Glomerulonephritis Flashcards
What are the main kinds of glomerular disease?
Diabetic Nephropathy
Glomerulonephritis (GN)
Amyloid/ Light Chain Nephropathy
Transplant Glomerulopathy
What are the two most common causes of end stage renal disease?
- Diabetes
- Chronic glomerulonephritis
What is glomerulonephritis?
An immune mediated disease of the kidneys affecting the glomeruli causing secondary tubulointerstitial damage
What are podocytes?
Cells that spread out around capillaries in branches, forming protein bridges (actin and myosin) between these branches to provide strong mechanical strength for the capillaries
What are mesangial cells?
Cells found between groups of capillaries that work in tandem with the glomerular basement membrane:
They act like smooth muscle cells and can cause vasoconstriction
They have immune function, releasing cytokines
What does the glomerular basement membrane consist of?
It is acellular and consists of collagen and protein
Which components of the glomerulus are injured in prolfierative glomerulonephritis?
Mesangial cells
Endothelial cells
Why does haematuria occur in proliferative GN?
Mesangial and endothelial cells are exposed to blood, so injury causes red cells in urine and a proliferative lesion and activation of the inflammatory cascade
This causes a nephritic syndrome
What does injury to podocytes result in?
Non-proliferative lesion and protein in urine
There is no activation of the inflammatory cascade since the podocytes are not exposed to blood
This causes nephrotic syndrome
What colour is urine typically in glomerulonephritis?
‘Smoky’, ‘rusty’ or coca-cola coloured
How should urine be examined if GN suspected and what would be expected?
Urinalysis: haematuria, proteinuria
Urine microsopy: RBC (dysmorphic), RBC & granular casts, lipiduria
Urine Protein: creatinine Ratio
24 hour urine - quantify proteinuria
How is haematuria normally picked up in glomerulonephritis?
Dipstick test - the haematuria is painless
How is proteinuria judged?
Microalbuminuria (30-300mg albuminuria/day)
Asymptomatic proteinuria (< 1 g/day)
Heavy proteinuria (1-3 g/day)
Nephrotic syndrome (> 3 g/day))
What is the usual diagnosis if red cell casts seen on microscopy of urine?
Indicates active, aggressive proliferative lesion
How does glomerulonephritis present?
Oedema
Hypoalbuminuria
Decresed renal function
Hypertension
Haematuria
Frothy urine
Why does hypertension occur in glomerulonephritis?
Fluid retention
Proliferative lesion causing increased renin secretion
What are the three indicators of nephrotic syndrome?
Oedema
Hypoalbuminuria
Proteinuria
Why does impaired immunity occur in nephrotic syndrome?
Opsonising antibodies are leaked out into urine
What is a complication of nephrotic syndrome that would make a patient present with unilateral loin pain and haematuria for the first time, and why?
Renal vein thrombosis
Hypoalbuminuria can change liver function, causing increased production of clotting and fibrotic factors
What are the features of nephrotic syndrome?
Proteinuria > 3 g/day (mostly albumin, also globulins)
Hypoalbuminaemia (<30)
Oedema
Hypercholesterolaemia
Usually normal renal function
What are the features of nephritic syndrome?
Acute Renal Failure
Oliguria
Oedema/ Fluid retention
Hypertension
Active urinary sediment: RBC’s, RBC and granular casts
What are the complications of nephrotic syndrome?
Infections
Renal vein thrombosis
Pulmonary emboli
Volume depletion: often due to overuse of ACEi, may lead to pre-renal AKI
Vit D deficiency
Subclinical hypothyroidism
What are the four components of histological classification of glomerulonephritis?
Proliferative/non-proliferative
Focal/diffuse (< or > 50% glomeruli affected)
Global/segmental (all or part glomerulus affected)
Crescentic
What does ‘crescentic’ mean on histological description of glomerulonephritis?
Presence of crescents: cells burst into Bowman’s space and form crescents around the glomerulus, causing ischaemia and death of the glomerulus
What are the principles of treatment of glomerulonephritis?
Reduce degree of proteinuria
Induce remission of nephrotic syndrome
Preserve longterm renal function
What are some of the non-immunosuppresive treatments of glomerulonephritis?
