Glomerular Disease - Clinical Flashcards
What is glomerulonephritis?
Inflammatory disorder of the kidney
What percentage of end-stage kidney disease is glomerulonephritis responsible for?
Up to 30%
What is the presentation of glomerulonephritis?
Can present in many ways Mostly vague symptoms/signs - proteinuria - renal failure - hypertension
What is the function of mesangial cells?
Provide extracellular support for the capillaries
What is the permeability of the glomerular basement membrane?
Selectively permeable - in normal, healthy people, protein should not be present in the urine
What is present in the nuclei/cells in proliferative glomerulonephritis?
Overlap and congestion of the nuclei/cells
What are the classes of glomerulonephritis?
Proliferative
Non-proliferative
What are the features of non-proliferative glomerulonephritis?
Glomeruli look normal or have areas of scarring
Normal numbers of cells
Tubules and interstitium may be damaged
What are the features of proliferative glomerulonephritis?
Characterised by excessive numbers of cells in the glomeruli, including infiltrating leukocytes
Presents with nephrotic syndrome
Blood on dipstick, no or minimal proteinuria
What are the types of proliferative glomerular disease?
Diffuse proliferative
Focal proliferative
Focal necrotising (crescentic) nephritis
Membrano-proliferative nephritis
What are the features of post-infective glomerulonephritis?
Diffuse, congested nuclei
Immune deposits due to activation of the complement system
Follows 10-21 days after infection, typically of throat or skin
What type of bacteria is post-infective glomerulonephritis most commonly associated with?
Lancefield group A streptococci
Acute nephritis is typical of what?
Post-infective glomerulonephritis
What are the features of acute nephritis?
Fluid retention with oedema - periorbital oedema common
Normal serum albumin
Little proteinuria
Renal impairment
What is the treatment of post-infective glomerulonephritis?
Antibiotics for any active infection
Loop diuretics e.g. furosemide for oedema
Vasodilator drugs e.g. amlodipine for hypertension
Consider immunosuppression in severe/unresolving disease
What is the commonest cause of glomerulonephritis?
IgA nephropathy
What are the features of IgA nephropathy?
Congestion
Mesangial and endocapillary inflammation
Most inflammatory deposits are in the mesangium
No characteristic serology
Diagnosed by renal biopsy
In what patients does IgA nephropathy typically occur in?
Young - presents in late 30s-40s
What indicates that a patient with IgA nephropathy is likely to deteriorate?
Heavy proteinuria
High creatinine
Hypotension
What is the presenting feature of IgA nephropathy?
Macroscopic haematuria
What is IgA nephropathy provoked by?
Intercurrent infection
What is the typical onset of IgA nephropathy in adults?
Insidious onset
What is the prognosis of IgA nephropathy in adults?
Worse in adults - 25% develop renal failure
What is the treatment of IgA nephropathy?
Non-specific
ACEIs and other hypotensives
What are the features of focal necrotising glomerulonephritis?
Segmental necrosis
Ruptured capillary
In what 3 main settings does focal necrotising glomerulonephritis occur?
In presence of anti-glomerular basement membrane antibodies (Goodpasture’s syndrome)
Associated with systemic vasculitis e.g. granulomatosis with polyangiitis, microscopic polyangiitis
As a complication of other types of glomerulonephritis, including post-streptococcal glomerulonephritis and mesangial IgA disease
What is Goodpasture’s disease?
Rare disease caused by autoimmunity to the glomerular basement membrane
How does Goodpasture’s disease typically present?
As nephritis, with or without lung haemorrhage
How is Goodpasture’s disease diagnosed?
By demonstrating anti-GBM antibodies in serum and kidney
How is Goodpasture’s disease treated?
Plasma exchange and immunosuppression
Kidney can only be saved if detected and treated early
What is the typical presentation of crescentic glomerulonephritis?
Rapidly progressive glomerulonephritis
May occur in isolation, or as a complication of other disease e.g. chronic nephritis
Medical emergency
What is the management of crescentic glomerulonephritis?
Immunosuppression - prednisolone, cytotoxic drugs, plasma exchange
What is the prognosis of crescentic glomerulonephritis?
Good, if treatment is started early enough
CASE 1
7 year old boy presents to GP Generally unwell, dark urine due to haematuria Puffy face, no rash, no oedema BP 125/80 Sore throat two weeks previously Hb 130 g/l WCC 11.3 x 109 Urea 11.2 mmol/l Creatinine 160umol/l Urine microscopy – RBC +++, casts + Complement – low C3 Spontaneous diuresis after 6 days Serum creatinine returned to normal
What is the most likely diagnosis?
Diffuse proliferative glomerulonephritis - post-streptococcal nephritis
CASE 2
14 year old boy presents to GP with bright red urine
No other urinary symptoms
Concurrent upper respiratory tract infection
Physical examination normal
Urine dipstick shows high blood and trace of protein
What investigations would you do?
FBC Creatinine, urea and electrolytes Urine microscopy Serology Renal ultrasound Renal biopsy
CASE 2
14 year old boy presents to GP with bright red urine
No other urinary symptoms
Concurrent upper respiratory tract infection
Physical examination normal
Urine dipstick shows high blood and trace of protein
Urine microscopy shows dysmorphic erythrocytes and red cell casts
What is the most likely diagnosis?
