Glomerulonephritis Flashcards
What are the different types of glomerular diseases?
Diabetic nephropathy
Glomerulonephritis
Amyloid nephropathy
Transplant glomerulopathy
What is the commonest cause of end stage renal disease (after diabetes)?
Chronic glomerulonephritis
What is glomerulonephritis?
Immune-mediated disease of the kidneys affecting the glomeruli (with secondary tubulointerstitial damage)
Disruption of the glomerular capillary wall (endothelium, basement membrane and podocytes) leads to haematuria +/- proteinuria
What does damage to the endothelial or mesangial cells lead to?
PROLIFERATIVE LESION
RED CELLS IN URINE
NEPHRITIC SYNDROME
What does damage to the podocytes lead to?
NON-PROLIFERATIVE LESION
PROTEIN IN URINE
NEPHROTIC SYNDROME
How do podocytes respond to damage?
Atrophy
Loss of size/charge specific barrier
How do mesangial cells react to damage?
Proliferate
Release angiotensin 2 (hypertension)
Chemokine release
Attract inflammatory cells
How do endothelial cells react to damage?
Vasculitis
How is GN diagnosed?
Clinical presentation
Blood tests
Urine: haematuria, proteinuria, dysmorphic RBC, RBC and granular casts, lipiduria, urine protein:creatinine 24hr ratio
Kidney biopsy
What present in urine microscopy is pathognomonic of glomerulonephritis?
RBC and granular casts
How can haematuria present?
Asymptomatic microscopic haematuria
Episodes of painless macroscopic haematuria = GN should be painless
How can proteinuria present?
Microalbuminuria - 30-300 mg albuminaura/day Asymptomatic proteinuria (<1 g/day) Heavy proteinuria (1-3 g/day) Nephrotic syndrome (>3 g/day)
What do dysmorphic RBC in urine suggest?
They’ve been squished through the glomerulus
What are clinical renal presentations of GN?
Impaired renal function: AKI (rapidly progressive GN)
CKD/ESRD
Hypertension
What is nephritic syndrome?
AKI
Oliguria
Oedema/ fluid retention (due to lack of excretion)
Hypertension (fluid overload)
Active urinary sediment: RBC, RBC and granular cast
What is nephritis syndrome indicative of?
Proliferative process
Affecting endothelial cells
What is nephrotic syndrome?
Proteinuria >3 g/day (mostly albumin) Hypoalbuminemia (<30) Oedema (loss of oncotic pressure) Hypercholesterolaemia Normal renal function
What is nephrotic syndrome indicative of?
Non-proliferative process
Affecting podocytes
What are complications of nephrotic syndrome?
Infections - you leak antibodies along with fluid
Renal vein thrombosis - polycythaemia
PE
Volume depletion - overaggressive diuretic use leading to pre-renal hypovolemia AKI
Vit D deficiency
Subclinical hypothyroidism
How will the presentation of GN differ from interstitial nephritis?
Presence of protein and blood in urine
What are the different types of GN?
Primary
Secondary: infections, drugs, malignancies, ANCA, SLE, goodpasture’s, HSP
How are the different types of GN differentiated histologically?
Renal biopsy
Light microscopy
Immunofluorescence (IgG deposits in GBM in goodpasture’s)
Electron micrograph (minimal change glomerulonephritis)
What does proliferative and nonproliferative refer to?
Presence of absence of proliferation of mesangial cells
What does focal or diffuse refer to?
More or less than 50% of glomeruli affected
What does global or segmental refer to?
All or part of glomerulus affected
What does crescentic refer to?
Presence of cresents - epithelial cell extracapillary proliferation e.g. RPGN in vasculitis
What are the treatment principles of GN?
Reduce degree of proteinuria
Induce remission of nephrotic syndrome
Preserve long term renal function
What are the non-immunosuppressive treatments of GN?
Anti-hypertensives (target BP <130/80 - <120/75 if proteinuria) ACEi/ARB Diuretics Statins Anticoagulants/aspirin/ antiplatelets
What immunosuppressive drugs are used in GN?
Corticosteroids (prednisolone)
Azathioprine
Alkylating agents (cyclophosphamide)
Calcineurin inhibitors (cyclosporin /tacrolimus)
What can be used for immunosuppression in GN?
Drugs
Plasmapheresis
Antibodies: IV immunoglobulin (monoclonal T or B cells)
What is the general treatment of a nephrotic patient?
Fluid restriction Salt restriction Diuretics ACEi/ARB Anticoagulation IV albumin if volume deplete Immunosuppression
What are the main types of primary GN?
Minimal change FSGS Membranous Membranoproliferative IgA nephropathy
What is the commonest cause of nephrotic syndrome in children?
Minimal change nephropathy
What can be seen histologically in minimal change nephropathy?
Normal renal biopsy on light microscopy and immunofluorescence with foot process fusion on EM
How is minimal change nephropathy treated?
Oral steroids
Does NOT cause progressive renal failure
What is the commonest cause of nephrotic syndrome in adults?
Focal segmental glomerulosclerosis (FSGS)
What can cause FSGS?
Primary
Secondary: HIV/heroin use/obesity/reflux nephropathy
What will FSGS look like histologically?
Light microscopy: focal segmental glomerulosclerosis
Minimal Ig/complement deposition on IF
How is FSGS treated?
Prolonged steroids
50% will progress to end stage renal failure after 10 years
What is the 2nd commonest cause of nephrotic syndrome in adults?
Membranous nephropathy
Thickened basement membrane
What causes membranous nephropathy?
Primary
Secondary: infections (hep B/ parasites), connective tissue disease (SLE), malignancies (carcinomas/ lymphomas), drugs (gold, penicillamine)
What will renal biopsy show in membranous nephropathy?
Subepithelial immune complex deposition in the basement membrane
How is membranous nephropathy treated?
Steroids
Alkylating agents
B cell monoclonal Ab
30% progress to end stage renal failure within 10 years
What is the commonest glomerulonephritis in the world?
IgA nephropathy
How will IgA nephropathy present?
Asymptomatic microhaematuria +/- non-nephrotic range proteinuria
Macroscopic haematuria after resp/GI infection
AKI/ CKD
What condition is IgA nephropathy associated with?
Henoch-schonlein purpura: arthritis, colitis, purpuric skin rash, renal involvement
What will renal biopsy show in IgA nephropathy?
Mesangial cell proliferation and expansion on light microscopy with IgA deposits in mesangium on IF
How is IgA nephropathy treated?
BP control - ACEi/ ARB
25% progress to end stage renal failure within 10-30 years
What is rapidly progressive glomerulonephritis?
Treatable cause of acute renal failure
Rapid deterioration in renal function over days/weeks
What will RPGN show on biopsy?
Glomerular crescents
What ANCA-positive conditions can cause RPGN?
GPA - c-ANCA
MPA - p-ANCA
What ANCA-negative conditions can cause RPGN?
Goodpasture’s disease - anti-GBM
Henoch Schonlein Purpura IgA
SLE
Describe what occurs in ANCA associated vasculitis?
Neutrophils primed inducing PR3 and MPO to cell surface where they interact with ANCA in blood stream
Neutrophils adhere to endothelial cells
Release of proteolytic enzymes and reactive oxygen species
ANCA activated neutrophils promote inflammatory process and perpetuate vasculitis
What is the treatment of RPGN?
Strong immunosuppression with supportive care including dialysis
Immunosuppression with IV steroids or cytotoxics (cyclophosphamide/ azathioprine)
Plasmapheresis
