Glomerulonephritis Flashcards
What is glomerulonephritis?
Immune mediated disease of the kidney affecting the glomerulus with secondary tubulo-interstitial damage = 2nd commonest cause of end stage renal failure
What is the pathogenesis of glomerulonephritis?
Humoral (antibody mediated) = intrinsic or planted antigen, deposition of immune complexes Cell mediated (T cells) Inflammatory cells, mediators and complements
What does disruption to the glomerular capillary wall cause?
Size and charge selective barrier = disruption leads to haematuria and/or proteinuria
What does damage to the endothelial and mesangial cells lead to?
Proliferative lesion and red cells in urine
What does damage to the podocytes lead to?
Non-proliferative lesion and protein in urine
What are some features associated with damage to the mesangium?
Proliferative, release angiotensin 2, chemokine release, attract inflammatory cells
What are some features associated with damage to the podocytes and endothelial cells?
Podocytes = atrophy, loss of size/charge specific barrier
Endothelial cells = vasculitis
How is glomerulonephritis diagnosed?
Clinical presentation and blood tests
Examination of urine
Kidney biopsy
How can urine be examined?
Urinalysis = haematuria, proteinuria
Urine microscopy = RBC (dysmorphic), RBC and granular casts, lipiduria
Urine protein:creatine ratio/24hr urine collection = quantify proteinuria
What is the renal presentation of glomerulonephritis?
Haematuria, proteinuria, impaired renal function, hypertension, nephrotic/nephritic/nephrotic-nephritic syndrome
How may haematuria present?
Asymptomatic microscopic haematuria
Episodes of macroscopic haematuria
What are the different forms of proteinuria?
Microalbuminuria = 30-300mg albuminuria/day
Asymptomatic proteinuria = 1g/day
Heavy proteinuria = 1-3g/day
Nephrotic syndrome = >3g/day
How may impaired renal function present?
AKI = rapidly progressive GN-RPGN
CKD/ESRD
What are the features of nephritic syndrome?
Acute renal failure, oliguria, oedema/fluid retention, hypertension, active urinary sediment
What may urinary sediment consist of?
RBC, RBC and granular casts
What is nephritic syndrome indicative of?
A proliferative process affecting the endothelial cells
What are some features of nephrotic syndrome?
Proteinuria >3g/day (mostly albumin, also globulin)
Hypoalbuminaemia (<30), oedema, hypercholesterolaemia, usually normal renal function
What is nephrotic syndrome indicative of?
A non-proliferative process affecting podocytes
What are some complications of nephrotic syndrome?
Infection = loss of opsonising antibodies
Renal vein thrombosis and pulmonary emboli
Volume depletion = due to over-aggressive diuretics use, may lead to ARF (pre-renal)
Vitamin D deficiency
Subclinical hypothyroidism
What are the two classes of glomerulonephritis?
10 (idiopathic) = majority of cases
20 = caused by infection/drugs, associated with malignancy or as part of systemic disease
How is glomerulonephritis looked at histologically?
Renal biopsy, light microscopy, immunofluorescence, EM
What does proliferative and non-proliferative classification refer to?
The presence or absence of proliferation of mesangial cells
What are the histological classifications of glomerulonephritis?
Proliferative and non-proliferative
Focal and diffuse = < or > 50% glomeruli affected
Global and segmental = all or part of glomeruli affected
Crescenteric = presence of crescents
What causes a crescenteric appearance?
Epithelial cell extracapillary proliferation
What are the principles of glomerulonephritis treatment?
Reduce degree of proteinuria
Induce remission of nephrotic syndrome
Preserve long term renal function
What are some non-immunosuppressive treatment options?
Anti-hypertensives, ACE inhibitors/ARBs, statins, diuretics, omega 3 fatty acids/fish oil, anticoagulants, aspirin, anti-platelets
What is the target BP for patients with glomerulonephritis?
<130/80 mmHg or <120/75 mmHg if proteinuria present
What are some immunosuppressive drugs used in the treatment of glomerulonephritis?