Anti-hypertensives
ACE inhibitors/ ARBs
Diuretics
Statins
What are some of the immunosuppressive drugs used to treat glomerulonephritis?
Corticosteroids (Prednisolone po/MethylPred IV)
Azathioprine
Alkylating agents (Cyclophosphamide/ Chlorambucil)
Calcineurin inhibitors (Cyclosporin/Tacrolimus)
Mycophenolate Mofetil (MMF)
Why is plasmapheresis used in immunosuppresive treatment of GN?
Used to remove antibodies causing the GN from the circulation
Why are antibodies used in immunosuppressive treatment of glomerulonephritis?
Monoclonal T or B cell antibodies can be used to switch off B cell production to stop production of antibodies causing GN
How are nephrotic patients managed?
Fluid restriction
Salt restriction
Diuretics
ACE Inhibitors/ ARBs
IV Albumin (only if volume depleted)
Immunosuppression
What values of proteinuria indicate remission from nephrotic syndrome?
Complete remission: proteinuria < 300 mg/day
Partial remission: proteinuria < 3g/day
What is the commonest cause of nephrotic syndrome in children?
Minimal change nephropathy
What is the pathology in minimal change nephropathy?
Podocyte foot process fusion
What is the first line treatment for minimal change nephropathy?
Oral steroids - 94% go into remission
What is the second-line treatment for minimal change nephropathy?
Cyclophosphamide
Does minimal change nephropathy cause progressive renal failure?
No
What is the commonest cause of nephrotic syndrome in adults?
Focal segmental glomerulosclerosis
What is the pathology in focal segmental glomerulosclerosis?
Affects small parts of the glomerulus in segments causing scarring and sclerosis
Stops formation of protein bridges between podocytes
Does focal segmental glomerulosclerosis cause renal damage?
50% progress to end stage renal failure after 10 years
What can cause focal segmental glomerulosclerosis?
HIV
Heroin use
Obesity
Reflux nephropathy
What is the second commonest cause of nephrotic syndrome in adults?
Membranous nephropathy: most common cause in the UK
What are some secondary causes of membranous nephropathy?
Infections (hepatitis B/ parasites)
Connective tissue diseases (lupus)
Malignancies (carcinomas/ lymphoma)
Drugs (gold/penicillamine)
What can be seen on renal biopsy with membranous nephropathy?
Subepithelial immune complex deposition in the basement membrane
What is the treatment for membranous nephropathy?
Steroids
Alkylating agents
B cell monoclonal Ab
What is the commonest glomerulonephritis in the world?
IgA nephropathy
How does IgA nephropathy present?
Asymptomatic microhaematuria ± non-nephrotic range proteinuria
Macroscopic haematuria after resp/GI infection
AKI/ CKD
What is IgA nephropathy associated with?
Associated with Henoch-Schonlein Purpura (HSP)
(arthritis/colitis/purpuric skin rash)
What is seen on renal biopsy?
Mesangial cell proliferation and expansion on light microscopy with IgA deposits in mesangium on IF
How is IgA nephropathy treated?
BP control
ACE inhibitors & ARBs
Fish oil
What is the disease process in IgA nephropathy?
Slight genetic abnormality in IgA causes it to become stuck in the kidney: tends to lodge in mesangial cell, stimulating proliferation
Endothelial depositon causes cytokine aggregation and an inflammatory cascade occurs
What may cause rapidly progressive glomerulonephritis in an ANCA positive patient?
Systemic Vasculitis
Wegener’s granulomatosis (Granulomatosis with polyangitis)
Microscopic polyangiitis
What are some of the ANCA negative causes of rapid progressive glomerulonephritis?
Goodpasture’s disease: Anti-GBM
Henoch Scholein Purpura HSP/IgA
Systemic Lupus Erythematosus
What is rapidly progressive glomerulonephritis?
A treatable cause of acute renal failure with rapid deterioration in renal function over days/weeks
There is active urinary sediment (RBC’s, RBC & Granular Casts) causing haematuria
What is the treatment for rapidly progressive glomerulonephritis?
Immediate immunosuppression and treatment of systemic cause:
Steroids (IV Methylprednisolone /oral prednisolone)
Cytotoxics (Cyclophosphamide/Mycophenolate/ Azathioprine
Plasmapheresis
