibody disease
- Type II – immune complex mediated
- Type III – Pauci-immune type
Type I: Anti-glomerular basement membrane antibody disease (anti-GBM antibody disease) is caused by the presence of antibodies against the type IV collagen in the GBM. These antibodies bind to the GBM and initiate an immune response. This type shows a linear pattern on immunofluorescence.
Anti-GBM antibodies can also bind and damage alveolar basement membranes, causing pulmonary haemorrhage. Goodpasture syndrome is the condition where a patient has both RPGN and pulmonary haemorrhage due to anti-GBM antibodies.
Type II: Any condition that causes immune complex deposition in the glomeruli can develop into RPGN. This includes poststreptococcal GN, SLE, IgA nephropathy, Henoch-Schönlein purpura. This type shows a granular pattern on immunofluorescence.
Type III: This type is called the Pauci-immune type. Pauci means “little” in Latin, indicating that this condition isn’t associated with any known immunological causes. It’s often idiopathic. Pauci-immune RPGN has no anti-GBM antibodies and show no immune complexes in the glomeruli. ANCAs are typically found in the serum. Pauci-immune RPGN shows no patterns on immunofluorescence – nothing can be seen.
All three types have the same histological finding – proliferation of fibroblasts and macrophages in the glomeruli, which forms characteristic crescents. These cells displace and compress the glomerular tuft and pushes it to the side, which creates the characteristic shape.
The kidneys of these patients are enlarged, pale and have petechial haemorrhages on the surface. The patients present with nephritic syndrome with severe oliguria and azotaemia. If they have Goodpasture syndrome they will have haemoptysis as well.
All three types are treated with steroids and cytotoxic drugs. Plasmapheresis is effective only in type I. Dialysis or kidney transplantation may be necessary.
Due to the high prevalence of diabetes is diabetic-related kidney damage the leading causing of end-stage renal disease in the developed world. Be warned; it causes nephrotic syndrome despite being in the same topic as nephritic syndrome. Chronic renal failure is a common outcome in diabetes.
Chronic hyperglycaemia causes glucose to bind to proteins all over the body, including the basement membrane, to form advanced glycation end-products (AGEs), a process called non-enzymatic glycation. This causes the basement membrane to thicken, which narrows blood vessels and causes them to become stiffer. This process is called hyaline arteriosclerosis, and in diabetes it especially occurs in the efferent arteriole. As this arteriole becomes narrower will the pressure inside the glomeruli increase, which increases the GFR. This causes hyperfiltration.
The hyperfiltration triggers mesangial cells to undergo mesangial expansion, where the cells produce more mesangial matrix. The matrix may become fibrotic, a process called diffuse glomerulosclerosis. As the matrix continues to expand it will form nodules called Kimmelstiel-Wilson nodules, which are PAS positive. This process is called nodular glomerulosclerosis.
The mesangial expansion causes the glomerulus to expand. This increases the size of the slit pores between the feet processes of the podocytes, which allows proteins to be filtered out. These changes damage the glomerulus in the long run, eventually causing it to become so damaged that GFR decreases.
The three aforementioned changes, GBM thickening, glomerulosclerosis and Kimmelstiel-Wilson nodules, are the three major histological changes in diabetic nephropathy. The more of these findings a patient has, the more progressed the diabetic nephropathy is.
The earliest manifestation of diabetic nephropathy is microalbuminuria (30 – 300 mg/day), which is a reliable sign that diabetic nephropathy is developing. As the disease progresses will there be macroalbuminuria, with more than 300 mg/day.
Strict long-term control of the blood glucose slows down the progression of diabetic nephropathy. ACE inhibitors and angiotensin receptor blockers may be useful as they treat hypertension and dilate the efferent arteriole.
20. Nephrosis syndrome: minimal change, membranous glomerulonephritis, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis.
22. IgA nephropathy, chronic glomerulonephritis. Glomerular lesions associated with systemic disorders (SLE, Henoch-Schönlein purpura, Wegener's granulomatosis, amyloidosis)