Corticosteroids = prednisolone/methylprednisolone IV
Azathioprine and mycophenolate mofetil (MMF)
Alkylating agents = cyclophosphamide, chlorambucil
Calcineurin inhibitors = cyclosporin, tacrolimus
What are the immunosuppressive treatment options for glomerulonephritis?
Immunosuppressive drugs
Plasmapharesis = therapeutic plasma exchange
IV immunoglobulin, monoclonal T/B cell antibodies
What is the treatment for nephrotic patients?
General = fluids, salt restriction, diuretics, ACEi/ARBs, anticoagulation, IV albumin (only if volume deplete)
Immunosuppression
What is the aim of treatment for nephrotic patients?
Induce sustained remission:
Complete remission = proteinuria < 300mg/day
Partial remission = proteinuria < 3g/day
What are the main idiopathic (10) types of glomerulonephritis?
Minimal change, focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative, IgA nephropathy
What are some features of minimal change nephropathy?
Commonest cause of nephrotic syndrome in children
Doesn’t cause progressive renal failure
What is a possible cause of minimal change nephropathy?
IL-3
How does minimal change nephropathy appear on biopsy?
Normal renal biopsy on LM and IF with foot process fusion on EM
How is minimal change nephropathy treated?
94% complete remission with oral steroids
Some are steroid resistant/dependent or have relapses
Second line agents = cyclophosphamide, CSA
What are some features of focal segmental glomerulosclerosis (FSGS)?
Commonest cause of nephrotic syndrome in adults
10 or 20 = HIV, heroin, obesity, reflux nephropathy
Minimal Ig/complement deposition on IF
What is the prognosis of focal segmental glomerulosclerosis?
Remission with prolonged steroids in 60%
50% progress to end stage failure after 10 years
What are some features of membranous nephropathy?
2nd commonest cause of nephrotic syndrome in adults
10 or 20 = hep B, parasites, lupus, carcinoma, lymphoma, gold, penicillamine
How does membranous nephropathy appear on biopsy?
Subepithelial immune complex deposition in basement membrane
What is antibody is implicated in membranous nephropathy?
Anti-PLA2r antibody present in >70% of primary cases
How is membranous nephropathy treated?
Steroids, alkylating agent, B cell monoclonal antibody
What is the prognosis of membranous nephropathy?
30% progress to end stage renal failure in 10 years
What are some features of IgA nephropathy?
Most common form of GN in the world
25% progress to end stage renal failure in 10-30 years
How does IgA nephropathy present?
Asymptomatic microhaematuria and non-nephrotic range proteinuria, AKI/CKD, macroscopic haematuria after resp/GI infection
What is IgA nephropathy associated with?
Henoch-Schonlein purpura = arthritis, colitis, purpuric skin rash
How does IgA nephropathy appear on biopsy?
Mesangial cell proliferation and expansion on light microscopy with IgA deposits in mesangium on IF
How is IgA nephropathy treated?
BP control, ACEi/ARBs, fish oil
What is rapidly progressive glomerulonephritis (RPGN)?
Rapid deterioration in renal function over days-weeks = may be part of systemic disease
What are some features of rapidly progressive glomerulonephritis?
Active urinary sediment
Associated with glomerular crescents on biopsy
What are some causes of rapidly progressive glomerulonephritis?
ANCA positive = GPA, microscopic polyangiitis
ANCA negative = Goodpasture’s (anti-GBM), Henoch-Schonlein purpura (IgA), SLE
What are the aims of treatment for rapidly progressive glomerulonephritis?
Treatment should be prompt and consist of strong immunosuppression with supportive care
What is the treatment of rapidly progressive glomerulonephritis?
Immunosuppression and plasmapharesis
What immunosuppressive agents can be used to treat rapidly progressive glomerulonephritis?
Steroids = IV methylprednisolone, oral prednisolone Cytotoxics = cyclophosphamide, MMF, azathioprine
