Glomerulonephritis

Question	Answer
Targets for injury in the nephron	- Mesangial cells (secrete matrix) - Basement membrane (collagen IV) - Epithelial cells (podocytes) - Capillary endothelial cells - Vasculature. - Tubular structures. - Integrity of glomerulus and tubules
extrinsic and intrinsic mechanisms of glomerulonephritis	EXTRINSIC Antibodies. Immune complexes. Complement. Cytokines. Lymphocytes Other infiltrating cells. INTRINSIC Cytokines. Growth factors. e.g. TGF-beta, PDGF, IFN-gamma. e.g. Vasoactive factors. Proteinuria.
Kidney biopsy - why - how examined	Required for clinical diagnosis of glomerulonephritis Biopsy of kidney cortex examined under - Light microscopy (glomerular and tubular structure) - Immunofluorescence (looking for Ig and complement) - Electron microscopy (glomerular basement membrane and deposits) Many diseases are a clinical and pathological spectrum
Subtypes of glomerulonephritis (5)	Image: Glom (binary/octet-stream)
Nephrotic syndrome - 4 features - types - risks	- 3.5g proteinuria per 24h (urine PCR >300) - Serum albumin <30 - Oedema - Hyperlipidaemia Non-proliferative, podocyte damage (scarring) Minimal change / FSGS / Membranous Risk of venous thromboembolism Increased risk of infection
Nephritic - features - causes	Blood and protein in urine, high blood pressure, rising sCr Proliferative / acute inflammation IgA / lupus / post-infectious
RPGN - features - causes	Rapidly progressive glomerulonephritis – rapid rise in serum creatinine Crescentic damage Vasculitis / lupus / IgA; often have other clinical features
Glomerulonephritis model and possible therapeutic strategies	Image: Model (binary/octet-stream)
pathophysiology of IgA nephropathy	Image: Iga (binary/octet-stream)
IgA nephropathy - epidemiology - secondary to?	The most common primary glomerular disease. Up to 1% of the “normal” population. Precipitated by infection? Synpharyngitic May be 2° to HSP, cirrhosis, coeliac disease.
IgA nephropathy - pathology - clinical features	Abnormal/ over-production of IgA1, IgA I/C. Mesangial IgA, C3 deposition. Mesangial proliferation. Tubular atrophy/interstitial fibrosis Haematuria. Hypertension. Proteinuria (varies with prognosis)
IgA nephropathy - progression - predictors of progression - therapy	About 1/3 progress to ESRF. 10% at 10 years, 20% at 20 years …….. Predictors of ESRF- uPCR, sCr at diagnosis, BP. No specific therapy. Antihypertensive Rx, ACE inhibitors.
Pathophysiology of membranous GN	Image: Gn (binary/octet-stream)
Epidemiology and aetiology of membranous GN	A disease of adults. Presents with the nephrotic syndrome – commonest primary cause. 10% secondary to malignancy, CTD, drugs
Pathology and progression of membranous GN	Anti-phospholipase A2 receptor antibody in 70% Immune Complexes in basement membrane/ sub-epithelial space. IC deposited (preformed) or formed in situ. Variable natural history. A third spontaneously remit. A third progress to ESRF over 1-2 years. A third persistent proteinuria, maintain GFR.
How to treat membranous nephropathy?	1. Treat underlying disease if secondary 2. Supportive non-immunological – ACEi, statin, diuretics, salt restriction 3. Specific immunotherapy - Steroids - Alkylating agents (cyclophosphamide) - Cyclosporin - Alternatives– rituximab, anti-CD20 MAb Outcomes – Complete remission, partial remission, ESRD, relapse, death.
Minimal Change Disease - who - causes what - pathogenesis - cause	The commonest form of GN in children. (90% of GN < 10 years, 20% of adults of all ages.) Causes the nephrotic syndrome. EM - foot process fusion. Pathogenesis - T cell, cytokine mediated. Target glom. epithelial cell, GBM charge Idiopathic but may be 2° to malignancy
Minimal change disease - presentation - GFR - outcome	Acute presentation - may follow URTI. GFR - normal, or reduced due to intravascular depletion. Very rarely causes renal failure. Relapsing course (50% will relapse).
Treatment of minimal change disease	1. High dose steroids. Prednisolone 1mg/Kg for up to 8 weeks. Failure to respond, consider FSGS 2. Cyclophosphamide / calcineurin inhibitor
Pathophysiology of post-infectious GN	Image: Pign (binary/octet-stream)
post-infectious GN - cause - pathology	Usually post-streptococcal type 12, gp A strep. Production of Ab (cross-reactive) and I/C. Sub-epithelial I/C deposition. Complement consumption and hypocomplementaemia. Days after URTI (10-21) – latent period Oliguric ARF. Haematuria, variable proteinuria, oedema. Hypertension. Urinary red cell casts.
outcome of post-infectious GN	Proliferation of all glomerular cells, crescents. Infiltrating cells. Resolves over weeks in most cases. May require dialysis. Antibiotics? no other specific therapy. The prognosis is usually, but not always, benign.
Image: Cresc (binary/octet-stream)	crescentic disease
Crescentic GN/RPGN - histology - progression	A group of conditions linked by natural history/ histology. Crescents on biopsy. Progression to ESRF over a few weeks, untreated high mortality.
common causes of crescentic GN/RPGN	- Goodpastures syndrome – Anti-GBM antibody. - Pauci-immune: Microscopic polyangiits – MPO antibody (positive pANCA) Granulomatosis with polyangiitis (GPA) – PR3 antibody (positive cANCA) - Post infectious/ bacterial endocarditis. - Lupus. - Idiopathic. - Rarely others e.g. IgA nephropathy.
Tests in renal disease (and associated diseases)	HbA1c/random glucose (diabetic nephropathy) ANCA/anti-GBM (vasculitis) ANA/PLA2R/virology (membranous) complement/ANA/dsDNA (lupus) complement/virology (hep BC, HIV)/Igs/RF (MPGN, FSGS) SEP/BJP/SFLC (amyloid/light chain deposition (myeloma)

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	Created by Ellie Britt over 6 years ago