Glomerular Nephritis Flashcards
What are the different glomerular diseases?
Diabetic Nephropathy
Glomerulonephritis (GN)
Amyloid/ Light Chain Nephropathy
Transplant Glomerulopathy
What is the 2nd most common cause of end stage renal failure?
Chronic GN
What is an important treatable cause of acute renal failure?
Acute GN
What is GN?
Immune-mediated disease of the kidneys affecting the glomeruli
(with secondary tubulointerstitial damage)
Pathogenesis of GN
recognise the kidney as an antigen and self-destruction
Humoral and Cell-mediated
How does the GN affect the barrier?
Disruption of the size and the charge selective barrier leading to proteinuria and haematuria
What determines the
damage to podocytes : not dramatic inflammatory response, non-proliferative - prevents the albumin from leaking out –> proteinuria
Damage to the endothelial cells –> proliferative lesion and red cells in urine.
Damage to mesangial cells –> inflammation, proliferative lesion and red cells in urine.
24 year old man incidentally found to have ++ blood and + protein on dip, BP 148/92.
Protein quantified at 0.7g/day. Creat 72.
What glomerular cells are most likely to be injured?
blood –> mesangial cell
How do we do the diagnosis of GN?
CLINICAL PRESENTATION
BLOOD TESTS
EXAMINATION of URINE
-Urinalysis - haematuria, proteinuria
-Urine microsopy - RBC (dysmorphic), RBC & granular casts, lipiduria
-Urine Protein: Creatinine Ratio / 24 hour urine - quantify proteinuria
KIDNEY BIOPSY
What should you think before biopsy?
What am i going to treat them with and is it worth it
PC of GN
Episodes of Painless macroscopic haematuria
asymptomatic microscopic haematuria
CP of Proteinuria
Microalbuminuria (30-300mg albuminuria/day) Asymptomatic proteinuria ( 1 g/day) Heavy proteinuria (1-3 g/day) Nephrotic syndrome (> 3 g/day))
heavier protein
glomerular proteins
Urine microscopy
To identify where the blood cells come from
if bleeding from lower tract will look like that -> glomerular bleeding
What is the use of red cell casts?
peed out
classic injury to the endothelium or mesangial cells
What is nephritic syndrome?
Acute Renal Failure Oliguria Oedema/ Fluid retention Hypertension Active urinary sediment RBC’s, RBC & Granular Casts - in dipstick
Indicative of a proliferative process
Affecting endothelial cells
oedema - due to fluid retention
What is the nephrotic syndrome?
Proteinuria 3 g/day (mostly albumin, also globulins) Hypoalbuminaemia (<30) Oedema Hypercholesterolaemia Usually normal renal function
Indicative of a non proliferative process
Affecting Podocytes
oedema - as the protein less and they can’t hold on to water
What are the complications of nephrotic syndrome?
Infections - loss of opsonising antibodies
Renal vein thrombosis
Pulmonary emboli - thick blood and clots in legs
Volume depletion (overaggressive use of diuretics) - may lead to ARF (pre-renal)
How does the presentation of GN differ from a non glomerular disease like Interstitial Nephritis?
Shouldn’t see blood or protein in urine
How do we classify GN?
AETIOLOGY Primary (Idiopathic) - THE MAJORITY(endocarditis)
Secondary caused by eg. infections or drugs associated with eg. malignancies or part of systemic disease eg. ANCA - associated systemic vasculitis, lupus, Goodpastures, HSP
HISTOLOGY
RENAL BIOPSY
Light Microscopy - can stain the different immunoglobulins/ Immunofluorescence/ EM
What is the histological classification in GN?
Proliferative or non-proliferative (usually refers to presence or absence of proliferation of mesangial cells)
Focal/Diffuse (< or > 50% glomeruli affected)
Global/Segmental (all or part glomerulus affected)
Crescentic (presence of crescents - epithelial cell extracapillary proliferation eg. RPGN in vasculitis)
What are the main principals aims for GN treatment?
Reduce degree of proteinuria
Induce remission of nephrotic syndrome
Preserve longterm renal function
What are the two arms for treatment in GN?
NON-IMMUNOSUPPRESSIVE
IMMUNOSUPPRESSIVE
What are the non-immunosuppressant treatment of GN?
Anti-hypertensives (target BP <130/80 - <120/75 if proteinuria) ACE inhibitors/ ARBs Diuretics Statins ? Anticoagulants/ Aspirin/ Antiplatelets ? Omega 3 fatty acids/ Fish oil
What are the immunosuppression treatments of GN?
Drugs
Corticosteroids (Prednisolone po/MethylPred IV)
Azathioprine
Alkylating agents (Cyclophosphamide/ Chlorambucil)
Calcineurin inhibitors (Cyclosporin/Tacrolimus)
Mycophenolate Mofetil (MMF)
Plasmapharesis (TPE-therapeutic plasma exchange)
Antibodies: IV Immunoglobulin
: Monoclonal T or B cell Antibodies
What is the major treatment of nephrotic patients?
Fluid restriction Salt restriction Diuretics ACE Inhibitors/ ARBs ? Anticoagulation IV Albumin (only if volume deplete)
What is the most commonest cause of nephrotic syndrome in children?
minical change disease
podocytes injury
normal in microscope
responds best to steroids
second line - cyclophosphamide/ CSA
Commonest cause of nephrotic syndrome in adults?
FSGS - FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Renal biopsy: As its name describes on light microscopy with minimal Ig/ Complement deposition on IF
Remission with prolonged steroids in 60 %
50 % progress to end stage renal failure after 10 years
What is the 2nd commonest cause of nephrotic syndrome in adults?
membranous nephropathy
What is the commonest GN in the world?
IgA nephropathy
Mesangial injury
causes renal failure over years
sore throat - darker urine and blood in urine,
if any infection -> it triggers more IgA release, starts in the mesangial cells –> HSPurpura –> the piurple skin patches
GPS
antibody against the arteriolar endothelium at the base of the lungs
74 year old woman. Hypoxic. Haemoptysis. creat 430. blood and protein on dip. Red cell casts on microscopy. Purpuric rash.
Cells affected?
Diagnosis?
What test next?
endothelial cells
ANCA positive vasculitis
ANCA test and biopsy
Most common cause of end stage renal failure?
Diabetic nephropathy