Focal proliferative nephritis caused by mesangial IgA disease
CASE 3
57 year old woman presents to GP
Three month history of increasing tiredness, anorexia and weight loss
Developed a cough with haemoptysis over last two weeks
Physical examination reveals rash on both ankles and lower legs and bilateral basal crepitations
Urine dipstick shows protein and blood
ANF and DNA binding negative
ANCA positive
What is the most likely diagnosis?
Focal necrotising glomerulonephritis secondary to systemic vasculitis
What are the types of non-proliferative glomerulonephritis?
Minimal change disease
Focal glomerulonephritis
Membranous nephropathy
Causes nephrotic syndrome
What is the presentation of nephrotic syndrome?
Clinical triad of pitting oedema, proteinuria (> 3.5g) and hypoalbuminaemia (< 30 g/l, normal > 45)
What is nephrotic syndrome?
A clinical syndrome in which severe oedema is caused by hypoalbuminaemia due to loss of protein in the urine
What are the additional features of nephrotic syndrome?
Hyperlipidaemia
Hypercoagulable state - increased DVT and venous thromboembolism risk
Increased risk of infection, especially pneumococcus
What are the differential diagnoses of nephrotic syndrome?
Congestive heart failure - raised JVP, normal albumin, minimal proteinuria
Hepatic disease - abnormal LFTs, no proteinuria
Presence of proteinuria in nephrotic syndrome differentiates from these
What are the principles of management of nephrotic syndrome?
Specific management
Treatment of oedema
Prophylaxis against complications - identify those at risk of DVT/VTE and give anticoagulation
What is the specific management of nephrotic syndrome?
Make specific diagnosis e.g. by renal biopsy
Specific treatment when indicated
Consider steroid treatment with prednisolone if severe
What is the treatment of oedema in nephrotic syndrome?
Fluid and sodium restriction
Normal/high protein diet
Loop diuretics e.g. furosemide
IV infusion of albumin furosemide for resistant oedema
What prophylaxis can be given against potential complications of nephrotic syndrome?
Penicillin V for prophylaxis against infection
Heparin
Treat hyperlipidaemia in those with persistent nephrotic syndrome
What are the features of minimal change nephrotic syndrome?
Most common form in children
Sudden onset of oedema
Complete loss of proteinuria with steroids
2/3rds of patients relapse despite most going into remission
What is the treatment of minimal change nephrotic syndrome?
Prednisolone 60mg/m^2 per day, with rapid tapering of dose after a maximum of 8 weeks
Initial relapse treated in the same way
Subsequent relapses treated with 8 week course of cyclophosphamide or continuous cyclosporine
Treat any infection aggressively with antibiotics
What are the complications of minimal change nephrotic syndrome?
Bacterial infection, especially with pneumococcus
Thrombosis
What is the prognosis of minimal change nephrotic syndrome?
Resolves eventually, long term prognosis good
Patients do not develop renal failure
What are the features of focal glomerulosclerosis (steroid resistant nephrotic syndrome)?
Severe nephrotic syndrome, especially in men in fourth decade
Very disabling symptoms
Incomplete (at best) response to steroids
Progresses to renal failure over 2-3 years
Can recur in renal transplants
Immunohistology negative
Sclerotic lesions
Why is recover from focal glomerulosclerosis not possible?
Podocytes are killed by the disease process
What is the aim of treatment of focal glomerulosclerosis?
To delay the time until end-stage kidney disease
What is the treatment of focal glomerulosclerosis?
Initial trial of steroids - if complete response then prognosis is the same as for minimal change, if no response then poor prognosis
Continue steroids if clinically useful response
Try cyclophosphamide or cyclosporine if steroids fail
Steroid-sparing agents can be used, variable success
Non-specific drugs to reduce proteinuria e.g. ACEIs and NSAIDs
Non-specific treatment for nephrotic oedema and prophylaxis against nephrotic complications
What is the commonest cause of nephrotic syndrome in adults?
Membranous nephropathy
What is the cause of membranous nephropathy?
About half of cases are idiopathic
The other half are associated with another disease e.g. malignancy, systemic lupus, rheumatoid arthritis
Can also be caused by hypersensitivity to drugs
Where are deposits located in membranous nephropathy?
Between the spikes
What is the management of membranous nephropathy?
Control nephrotic symptoms
Immunosuppression for those with deteriorating renal function
Prednisolone and chorambucil, alternating monthly for six months
Cyclosporine probably ineffective
General measures in treatment should be done for 6 months before starting immunosuppression
What is the prognosis of membranous nephropathy?
Resolves spontaneously in 25% over 5-10 years
Prognosis is good in treated patients whose proteinuria resolves
About 25% will be on dialysis at 10 years
Can recur in renal transplants
CASE 4
22 year old woman Severe oedema which had developed suddenly over a week Breathless Left sided chest pain Urine contained high level of protein Nephrotic syndrome Creatinine upper level of normal Serum albumin low - 15 g/l
What is the likely diagnosis?
Minimal change nephrotic syndrome
CASE 5
66 year old man Steadily increasing oedema Recent change in bowel habit High level of proteinuria Serum creatinine high at 135mmol/l
What is the likely diagnosis?
Membranous nephropathy
Need to determine if it is associated with malignancy
